HPN Dec 2022

Non-fixed dose combination of MEKINIST® and TAFINLAR® Before prescribing Mekinist and Tafinlar in combination, please refer to the Summary of Product Characteristics (SmPC) of both products.

Presentation of each product: MEKINIST (trametinib) 0.5 mg and 2.0 mg film-coated tablets. Each film-coated tablet contains trametinib dimethyl sulfoxide equivalent to 0.5 mg and 2.0 mg of trametinib respectively. TAFINLAR (dabrafenib) 50 mg and 75 mg hard capsules. Each capsule contains dabrafenib mesilate, equivalent to 50 mg and 75 mg of dabrafenib respectively.

Indications: Combination of Mekinist and Tafinlar: • for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600 mutation.

• for the adjuvant treatment of adult patients with stage III melanoma with a BRAF V600 mutation following complete resection.

• for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with a BRAF V600 mutation.

Dosage and Administration: Adults: recommended dose of Mekinist is 2mg once daily in combination with Tafinlar 150mg twice daily. Dose modification: Management of ADRs may require treatment interruption, dose reduction, or discontinuation. Elderly: No initial dose adjustment required in patients >65 years. Paediatrics: Safety and efficacy not established in patients <18 years. Renal impairment: No dose adjustment required in mild or moderate impairment. Caution advised in severe renal impairment. Hepatic impairment: No dose adjustment required in mild hepatic impairment. Caution advised in moderate and severe hepatic impairment. In the adjuvant melanoma setting, patients should be treated for a period of 12 months unless there is disease recurrence or unacceptable toxicity. Contraindications: Hypersensitivity to active substance or excipients. Warnings/Precautions for Mekinist (used as a monotherapy or in combination with Tafinlar): Left ventricular ejection fraction (LVEF) reduction/Left ventricular dysfunction: Cases of LVEF decrease have been reported. Should be used with caution when conditions could impair left ventricular fraction. All patients should be evaluated for LVEF prior to initiation of treatment with continued evaluation during treatment. Consider dose modification guidelines. In patients receiving Mekinist in combination with Tafinlar, there have been occasional reports of acute, severe LVEF due to myocarditis. Full recovery was observed when stopping treatment. Physicians should be alert to the possibility of myocarditis in patients who develop new or worsening cardiac signs or symptoms. Haemorrhage: Haemorrhagic events including major and fatal haemorrhagic events occurred in patients taking Mekinist as monotherapy and in combination with Tafinlar. Hypertension: Blood pressure should be measured at baseline and monitored during treatment with Mekinist, with control of hypertension by standard therapy as appropriate. Interstitial lung disease (ILD)/Pneumonitis: Mekinist should be withheld in patients with suspected ILD or pneumonitis, including patients presenting with new or progressive pulmonary symptoms and findings including cough, dyspnoea, hypoxia, pleural effusion, or infiltrates, pending clinical investigations. Mekinist should be permanently discontinued for patients diagnosed with treatment-related ILD or pneumonitis. If Mekinist is being used in combination with Tafinlar then therapy with Tafinlar may be continued at the same dose. Rhabdomyolysis: Signs or symptoms of rhabdomyolysis should warrant an appropriate clinical evaluation and treatment as indicated. Visual impairment: visual disturbances, including chorioretinopathy or retinal pigment epithelial detachment (RPED) and retinal vein occlusion (RVO) have been observed. Not recommended for patients with history of RVO. Ophthalmological evaluation should be performed at baseline and during treatment if clinically warranted. If retinal abnormality is observed, treatment should be interrupted immediately and referral to specialist should be considered. Permanently discontinue treatment if RVO is noticed. Rash: observed in 60% of patients in monotherapy and 24% of patients in combination with Tafinlar. Severe cutaneous adverse reactions (SCARs): SCARs, including Stevens-Johnson syndrome, and drug reaction with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported with Mekinist in combination with Tafinlar. Before initiating treatment, patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms

suggestive of SCARs appear, Mekinist and Tafinlar should be withdrawn. Deep vein thrombosis (DVT)/pulmonary embolism (PE): can occur when used as a monotherapy or in combination with Tafinlar. Seek immediate medical care if patients develop symptoms of DVT or PE. Pyrexia: Pyrexia including severe rigors, dehydration and hypotension (including acute renal insufficiency) reported. Incidence and severity increased when Mekinist used in combination with Tafinlar. Monitoring serum creatinine and other evidence of renal function impairment during and following severe pyrexia events. Serious non-infectious febrile events observed. For management of pyrexia, therapy should be interrupted if the patient’s temperature is ≥38°C (100.4°F). In case of recurrence, therapy can also be interrupted at the first symptom of pyrexia. Colitis and gastrointestinal perforation: Colitis and gastrointestinal perforation, including fatal outcome, have been reported. Treatment with Mekinist monotherapy or in combination with Tafinlar should be used with caution in patients with risk factors for gastrointestinal perforation, including a history of diverticulitis, metastases to the gastrointestinal tract and concomitant use of medications with a recognized risk of gastrointestinal perforation. If patients develop symptoms of colitis and gastrointestinal perforation they should immediately seek medical care. Sarcoidosis: Cases of sarcoidosis have been reported in patients treated with trametinib in combination with dabrafenib, mostly involving the skin, lung, eye and lymph nodes. In the majority of the cases, treatment with trametinib and dabrafenib was maintained. In case of a diagnosis of sarcoidosis, relevant treatment should be considered. It is important not to misinterpret sarcoidosis as disease progression Sodium: This medicine contains less than 1mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium free’. Warnings/Precautions for Tafinlar (used as a monotherapy or in combination with Mekinist): Pyrexia including severe rigors, dehydration and hypotension (including acute renal insufficiency) reported. Incidence and severity increased when used in combination with Mekinist. During and following severe pyrexia events, serum creatinine and other evidence of renal function should be monitored. Serious non-infections febrile events have been observed. For management of pyrexia therapy should be interrupted if the patient’s temperature is ≥38°C (100.4°F). In case of recurrence, therapy can also be interrupted at the first symptom of pyrexia. Cutaneous squamous cell carcinoma (cuSCC) and new primary melanoma: skin examination prior, during and for 6 months after discontinuation of treatment or until initiation of another anti-neoplastic therapy. Non-cutaneous secondary/recurrent malignancy: monitoring as clinically appropriate for up to 6 months after discontinuation of Tafinlar or until initiation of another anti-neoplastic therapy. Pancreatitis: unexplained abdominal pain should be promptly investigated to include measurement of serum amylase & lipase. Close monitoring when re-starting Tafinlar. Uveitis: monitoring patients for visual signs and symptoms during therapy. Colitis and gastrointestinal perforation: Colitis and gastrointestinal perforation, including fatal outcome, have been reported in patients taking dabrafenib in combination with trametinib. Sarcoidosis: Cases of sarcoidosis have been reported in patients treated with dabrafenib in combination with trametinib, mostly involving the skin, lung, eye and lymph nodes. In the majority of the cases, treatment with dabrafenib and trametinib was maintained. In case of a diagnosis of sarcoidosis, relevant treatment should be considered. It is important not to misinterpret sarcoidosis as disease progression. Interactions: Mekinist: Effect of trametinib on other medicinal products: Based on clinical data, no loss of efficacy of hormonal contraceptives is expected when co-administered with trametinib monotherapy Tafinlar: Effect of other medicinal products on dabrafenib: Caution with co-administration of strong inhibitors (e.g. ketoconazole, gemfibrozil, nefazodone, clarithromycin, ritonavir, saquinavir, telithromycin, itraconazole, voriconazole, posaconazole, atazanavir) of CYP2C8 or CYP3A4. Avoid co-administration with strong inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital, or St John’s wort (Hypericum perforatum) of CYP2C8 and CYP3A4. Avoid agents that increase gastric pH, when possible. Effect of dabrafenib on other medicinal products: Avoid concomitant use with medicinal products that are sensitive substrates of certain metabolising enzymes or transporters, if monitoring for efficacy and dose adjustment is not possible. Please refer to Section 4.5 of SPC for groups of medicinal products that can be affected. A drug utilisation review (DUR) is essential on initiating dabrafenib treatment. Exercise caution when co-administering with warfarin and consider additional INR (lnternational Normalised Ratio) monitoring. Exercise caution

REFERENCES:

Novartis Ireland Ltd, Vista Building, Elm Park Business Park, Merrion Road, Dublin 4, D04 A9N6

when co-administering with digoxin and additional monitoring is recommended. Effects of dabrafenib on substance transport systems: Tafinlar inhibits OATP1B1 and OATP1B3. Monitoring recommended of drugs that are sensitive substrates of OATP1B1 and OATP1B3 and known to have a narrow therapeutic index with regards to high peak concentrations (Cmax). Fertility, Pregnancy & Lactation: Women of child-bearing potential: When Mekinist and Tafinlar are use in combination, use effective methods of contraception during therapy and for at least 16 weeks after stopping treatment. Tafinlar may decrease the efficacy of oral or any systemic hormonal contraceptives; use an effective alternative method of contraception. Pregnancy: Caution should be exercised by considering the expected benefit to the mother against possible risk to the foetus. Breastfeeding: Caution should be exercised by considering the benefit of breastfeeding for the child and the benefit of therapy for the woman. Fertility: Mekinist may impair human fertility. Tafinlar represents a potential risk for impaired spermatogenesis, which may be irreversible. Ability to Drive and Use Machines: Trametinib and Dabrafenib have minor influence. Patients should be made aware of the potential for fatigue, dizziness and eye problems. Adverse reactions with Mekinist monotherapy in metastatic melanoma: Very common (≥ 1/10): hypertension, haemorrhage, cough; dyspnoea, diarrhoea, nausea, vomiting, constipation, abdominal pain, dry mouth, rash, dermatitis acneiform, dry skin, pruritus, alopecia, fatigue, oedema peripheral, pyrexia, asparate aminotransferase increased. common (≥ 1/100, < 1/10): folliculitis; paronychia; cellulitis; rash pustular; anaemia; hypersensitivity; dehydration; vision blurred; periorbital oedema; visual impairment; left ventricular dysfunction; ejection fraction decreased; bradycardia; lymphoedema; pneumonitis; stomatitis; erythema; palmar-plantar erythrodysaesthesia syndrome; skin fissures; skin chapped; face oedema; mucosal inflammation; asthenia; alanine aminotransferase increased; blood alkaline phosphatase increased; blood creatine phosphokinase increased. Adverse reactions with Tafinlar monotherapy: Very common (≥ 1/10): papilloma; decreased appetite; headache; cough; nausea, vomiting, diarrhoea; hyperkeratosis, alopecia, rash, PPE, arthralgia, myalgia, pain in extremity, pyrexia, fatigue, chills, asthenia. common (≥ 1/100, < 1/10): cuSCC; seborrhoeic keratosis; skin tags; basal cell carcinoma; hypophosphataemia; hyperglycaemia; constipation; dry skin; pruritus; actinic keratosis; skin lesion; erythema; photosensitivity reaction; influenza-like illness. Adverse reactions observed when Mekinist and Tafinlar are used in combination: Very common (≥ 1/10): nasopharyngitis, decreased appetite, headache, dizziness, hypertension, haemorrhage, cough; abdominal pain, constipation, diarrhoea, nausea, vomiting, alanine aminotransferase increased, aspartate aminotransferase increased, dry skin, pruritus, rash, erythema, arthralgia, myalgia, pain in extremity, muscle spasms, fatigue, oedema peripheral, pyrexia, chills, asthenia, influenza-like illness. common (≥ 1/100, < 1/10): urinary tract infection, cellulitis; folliculitis; paronychia; rash pustular; cuSCC; papilloma; seborrhoeic keratosis; neutropenia,; anaemia; thrombocytopenia; leukopenia; dehydration; hyponatraemia; hypophosphataemia; hyperglycaemia; vision blurred; visual impairment; uveitis; ejection fraction decreased; hypotension; lymphoedema; dyspnoea; dry mouth; stomatitis; dermatitis acneiform; actinic keratosis; night sweats; hyperkeratosis; alopecia; palmar-plantar erythrodysaesthesia syndrome; skin lesion; hyperhidrosis; panniculitis; skin fissures; photosensitivity; mucosal inflammation; face oedema; blood alkaline; phosphatase increased; gamma-glutamyltransferase increased; blood creatine phosphokinase increased. For more details on adverse reactions, please see SmPC. Pack Size: Mekinist is supplied in bottles of 30 tablets. Tafinlar is supplied in packs of 120 hard capsules. Legal category: POM. Marketing Authorisation Numbers: Mekinist: EU/1/14/931/002 (0.5mg), EU/1/14/931/006 (2.0mg). Tafinlar: EU/1/13/865/002 (50 mg), EU/1/13/865/004 (75 mg). Marketing Authorisation Holder: Novartis Europharm Ltd, Vista Building, Elm Park, Merrion Road, Dublin 4, Ireland.

Date of revision of text: Aug 2021.

Full prescribing information is available upon request from: Novartis Ireland Limited, Vista Building, Elm Park Business Park, Elm Park, Dublin 4. Tel: 01-2601255 or at www. medicines.ie. Detailed information on this product is also available on the website of the European Medicines Agency http://www.ema.europa.eu.

1. Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med 2017;377(19):1813-1823. 2. Kirkwood JM, Manola J, Ibrahim J, et al; for Eastern Cooperative Oncology Group. A pooled analysis of Eastern Cooperative Oncology Group and Intergroup trials of adjuvant high-dose interferon for melanoma. Clin Cancer Res. 2004;10(5):1670-1677.

3. TAFINLAR Summary of Product Characteristics. Novartis Pharmaceuticals available at www.medicines.ie 4. Zelboraf Summary of Product characteristics. Roche available at www.medicines.ie 5. Cotellic Summary of Product Characteristics. Roche available at www.medicines.ie

6. Braftovi Summary of Product Characteristics. Pierre Fabre Medicament available at www.medicines.ie 7. Mektovi Summary of Product Characteristics.Pierre Fabre Medicament available at www.medicines.ie 8. Hauschild A, Dummer R, Schadendorf D, et al. Longer follow-up confirms relapse-free survival benefit with adjuvant dabrafenib plus trametinib in patients with resected BRAF V600–mutant stage III melanoma. J Clin Oncol. 2018;36(35):3441-3449. 9. Supplement to: Long GV, Hauschild A, Santinami M, et al. Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med. 2017;377(19):1813-1823. 10. Hauschild A, Dummer R, Santinami M, et al. Long-term benefit of adjuvant dabrafenib plus trametinib in patients with resected stage III BRAF V600-mutant melanoma: year analysis of COMBI-AD. Presented at: the American Society for Clinical Oncology Annual Meeting; May 29-31, 2020; Chicago, IL

ABBREVIATED PRESCRIBING INFORMATION

Contents Foreword

Galway academics named as ‘World’s Best Minds’ P4

Fighting Blindness host Annual Conference P6

HSE publishes National Stroke Strategy P8

Page 10: Study hears Hundreds of Cancer Deaths are Preventable P10

End of Year Review for Medicines for Ireland P12

2022 for the National Hospital Pharmacy Technicians Association P24

IPHA discusses the future of biopharmaceuticals P28

REGULARS

Feature: Prostate Cancer P36

CPD: Atrial Fibrillation P43

Feature: Asthma Care P49

Feature: Kidney Disease P90

R&D: P96

Hospital Professional News is a publication for Hospital Professionals and Professional educational bodies only. All rights reserved by Hospital Professional News. All material published in Hospital Professional News is copyright and no part of this magazine may be reproduced, stored in a retrieval system of transmitted in any form without written permission. IPN Communications Ltd have taken every care in compiling the magazine to ensure that it is correct at the time of going to press, however the publishers assume no responsibility for any effects from omissions or errors.

PUBLISHER

IPN Communications Ireland Ltd Clifton House, Lower Fitzwilliam Street, Dublin 2 (01) 669 0562 GROUP DIRECTOR

Natalie Maginnis n-maginnis@btconnect.com EDITOR Kelly Jo Eastwood

4

Editor

As T.S. Eliot said, “For last year’s words belong to last year’s language and next year’s words await another voice. And to make an end is to make a beginning.”

In one of our lead news stories this month, a leading Economist and Lecturer at Cork University Business School has said the Irish health service is effectively having to “ration care” through long waiting lists and wait times for care, as a result of serious capacity and resourcing deficits.

Speaking in a new video as part of the Irish Hospital Consultants Association’s (IHCA) Care Can’t Wait campaign, Dr Brian Turner echoed comments made by IHCA President, Professor Robert Landers, at the Association’s recent Annual Conference that demand has now outstripped supply and is impacting on the health service’s ability to deliver care. You can read more about this on page 5.

Meanwhile, Medicines for Ireland (MFI) have highlighted the growing risk of medicines shortages as inflation, energy and transport costs continue to rise, and global supply chain disruptions persist. According to the Health Products Regulatory Authority (HPRA) website there are currently 186 medicines in short supply in Ireland. Without intervention this situation has the potential to significantly worsen.

Commenting on MFI’s Pre-Budget Submission, Chairperson Padraic O’Brien said, “The greater use of generic medicines in Ireland helps patients access high quality treatments at considerably lower costs, it also produces significant savings for the State. “However, skyrocketing inflation, supply chain disturbances and soaring energy costs have created unforeseen challenges for the generic medicines sector across Europe including Ireland, resulting in thousands of generic medicines disappearing from the market”.

This issue also features our end of year reviews from some of the leading regulatory and representative bodies. On page 14 Professor Robert Landers notes that ‘opportunity exists for sustainable solutions to address a decade of despair for patients’ while Dr Lorraine Nolan, Chief Executive, Healthcare Products Regulatory Authority highlights (on page 21) that, “This year has seen significant progress in several key areas of focus for the HPRA as we continued our work in response to the pandemic in combination with ongoing activities to ensure the successful implementation of new regulations and management of medicines shortages.”

We also feature our annual Professional 100 in this issue. It is fair to say the dedication, passion and innovation behind the profession is never lacking.

Finally, may I take this opportunity on behalf of the entire HPN team to wish all our readers and supporters a very Merry Christmas, and a prosperous New Year. See you in 2023!

Galway Academics among ‘World’s Top

University of Galway professors Henry Curran and Patrick W. Serruys have been named on the annual Highly Cited Researchers 2022 list from Clarivate.

The researchers have once again joined the prestigious list of more than 6,900 researchers from across the globe who demonstrated significant influence

in their chosen field or fields through the publication of multiple highly cited papers during the last decade.

The highly anticipated annual list identifies researchers whose names are drawn from the publications that rank in the top 1% by citations for field and

¤2.7million Bon Secours Endoscopy Unit

publication year in the Web of Science citation index.

Professor Henry Curran, listed in the Engineering category, is Director of the Combustion Chemistry Centre at University of Galway’s School of Biological and Chemical Sciences and Priority Area Lead of the Energy Research Centre at the Ryan Institute.

Professor Patrick W. Serruys, listed in the Clinical Medicine category, is Established Professor of Interventional Medicine and Innovation, Director of the CORRIB Research Centre for Advanced Imaging and Core Laboratory at the College of Medicine, Nursing and Health Sciences. He is a world-renowned expert in interventional cardiology and imaging with more than four decades experience in clinical trials and innovation in medicine.

Minister of State for Sport and the Gaeltacht, Jack Chambers TD, has officially opened a new ¤2.7 million Bon Secours Hospital Dublin endoscopy unit in Glasnevin.

Part of a wider ¤300 million national investment by Bon Secours Health System in line with its 2025 Strategic Plan, the Dublin hospital’s fourth procedure room will increase patient capacity by 25%, meaning its endoscopy unit becomes the 2nd busiest in Ireland, performing over 15,000 procedures annually with this figure set to grow further next year.

In June of this year, Bon Secours Hospital Dublin announced a new ¤14 million surgical and oncology day ward and the creation of 80 new jobs. This followed the group’s ¤300 million national commitment in March to invest in enhancing and expanding its services as part of a new strategy, “Resilience, Reliability and Readiness – The 2025 Plan”. Bon Secours Health System also opened new ¤10 million operating theatres in Cork in January, with the hospital group also in the process of developing a new 150-bed medical facility in Limerick City which will greatly expand services currently offered to patients in the mid-west. Bon Secours Tralee also plans to open a new ¤10 million Medical Assessment Unit and surgical day ward in 2024.

Pharmacist engagement in Cardiovascular Care

A wide range of opportunities for pharmacists to provide cardiovascular disease (CVD) services are described in a new practice support handbook published by the International Pharmaceutical Federation (FIP).

According to the World Health Organization, deaths from CVDs currently represent 32% of all deaths globally, with over 75% of these occurring in low- and middle-income countries. With deaths from CVDs projected to increase from 18.9 million in 2020 to 32.3 million by 2030, demand for cardiovascular prevention, care and treatments continues to grow. “Cardiovascular diseases: A handbook for pharmacists”

covers prevention, care and management roles, including: health promotion and education; early detection; triage and referral; interprofessional collaborative practice; disease management (including medication adherence); treatment optimisation; and helping to shape public policies. In particular, it contains a chapter on practice-based research.

“Care goes beyond medicines use and optimising effectiveness and safety. Pharmacists can also be involved in practicebased research to evaluate the impact of CVD services. This new handbook contains several evidence-based interventions by pharmacists around the world that

have led to positive health and economic outcomes for patients, which readers will find valuable and inspirational,” said Dr Inês Nunes da Cunha, FIP practice development and transformation projects manager and lead author of the handbook.

“It is important that pharmacists are able to meet needs, expanding and consolidating their CVD services and roles with the appropriate knowledge and skills as defined in the ‘FIP Knowledge and skills reference guide for professional development in cardiovascular diseases’ [also published by FIP today]. It is also essential that pharmacy professional organisations at

global, regional and national levels support practitioners in implementing and providing services in this area,” she said.

The new handbook has been developed in collaboration with the World Heart Federation (WHF) and the European Society of Clinical Pharmacy. In a foreword to the handbook, WHF president Professor Fausto Pinto writes: “The pharmaceutical workforce is an essential pillar of the healthcare system and is ideally positioned to strengthen primary care delivery. This is particularly true for CVD, which can often be addressed by simple, affordable interventions that can be delivered in the pharmacy setting.”

Professor Patrick Serrys, University of Galway

Ireland ‘Rationing Care’ Warns Economist

A leading Economist and Lecturer at Cork University Business School has said the Irish health service is effectively having to “ration care” through long waiting lists and wait times for care, as a result of serious capacity and resourcing deficits.

Speaking in a new video as part of the Irish Hospital Consultants Association’s (IHCA) Care Can’t Wait campaign, Dr Brian Turner echoed comments made by IHCA President, Professor Robert Landers, at the Association’s recent Annual Conference that demand has now outstripped supply and is impacting on the health service’s ability to deliver care.

A near record 907,700 people are currently on some form of waiting list, with almost a quarter of these patients (207,600 or 23%) waiting more than a year for assessment or

treatment. Dr Turner believes this shows the direct impact of capacity deficits on the ground in the country’s acute public hospitals.

Meanwhile, the IHCA says that over 900 permanent hospital Consultant posts are not filled as needed as decades of underinvestment, staff and bed shortages, and unsustainable working conditions are driving our highly trained medical specialists abroad. Approximately 1,400 specialists have voluntarily withdrawn their registration from the Medical Council’s Specialist Division since the pay inequity was imposed by Government on Consultants appointed since October 2012.

Dr Turner suggests a holistic approach is needed when looking at improving the health service

for patients, with a clear need to increase bed capacity and Consultant numbers in order to ensure timely access to care.

“We have much lower specialist doctor numbers than the OECD average, so that’s going to be a crucial area to build up again. In a situation where you have higher demand than supply, you have rationing - and that’s what we’re seeing in the Irish health system, rationing via waiting lists and wait times.”

Dr Turner also believes the Government may need to review the Sláintecare plan to change projections in light of a faster than expected rise in population and fresh data from the ESRI, which suggests up to a 64% increase in Consultant numbers may be needed by 2035.

Growing Risk of Medicine Shortages

Medicines for Ireland (MFI) have highlighted the growing risk of medicines shortages as inflation, energy and transport costs continue to rise, and global supply chain disruptions persist.

According to the Health Products Regulatory Authority (HPRA) website there are currently 186 medicines in short supply in Ireland. Without intervention this situation has the potential to significantly worsen.

The Medicines for Ireland, PreBudget Submission 2023 sets out recommendations to tackle and prevent any potential shortages.

medicine shortages; exploring the possibility of the establishment of a National Medicines Reserve; and the extension of the 0% VAT rate that currently applies to certain oral medicines and nonoral medicines.

Commenting on MFI’s Pre-Budget Submission, Chairperson Padraic O’Brien said, “The greater use of generic medicines in Ireland helps patients access high quality treatments at considerably lower costs, it also produces significant savings for the State.

“However, skyrocketing inflation, supply chain disturbances and

Europe including Ireland, resulting in thousands of generic medicines disappearing from the market”.

“According to our sister association Medicines for Europe, several countries around the EU are experiences shortages, for example Romania have seen 2000 medicines disappear from the market and in Belgium one in five medicines available last year, are now no longer available.”

He added, “As a small market Ireland is more likely to be badly impacted by inflationary pressure and as costs continue to rise, market conditions will

for companies supplying generic

Dr Brian Turner, economist

pharmacies. Additionally, in some cases, our reimbursement prices for certain medicines are too low compared to other EU countries and price adjustments in Ireland are historically downward only. This adds to unsustainable market conditions for suppliers.”

Visit www.thepmi.com for booking information.

The Pharmaceutical Managers’ Institute will hold a Pharma Manager Series event on Wednesday, January 25th,

pharmacoeconomic evaluations on medicines prior to reimbursement under the Community Drugs schemes in Ireland.

Unearthing Potential Secret to Viral Resistance

Scientists from Trinity have unearthed a secret that may explain why some people are able to resist viral infections, having screened the immune systems of women exposed to hepatitis C (HCV) through contaminated anti-D transfusions given over 40 years ago in Ireland.

The extraordinary work, just published in leading journal Cell Reports Medicine, has wide-ranging implications from improving our fundamental understanding of viral resistance to the potential design of therapies to treat infected people.

Between 1977-79 in Ireland, several thousand women were exposed to the hepatitis C virus through contaminated anti-D, which is a medication made using plasma from donated blood and given to Rhesus negative women who are pregnant

with a Rhesus positive foetus. The medication prevents the development of antibodies that could be dangerous in subsequent pregnancies. Some of the anti-D used during the 1977-79 period was contaminated with hepatitis C.

From this outbreak, three groups of people were identifiable: those who were chronically infected; those who cleared the infection with an antibody response; and those who appeared protected against infection without making antibodies against hepatitis C.

Cliona O’Farrelly, Professor of Comparative Immunology in Trinity’s School of Biochemistry and Immunology, is the senior author of the research article.

Cliona, who is based in the Trinity Biomedical Sciences Institute, said, “We hypothesised that women who seemed to resist HCV infection must have an enhanced

innate immune response, which is the ancient part of the immune system that acts as a first line of defence.

“To test this we needed to make contact with women exposed to the virus over forty years ago and ask them to help us by allowing us to study their immune systems to hunt for scientific clues that would explain their differing responses.

The scientists ultimately recruited almost 40 women from the resistant group, alongside 90 women who were previously infected.

In collaboration with the Institute Pasteur in Paris they then invited almost 20 women in each group to donate a blood sample that they stimulated with molecules that mimic viral infection and lead to activation of the innate immune system.

Fighting Blindness Conference

Pictured (right) at the Fighting Blindness Retina conference, which took place in the Radisson Blu Royal Hotel, Dublin 2, on November 3 & 4, were Oliver Blacque, Associate Professor, School of Biomolecular and Biomedical Science, University College Dublin, Michael Griffith, Founder, Fighting Blindness, and Finbarr Roche, CEO, Fighting Blindness.

Now in its 23rd year, Retina brought together leading clinicians and scientists working in ophthalmology research to share advances being made and provide opportunities for future collaboration. Proceedings from Retina can be found at www.fightingblindness.ie/ retina-2022. The event was proudly supported by AbbVie, Novartis, Roche and Specsavers.

Pictured at the Fighting Blindness Retina conference, which took place in the Radisson Blu Royal Hotel, Dublin 2, on November 3 & 4, were Prof. John Flannery, University of California, Berkeley, USA, and Neil Ward, Head of Advocacy & Communications, Fighting Blindness

Pictured at the Fighting Blindness Retina conference, which took place in the Radisson Blu Royal Hotel, Dublin 2, on November 3 & 4, were Dr Elaine McSherry, Medical Manager, Roche, Catherine Moynagh, Patient Partnership Lead, Roche and Dr Julia Zhu, IRD Fellow, The Mater Hospital

Jamie Sugrue, PhD Candidate in Trinity’s School of Biochemistry and Immunology, is first author of the research article. He said, “We think that the increased type I interferon production by our resistant donors, seen now almost 40 years after the original exposure to hepatitis C, is what protected them against infection.

“These findings are important as resistance to infection is very much an overlooked outcome following viral outbreak, primarily because identifying resistant individuals is very difficult – since they do not become sick after viral exposure, they wouldn’t necessarily know that they were exposed. That’s why cohorts like this, though tragic in nature, are so valuable – they provide a unique opportunity to study the response to viral infections in an otherwise healthy population."

Pictured at the Fighting Blindness Retina conference, which took place in the Radisson Blu Royal Hotel, Dublin 2, on November 3 & 4, were Dr Ellen Moran, Research Manager, Fighting Blindness, Dr Colla Cunneen, AbbVie and Dr Julia Zhu, IRD Fellow, The Mater Hospital

STUDY DESIGN

Double-blind, active comparator-controlled study in which pneumococcal vaccine-naïve participants 50 years of age and older were randomized to receive either VAXNEUVANCE (N=604) or PCV13 (N=601). aGMT ratio vs PCV13: 1.62 (95% Cl: 1.40-1.87).

Randomized controlled trials assessing the clinical efficacy of VAXNEUVANCE compared to PCV13 have not been conducted.

VAXNEUVANCE® ▼

Suspension for injection in pre-filled syringe. Pneumococcal polysaccharide conjugate vaccine (15-valent, adsorbed)

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SPC for how to report adverse reactions.

ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before prescribing. PRESENTATION 1 dose (0.5 mL) con tains 2.0 mcg of each of the following pneumococcal polysaccharide serotypes: 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F and 4 mcg serotype 6B; 125 mcg aluminium (Al3+) and approximately 30 mcg CRM197 carrier protein. INDICATIONS For active immunisation to prevent invasive disease and pneumonia caused by Streptococcus pneumoniae in individuals 18 years of age and older. Use in accordance with official recommendations. DOSAGE AND ADMINISTRATION Adults: Single dose of 0.5 ml given by intramuscular injection. Need for a booster dose not established. Children and adolescents aged under 18 years: Safety and efficacy not established. CONTRAINDICATIONS Hypersensitivity to any component of the vaccine or to any diphtheria toxoid containing vaccine. PRECAUTIONS AND WARNINGS Do not give intravascularly. Ensure appropriate facilities and medication are available in case of anaphylaxis. Delay vaccination in presence of acute, severe febrile illness or other significant infection. Use with caution in individuals on anticoagulants, or those with thrombocytopaenia or any coagulation disorder, as bleeding or bruising may occur. Vaccine may not provide complete protection in all recipients. Immunocompromised individuals may have reduced antibody response to Vaxneuvance. Availability of safety and immunogenicity data in presence of immunosuppression is limited to individuals with HIV infection. INTERACTIONS Can be administered concomitantly with seasonal quadrivalent influenza vaccine (split virion, inactivated); no data on concomitant administration of Vaxneuvance with other vaccines. Different injectable vaccines should always be administered at different injection sites. Immunosuppressive therapies may reduce the immune responses to vaccines. FERTILITY, PREGNANCY AND LACTATION Pregnancy and lactation: Limited experience in pregnant women. Only consider use in pregnancy when risk: benefit ratio is positive for mother and foetus. No

VAXNEUVANCE is indicated for active immunisation for the prevention of invasive disease and pneumonia caused by Streptococcus pneumoniae in individuals 18 years of age and older.1

VAXNEUVANCE contains 15 purified pneumococcal capsular polysaccharides from Streptococcus pneumoniae (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F), each conjugated to a carrier protein (CRM197).1

VAXNEUVANCE elicits a T-cell dependent immune response to induce antibodies that enhance opsonisation, phagocytosis, and killing of pneumococci to protect against pneumococcal disease.1

VAXNEUVANCE is available to order privately from MSD msd@united-drug.com Freephone orderline 1800 200 845 Freefax orderline 1800 200 846

For more information on the VAXNEUVANCE visit MSDConnect.ie or scan the QR code with your phone.

1. Vaxneuvance Summary of Product Characteristics, September 2022, available at www.medicines.ie.

World Stroke Day: HSE Launch National Stroke Strategy

59% increase predicted in the total number of strokes by 2035

Acute Care includes:

• Acute stroke services must have adequate staffing and diagnostic resources to provide 24/7 acute stroke care and treatment

• All hospitals receiving acute stroke patients must have an acute stroke unit.

• Appropriate staffing of specialist stroke units with a number of trained physicians, nurses, healthcare assistants, health and social care professionals

public engagement on the issue of stroke are a significant challenge over the next decade.

The HSE National Clinical Programme for Stroke mark World Stroke Day by launching the new National Stroke Strategy 2022-2027.

Stroke is the second leading cause of death in middle to higher income countries and the leading cause of acquired neurological disability in Ireland. Approximately 5,800 adults were admitted to hospitals with a stroke in 2020. This figure does not include the estimated 1,500-2,000 people admitted or evaluated urgently for a suspected / threatened stroke or a transient ischaemic attack (TIA).

Professor Rónán Collins, Clinical Lead for the HSE National Clinical Programme for Stroke says, “Stroke is a major cause of mortality and morbidity in our population and a major cost to our health service when outcomes are poor. Much improvement in services and outcomes has occurred since the inception of the National Clinical Programme for Stroke, but the nature of our changing demography, development of new stroke treatments and technologies, and the need for healthcare staff and

“The programme has prioritised an ambitious but realistic strategy to improve resourcing of stroke services and seeks commitment from government for a structured implementation, review and a ‘next steps for stroke’ strategy, to commence in 2026 with the aim of full realisation of the Stroke Action Plan for Europe by 2031.”

To meet the challenge of a predicted 59% increase in the total number of strokes in Ireland four pillars of the new National Stroke Strategy were identified which focus on:

1. Stroke Prevention

2. Acute Care and Cure 3. Rehabilitation and Restoration to Living

4. Education and Research

Dr Colm Henry, Chief Clinical Officer, HSE added, “I welcome the launch of the new National Stroke Strategy which has been developed to provide safe, effective stroke care with improved outcomes for patients. The strategy will bring stroke care in Ireland in line with other

allied national strategies and the stroke action plan for Europe 2018-2030 of the European Stroke Organisation. I am confident it will pay significant dividend for patients, healthcare and society as a whole for years to come.”

National Stroke Strategy Recommendations:

Stroke Prevention includes:

• Many strokes are preventableprincipal risk factors for stroke, such as high blood pressure and atrial fibrillation are increasing in prevalence.

• Develop a pathway for the casefinding, diagnosis and treatment of high blood pressure in over 45 year olds

• Develop a pathway for the prevention and case detection of atrial fibrillation (AF)

• Ensure all hospitals receiving acute stroke patients have a specialist-led rapid access stroke service or access to such a service within their hospital network.

• Ensure that all patients recovering from a stroke have access to a specialist secondary prevention stroke service and diagnostics.

• All patients must have 24/7 access to emergency acute stroke assessment and treatment by a stroke specialist

Rehabilitation includes:

• Early Supported Discharge teams to be fully commissioned across 21 high activity sites over a three-year period to cover 92% of the stroke inpatient population

• ‘Stroke Key Worker*’ resource to be by appointed in each CHO so that discharged stroke patients and their families have access to the specific support and advice

• All stroke patients to have a ‘stroke passport’

Education & Research includes

• Funding for a sustained public awareness campaign on stroke

• Creation of Professorships in Neurovascular and Stroke Medicine in our six medical schools to improve Irish research and teaching in stroke

• Creation of three Stroke Research Fellowships to enhance research and career opportunity and help retain our excellent medical graduates in stroke medicine

To view the National Stroke Strategy document, see https:// www.hse.ie/eng/about/who/cspd/ ncps/stroke/

University Hospital Galway hosts world renowned surgeon

University Hospital Galway was delighted to welcome world pioneering surgeon, Professor Diego González Rivas to the hospital last month. During his visit Professor González Rivas, delivered a lecture to colleagues across the Department of Cardiothoracic Surgery entitled “The Journey of Uniportal Thoracic Surgery from VATS to Robotics.” He also performed two complex cases alongside the cardiothoracic team in UHG.

Prof González Rivas is a world-renowned surgeon who has pioneered multiple innovative techniques over the years. He was the first surgeon in the world to perform the single-port VATS technique. The single-port VATS surgical technique is innovative at world level, since it enables the removal of more complex tumours through a single incision. He also has over 15 years’ experience in performing major single-port lung surgery in patients without intubation and with spontaneous breathing.

Dr. González-Rivas was the pioneer surgeon in the world performing uniportal VATS lobectomies. Research has shown that patients who have undergone this surgery have demonstrated less postoperative pain, a speedier recovery and superior cosmetic results when compared to those where a multi-port approach was utilised.

Professor Rónán Collins, Clinical Lead for the HSE National Clinical Programme for Stroke

“The programme has prioritised an ambitious but realistic strategy to improve resourcing of stroke services and seeks commitment from government for a structured implementation, review and a ‘next steps for stroke’ strategy, to commence in 2026 with the aim of full realisation of the Stroke Action Plan for Europe by 2031.”

New Study shows Many Cancer Deaths Avoidable

Hundreds of deaths from cancer could be avoided every year if Ireland’s survival rates from the disease were similar to the best-performing countries in western Europe, according to a new study by the Swedish Institute for Health Economics (IHE) for the Irish Pharmaceutical Healthcare Association (IPHA), the representative organisation for the international research-based biopharmaceutical industry.

The study, ‘Comparator Report on Cancer in Ireland – Disease Burden, Costs and Access to Medicines’, examined 15 western European countries, benchmarking Ireland against Austria, Belgium, Denmark, Spain, Finland. France, Germany, Greece, Italy, Luxembourg, Netherlands, Portugal, Sweden and the UK.

The study, launched at the IPHA Forum Series, a virtual thought-

leadership events platform, found that cancer is Ireland’s leading cause of mortality, accounting for more than one in four deaths. Although cancer survival has improved since the 1990s, the study argues that more progress is needed to bring the standard of care for the disease to above average in the 15 western European countries.

Cancer is associated with ageing and population growth, with the doubling of newly diagnosed cancer cases since 1995 to 24,000 cases annually in 2017-2019 driven mostly by demographic changes. In multiple myeloma, the five-year survival rate has risen from 27% in 1994-1998 to 64% in 2014-2018 but, for survival rates in breast and ovarian cancer, Ireland ranks last, according to the study. Prostate, breast, colorectal and lung cancer account for just over half of all new cases.

The study found that improvements in cancer care are needed to avert at least some of the 15,000 extra annual new cancer cases and 8,000 extra annual cancer deaths expected by 2040. These projections, cited in the study from the International Agency for Research on Cancer, show that demographic pressures alone could raise cancer diagnoses annually to 42,000 cases by 2040. By then, the annual number of cancer deaths could rise from 10,000 to 18,000. Better cancer care could save up to 3,500 lives in 2040 alone, according to the study.

Better patient outcomes are reducing the indirect costs of cancer, with more people staying active in the workforce for longer. Between 2012 and 2020, 10 new cancer medicines annually were approved by the European Medicines Agency (EMA), the EU’s medicines regulator. By 2021, that number had risen to 17. Of all new cancer medicines approved by the EMA between 2017 and 2020, just 51% were reimbursed locally by the Health Service Executive (HSE) at the beginning of this year. For reimbursed cancer medicines, the average time to the reimbursement decision following EMA approval was almost two years, placing Ireland ahead of Portugal only. When cancer medicines are reimbursed, their use is close to the average in 15 peer countries in Europe.

Using a sample of 11 recently EMA-approved cancer medicines, the study found that the time to reimbursement by the HSE cumulatively accounted for 2,600 years of potential life lost. That figure included 1,000 years in working-age patients, with an economic loss of ¤34 million.

Michael O’Connell, IPHA’s President, said he hoped the study would be a constructive, evidencebased input for policymaking.

“Cancer is close to too many us, with sometimes devastating results for individuals and families across the country. This study shows some of what we’re getting right in cancer care and we should acknowledge that survival is improving. Innovation in cancer medicines is moving at pace. Cancer medicines are vital in the fight against the disease. But we still lag our European peers on access to new medicines, even though the Government’s investments in the latest treatments should, in time, arrest the slide. We are working on ideas that can improve the reimbursement process. Allied with sustained, adequate investment in new medicines, reimbursement process reform can help to raise standards of care,” said Mr O’Connell.

Dr Austin Duffy, a Consultant Medical Oncologist at the Mater Hospital, Dublin, described the study as an important overview of the cancer landscape.

“Clearly, we have made important strides in the treatment of cancer in Ireland. Survival is improving but more cases are diagnosed due to our ageing and increasing population. What is concerning is that Irish patients clearly have much slower access to new medicines, some of which can have a very dramatic impact on their conditions and prognoses,” said Dr Duffy.

IPHA President Michael O’Connell

“Cancer medicines are vital in the fight against the disease. But we still lag our European peers on access to new medicines, even though the Government’s investments in the latest treatments should, in time, arrest the slide”

Fresenius Kabi Oncology

Perfecting the steps to help improve quality of life for patients

With

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End of Year Report: Medicines for Ireland

Safeguarding Medicines Access

“There are challenges upcoming to patients’ access to medicines in Northern Ireland and beyond. Time is running out to fix this. Thankfully, the European Parliament will shortly consider legislative changes to help the situation. But, we haven’t seen the proposals yet. The UK and Irish Governments and their regulators have worked tirelessly on related solutions. Let’s redouble all our efforts.

associated with increased usage of generic medicines.

It has been a busy year for the team at Medicines for Ireland as the representative body has worked to safeguard access to medicines, advancing medicines repurposing, ensured uninterrupted supply of medicine between Ireland and the UK and carried out research into the generics market.

We spoke to David Delaney, Head of Policy and Market Access for Europe with Viatris and Chair of the EU Affairs Committee, Medicines for Ireland about the key challenges with regards to medicines access and equality.

David leads advocacy at the European Parliament and Trade Committees for MFI and as a Board member of Medicines for Europe. David helps manage the MFI relationship with Ireland’s Department of Health, other Government Departments, regulators and media on key industry related matters.

Towards the end of last year, David was an invited live speaker at Ireland’s National Parliament Seanad (Senate) Special Committee on the Withdrawal of the UK from the EU.

The industry group has warned that imminent regulatory requirements threaten medicine supplies from Britain to Northern Ireland.

The Brexit agreement for Northern Ireland, designed to avoid a hard border on the island of Ireland,

leaves Northern Ireland within the EU’s regulatory system for pharmaceuticals.

The Northern Ireland Protocol states that the “marketing authorisation holder” – the company or other legal entity authorised to market a product –for any medicines sold in Northern Ireland must be in the EU, the European Economic Area or Northern Ireland but not in Britain.

It is this requirement which is forcing medicines manufacturers to invest in reorganising regulatory filings, packaging and licences on bespoke boxes of medicines for Northern Ireland to service a market in European teams that would be like making special arrangements in the Republic for medicines being sold in Mayo.

David commented, “Before the power cut issues in Dublin today impacting Parliament, we planned to focus on urgently needed solutions to ensure stable patient access to medicines in Northern Ireland and beyond.

“Many thanks to the Committee Cathaoirleach (Chairperson) Senator Lisa Chambers for the invitation to speak and at the new date in October, to express the views and suggested solutions of Medicines for Ireland and Medicines for Europe who represent companies who supply the majority of medicines daily across the island of Ireland, and throughout the EU.

“With many political representatives engaging with the Committee from Northern Ireland, EU and the U.S. such as Congressman Richard Neal and EU Commissioner Mairead McGuinness, the expert analysis of solutions and issues for the island of Ireland is a great service and legacy from this Committee. We look forward to playing our role too.”

In May of this year, David met with the UK Department of Health and Social Care’s Noah Thorold.

David met with Noah in London representing Medicines for Europe – whose member companies make and research & develop the majority of medicines used daily in Northern Ireland and across Europe.

“Stakeholders continue work to ensure continued stable patient access to medicines in Northern Ireland, in the context of the Northern Ireland Protocol and beyond,” he said.

The following month, in June, MFI reported that generic medicines now account for 57% of the volume of the total prescription market in Ireland. According to findings commissioned by MFI and compiled by IQVIA, Over the past ten years the volume of generic medicines across Ireland has risen by 24%, this is due to effective Government policies and legislative changes regarding procurement and supply, as well as consistent activity for MFI members to promote the advantages

Chairperson for Medicines for Ireland, Padraic O’Brien said “Every time a generic medicine is dispensed, it represents a cost saving to the State and an opportunity for additional funding to be channelled to other areas of the healthcare system. Now more than ever a focus on quality and value is crucial for the State and the patients who rely on timely access to affordable medicines.”

“As an organisation MFI are proud that our membership will supply over 60 million packs of prescription medicines to Irish patients this year. This equates to an average of 2 packs of medicines every second.”

They also published a new report new report focused on the benefits of using VAMs in an EU context. ‘Value Added Medicines: Advancing Medicine Repurposing in the EU’ builds on the 2021 published report ‘Discussion Document on the Contribution of Value Added Medicines (VAMs) in Ireland’. It has been produced in conjunction with sister organisation, Medicines for Europe.

Value Added Medicines (VAMs) are medicines based on known molecules that address healthcare needs and deliver relevant improvements for patients and healthcare professionals. VAMs are key drivers for access to medicines and are increasing patient quality of life for chronic diseases, while offering significant benefits to the healthcare community.

VAMs offer a wide range of benefits from ensuring better adherence and compliance, to keeping healthcare costs down by reducing the need for patients to be moved to expensive next line therapies. The importance of using VAMs to address unmet medical needs in a timely and cost-effective manner has been highlighted during the Covid 19 pandemic.

David Delaney,

Head of Policy

and Market Access for Europe with Viatris and Chair of the EU Affairs Committee

It has been a busy year for the team at Medicines for Ireland as the representative body has worked to safeguard access to medicines, advancing medicines repurposing, ensured uninterrupted supply of medicine between Ireland and the UK and carried out research into the generics market.

50mgs once daily

Her 10th shopping trip since the day she started BETMIGA1

Prescribing Information: Please read the Summary of Product Characteristics (SPC) before prescribing. Presentation: Prolonged-release tablet, containing mirabegron 25mg/50mg. Indication: Symptomatic treatment of urgency, increased micturition frequency and/or urgency incontinence as may occur in adult patients with overactive bladder (OAB) syndrome. Posology and method of administration: The recommended dose is 50 mg once daily. A lower dose of 25mg is recommended for specific patient populations (renal and hepatic impairment) as well as in specific patient populations in combination with strong CYP3A inhibitors such as itraconazole, ketoconazole, ritonavir and clarithromycin. Renal impairment: End stage renal disease (GFR < 15 mL/min/1.73 m2 or patients requiring haemodialysis): Not recommended. Severe renal impairment (GFR 15 to 29 mL/min/1.73 m2): Reduce dose to 25 mg. Severe renal impairment and concomitant strong CYP3A inhibitors: Not recommended. Moderate renal impairment (GFR 30 to 59 mL/min/1.73 m2): 50 mg. Moderate renal impairment and concomitant strong CYP3A inhibitors: Reduce dose to 25 mg. Mild renal impairment (GFR 60 to 89 mL/min/1.73 m2): 50 mg. Mild renal impairment and concomitant strong CYP3A inhibitors: Reduce dose to 25 mg. Hepatic impairment: Severe hepatic impairment (Child-Pugh Class C): Not recommended. Moderate hepatic impairment (Child-Pugh B): Reduce dose to 25 mg. Moderate hepatic impairment and concomitant strong CYP3A inhibitors: Not recommended. Mild hepatic impairment (Child-Pugh A): 50 mg. Mild hepatic impairment and concomitant strong CYP3A inhibitors: Reduce dose to 25 mg. The tablet is to be taken once daily, with liquids, swallowed whole and is not to be chewed, divided, or crushed. It may be taken with or without food Contraindications: Hypersensitivity to the active substance or to any of the excipients (see the SPC for a list of excipients). Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg. Special warnings and precautions for use: Renal impairment: Betmiga has not been studied in patients with end stage renal disease (GFR < 15 mL/min/1.73 m2 or patients requiring haemodialysis) and, therefore, it is not recommended for use in this patient population. Data are limited in patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2); based on a pharmacokinetic study a dose reduction to 25 mg is recommended in this population. This medicinal product is not recommended for use in patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2) concomitantly receiving strong CYP3A inhibitors. Hepatic impairment: Betmiga has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) and, therefore, it is not recommended for use in this patient population. This medicinal product is not recommended for use in patients with moderate hepatic impairment (Child-Pugh B) concomitantly receiving

strong CYP3A inhibitors. Hypertension: Mirabegron can increase blood pressure. Blood pressure should be measured at baseline and periodically during treatment with mirabegron, especially in hypertensive patients. Data are limited in patients with stage 2 hypertension (systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 100 mm Hg). Patients with congenital or acquired QT prolongation: Betmiga, at therapeutic doses, has not demonstrated clinically relevant QT prolongation in clinical studies. However, since patients with a known history of QT prolongation or patients who are taking medicinal products known to prolong the QT interval were not included in these studies, the effects of mirabegron in these patients is unknown. Caution should be exercised when administering mirabegron in these patients. Patients with bladder outlet obstruction and patients taking antimuscarinic medicinal products for OAB: Urinary retention in patients with bladder outlet obstruction (BOO) and in patients taking antimuscarinic medicinal products for the treatment of OAB has been reported in postmarketing experience in patients taking mirabegron. A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in patients treated with Betmiga; however, Betmiga should be administered with caution to patients with clinically significant BOO. Betmiga should also be administered with caution to patients taking antimuscarinic medicinal products for the treatment of OAB. Interactions: Pharmacokinetic interactions: Mirabegron is a substrate for CYP3A4, CYP2D6, butyrylcholinesterase, uridine diphosphoglucuronosyltransferases (UGT), the efflux transporter P-glycoprotein (P-gp) and the influx organic cation transporters (OCT) OCT1, OCT2, and OCT3. Pharmacokinetic interactions involving the potential for other medicinal products to affect mirabegron exposures: Increases in mirabegron exposure due to drug-drug interactions may be associated with increases in pulse rate. Strong CYP3A inhibitors See Posology and administration above for dose adjustments recommended during concomitant use of strong CYP3A inhibitors in patients with renal or hepatic impairment. Mirabegron exposure (AUC) was increased 1.8-fold in the presence of the strong inhibitor of CYP3A/P-gp ketoconazole. CYP2D6 inhibitors: No dose adjustment is needed for mirabegron when administered with CYP2D6 inhibitors (or in patients who are CYP2D6 poor metabolisers). Inducers: Inducers of CYP3A (such as rifampicin) or P-gp may decrease the plasma concentrations of mirabegron. No dose adjustment of mirabegron is required as this effect is not expected to be clinically relevant.

Pharmacokinetic interactions involving the potential for mirabegron to affect exposures to other medicinal products: Inhibition of CYP2D6: Moderate and time dependent inhibition of CYP2D6 by mirabegron may result in clinically relevant drug interactions. CYP2D6 activity recovers within 15 days after discontinuation of mirabegron. Caution is advised if mirabegron is co-administered with medicinal

products metabolized by CYP2D6 with a narrow therapeutic index such as thioridazine, Type 1C antiarrhythmics (e.g.flecainide, propafenone) and tricyclic antidepressants (e.g., imipramine, desipramine). Caution is also advised if mirabegron is co-administered with CYP2D6 substrates that are individually dose titrated. Inhibition of P-gp: Mirabegron is a weak inhibitor of P-gp. For patients who are initiating a combination of Betmiga and digoxin, the lowest dose for digoxin should be prescribed initially. Serum digoxin concentrations should be monitored and used for titration of the digoxin dose to obtain the desired clinical effect. The potential for inhibition of P-gp by mirabegron should be considered when Betmiga is combined with sensitive P-gp substrates e.g. dabigatran. Fertility, pregnancy and lactation: The effect of mirabegron on human fertility has not been established. Betmiga is not recommended during pregnancy and in women of child-bearing potential not using contraception. Mirabegron should not be administered during breast feeding. Refer to SPC for full guidance. Driving and use of machines: Betmiga has no or negligible influence on the ability to drive and use machines. Undesirable effects: Summary of the Safety Profile: the safety of Betmiga was evaluated in 8433 patients with OAB, of which 5648 received at least one dose of mirabegron in the phase 2/3 clinical program, and 622 patients received Betmiga for at least 1 year (365 days). In the three 12-week phase 3 double blind, placebo controlled studies, 88% of the patients completed treatment with this medicinal product, and 4% of the patients discontinued due to adverse events. Most adverse reactions were mild to moderate in severity. The most common adverse reactions reported for patients treated with Betmiga 50 mg during the three 12-week phase 3 double blind, placebo controlled studies are tachycardia and urinary tract infections. The frequency of tachycardia was 1.2% in patients receiving Betmiga 50 mg. Tachycardia led to discontinuation in 0.1% patients receiving Betmiga 50 mg. The frequency of urinary tract infections was 2.9% in patients receiving Betmiga 50 mg. Urinary tract infections led to discontinuation in none of the patients receiving Betmiga 50 mg. Serious adverse reactions included atrial fibrillation (0.2%). Adverse reactions observed during the 1-year (long term) active controlled (muscarinic antagonist) study were similar in type and severity to those observed in the three 12-week phase 3 double blind, placebo controlled studies. The following adverse reactions were observed with mirabegron in the three 12-week phase 3 double blind, placebo controlled studies. The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be established from the available data) Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The adverse events

are grouped by MedDRA system organ class. Infections and infestations: Common: urinary tract infection Uncommon: vaginal infection, cystitis Psychiatric disorders: Not known: Insomnia*, confusional state* Nervous system disorders: Common: headache* dizziness* Eye disorders: Rare: eyelid oedema Cardiac disorders: Common: tachycardia Uncommon: palpitation, atrial fibrillation Vascular disorders: Very rare: Hypertensive crisis* Gastrointestinal disorders: Common: nausea*, constipation*, diarrhoea* Uncommon: dyspepsia, gastritis Rare: lip oedema Skin and subcutaneous tissue disorders: Uncommon: urticaria, rash, rash macular, rash papular, pruritus Rare: leukocytoclastic vasculitis, purpura, angioedema* Musculoskeletal and connective tissue disorders: Uncommon: joint swelling Renal and urinary disorders: Rare: urinary retention* Reproductive system and breast disorders: Uncommon: vulvovaginal pruritus Investigations Uncommon: blood pressure increased, GGT increased, AST increased, ALT increased (*observed during post-marketing experience) Reporting of suspected adverse reactions: see below. Legal category: POM (S1B)

End of Year Review: IHCA

Health Service at a ‘Critical Juncture’

Opportunity exists for

solutions

address ‘decade of despair’ for patients

Written by Professor Robert Landers, President, Irish Hospital Consultants Association

when it comes to tackling the record public hospital waiting lists. The fact that just half of this ¤350 million allocation could be spent was not a surprise to the Association, as the Action Plan was based on the false premise that as much as 25% of the backlog of care could be outsourced to the private system. This was always questionable in view of the capacity limits in the sector. Funding should be provided to expand the capacity of public hospitals to ensure sustainable, workable solutions to waiting lists and trolley problems, which are now a yearround problem.

The Irish Hospital Consultants Association continues to highlight the deteriorating capacity deficits in our public hospitals to the Health Service Management and the Government. There is a pressing need for practical, sustainable solutions that will address the record waiting lists. The Government must agree solutions with the Association to fill the 900 permanent Consultant posts that are not filled and address the severe shortage of public hospital beds, theatres, diagnostic and other facilities. These priority actions are essential to ensure more timely care for patients and the almost 1 million people on waiting lists.

All sectors of Irish life have gone through extreme challenges in the past three years, but none more so than our public hospitals. Our frontline Consultants, doctors and other staff have carried an enormous burden, as have patients. They have performed exceptionally well in the face of once-in-acentury global health challenges.

The pandemic came against a background of major capacity deficits in our public hospitals, which successive governments over the past two decades have failed to address. Ireland has one of the lowest levels of acute hospital beds and Consultant numbers on a populationadjusted basis in the EU. On both parameters, we have about 40% less than the EU average. This includes an even greater deficit in the number of ICU beds, despite an HSE/Department of Health report, commissioned over a decade ago, which recommended a doubling of ICU capacity by

2020. In the interim, the population has increased by over 600,000 and the number of people aged 65 and over has increased substantially, by approximately 53% since 2008.

Flawed, costly and damaging Government policies over the past decade have been instrumental in driving our highly trained medical specialists abroad. In particular, the ongoing pay discrimination imposed by Government on Consultants in October 2012 has resulted in a ‘decade of despair’ for Irish patients because they are denied timely hospital treatment due to the increasing shortage of hospital Consultants. The number of people awaiting an outpatient appointment has increased by 240,000 over the past decade since the pay inequity was imposed – an increase of 62%.

It is important to remember that behind every waiting list statistic is a person and a family seeking healthcare, often while experiencing pain, suffering, and the psychological distress at not knowing when they will be able to receive treatment. Sadly, this can also be a matter of life and death.

Despite the immense pressures placed on those on the frontline at the height of Covid, there was a semblance of hope that its impact would be a catalyst to finally tackle the obvious problems. Instead, another year and momentum has been lost, resulting in worsening patient wait times that could deteriorate further over the winter months.

It is still unclear how bad this year’s flu season will be, on top of growing Covid challenges. The concern is that we could

see an increase in people coming to hospital with severe symptoms, resulting in further increased pressure on an already overstretched public hospital service. This could result in the cancellation of thousands of planned appointments and procedures, further exacerbating the ever-growing waiting lists, which nationally stand at over 900,000 people, and leading to poorer outcomes for patients.

The provision of ¤169 million announced in the Winter Plan is welcome, but much of this funding had been previously included in existing allocations. The Association has grave concerns that it will not be nearly sufficient to address the magnitude of deficits in our public hospitals and the enormity of the challenges they face in the coming months.

There needs to be a laser like focus on the two things every patient relies upon most: hospital beds and hospital Consultants. Unfortunately, this Winter Plan is unlikely to make in-roads in delivering the significant numbers required of both resources.

Attempts by Government to tackle the waiting lists crisis also continue to fail because their plans do not address the core issue of the overwhelming capacity deficits including the severe shortage of Hospital Consultants and public hospital beds and other frontline facilities which are needed to provide timely, safe care to patients. The ¤350 million Waiting List Action Plan for 2022 has spectacularly failed to reach any of its targets and shows the Government has run out of ideas

This summer record numbers of admitted patients had to be treated on trolleys while waiting for admission to a hospital bed because our wards were full. This was the worst June and August for ED overcrowding in the past 16 years, and the second worst September on record. It is now expected the situation could get significantly worse as we face into a potential ‘twindemic’ of flu combined with further expected Covid cases.

Talk of ‘prioritising’ the opening of outstanding hospital beds already promised but not delivered will not address the problem or the impact of bed shortages on patients in our wards this winter. There are still 250 inpatient beds to be opened as part of the additional 1,146 hospital beds which were funded and committed to two years ago in Budget 2021. In fact, what we need is an additional 5,000 hospital beds by 2030 to meet current and future demand.

Plans to recruit an additional 50 Consultants in Emergency Medicine will also have little to no impact this year given the average timeline of over 500 days to recruit a Consultant. This means if any candidates are found, they may not even be in post to deliver on next year’s Winter Plan.

We have a chronic Consultant recruitment and retention crisis in all specialties and regions with over 900 (22% of the total) permanent posts across the country not filled as needed. We know what the problems are, and we know what it takes to fix them: fill these vacant

sustainable

to

permanent Consultant posts, open the required number of public hospital beds and other facilities on a properly resourced and staffed basis.

The Consultant contract negotiations, which were ongoing at time of writing, need to result in a contract that will work in practice. Those negotiations must restore trust by honouring the ‘unambiguous commitment’ made by the Minister for Health Stephen Donnelly to end the 2012 pay discrimination.

It is astonishing that the Government keeps trying to impose decade-long discriminatory terms on new Consultants and expects a

different outcome. Such action is in stark contrast to the collaborative and supportive terms which consultants experience in other countries which are successfully competing in attracting an increasing number of our highly trained specialists to pursue their careers abroad instead of in our public hospitals. Unless an attractive contract is agreed with the Association, our public hospitals will not fill the 900 existing vacant posts, not to mention the thousands of new Consultant positions that are needed.

The onus is now on the Government and the Health Service Management to provide

attractive working conditions in our health service, for our existing Consultants, our Consultants in training and the new medical talent we need to attract into permanent posts. If the opportunity is not availed of it will be lost to the detriment of the population that depends on public hospital services.

The health service is at a critical juncture as we approach 2023, with decisions made around both the Cabinet and the negotiation table pointing it in one of two directions. One direction involves implementing the practical, sustainable solutions as proposed by the Association;

the other ignores the practical, workable solutions resulting in unacceptable waiting times and poorer patient outcomes.

It is time to restore trust through collaborative engagement by the Government and the health service management with the Association and its frontline members who provide medical and surgical care to over 6 million people annually in our public hospitals. Agreement on a new Consultant Contract that is as attractive as possible for current and future cohorts of Consultants is vital for these 6 million patients and for the additional 1 million people awaiting care.

End of Year Review: Urology Foundation

Why we should be talking TUF

Written by Louise de Winter, Director of Research & Operations

in ground-breaking research to find better ways to diagnose, treat and manage these diseases.

and communications with patients and carers - Up to £10,000

Did you know that The Urology Foundation (TUF, pronounced tough) has Irish roots? It was the brainchild of Professor Roger Kirby and Professor John Fitzpatrick (1948 - 2014), an Irish urologist, emeritus professor of surgery at the University College Dublin School of Medicine & Medical Science and Head of Research at the Irish Cancer Society. They wanted to do something to counteract the woeful under investment in urological research and to promote the training and development or urology professionals.

For over 25 years, The Urology Foundation (TUF) has been leading the fight against urology disease. We are the only charity across the UK and Ireland that addresses all urological diseases including prostate cancer and kidney, bladder, testicular and penile cancers, which are devastating in their impact. Importantly, we also focus on non-malignant conditions including incontinence, urinary tract infections and kidney stones, which have a debilitating effect on people’s lives. We are committed to improving patient outcomes and saving lives through investing

We support educational training for urology professionals to care for and help people affected by urology conditions, and awareness campaigns such as the annual Urology Awareness Month. Working with leading researchers, urologists, nurses and allied healthcare professionals, decision makers and influencers, patients and their families, TUF is improving the nation’s urology care.

Over the years we have funded a number of research projects in Ireland, covering topics such as renal blood flow, benign prostate hyperplasia (BPH), prostate cancer and uteric obstructions. We have also funded Irish urologists to undertake clinical visits to centres of expertise around the world, to hone their skills and experience to the benefit of their patients. We would like more urology professionals from Ireland to benefit from TUF funding and the following are some of the programmes to which urologists, trainees and urology nurses can apply.

Innovation & Research Award

- To fund projects that seek to use new, exciting, innovative approaches to address urological diseases and disorders - Up to £60,000

Small projects - Nurse-led and/or Clinician-led projects that seek to improve services and treatments

Urological trials - We welcome ideas for measuring a medical, surgical or behavioural intervention that will provide potential for transformational discoveries and drive improvements in services. Our TUF urological trials unit (TTU) will provide multi-disciplinary support to develop study protocols and grant applications for urological trials - On hand support

Malcolm Coptcoat FellowshipTo support travel to international centres of excellence to gain invaluable experience and skillsUp to £5,000

Urolink Trainee Fellowship

- To enable senior trainees to experience working in Low or Middle income (LMIC) environments - Up to £1,500

TUF Urology Nurse of the Year

- To recognise a nurse who has demonstrated an outstanding contribution to their role - £2,000

Urology Nurse Travel GrantTo attend a training course or conference - £500

Urology Nurse bursaries (coming soon) - To attend further education/post graduate courses - £2,000 grants

TUF professional development courses for urologists and nurses - Providing training in communications, influencing & leadership skills - Free to attend

In addition to the above, TUF runs an annual awareness campaign every September, Urology Awareness Month, to raise the profile of urological diseases among the general public, particularly signs and symptoms, and to encourage them to take control of their urology health. A number of information materials and leaflets are available for the campaign for urology professionals in Ireland hoping to take part.

One in two of us will suffer from a urological condition in our lifetime. Yet it’s an area that we rarely talk about. Diseases of the bladder, kidney, prostate and male reproductive organs do not get the attention they need, and urology research and support are still underfunded. The increase in urological cancers and other conditions is putting greater strain on the health service and having a devastating impact on the lives of millions of men, women and children.

Everyone affected by urology disease deserves the best care. That’s why TUF is providing ground-breaking research, advanced training and support for innovation to maximise survival and quality of life. We cannot do this without the help and support of urology colleagues across the UK and Ireland.

For more information about The Urology Foundation and our work, see: theurologyfoundation.org

End of Year Review: Asthma Society of Ireland

Our Year in Review

Written by Ruth Morrow, Respiratory Nurse Specialist, Asthma Society Ireland

on our patients with chronic respiratory disease who require oxygen or nebulized medication. Again, reduced use of treatments due to financial constraints leads to increased morbidity.

Our mission is to eliminate asthma deaths and transform the lives of people with asthma. 2022 was a productive but challenging year for the organisation. We continue to support people with asthma, parents, carers, health care professionals, teachers and special needs assistants. We learn together and collaborate with healthcare, research and educational professionals to improve our understanding of how asthma works and how to combat it. The Asthma Society contributes at every level of health care – GP, integrated care, secondary and tertiary care working closely with the National Clinical Programme Respiratory (NCPR).

Challenges

COVID19 was a challenge in recent years when we had to adapt to working remotely, supporting and responding to the needs of people with asthma. It is important to remember that COVID19 remains a challenge for people living with asthma with the impact of this being reported to us on our two patient support services – Beating Breathlessness WhatsApp nurse messaging service and the Adviceline service. Both services are governed by the Medical Advisory Group which is comprised of asthma and respiratory experts.

This year also brings other unique challenges for our patients and the Asthma Society services. The cost-of-living crisis and inflation has a number of consequences. Patients might not attend the GP or buy their asthma medications due to financial constraints. This results in poor asthma control and an increased need for our services. The energy crisis, inflation and cost of living crisis also impacts

The Asthma Society is truly grateful to the public for their donations and generosity, which are critical to the continued delivery of our services. Another possible knock-on effect of the current economic climate is that income generation could be hampered. In addition, overheads associated with running an organization will become more costly such as electricity bills, phone bills, and rent of premises.

Achievements

WhatsApp Nurse messaging Service - This nurse-led service allows patients with asthma and/ or COPD, and their family and carers, to confidentially message a respiratory nurse about all aspects of their disease. Service learnings indicate that once-off usage of the WhatsApp messaging service is effective but builds in impact when patients return and use it repeatedly. The nurses provided support to over 700 service users in 2022. Survey results show that those who have used the service are happy to recommend it to others. The WhatsApp Nurse messaging service was funded by the Sláintecare Integrated Fund. It is now funded by the HSE Primary Care Team, with funding fully confirmed to end 2023. This reflects the success and need for this service to the public as part of the holistic care of patients with respiratory illness.

Webinars - Alongside the nurseled WhatsApp service, educational webinars are conducted for patients, carers and healthcare professionals. The webinar series runs on a 6 weekly basis and has included topics such as Women and Asthma, Ask the Doctor, Children and Asthma, Back2School, and more recently a webinar for Teachers and SNAs on managing asthma in schools.

These webinars have proven extremely popular. For each webinar an expert physician in the specialised area and a nurse specialist give a short presentation. In addition to this, the Backto-School webinars featured a teacher and a parent coach. The question and answer session gives attendees unique access to the specialists on the panel with an average of 30 questions being asked. Unanswered questions at the live event can be answered the following day by using the WhatsApp nurse messaging service or the Adviceline. This year, between 200 and 300 people registered for each webinar. On average, 130 attended each webinar (74-250). Registrants can watch recordings on our website, with approximately 70 people availing of this feature each time. The next webinar to be held on Wednesday November 30th is entitled Winter Wellness for People with Asthma

Asthma Adviceline This is a free service available to people with asthma in Ireland and their carers. It operates as a call back service whereby a person can book a 30-minute consult with an asthma nurse. This service has been in existence for many years and has grown responding to increased demand particularly since the Covid pandemic. The total number of consultations to Adviceline, combining Asthma and COPD to end of September, was 2889. These calls include new and return consultations. The Adviceline provides up-to-date expert information and advice from asthma specialist nurses. The Asthma Society identified healthcare professional awareness of and referral to the services as being a key priority for the service growth in the future and created a healthcare professional referral strategy, which includes specific actions to support GPs and GP practice nurses in their work to deliver the Chronic Disease Management Programme.

Chronic Obstructive Pulmonary Disease (COPD) Adviceline - The COPD Adviceline is a collaboration between the Asthma Society of

Ireland, COPD Support Ireland and the HSE. The Asthma Society has a service growth strategy in place to build new and recurring callers and a major focus has been to work closely with COPD Support Ireland to grow COPD calls specifically. A part -time nurse and a part-time physiotherapist continue to specifically meet the needs of COPD patients.

Asthma Safe School Programme

The Asthma Safe School Programme engages with principals, teachers, SNAs, parents/carers and children to prevent asthma deaths. The aim is to train one teacher per school in PHECC (Pre-Hospital Emergency Care Council) approved and certified basic life support and administration of Salbutamol for emergency treatment of adults and children with an acute asthma attack. It also enables school staff to know what to do in the case of an asthma attack, to encourage schools to provide a supportive environment for students with asthma and to create better public awareness of the 5 Step Rule.

The Society received funding from the HSE National Lottery Fund for programme delivery in four CHO areas 2, 5, 7 & 9 in 2021/22. We ran an Asthma Safe School webinar, for all principals, teachers and SNAs in September 2022.

The number of registrations was 184, attendance was 138 and 42 questions were asked. Funding has been received from CHO areas 3, 7 and 8 for the coming year to continue this valuable programme.

Future Plans

2023 will see the Asthma Society continue to buildup and develop. It is planned to develop a communications and digital strategy. A fundraising strategy has been developed and we look forward to its implementation. Meeting the needs of people with asthma, marginalised groups and health professionals will continue to be a priority for the organisation. Increasing the number of patients who access our free patient support services is a key priority through collaboration and engagement with the NCPR.

Acknowledgments

The author would like to acknowledge the help of Mary McDonald, Patient Services Manager and Eilis Ní Chaithnía Interim CEO for their assistance with this article.

Abbreviated Prescribing Information - Vesomni 6 mg/0.4 mg modified release tablets. Please read the Summary of Product Characteristics (SPC) before prescribing. Presentation: Each tablet contains a layer of 6 mg solifenacin succinate, corresponding to 4.5 mg solifenacin free base and a layer of 0.4 mg tamsulosin hydrochloride, corresponding to 0.37 mg of tamsulosin free base. Indication: Treatment of moderate to severe storage symptoms (urgency, increased micturition frequency) and voiding symptoms associated with benign prostatic hyperplasia (BPH) in men who are not adequately responding to treatment with monotherapy. Posology and method of administration: Adultmales,includingolderpeople: One Vesomni tablet (6 mg/0.4 mg) once daily taken orally with or without food. The maximum daily dose is one Vesomni tablet. The tablet must be swallowed whole, intact without biting or chewing. Do not crush the tablet. Special populations (see also contraindications below): Renal impairment: Severe renal impairment (creatinine clearance ≤ 30 mL/min): Treat with caution, maximum daily dose in these patients is one Vesomni tablet. Hepatic impairment: Moderate hepatic impairment (Child-Pugh score of 7-9): Treat with caution, maximum daily dose in these patients is one Vesomni tablet. In patients with severe hepatic impairment (Child-Pugh score > 9), the use of Vesomni is contraindicated. Concomitant treatment withmoderateandstronginhibitorsofCYP4503A4: e.g. verapamil, ketoconazole, ritonavir, nelfinavir, itraconazole: Treat with caution, maximum daily dose should be limited to one Vesomni tablet. Paediatricpopulation:There is no relevant indication for use of Vesomni in children and adolescents.

Contraindications: Patients with hypersensitivy to the active substance(s) or to any of the excipients (see SPC). Patients undergoing haemodialysis. Patients with severe hepatic impairment. Patients with severe renal impairment who are also treated with a strong cytochrome P450 (CYP)3A4 inhibitor e.g. ketoconazole. Patients with moderate hepatic impairment who are also treated with a strong CYP3A4 inhibitor e.g. ketoconazole. Patients with severe gastrointestinal conditions (including toxic megacolon), myasthenia gravis or narrow-angle glaucoma and patients at risk for these conditions.

Patients with a history of orthostatic hypotension. Special Warnings and Precautions for Use: Vesomni should be used with caution in patients with: severe renal impairment; risk of urinary retention; gastrointestinal obstructive disorders; risk of decreased gastrointestinal motility; hiatus hernia/ gastroesophageal reflux and/or who are concurrently taking medicinal products (such as bisphosphonates) that can cause or exacerbate oesophagitis; autonomic neuropathy. The patient should be examined in order to exclude the presence of other conditions, which can cause similar symptoms to benign prostatic hyperplasia. Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment with Vesomni is initiated. If a urinary tract infection is present, appropriate antibacterial therapy should be started. QT prolongation and Torsade de Pointes have been observed in patients with risk factors, such as pre-existing long QT syndrome and hypokalaemia, who are treated with solifenacin succinate. Angioedema with airway obstruction has been reported in some patients on solifenacin succinate and tamsulosin. If angioedema occurs, Vesomni should be discontinued and not restarted. Appropriate therapy and/or measures should be taken. Anaphylactic reaction has been reported in some patients treated with solifenacin succinate. In patients who develop anaphylactic reactions, Vesomni should be discontinued and appropriate therapy and/or measures should be taken. As with other alpha1-adrenoceptor antagonists, a reduction in blood pressure can occur in individual cases during treatment with tamsulosin, as a result of which, rarely, syncope can occur. Patients starting treatment with Vesomni should be cautioned to sit or lie down at the first signs of orthostatic hypotension (dizziness, weakness) until the symptoms have disappeared. The ‘Intraoperative Floppy Iris Syndrome’ (IFIS, a variant of small pupil syndrome) has been observed during cataract and glaucoma surgery in some patients on or previously treated with tamsulosin hydrochloride. IFIS may increase the risk of eye complications during and after the operation. Therefore, the initiation of therapy with Vesomni in patients for whom cataract or glaucoma surgery is scheduled is not recommended. Discontinuing treatment with Vesomni 1-2 weeks prior to cataract or glaucoma surgery is anecdotally considered helpful, but the benefit of treatment discontinuation has not been established. During pre-operative assessment, surgeons and ophthalmic teams should consider whether patients scheduled for cataract or glaucoma surgery are being or have been treated with Vesomni in order to ensure that appropriate measures will be in place to manage IFIS during surgery. Vesomni should be used with caution in combination with moderate and strong inhibitors of CYP3A4 and it should not be used in combination with strong inhibitors of CYP3A4, e.g., ketoconazole, in patients who are of the CYP2D6 poor metaboliser phenotype or who are using strong inhibitors of CYP2D6, e.g., paroxetine.

Interactions: Pharmacological interactions: Concomitant medication with other anticholinergic medicinal products may result in more pronounced therapeutic and undesirable effects. Allow approximately one week after stopping treatment with Vesomni before commencing any anticholinergic therapy. The therapeutic effect of solifenacin may be reduced by concomitant administration of cholinergic receptor agonists. Pharmacokinetic interactions: Pharmacokinetic interactions involving the potential for other medicinal products to affect Vesomni exposures: InteractionswithCYP3A4andCYP2D6inhibitors:See Contraindications, Posology and administration and Special warnings and precautions above. Concomitant administration may lead to increased exposure to both solifenacin (ketoconazole 400 mg/day resulted in a 1.5-fold increase in Cmax and a 2.8-fold increase in AUC). and tamsulosin (ketoconazole 400 mg/day resulted in a 2.2-fold increase in Cmax and a 2.8-fold increase in AUC). Vesomni should be used with caution in combination with strong CYP3A4 inhibitors. Vesomni should not be given together with strong CYP3A4 inhibitors in patients who are also CYP2D6 poor metabolizer phenotype or who are using strong CYP2D6 inhibitors. See SPC for details of the effects of other CYP3A4 and CYP2D6 inhibitors. Inducers: Inducers of CYP3A4 (e.g. rifampicin) may decrease the plasma concentrations of solifenacin and tamsulosin. Information available for the individual active substances Solifenacin can reduce the effect of medicinal products that stimulate the motility of the gastrointestinal tract, such as metoclopramide and cisapride. Solifenacin did not affect the pharmacokinetics of digoxin, or the pharmacokinetics or effect on prothrombin time of R- or S-warfarin. Co-administration of tamsulosin and other alpha1-adrenoreceptor antagonists could lead to hypotensive effects. Diclofenac and warfarin may increase the elimination rate of tamsulosin. No interactions have been seen when tamsulosin was given concurrently with atenolol, enalapril or theophylline. Fertility, pregnancy and lactation: The effect of Vesomni on fertility has not been established. Ejaculation disorders have been observed in short and long term clinical studies with tamsulosin. Events of ejaculation disorder, retrograde ejaculation and ejaculation failure have been reported in the post authorization phase. Vesomni is not indicated for use in women. Driving and use of machines: No studies have been performed, however patients should be informed about the possible occurrence of dizziness, blurred vision, fatigue and uncommonly somnolence, which may negatively affect the ability to drive or use machines. Undesirable Effects: Summary of the safety profile: Vesomni may cause anticholinergic undesirable effects of, in general, mild to moderate severity. The most frequently reported adverse reactions during the clinical studies performed for the development of Vesomni were dry mouth (9.5%), followed by constipation (3.2%) and dyspepsia (including abdominal pain; 2.4%). Other common undesirable effects are dizziness (including vertigo; 1.4%), vision blurred (1.2%), fatigue (1.2%), and ejaculation disorder (including retrograde ejaculation; 1.5%). Acute urinary retention (0.3%, uncommon) is the most serious adverse drug reaction that has been observed during treatment with Vesomni in clinical studies. List of adverse reactions: the ‘Vesomni frequency’ below reflects adverse drug reactions that have been observed during the double-blind clinical studies performed for the development of Vesomni (based on reports of treatment-related adverse events, which have been reported by at least two patients and occurred with a frequency higher than for placebo in the double-blind studies). The ‘solifenacin frequency’ and ‘tamsulosin frequency’ below reflect adverse drug reactions (ADRs) previously reported with one of the individual components (as presented in the Summary of Product Characteristics (SmPCs) of solifenacin 5 and 10 mg and tamsulosin 0.4 mg respectively that may also occur when receiving Vesomni (some of these have not been observed during the clinical development program of Vesomni). The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data). The adverse events are grouped by MedDRA system organ class preferred term (PT). Vesomni frequency: Nervous system disorders: Common: dizziness Eye disorders: Common: vision blurred Gastrointestinal disorders: Common: dry mouth, dyspepsia, constipation Skin and subcutaneous tissue disorders: Uncommon: pruritus Renal and urinary disorders: Uncommon: Urinary retention*** Reproductive system and breast disorders: Common: ejaculation disorders including retrograde ejaculation and ejaculation failure General disorders and administration site conditions: Common: fatigue Solifenacin5mg&10mgfrequency#: Infections and infestations: Uncommon: urinary tract infection, cystitis Immune system disorders: Not known: anaphylactic reaction* Metabolism and nutrition disorders: Not known: decreased appetite*, hyperkalemia* Psychiatric disorders: Very rare: hallucination*, confusional state* Not known:

Pointes*,

atrial fibrillation*,

known:

Gastrointestinal disorders: Very common: dry mouth Common: dyspepsia, constipation, nausea, abdominal pain Uncommon: gastro-oesophageal reflux disease, dry throat Rare: vomiting*, colonic obstruction, faecal impaction, Not known: ileus*, abdominal discomfort* Hepatobiliary disorders: Not known: liver disorder*, liver function test abnormal* Skin and subcutaneous tissue disorders: Uncommon: dry skin Rare: pruritus*, rash* Very rare: urticaria*, angioedema*, erythema multiforme* Not known: exfoliative dermatitis* Musculoskeletal and connective tissue disorders: Not known: muscular weakness* Renal and urinary disorders: Uncommon: difficulty in micturition Rare: urinary retention***Not known: renal impairment* General disorders and administration site conditions: Uncommon: fatigue, perhiperal oedema Tamsulosin 0.4mg frequency#: Nervous system disorders: Common: dizziness Uncommon: headache Rare: syncope Eye disorders: Not known: vision blurred*, Intraoperative Floppy Iris Syndrome (IFIS)**, visual impairment* Cardiac disorders: Uncommon: palpitations Not known: atrial fibrillation*, arrhythmia*, tachycardia* Vascular disorders: Uncommon: orthostatic hypotension Respiratory, thoracic and mediastinal disorders: Uncommon: rhinitis Not known: dyspnoea*, epistaxis* Gastrointestinal disorders: Uncommon: constipation, nausea, diarrhea, vomiting Skin and subcutaneous tissue disorders: Uncommon: pruritus, rash, urticaria Rare: angioedema Very Rare: Stevens-Johnson syndrome Not known: erythema multiforme*, exfoliative dermatitis* Reproductive system and breast disorders: Common: ejaculation disorders including retrograde ejaculation and ejaculation failure Veryrare: priapism General disorders and administration site conditions: Uncommon: asthenia. #: The ADRs from solifenacin and tamsulosin included are the ADRs listed in the summary of product characteristics of both products. *: from post-marketing reporting. Because these spontaneously reported events are from the worldwide post-marketing experience, the frequency of events and the role of solifenacin or tamsulosin and their causation cannot be reliably determined. **: from post-marketing reporting, observed during cataract and glaucoma surgery. ***: see Special warnings and precautions for use. Long-term safety of Vesomni: The profile of undesirable effects seen with treatment up to 1 year was similar to that observed in the 12-week studies. The product is well-tolerated and no specific adverse reactions have been associated with long-term use. Description of selected adverse reactions: For urinary retention see Special warnings and precautions for use. Older people: The therapeutic indication of Vesomni, moderate to severe storage symptoms (urgency, increased micturition frequency) and voiding symptoms associated with BPH, is a disease affecting elderly men. The clinical development of Vesomni has been performed in patients 45 to 91 years of age, with an average age of 65 years. Adverse reactions in the elderly population were similar to the younger population. Reporting of suspected adverse reactions: see below. Overdose: Overdosage with the combination of solifenacin and tamsulosin can potentially result in severe anticholinergic effects plus acute hypotension. Refer to SPC for details of treatment of overdose. Legal Category: Prescription Only Medicine (SIB).

End of Year Review: Irish Cancer Society

Challenges and Areas of Focus for 2022/2023

This year saw another challenging period for cancer care, amidst concerns in the medical community about the extent of undetected cancers due to delays in screening. However, there were great achievements too including the ending of in-patient charges.

Top jockeys, GAA, sporting and TV stars took in the hurling match in aid of the Irish Cancer Society. We also held our very first hybrid conference for cancer survivors. The ‘Living Well With and Beyond Cancer 2022’ conference took place online and in-person with a wide range of speakers sharing their experiences, stories and expert knowledge on living well after a diagnosis.

channel in their native language if needed. We also introduced a dedicated webpage www.cancer. ie/ukraine along with printed material to help people understand the supports available to them.

A survey published by the Irish Cancer Society in January indicated that in the previous three months around one in seven people had put off seeking medical advice even though they have felt unwell. Half of those who put off seeking medical advice were still experiencing symptoms and had yet to make an appointment to see their GP. In response to this, the Irish Cancer Society’s early detection campaigns focused on raising awareness of lung, bowel, skin and breast cancers throughout the year.

The early detection message was further promoted by our Your Health Matters Roadshow, which at the time of writing had visited 17 different locations around the country (9 locations in 2021). To date this year, over 16,500 people have learned about the importance of early detection, and over 1,385 people have received health checks in 2022. An evaluation of the impact of the Roadshow was carried out by the School of Public Health, Physiotherapy and Sport Sciences at UCD.

In February, we announced record ¤450K funding for emerging clinician research leaders being supported in projects across all areas including lung cancer, breast

cancer and cancer genetics. The funding is provided as part of the Society’s Clinician Research Leadership Award and will see cancer surgeon Prof Aoife Lowery use her award to dedicate her time to a range of cutting-edge projects that focus on reducing the burden of treatment for people affected by cancer. Cancer geneticist and ovarian cancer specialist Prof Karen Cadoo will use the award to focus on critical research in the inherited cancer sphere. Prof Jarushka Naidoo will be dedicating her efforts to advancing clinical trials for patients with lung cancer, including a novel investigatorinitiated clinical trial of a new targeted therapy for lung cancer.

For the first time in two years, Daffodil Day, the Irish Cancer Society’s biggest fundraiser, returned to the streets. Thanks to the generous support of the Irish public, the Society was able to fund critical supports including our Freephone Support Line on 1800 200 700; free counselling and our Night Nurses to provide end-of-life care and financial support for families of children affected by cancer.

We were also able to welcome the return of Hurling For Cancer Research after a two-year break.

We were delighted to develop new CAYA (Children and Young Adults) supports and services such as the introduction of a cancer coordinator nurse in Our Lady’s Hospital, Crumlin. An exciting new partnership was the introduction of camps, which cater for families with children with a cancer diagnosis, in collaboration with Barretstown. Our Volunteer Driver Service was also expanded to provide transport for children and adolescents with cancer who are receiving chemotherapy and/or radiation at CHI, Crumlin.

In October, we announced the extension of a major research programme in the west of Ireland with a focus on improving support for women during and after cancer treatment. The Irish Cancer Society Women’s Health initiative supports a range of studies including the LYSA (Linking You to Advice and Support) trial led by cancer researchers at University College Cork. Previously only available through hospitals in Dublin and Cork, the trial is now being brought to Galway where it will be trialled by selected participants who have undergone cancer treatment at University Hospital Galway and led by University of Galway researchers.

In response to the war in Ukraine, we initiated a number of actions to support the children and adults with cancer who were forced to flee their homes and who need to continue their treatment in Ireland. These included organising a translation service so that can continue to provide cancer support and information through our Support Line and our email

The cost of living crisis loomed large this year and through our advocacy work, we continued to focus on reducing the burden of cost on cancer patients. We welcomed the decision in this year’s Budget that hospital in-patient changes are to be abolished. This has been a central plank of our advocacy and the abolition of hospital charges will also mean an end to debt collectors hounding cancer patients if they do not pay within 47 days. We will continue to campaign on measures such as reductions in the cost of hospital car parking and the entitlement of every cancer patient to a medical card. This year also saw the Irish Cancer Society highlight the plight of women who are diagnosed with cancer during pregnancy calling on Government to change current legislation that prevents women from deferring their maternity leave while they are being treated and recovering from cancer. The Society also supported a new Bill brought before the Seanad, which will seek to revise current legislation and outlines that a person seeking access to financial services will no longer have to declare a cancer diagnosis five years after finishing active treatment. Furthermore, a new service, in partnership with the Capuchin Day Centre and Safetynet Primary Care began, which aims to identify symptoms of cancer across homeless and marginalised communities.

Throughout the year, we continued to support cancer patients on their journey and will continue to do so in the year ahead. As ever, we urge anyone affected by a cancer diagnosis to get in touch with our Support Line at on 1800 200 700 and SupportLine@IrishCancer.ie

Written by Claire O’Mahony, Communications Officer,

Irish Cancer Society

KISQALI—the

longest median overall survival reported for a CDK4/6 inhibitor in HR+/HER2- aBC 1,5,6

KISQALI + ET vs ET alone

OVER 5 YEARS

+ AI in

MONALEESA-2: N=668, 1:1 randomization. As 1L in advanced disease. KISQALI 600 mg or placebo once daily (3 weeks on/1 week off) + letrozole 2.5 mg4

MONALEESA-7: N=672, 1:1 randomization. As 1L in advanced disease. KISQALI 600 mg or placebo once daily (3 weeks on/1 week off) + ET (letrozole 2.5 mg or anastrozole 1 mg, or tamoxifen 20 mg orally) + LHRH agonist 3.6 mg4

MONALEESA-3: N=726, 2:1 randomization. As 1L or after 1L progression for advanced disease. KISQALI 600 mg or placebo once daily (3 weeks on/1 week off) + fulvestrant 500 mg4

1.

2.

1L, first line; 2L, second line; ET, endocrine therapy; LHRH, luteinizing hormone-releasing hormone, aBC, advanced breast cancer.

REFERENCES:

1. Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall survival results from the phase III MONALEESA-2 trial of postmenopausal patients with HR+/HER2− advanced breast cancer treated with endocrine therapy ± ribociclib. Presented at: European Society of Medical Oncology; September 16-21, 2021.

2. Slamon DJ, Neven P, Chia S, et al. Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival. Ann Oncol. 2021;32(8):1015- 1024.

3. Tripathy D, Im S-A, Colleoni M, et al. Updated overall survival (OS) results from the phase III MONALEESA-7 trial of pre- or perimenopausal patients with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/ HER2–) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib. Presented at: San Antonio Breast Cancer Symposium; December 8-12, 2020; San Antonio, TX. Poster PD2-04.

4. KISQALI [Summary of Product Characteristics]. Novartis, available at www.medicines.ie.

ABBREVIATED PRESCRIBING INFORMATION

Please refer to Summary of Product Characteristics (SmPC) before prescribing. Kisqali (ribociclib) 200 mg film-coated tablets

Presentation: Film coated tablets (FCT) containing 200 mg of ribociclib and 0.344 mg soya lecithin.

Indications: Kisqali is indicated for the treatment of women with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally advanced or metastatic breast cancer in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or in women who have received prior endocrine therapy In pre or perimenopausal women, the endocrine therapy should be combined with a luteinising hormone releasing hormone (LHRH) agonist.

Dosage and administration:

Adults: The recommended dose is 600 mg (3 x 200 mg FCT) taken orally, once daily for 21 consecutive days followed by 7 days off treatment, resulting in a complete cycle of 28 days. Kisqali should be used together with 2.5 mg letrozole or another aromatase inhibitor or with 500 mg fulvestrant.

When Kisqali is used in combination with an aromatase inhibitor, the aromatase inhibitor should be taken orally once daily continuously throughout the 28 day cycle. Please refer to the Summary of Product Characteristics (SmPC) of the aromatase inhibitor for additional details.

When Kisqali is used in combination with fulvestrant, fulvestrant is administered intramuscularly on days 1, 15 and 29, and once monthly thereafter. Please refer to the SmPC of fulvestrant for additional details.

Treatment of pre and perimenopausal women with the approved Kisqali combinations should also include an LHRH agonist in accordance with local clinical practice. Management of severe or intolerable adverse reactions (ARs) may require temporary dose interruption, reduction or discontinuation of Kisqali. Please see section 4.2 of SmPC for recommended dose modification guidelines.

Kisqali can be taken with or without food (see section 4.5).The tablets should be swallowed whole and should not be chewed, crushed or split prior to swallowing.

Special populations: ♦Renal impairment: Mild or moderate: No dose adjustment is necessary. Severe: A starting dose of 200 mg is recommended in patients with severe renal impairment. Kisqali has not been studied in breast cancer patients with severe renal impairment. Caution should be used in patients with severe renal impairment with close monitoring for signs of toxicity. ♦Hepatic impairment: Mild: No dose adjustment is necessary. Moderate or severe: Dose adjustment is required, and the starting dose of 400 mg once daily is recommended. ♦Elderly (>65 years): No dose adjustment is required.

♦Pediatrics(<18 years): Safety and efficacy have not been established.

Contraindications: Hypersensitivity to the active substance or to peanut, soya or any of the excipients.

Warnings/Precautions: ♦Neutropenia was most frequently reported AR. A complete blood count (CBC) should be performed before initiating treatment. CBC should be monitored every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, then as clinically indicated. Febrile neutropenia was reported in 1.4% of patients exposed to Kisqali in the phase III clinical studies. Patients should be instructed to report any fever promptly.Based on the severity of the neutropenia, Kisqali may require dose interruption, reduction, or discontinuation. ♦Hepatobiliary toxicity - increases in

transaminases have been reported. Liver function tests (LFTs) should be performed before initiating treatment. LFTs should be monitored every 2 weeks for the first 2 cycles, at the beginning of each of the subsequent 4 cycles, then as clinically indicated. If grade ≥ 2 abnormalities are noted, more frequent monitoring is recommended. Recommendations for patients who have elevated AST/ALT grade ≥ 3 at baseline have not been established. Based on the severity of transaminase elevations, Kisqali may require dose interruption, reduction, or discontinuation. ♦QT interval prolongation has been reported with Kisqali. The use of Kisqali should be avoided in patients who have already or who are at significant risk of developing QTc prolongation. The ECG should be assessed prior to initiation of treatment. Treatment with Kisqali should be initiated only in patients with QTcF values <450 msec. The ECG should be repeated at approximately Day 14 of the first cycle and at the beginning of the second cycle, then as clinically indicated. In case of QTcF prolongation during treatment, more frequent ECG monitoring is recommended Appropriate monitoring of serum electrolytes (including potassium, calcium, phosphorous, and magnesium) should be performed prior to initiation of treatment, at the beginning of the first 6 cycles, and then as clinically indicated. Any abnormality should be corrected before the start of Kisqali treatment. Based on the observed QT prolongation during treatment, Kisqali may require dose interruption, reduction, or discontinuation. Based on the E2301 study QTcF interval data, Kisqali is not recommended for use in combination with tamoxifen. ♦Critical visceral disease. The efficacy and safety of ribociclib have not been studied in patients with critical visceral disease. ♦Severe cutaneous reactions Toxic epidermal necrolysis (TEN) has been reported with Kisqali treatment. If signs and symptoms suggestive of severe cutaneous reactions (e.g. progressive widespread skin rash often with blisters or mucosal lesions) appear, Kisqali should be discontinued immediately. ♦Interstitial lung disease/pneumonitis ILD/pneumonitis has been reported with CDK4/6 inhibitors including Kisqali. Based on the severity of the ILD/pneumonitis, which may be fatal, Kisqali may require dose interruption, reduction or discontinuation as described in SmPC. Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis which may include hypoxia, cough and dyspnoea and dose modifications should be managed in accordance with Table 5 (see section 4.2)

♦Blood creatinine increase ribociclib may cause blood creatinine increase – if this occurs it is recommended that further assessment of the renal function be performed to exclude renal impairment.

♦CYP3A4 substrates. ribociclib may interact with medicinal products which are metabolised via CYP3A4, which may lead to increased serum concentrations of CYP3A4 substrates (see section 4.5). Caution is recommended in case of concomitant use with sensitive CYP3A4 substrates with a narrow therapeutic index and the SmPC of the other product should be consulted for the recommendations regarding co administration with CYP3A4 inhibitors.

Pregnancy, Fertility and Lacation

♦Pregnancy: Pregnancy status should be verified prior to starting treatment as Kisqali can cause foetal harm when administered to a pregnant woman.

♦Women of childbearing potential who are receiving Kisqali should use effective contraception (e.g. double-barrier contraception) during therapy and for at least 21 days after stopping treatment with Kisqali. ♦Breast feeding: Patients receiving Kisqali should not breast feed for at least 21 days after the last dose. ♦Fertility: There are no clinical data available regarding effects of ribociclib on fertility. Based on animal studies, ribociclib may impair fertility in males of reproductive potential.

♦Effects on ability to drive and use machines Patients should be advised to be cautious when driving or using machines in case they experience fatigue, dizziness or vertigo during treatment with Kisqali.

Interactions: ♦Concomitant use of strong CYP3A4 inhibitors should be avoided, including, but not limited to, clarithromycin, indinavir, itraconazole, ketoconazole, lopinavir, ritonavir, nefazodone, nelfinavir, posaconazole, saquinavir, telaprevir, telithromycin, verapamil, and voriconazole. Alternative concomitant medicinal products with less potential to inhibit CYP3A4 should be considered. Patients should be monitored for ARs. If concomitant use of a strong CYP3A4 inhibitor cannot be avoided, the dose of Kisqali should be reduced (see section 4.2 of SmPC). ♦Grapefruit or grapefruit juice should be avoided. ♦Concomitant use of strong CYP3A4 inducers should be avoided, including, but not limited to, phenytoin, rifampicin, carbamazepine and St John’s Wort (Hypericum perforatum). An alternative medicinal product with no or minimal potential to induce CYP3A4 should be considered. ♦Caution is recommended when Kisqali is administered with sensitive CYP3A4 substrates with narrow therapeutic index (including, but not limited to, alfentanil, ciclosporin, everolimus, fentanyl, sirolimus, and tacrolimus), and their dose may need to be reduced. ♦Concomitant administration of Kisqali at the 600 mg dose with the following CYP3A4 substrates should be avoided: alfuzosin, amiodarone, cisapride, pimozide, quinidine, ergotamine, dihydroergotamine, quetiapine, lovastatin, simvastatin, sildenafil, midazolam, triazolam. ♦Caution and monitoring for toxicity are advised during concomitant treatment with sensitive substrates of drug transporters P-gp, BCRP, OATP1B1/1B3, OCT1, OCT2, MATE1 and BSEP which exhibit a narrow therapeutic index, including but not limited to digoxin, pitavastatin, pravastatin, rosuvastatin and metformin. ♦Co-administration of Kisqali with medicinal products with known potential to prolong the QT interval should be avoided such as anti-arrhythmic medicinal products (including, but not limited to, amiodarone, disopyramide, procainamide, quinidine and sotalol) and other medicinal products known to prolong the QT interval including, but not limited to, chloroquine, halofantrine, clarithromycin, ciprofloxacin, levofloxacin, azithromycin, haloperidol, methadone, moxifloxacin, bepridil, pimozide and intravenous ondansetron. Kisqali is not recommended for use in combination with tamoxifen.

Adverse reactions: ♦Very common: Infections, neutropenia, leukopenia, anaemia lymphopenia, decreased appetite, headache, dizziness, dyspnoea, cough, nausea, diarrhoea, vomiting, constipation, stomatitis, abdominal pain, dyspepsia alopecia, rash, pruritus, back pain, fatigue, peripheral oedema, asthenia, pyrexia, abnormal liver function tests. ♦Common:, thrombocytopenia, febrile neutropenia, hypocalcaemia, hypokalaemia, hypophosphataemia, vertigo, lacrimation increased, dry eye, syncope, dysgeusia, , hepatotoxicity, erythema, dry skin, vitiligo, dry mouth, oropharyngeal pain, blood creatinine increased, electrocardiogram QT prolonged. ♦Please refer to SmPC for a full list of adverse reactions.

Legal Category: POM

Pack sizes: Unit packs containing 21, 42 or 63 FCTs. Not all pack sizes may be marketed.

Marketing Authorisation Holder: Novartis Europharm Limited Vista Building, Elm Park, Merrion Road, Dublin 4 Ireland

Marketing Authorisation Numbers: EU/1/17/1221/003 & 005.

Full prescribing information is available on request from Novartis Ireland Ltd, Vista Building, Elm Park Business Park, Dublin 4. Tel: 01 2601255 or at www.medicines.ie

Prescribing information last revised: April 2022

Novartis Ireland Ltd, Vista Building, Elm Park Business Park, Merrion Road, Dublin 4, D04 A9N6

KISQALI is not indicated for concomitant use with tamoxifen 4

ESMO - European society of medical oncology

SABC - San Antonio Breast Cancer Conference

ABBREVIATED PRESCRIBING INFORMATION

Please refer to the Summary of Product Characteristics (SmPC) before prescribing Pelgraz▼(peg lgrastim) 6 mg solution for injection in pre- lled syringe or prelled injector. Presentation: Each pre- lled syringe or pre- lled injector contains 6 mg of peg lgrastim* in 0.6 mL solution for injection. The concentration is 10 mg/mL based on protein only**. *Produced in Escherichia coli cells by recombinant DNA technology followed by conjugation with polyethylene glycol (PEG). ** The concentration is 20 mg/mL if the PEG moiety is included. Indications: Reduction in the duration of neutropenia and the incidence of febrile neutropenia in adult patients treated with cytotoxic chemotherapy for malignancy (with the exception of chronic myeloid leukaemia and myelodysplastic syndromes). Dosage and Administration: Pelgraz therapy should be initiated and supervised by physicians experienced in oncology and/or haematology. Posology: One 6 mg dose (a single pre- lled syringe or pre- lled injector) of Pelgraz is recommended for each chemotherapy cycle, given at least 24 hours after cytotoxic chemotherapy. Safety and e cacy of Pelgraz in children and adolescents has not yet been established and no recommendation on a posology can be made. No dose change is recommended in patients with renal impairment, including those with end-stage renal disease. Method of administration: Pelgraz is for subcutaneous use. The injections should be given subcutaneously into the thigh, abdomen or upper arm. See SmPC for instructions on handling of the medicinal product before administration. Contraindications: Hypersensitivity to peg lgrastim or any of the excipients in Pelgraz. Warnings and precautions: To improve the traceability of biological medicinal products, the trade name of the administered product should be clearly recorded. The long-term e ects of peg lgrastim have not been established in acute myeloid leukaemia (AML); therefore, it should be used with caution in this patient population. Granulocytecolony stimulating factor (G-CSF) can promote growth of myeloid cells in vitro and similar e ects may be seen on some non-myeloid cells in vitro. The safety and e cacy of peg lgrastim have not been investigated in patients with myelodysplastic syndrome, chronic myelogenous leukaemia, and in patients with secondary AML; therefore, it should not be used in such patients. Particular care should be taken to distinguish the diagnosis of blast transformation of chronic myeloid leukaemia from AML. The safety and e cacy of peg lgrastim administration in de novo AML patients aged < 55 years with cytogenetics t(15;17) have not been established. The safety and e cacy of peg lgrastim have not been investigated in patients receiving high dose chemotherapy. This medicinal product should not be used to increase the dose of cytotoxic chemotherapy beyond established dose regimens. Pulmonary adverse reactions, in particular interstitial pneumonia, have been reported after G-CSF administration. Patients with a recent history of pulmonary in ltrates or pneumonia may be at higher risk. The onset of pulmonary signs such as cough, fever, and dyspnoea in association with radiological signs of pulmonary in ltrates, and deterioration in pulmonary function along with increased neutrophil count may be preliminary signs of adult respiratory distress syndrome (ARDS). In such circumstances peg lgrastim should be discontinued at the discretion of the physician and the appropriate treatment given. Glomerulonephritis has been reported in patients receiving lgrastim and peg lgrastim. Generally, glomerulonephritis resolved after dose reduction

or withdrawal of lgrastim and peg lgrastim. Urinalysis monitoring is recommended. Capillary leak syndrome has been reported after G-CSF administration and is characterised by hypotension, hypoalbuminaemia, oedema and haemoconcentration. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care. Generally asymptomatic cases of splenomegaly and cases of splenic rupture, including some fatal cases, have been reported following administration of peg lgrastim. Spleen size should be carefully monitored (e.g. clinical examination, ultrasound). A diagnosis of splenic rupture should be considered in patients reporting left upper abdominal pain or shoulder tip pain. Treatment with peg lgrastim alone does not preclude thrombocytopenia and anaemia because full dose myelosuppressive chemotherapy is maintained on the prescribed schedule. Regular monitoring of platelet count and haematocrit is recommended. Special care should be taken when administering single or combination chemotherapeutic medicinal products which are known to cause severe thrombocytopenia. Peg lgrastim in conjunction with chemotherapy and/or radiotherapy has been associated with development of myelodysplastic syndrome (MDS) and acute myeloid leukaemia (AML) in breast and lung cancer patients. Patients treated in these settings should be monitored for signs and symptoms of MDS/AML. Sickle cell crises have been associated with the use of peg lgrastim in patients with sickle cell trait or sickle cell disease. Therefore, use caution when prescribing peg lgrastim in patients with sickle cell trait or sickle cell disease, monitor appropriate clinical parameters and laboratory status and be attentive to the possible association of this medicinal product with splenic enlargement and vasoocclusive crisis. White blood cell (WBC) counts of 100 × 109/L or greater have been observed in less than 1% of patients receiving peg lgrastim. No adverse reactions directly attributable to this degree of leukocytosis have been reported. Such elevation in WBCs is transient, typically seen 24 to 48 hours after administration and is consistent with the pharmacodynamic e ects of this medicinal product. Consistent with the clinical e ects and the potential for leukocytosis, a WBC count should be performed at regular intervals during therapy. If leukocyte counts exceed 50 × 109/L after the expected nadir, this medicinal product should be discontinued immediately. Hypersensitivity, including anaphylactic reactions, have been reported with peg lgrastim. Permanently discontinue peg lgrastim in patients with clinically signi cant hypersensitivity. Do not administer peg lgrastim to patients with a history of hypersensitivity to peg lgrastim or lgrastim. If a serious allergic reaction occurs, appropriate therapy should be administered, with close patient follow-up over several days. Stevens-Johnson syndrome (SJS), which can be life-threatening or fatal, has been reported rarely in association with peg lgrastim treatment. If the patient has developed SJS with the use of peg lgrastim, treatment must not be restarted at any time. As with all therapeutic proteins, there is a potential for immunogenicity. Rates of generation of antibodies against peg lgrastim is generally low. Binding antibodies do occur as expected with all biologics; however, they have not been associated with neutralising activity at present. Aortitis has been reported after lgrastim or peg lgrastim administration in healthy subjects and in cancer patients. The symptoms experienced included fever, abdominal pain, malaise, back pain and increased in ammatory markers (e.g. C-reactive protein and WBC count). In most cases aortitis was

diagnosed by CT scan and generally resolved after withdrawal of lgrastim or peg lgrastim. The safety and e cacy of Pelgraz for the mobilisation of blood progenitor cells in patients or healthy donors has not been adequately evaluated. Increased haematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone-imaging ndings. This should be considered when interpreting bone-imaging results. The additive e ect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account. Pelgraz contains less than 1 mmol sodium (23 mg) per 6 mg dose, that is to say essentially ‘sodium-free’. The needle cover contains dry natural rubber (a derivative of latex), which may cause allergic reactions. Pregnancy and Lactation: Peg lgrastim is not recommended during pregnancy and in women of childbearing potential not using contraception. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from peg lgrastim therapy taking into account the bene t of breastfeeding for the child and the bene t of therapy for the woman. Adverse Events include: Adverse events which could be considered serious include: Common: Thrombocytopenia. Uncommon: Myelodysplastic syndrome, acute myeloid leukaemia, sickle cell anaemia with crisis, capillary leak syndrome, glomerulonephritis, hypersensitivity reactions (including angioedema, dyspnoea, anaphylaxis), splenic rupture (including some fatal cases), Sweet’s syndrome (acute febrile neutrophilic dermatosis), pulmonary adverse reactions including interstitial pneumonia, pulmonary oedema and pulmonary brosis have been reported. Uncommonly cases have resulted in respiratory failure or ARDS which may be fatal. Rare: Aortitis, pulmonary haemorrhage, Stevens-Johnson syndrome. Other Very Common adverse events: Headache, nausea, bone pain. Other Common adverse events: Leukocytosis, musculoskeletal pain (myalgia, arthralgia, pain in extremity, back pain, musculoskeletal pain, neck pain), injection site pain, non-cardiac chest pain. See SmPC for details of other adverse events. Shelf Life: 3 years. Store in a refrigerator (2∞C – 8∞C). Pelgraz may be exposed to room temperature (not above 25°C ± 2°C) for a maximum single period of up to 72 hours. Pelgraz left at room temperature for more than 72 hours should be discarded. Do not freeze. Accidental exposure to freezing temperatures for a single period of less than 24 hours does not adversely a ect the stability of Pelgraz. Keep the container in the outer carton in order to protect from light. Pack Size: One pre lled syringe or pre lled syringe injector with one alcohol swab, in a blistered packaging.

Marketing Authorisation Numbers: Pre- lled syringe: EU/1/18/1313/001, Prelled injector: EU/1/18/1313/002. Marketing Authorisation Holder (MAH): Accord Healthcare S.L.U, World Trade Center, Moll de Barcelona, s/n, Edi ci Est, 6a planta, Barcelona, 08039 Spain. Legal Category: POM. Full prescribing information including the SmPC is available on request from Accord Healthcare Ireland Ltd, Euro House, Little Island, Co. Cork, Tel: 021-4619040 or www.accord-healthcare.ie/products Adverse reactions can be reported to Medical Information at Accord Healthcare Ltd. via E-mail: medinfo@accord-healthcare.com or Tel: +44(0)1271385257.

Date of Generation of API: May 2021. IE-01426

Adverse events should be reported. Reporting forms and information can be found on the HPRA website (www.hpra.ie), or by e-mailing medsafety@hpra.ie. Adverse events should also be reported to

(0) 1271 385257

End of Year Review: HPRA

Significant Progress with a Focus on the Future

Central to the success of all these initiatives continues to be close collaborative relationships with all our partners across the broader healthcare system. Indeed, maintaining and establishing new collaborative partnerships with key stakeholders will continue to be a primary focus for the organisation into 2023 as we look to enhance and protect public health through the effective regulation of health products.

COVID-19 Response and Lessons Learned

There is no doubt that 2022 was a much more positive and optimistic time for our country following the challenges presented by the COVID-19 pandemic during the previous almost two-year period. While there are currently no COVID-19 restrictions in Ireland, public health advice, combined with safe and effective vaccines, continue to help protect our communities. As we enter a new phase in our response to COVID-19, it is important we remain vigilant given the potential for future waves of infections driven by different subvariants. From a regulatory perspective, there was considerable focus on the authorisation of adapted bivalent vaccines to help protect against severe disease and hospitalisation in response to the Omicron variant. Experts from across our organisation, in collaboration with colleagues throughout Europe, conducted rigorous assessments to ensure that newly authorised adapted vaccines continue to demonstrate extremely high levels of safety, effectiveness and quality. In addition to the authorisation of COVID-19 related therapies and vaccines, regulators from across the globe are currently undertaking a period of reflection to understand how best to retain and implement some of the extraordinary regulatory agilities introduced during the pandemic to support the accelerated development and authorisation of medicines. Indeed, the HPRA continue to engage with colleagues across Europe to ensure efficiencies in the regulation of medicines are retained, wherever possible.

Implementation of New Regulations

The past year was also a time of

significant progress regarding the implementation of new legislative frameworks that will positively affect human health for many years. The new Medical Devices Regulation (MDR) and In-Vitro Diagnostics Regulation (IVDR), for example, will ultimately strengthen existing regulatory systems for medical devices and diagnostics across Europe. The regulations aim to provide, among other things, clearer requirements on clinical data for medical devices and in-vitro diagnostics (IVDs), more specific product requirements and enhanced provisions for market surveillance and performance assessment. Despite the clear and obvious benefits for patients and healthcare providers associated with the MDR and IVDR – in terms of an enhanced focus on clinical safety and innovation support – there are challenges that will need to be addressed before fully realising the system-strengthening opportunities provided by each regulation. Specifically, the coordinated and consistent application and operation of both regulations is critical to deliver for patients and ensure their success. The HPRA, in collaboration with colleagues from other European agencies, are providing leadership, influence and strategic direction to enhance cooperation and coordination within the EU regulatory system to deliver the successful implementation of MDR and IVDR.

We also saw the new Clinical Trials Regulation (CTR) coming into effect in January of this year. Like the MDR and IVDR, the CTR aims to maintain high standards of public transparency and safety for clinical trial participants, while at the same time demonstrating the EU offers an attractive and favourable environment for conducting clinical research on a large scale. The CTR enables sponsors to submit one application via a single online platform, known as the Clinical Trials Information System (CTIS), for approval to run a clinical trial in several European countries. In this way, it makes it more efficient to carry out such multinational trials. Following “golive” in January, the majority of trials submitted to the CTIS have been authorised (+75 trials), with many more currently under evaluation.

Written by Dr Lorraine Nolan, Chief Executive, Healthcare Products Regulatory Authority

Despite the relative success of CTIS, submission numbers remain lower than expected at this time and users have experienced technical issues with the platform resulting in the delayed approval of applications. The European Medicines Agency (EMA), together with national regulatory authorities across Europe, including the HPRA, are working collaboratively to resolve high-priority technical issues associated with the CTIS. The goal for all involved is to enable the timely, effective, and efficient authorisation of clinical trials that are so important to facilitating patient access to innovative medicines.

Enhancing our Approach to the Management of Medicines Shortage Management

Indeed, a primary focus throughout 2022 was ensuring the continued availability of medicines to meet patient need through our role in coordinating the management of medicines shortages. The HPRA has recently conducted a review of national data associated with the underlying root causes of shortages from the previous twoyear period. This is with a view to establishing the next phase of our multistakeholder response to shortage management in Ireland. Key stakeholders, including healthcare professionals and pharmaceutical companies, were consulted on this review, with recommendations on ways to help prevent and mitigate the effect of medicines shortages on patients due for publication in the coming year. This represents an exciting new phase in our approach to managing a multistakeholder approach and ensuring the continued availability of critical medicines on the Irish market to meet patient needs.

HPRA Contributions in Europe

Finally, from a personal perspective, it was a great honour to be appointed to lead the EMA’s Management Board. What has been evident throughout the years of the pandemic is that EMA must remain agile, responsive, and ready to show leadership

and solidarity in the context of significant developments in the operating environment. As chair, my focus will be to continue and further enhance the strong partnership between the EMA, national agencies and the European Commission. It is imperative that the EMA continues to deliver the highest standards of public health protection while maintaining its global reputation as a modern, progressive, and transparent regulator. This will be achieved through the continued close cooperation and partnership approach of the broader European medicines regulatory network. My role as chair of the EMA Management Board only serves to complements other HPRA staff holding prominent positions of influence at European level. Despite being a medium sized agency in the context of Europe, we continue to provide leadership on a range of important regulatory issues impacting public health.

Conclusion

As we look forward to 2023, I am excited to build on the achievements of the organisation throughout the year as we continue to work in partnership with colleagues from across the national public health system. This is in addition to our well-established commitment to the European, and increasingly global, regulatory network. While we have set ambitious goals and objectives for the coming year, I believe the HPRA will continue to excel in health product regulation through science, collaboration, and innovation.

This year has seen significant progress in several key areas of focus for the HPRA as we continued our work in response to the pandemic in combination with ongoing activities to ensure the successful implementation of new regulations and management of medicines shortages.

End of Year Review: Migraine Ireland

Not Just a Headache

2022 has been a year full of big wins for The Migraine Association of Ireland (MAI), which we are delighted to share, and which will produce exciting opportunities for 2023. These opportunities have come to fruition by building strong relationships with national and global migraine and headache associations, pharma companies, healthcare professionals and experts, pharmacists, and alternative treatment providers. We continue with our primary aim of supporting and advocating on behalf of patients.

Written by Hazel Breen, Communications and Information Officer, The Migraine Association of Ireland

• HSE price discussions and drugs review and approval takes 307 days.

Totalling 549 days.

Belgium’s medication approval process timeframe is broken down as follows:

Programme success to date now lays the foundation for a national rollout for this new headache pathway to care across 10 headache clinic locations nationwide.

MAI Events

Migraine Ireland had a jam-packed year full of patient, workplace, awareness, fundraising events list is as follows:

who sign up for Supportership with MAI where they can post, comment or chat between themselves. Much like their very own private social media platform!

We are delighted to share that we have been inundated with kind feedback from global organisations for being at the forefront for migraine, particularly for how visual we have become online and our Migraine at Work initiatives, which is a huge compliment to the MAI and everyone we work closely with, as we are being recognised as a leader in migraine worldwide. And that’s a big achievement for a small island!

However, 2022 was not without its challenges. COVID-19 challenges for people living with migraine nationwide produced a spike in Chronic Migraine (at least 15 days of migraine per month) cases. This was due to many factors including stress which is a huge trigger for migraine. The return to On-site work also presented challenges to migraine patients as they had become used to their more stable ‘work from home’ environment as migraine loves routine.

In addition, access to care and medication was highly challenging for migraine patients and healthcare professionals throughout the year due to many factors; some of which included medication shortages and a transition to a high-tech drug protocol processes which while necessary, required a lot of time for Neurologists and their teams to work through. The medication approval process in Ireland remains extremely slow in comparison to neighbouring countries. For example:

Irelands medication approval process timeframe is broken down as follows:

• NCPE Rapid Review and NCPE HTA takes 242 days.

• INAMI-RIZIV Assessment, CRM/ CTG Assessment, Minister Recommendation and Postminister.

Recommendation takes 210 days in total.

Headache clinic wait lists remain long for migraine patients to access specialist care from Neurologists. However, the Sláintecare Headache Pathway Pilot Programme created a more direct route to care and reductions across emergency departments of migraine patients presenting for acute care. (More on this in the MAI & Sláintecare section)

One of the biggest challenges we faced as an association in 2022 was a slow turnaround to funding applications from third parties outside of the HSE. In addition, one of our largest and long-term funding applications was denied. This funding was intended to cover a large proportion of operational costs over the next three years. Therefore, we find ourselves in unpredictable waters but the team is working relentlessly to problem solve and think of ways to generate this funding elsewhere, leaving no stone unturned. This means reducing costs where possible and endeavouring to generate funding from other avenues. MAI are highly optimistic that we can turn this negative outcome into a positive one, so we can continue to fight the good fight!

On a more positive note, we had many great achievements throughout 2022.

MAI & Sláintecare

The release of the Sláintecare Headache Pathway Pilot

Our inaugural Migraine Ireland Cycling Event took place on June 25th, 2022, with the legendary Irish Pro cyclist, Sean Kelly (King Kelly) and 100 cyclists who cycled 50KM and 100KM flat routes from The Avon in Co. Wicklow.

We ran over 20 Patient Focused highly successful events covering multiple areas from national and global experts which were very well received by our patient community. These events included 3 Self-Management Courses for Chronic Migraine, 3 Healthcare Professional events covering Hospital A&E, GPs and Pharmacies, Vestibular Migraine, Migraine in Men: Emotional Coping Strategies, Families and Carers of Migraineurs, Non-Headache Symptoms with Migraine and much more.

Our Workplace Events have hit the ground running. As this was a new service delivery by MAI starting late in 2021, since then we have had over 20 Workplace Events with employers who know that to get the best from their employee, they need to look after their wellbeing and be informed of reasonable accommodations they can make as 1 in 10 people live with migraine in Ireland.

Communications

Our comprehensive communications plan generated large volumes of awareness throughout 2022.

In the first 6 months we reached 1,000,000 people online through our website and social media channels. We managed to secure over 60 pieces of media coverage on TV and Radio, as well as Ireland’s top publications.

We created a peer-to-peer private supporters’ platform for migraineurs

We introduced a new Fundraiser platform by Enthuse which allows us to create our own events, receive donations and allow people to set up online Fundraisers securely which has been a great addition to MAI and a seamless and trustworthy tool to use.

Exciting times ahead for 2023

The team at MAI are excited to see how 2023 unfolds as we have so many great opportunities in the pipeline, such as:

A potential new medical resource joining The Migraine Association of Ireland which will be hugely beneficial to migraine patients, healthcare professionals nationwide and the team at MAI.

Website revamp – This project when complete will include dedicated resources on our website for patients, workplace, and healthcare professionals.

MAI plan to produce an experiential video in 2023, we are awaiting funding and will get started as soon as we can.

Rollout of Migraine FittnessTM at Work Programme – a learning tool for employers to reduce migraine stigma and create more accessible workplaces.

Digitisation of Brainstorm Magazine and our book.

With 2023 approaching, our main goal is to secure funding so that we can continue to work closely with patients, healthcare professionals, workplaces and interested third parties nationwide and worldwide to increase migraine awareness, to advocate for migraineurs nationwide, educate and support those with migraine in Ireland, provide updates on medication and care, support healthcare services, and help over 600,000 people in Ireland living with migraine to manage their condition.

For more information on migraine, please visit www.migraine.ie

End of Year Review: NAHPT

Hospital Pharmacy Technicians look back at 2022

Pharmacy Technicians have expanded their roles particularly in the last two years and it is widely recognised that the experience they have is invaluable and a huge support to pharmacists not only in their traditional roles but also in the development of new systems.

In order to ensure that pharmacy technicians are of a consistently high standard to meet the needs of the ever-expanding roles we are now involved in, it is important to ensure standards of education and training and continued professional development are high.

The NAHPT would like to see the introduction of professional registration of pharmacy technicians to ensure that the standard of excellence which is

very often reflected in the work that we do is consistent amongst all pharmacy technicians through regulation.

We are continuing to look at our options for regulation and conducted a fact-finding exercise to ascertain the requirements for regulation. We met with pharmacy technician course co-ordinators, contacted professional healthcare regulators and met with the PSI registrar to assess the support for and process required to proceed with the regulation of pharmacy technicians. The PSI agreed that they would be the most natural fit as a pharmacy regulator for pharmacy technicians to be registered with as opposed to other professional healthcare

Some of the roles that pharmacy technicians are now involved in include:

Sector

Education: RCSI, University of Medicines and Health Sciences

HSE Procurement: National Pharmacy Procurement Team

Professional Representative Organisation: Irish Pharmacy Union (IPU) CPD:

Pharmacy Technician roles and responsibilities

regulators but at present pharmacy technicians are not designated for professional registration by the department of health. We therefore would need support for pharmacy technicians to be added to the department of health list of healthcare professions that require registration. We provided feedback to our members and conducted an initial hospital pharmacy technician survey to establish the interest/support for registration before we pursue this challenging process any further. Although not exhaustive the initial results of the survey showed that 94% of the pharmacy technicians that responded are in favour of pursing professional registration.

• Contribute to the design, development, and delivery of the school’s educational programmes at both undergraduate and postgraduate levels.

• Assisting the development, preparation, delivery, and assessment in the broad areas of pharmacy including pharmacy practice, clinical pharmacy and pharmaceutics.

• Work alongside academic staff, teacher-practitioners, practice educators and the technical team to ensure an authentic learning experience for students.

• Manage tender processes for high-cost drugs.

• Develop documentation for tender processes.

• Qualify applications from drug companies for registration to the HSE Dynamic Purchasing System for authorised medicines.

• Contract administrator.

• Advising and assisting IPU members on the administration of the Community Pharmacy Contractors Agreement, in particular processing claims and payments, and administering the HSE community drugs schemes.

• Operations coordinator.

• Look after the Institute’s Finance system and provide administrative support to the IIOP Team.

• Support a range of projects in the IIOP including the webinar series, the IIOP newsletter and the support helpdesk.

• Processing and analysing new medicinal product applications.

• Receipt and management of Product Discontinuation Notifications and of Product Shortages Notifications.

• Co-operate with other PCRS functions (e.g., Drugs Unit, Finance, Operations) to ensure appropriate reimbursement (including governance and reporting) arrangements are in place for all medicines.

• Medicines management.

• Receipt and secure storage of vaccines.

• Distribution, workflow management and dose reconciliation.

• Validation and management of the cold chain.

The three roles are;

1. Cancer Drug Management programme – primarily focused on the development and review of the national chemotherapy regimens as well as quality services.

2. Systemic Therapy Programme – primarily focused on funding and audit considerations for cancer drugs including ODMS and other streams.

3. National Cancer Information system (NCIS) – primarily focused on national regimen building for NCIS.

• The technicians play a key role within each of these small teams and their roles continue to grow and evolve in response to the service needs.

Written by Leonor O’Connor, President, National Association of Hospital Pharmacy Technicians

It has been a very interesting and professionally progressive year for hospital pharmacy technicians.

with VOCABRIA + REKAMBYS, the first and only, complete long-acting injectable regimen, dosed once every 2 months, for virologically suppressed* patients

First and only, complete long-acting regimen for HIV-1

N O W I N CLUDED I N VOCABRIA + REKAMBYS

EACS 2021 GUIDELINES

as a switch strategy for virologically suppressed* patients

The efficacy you have come to expect from daily HIV regimens

Vocabria injection is indicated, in combination with Rekambys injection, for the treatment of HIV-1 infection in adults who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen without present or past evidence of viral resistance to, and no prior virological failure with agents of the NNRTI and INI class.

*HIV-1 RNA <50 copies/mL. HIV-1=human immunodeficiency virus type 1.

Abbreviated Prescribing Information

Vocabria(cabotegravir) 600 mg prolonged-release suspension for injection.

Rekambys(rilpivirine) 900 mg prolonged-release suspension for injection.

See Summaries of Product Characteristics (SmPC) before prescribing.

Preferred by 98% of patients over daily oral therapy in the

ATLAS-2M

clinical trial

At Week 48, 98% of 306 patients with no prior exposure to VOCABRIA + REKAMBYS who responded to the questionnaire preferred every 2-month injections vs 1% of 306 patients who preferred the study daily oral lead-in (1% reported no preference).

Presentation: Vocabria vials contain 600 mg cabotegravir in 3 mL. Rekambys vials contain 900 mg rilpivirine in 3 mL. Indication: Vocabria and Rekambys in combination are indicated for the treatment of HIV-1 infection in adults who are virologically suppressed (HIV-1RNA <50 copies/mL) on a stable antiretroviral regimen without present or past evidence of viral resistance to, and no prior virological failure with agents of the NNRTI and INI class. Dosing: Therapy should be prescribed by a physician experienced in the management of HIV infection. Prior to starting Vocabria and Rekambys, healthcare professionals should have carefully selected patients who agree to the required injection schedule and counsel patients about the importance of adherence to scheduled dosing visits. Following discontinuation of Vocabria and rilpivirine injection, it is essential to adopt an alternative, fully suppressive antiretroviral regimen no later than two months after the final injection of Vocabria 600 mg. The healthcare provider and patient may decide to use cabotegravir tablets as an oral lead-in prior to the initiation of Vocabria and Rekambys injection to assess tolerability to cabotegravir or may proceed directly to Vocabria and Rekambys injections. If oral lead-in is used: Prior to the initiation of injections, oral cabotegravir together with oral rilpivirine should be taken for approximately one month (at least 28 days) to assess tolerability to cabotegravir and rilpivirine. One cabotegravir 30 mg tablet should be taken with one rilpivirine 25 mg tablet, once daily. When administered with rilpivirine, cabotegravir tablets should be taken with a meal. Initiation injection: On the final day of current antiviral therapy or oral-lead in therapy, the recommended initial dose is a single intramuscular injection of Vocabria 600 mg injection and rilpivirine 900 mg administered at separate gluteal injection sites at the same visit and at a second date one month later. After the second Vocabria 600 mg injection and rilpivirine 900 mg injection the continuation injection dose is Vocabria 600 mg injection and rilpivirine 900 mg injection administered at separate gluteal injection sites at the same visit every two months. Patients may be given injections up to 7 days before or after the date of the two monthly injection schedule. No dose adjustment requirement in the elderly, in patients with mild to severe renal impairment (CrCl <30 mL/min and not on dialysis) and in patients with mild or moderate hepatic impairment (Child-Pugh score A or B). Use with caution in patients on renal replacement therapy or with severe hepatic impairment (Child-Pugh class C). Contraindications: Hypersensitivity to any ingredient. Co-administration with rifampicin, rifapentine, rifabutin, carbamazepine, oxcarbazepine, phenytoin, phenobarbital, dexamethasone (except as a single dose treatment) or St John’s Wort. Special warnings/ precautions: To minimise the risk of developing viral resistance it is essential to adopt an alternative, fully suppressive antiretroviral regimen no later than two months after the final injection of Vocabria and Rekambys. Consider the prolonged release characteristics of Vocabria and Rekambys injections (up to 4 years) when discontinuing. A combination of at least two of the following factors at baseline - archived rilpivirine resistance mutations, HIV 1 subtype A6/A1, or BMI ≥ 30 kg/m2 may be associated with increased risk of virological failure. Risk of hypersensitivity reactions including dyspnoea, agitation, abdominal cramping, flushing, sweating, oral numbness and changes in blood pressure. Discontinue Vocabria and Rekambys and other suspect agents immediately if suspected. Use with caution when co-administered with products with a known risk of Torsade de Pointes. Monitor LFTs and discontinue if hepatotoxicity suspected. Not recommended in patients with HBV co-infection. Monitor LFTs in patients with HCV co-infection. Do not administer Vocabria and Rekambys with other antiretroviral products. In HIV-infected patients with severe immune deficiency at the time of institution of combination antiretroviral therapy, an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise for example cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, and Pneumocystis jirovecii pneumonia. Any inflammatory symptoms should be evaluated, and treatment instituted when necessary. Autoimmune disorders (Graves’ disease and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution. Caution when co-dosing with narrow therapeutic index OAT1/3 substrate drugs. Fertility, pregnancy and lactation: Human fertility: No data. Animal fertility studies indicate no effects. Pregnancy: Not recommended unless expected benefit justifies the potential risk to the foetus. If used viral load should be monitored closely. Do not breast-feed. Side effects: Very common (≥1/10): Headache, injection site reactions (pain and discomfort, nodule, induration), increased total cholesterol (fasted), increased LDL cholesterol (fasted), increased pancreatic amylase, pyrexia (majority of cases reported within one week of injection. Common (≥1/100 to <1/10): Depression, anxiety, abnormal dreams, insomnia, sleep disorder, dizziness, GIT symptoms, rash, myalgia, injection site reactions (swelling, erythema, pruritus, bruising, warmth, haematoma), fatigue, asthenia, malaise, weight increased, decreased white blood cell count, decreased haemoglobin, decreased platelet count, decreased appetite, increased triglycerides (fasted), abdominal discomfort, dry mouth, increased lipase. Uncommon (≥1/1,000 to <1/100): Immune reactivation syndrome, suicide attempt, suicidal ideation (particularly in patients with a pre-existing history of psychiatric illness), somnolence, vasovagal reactions (in response to injections), hepatoxicity, injection site reactions (cellulitis, abscess, anaesthesia, haemorrhage, discolouration), transaminase increased, bilirubin increased. Vocabria: MA Nr: EU/1/20/1481/003. Vocabria MA holder: ViiV Healthcare BV, Van Asch van Wijckstraat 55H, 3811 LP Amersfoort, Netherlands. Rekambys MA Nr: EU/1/120/1482/002. Rekambys MA holder: Janssen-Cilag International NV, Turnhoutseweg 30, B 2340 Beerse, Belgium. Legal Category: POM A. Date of preparation of API: March 2022. Code: PI-8819. Further information available from GlaxoSmithKline, 12 Riverwalk, Citywest, Business Campus, Dublin 24. Tel: 01-4955000.

Adverse events should be reported directly to the Health Products Regulatory Authority (HPRA) on their website: www.hpra.ie. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255.

 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information.

Healthcare professionals are asked to report any suspected adverse reactions.

REKAMBYS (rilpivirine long acting ), including the trademark, is owned by the Janssen Pharmaceutical Companies and used under license by the ViiV Healthcare group of companies. All other trademarks are owned by the ViiV Healthcare group. ©2022 ViiV Healthcare group of companies or its licensor.

PM-IE-CBR-JRNA-220001. Date of preparation: April 2022

Sector Pharmacy Technician roles and responsibilities

• Medicines management.

• Compiling stock orders of all medicines as well as dressings/ostomy products/sharps bins/PPE etc.

• Monitoring of and stocking medication bags for house calls.

• Working alongside Doctors and Clinical nurses.

• Maintenance of ECG machines and defibrillator.

Wholesale: Uniphar

HSE: GUIDe (Sexual Health

Research: Clinical Trials

Hospital: Medicines Management / Ward Based**

Commercial Sales: Key Account Manager in Specialised Medicines, ULM supply, and Medication shortages

• Customer service role concerned with the supply of EMP’s and other procured goods.

• Customer advisory services.

• Provision of technical support.

• Dispensing and counselling of patients on appropriate use of ARVs, ID and STI medications.

• Medicines reconciliation DDI checking for patients.

• Maintaining stock levels for pharmacy and liaising with procurement around expected shorts.

• Liaising with Irish prison services managing ART for inmates.

• Creating reports on cost/usage.

• Adhere to procedures to ensure the safe and correct ordering, receipt, recording, handling, storage, dispensing, administration, quarantining and destruction of investigational medicinal products (ATIMPS/ IMPs) including investigation and rectification of discrepancies.

• Providing technical direction and assistance with clinical trial protocols.

• Liaise with trial sponsor representatives and prepare pharmacy documentation for monitoring visits and follow up and action any monitoring visit finding.

• Medicines reconciliation and kardex review.

• Review of drug trolleys/presses.

• Provide patient education.

• Ordering and supply of non-stock medications.

• Support audit and data collection for service-based activities.

• This position requires the Pharmacy Technician to assess the supply chains globally, review product suitability and help ensure continuity of supply.

There is a requirement to be able to:

• Maintain and develop relationships with Hospital Pharmacy Teams

• React quickly to shortages

• Offer solutions to supply new therapies that currently are unavailable in Ireland due to external challenges, by partnering with companies in other markets i.e Brexit, Temp Controlled Shipments

• Managing logistics and meeting quality standards throughout

• Identify potential critical medication unavailable in the market

Clinical Support Specialist for a pharmaceutical wholesale business.

HSE Acute Hospitals Drugs Management Programme (AHDMP)

• The focus of the role is to provide expert clinical support to the business, liaising with both internal and external stakeholders.

• The role supports the growth of the business by working with management to assess the market landscape, provide product training and demonstrations to both internal and external stakeholders, educate the business on clinical indications for both existing and new products, Review SmPC’s, and Analyse clinically, market opportunities to identify gaps in the market and opportunities to optimise product portfolio.

• Role in the Hospital Medicines Management System (HMMS) project team.

• Responsible for the implementation of a national hospital pharmacy medicines management system. This is modern pharmacy software with increased functionality in key areas such systems integration, drug procurement, inventory management, ward-based activities and finance. HMMS will also become the platform to support electronic prescribing and electronic medicines in the future in Irish hospitals.

• Involved in building a drug file and supplier builds, working with pharmacy focus groups e.g., dispensary, clozapine, clinical trials to map workflows and identify how they use pharmacy software systems at present.

• Currently training on this new software and will be involved in testing before we go live as well as providing on-site support to pharmacy staff.

** This year Connolly Hospital Medicines management technician (MMT) service was shortlisted for a HSE excellence award.

The HSE excellence awards are an opportunity to showcase and celebrate the good work that is happening in the HSE every day.

The MMT service was entered under the Innovation and service delivery category and the title of project was “Delivering safer, more cost-effective medication management through Pharmacy skill-mix innovation”

Update on some of the additional activities of the Association this year:

All educational in person events and our annual conference was cancelled or delayed due to Covid-19. Our members were surveyed regarding their continued preference for online or delayed in-person conference and chose to postpone our annual conference over participating in an online conference.

We hosted an online educational

and wellness event for our members which included a talk by one our unlicensed medicines suppliers Medfind on the sourcing of drugs in short supply and we had workshop entitled “Resilience Minds at Work” provided by a psychologist, to support and encourage the wellbeing of our members. The aim for members was to have an understanding of how their mind works, how stress works, the relationship between thoughts and emotional reactions and how to reduce stress.

Uniphar Site Visit - We had a very interesting day visiting the Uniphar Citywest premises which gave members a really good insight into the sourcing and supply of medicines.

NAHPT are now part of an advisory committee for one of the colleges (TU, Dublin) providing a pharmacy technician course, participating in the pharmacy technician studies programme development.

Our committee member and former Nahpt president Laura

Lyons was elected secretary of the EAPT (European Association of Pharmacy Technicians)

NAHPT committee have provided support and answered regular queries from pharmacy technicians working in hospitals and community pharmacy in relation to pharmacy work practices.

We look forward to another interesting, productive, and progressive year next year for pharmacy technicians.

nahptirl@outlook.com | www.nahpt.ie

BIKTARVY® offers long-term treatment success for a broad range of people living with HIV* 1–5 A robust** regimen delivering long-term efficacy with 0 resistance in randomised clinical trials†‡1,2 A small STR with low potential for DDIs, simple dosing and no food requirements¶1

A well-tolerated regimen with low rates of discontinuation in randomised clinical trials§ll2,5–7

Footnotes:

*BIKTARVY® was assessed in four Phase 3, randomised clinical trials: two double-blind trials in treatment-naive adults through to 144 weeks (Study 1489 [BIKTARVY® vs ABC/3TC/DTG, n=629] and Study 1490 [BIKTARVY® vs DTG + FTC/ TAF, n=645]) and two in virologically suppressed adults through to 48 weeks (Study 1844 [double-blind trial, switching from DTG + ABC/3TC or ABC/3TC/DTG to BIKTARVY®, n=563] and Study 1878 [openlabel trial, switching from ABC/3TC or FTC/TDF plus boosted ATV or DRV to BIKTARVY®, n=577]).1 The primary endpoint of Studies 1489 and 1490 was HIV-1 RNA <50 copies/mL at Week 48, as defined by the US FDA snapshot algorithm, with a prespecified non-inferiority margin of –12%.3,4 The primary endpoint of Studies 1844 and 1878 was HIV-1 RNA ≥50 copies/mL at Week 48, as defined by the US FDA snapshot algorithm, with a prespecified noninferiority margin of 4%.5,6 Efficacy defined as viral load <50 copies/mL.1 **Defined as maintained efficacy, which is dependent on patient adherence. Adherence is impacted by tolerability and simplicity of treatment.8–11 †At Week 144, in Study 1489 (BIKTARVY® [n=314] vs ABC/3TC/DTG [n=315]) efficacy was 82% vs 84% (95% CI: –2.6 [–8.5– 3.4]) and in Study 1490 (BIKTARVY® [n=320] vs DTG + FTC/TAF [n=325]) efficacy was 81% vs 84% (95% CI: –1.9 [–7.8–3.9]), with BIKTARVY® demonstrating noninferior efficacy vs comparator in both trials. 2 At Week 48, in Study 1844 (BIKTARVY® [n=282] vs ABC/3TC/DTG [n=281]) efficacy was 94% vs 95% (95% CI: –1.4 [–5.5–2.6]) and in Study 1878 (BIKTARVY® [n=290] vs ABC/3TC or FTC/TDF plus boosted ATV or DRV [n=287]) efficacy was 92% vs 89% (95% CI: 3.2 [–1.6–8.2]).1

‡At Week 144, in pooled treatment-naïve patient data from Study 1489 (n=629) and Study 1490 (n=645), and Week 48 in Study 1844 (n=563), there were 0 cases of treatment emergent resistance to study regimens [BIKTARVY® (n=0/834), ABC/3TC/DTG (n=0/315) and DTG + FTC/ TAF (n=0/325)].2,5 At Week 24, in Study 1878 (n=577) one participant in the ABC/3TC plus boosted DRV group developed treatment-emergent resistance; no participants in the BIKTARVY® group developed treatmentemergent resistance through Week 48.6 § At Week 144, in patients receiving BIKTARVY®, the most frequently reported study-drug-related adverse reactions (≥5%) in Study 1489 were diarrhoea 6% (n=19/314), nausea 6% (n=18/314) and headache 5% (n=16/314); in Study 1490 they were headache 4% (n=14/320), diarrhoea 3% (n=10/320) and nausea 3% (n=10/320).2

ll 44-week data on AEs leading to study drug discontinuation % (n). Study 1489 (vs ABC/3TC/DTG): 0% (n=314) vs 2% (n=5 /315); Study 1490 (vs FTC/TAF + DTG): 2% (n=6/320) vs 2% (n=6/325).2 48-week data on AEs leading to study drug discontinuation % (n). No discontinuations due to weight gain in Study 1489 or Study 1490. Study 1844 (vs ABC/3TC/DTG): 2% (n=6/282) vs 1% (n=2/281); Study 1878 (vs boosted DRV or ATV + 2 NRTIs): 1% (n=2/290) vs <1% (n=1/287).5,6

¶Small STR with flexible daily dosing. Each BIKTARVY® tablet is approximately 15 mm x 8 mm.1

References:

1. BIKTARVY® (BIC/FTC/TAF) Summary of Product Characteristics.

2. Orkin C, et al. Lancet HIV. 2020; 7: e389 e400.

3. Sax PE, et al. Lancet. 2017; 390: 2073–2082.

4. Gallant J, et al. Lancet. 2017; 390: 2063–2072.

5. Molina JM, et al. Lancet HIV. 2018; 5: e357–e365.

6. Daar ES, et al. Lancet HIV. 2018; 5: e347–e356.

7. Wohl D. et al. Patient. 2018; 11: 561–573.

8. US Department of Health and Human Sciences (DHHS). Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. June 2021. Available from: https://clinicalinfo.hiv. gov/sites/default/ files/guidelines/documents/ AdultandAdolescentGL.pdf (Accessed June 2021)

9. Cihlar T and Fordyce M. Curr Opin Virol. 2016; 18: 50–56.

10. Trottier B, et al. J Int AIDS Soc. 2014; 17(4 Suppl 3): 19765.

11. Orkin C, et al. HIV Med. 2018; 19: 18–32.

Abbreviations:

3TC, lamivudine

ABC, abacavir

AE, adverse event

ATV, atazanavir

BIC, bictegravir

CI, confidence interval

DRV, darunavir

DTG, dolutegravir

FDA, Food and Drug Administration

FTC, emtricitabine

PLWH, people living with HIV

RNA, ribonucleic acid

STR, single-tablet regimen

TAF, tenofovir-alafenamide fumarate

TFV, tenofovir

TDF, tenofovir disoproxil fumarate

US, United States

Prescribing Information:

Consult the Summary of Product Characteristics (SmPC) before prescribing.

BIKTARVY® bictegravir 50mg/emtricitabine 200mg/ tenofovir alafenamide 25mg film-coated tablets.

INDICATION: Treatment of adults with HIV-1 infection without present or past evidence of viral resistance to the integrase inhibitor class, emtricitabine or tenofovir DOSAGE: Adults: One tablet, once daily, taken orally and whole with/without food. Elderly: No dose adjustment is required in patients ≥ 65 years. Renal impairment: Patients with estimated creatinine clearance (CrCl) ≥ 30 mL/min: No dose adjustment required. Patients with CrCl ≥ 15 mL/min and < 30 mL/min or Patients with end stage renal disease (ESRD, CrCl < 15 mL/min) who are not receiving chronic haemodialysis: Should be avoided. Patients with ESRD on chronic haemodialysis: No dose adjustment, but only use if potential benefit outweighs the potential risks. Hepatic impairment: Mild/moderate hepatic impairment: no dose adjustment required. Severe hepatic impairment: not recommended. Paediatric population (<18 years): Safety and efficacy has not been established. Refer to SmPC for full information CONTRAINDICATIONS: Hypersensitivity to active substances / any excipients. Co-administration with rifampicin and St John’s wort. Refer to SmPC for full information. WARNINGS/ PRECAUTIONS: Should not be co-administered with other antiretroviral products. Limited safety and efficacy data in HCV co-infection. Tenofovir alafenamide is active against HBV. Co-infected HIV/HBV patients should be closely monitored for at least several months following discontinuation for symptoms of severe acute exacerbations of hepatitis. Should not be administered simultaneously with magnesium/aluminium-containing antacids or iron supplements under fasted conditions. See SmPC for more information on liver disease, weight and metabolic parameters, risk of mitochondrial dysfunction following exposure in utero, immune reactivation syndrome, opportunistic infections, osteonecrosis with CART therapy or nephrotoxicity and patients with ESRD on chronic haemodialysis. Co- administration: Biktarvy is not recommended for coadministration with atazanavir, carbamazepine, ciclosporin (IV or oral use), oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, or sucralfate. Excipients: Contains less than 1 mmol sodium (23 mg) per tablet, i.e. essentially ‘sodium free’. Refer to SmPC for full information on warnings and precautions. INTERACTIONS: See SmPC for full list. PREGNANCY/LACTATION: Use only if potential benefit justifies the potential risk. Breast-feeding: not recommended. Refer to SmPC for full information. DRIVING/USING MACHINERY: dizziness has been reported. SIDE EFFECTS: Refer to SmPC for full information Common (≥1/100 to <1/10): depression, abnormal dreams, headache, dizziness, diarrhoea, nausea, fatigue. Serious adverse events: suicidal ideation, suicide attempt behaviour (particularly in patients with a pre-existing history of depression or psychiatric illness), anxiety, sleep disorders, angioedema and Stevens-Johnson syndrome. LEGAL CATEGORY: POM. PACK: Bottle of 30 film-coated tablets. PRICE: UK NHS List Price - £879.51; Éire/ Ireland – POA. MARKETING AUTHORISATION NUMBER: Great Britain: PLGB 11972/0008 Ireland and United Kingdom (Northern Ireland: EU/1/18/1289/001 & EU/1/18/1289/002 FURTHER INFORMATION: Gilead Sciences Ltd, 280 High Holborn, London, WC1V 7EE, UK; Great Britain & Northern Ireland: +44 (0) 8000 113700, For Ireland: +353 214 825 999. E-mail: ukmedinfo@gilead.com Biktarvy is a trademark. DATE OF PREPARATION: March 2021; UK-HIV-2021-03-0032.

Additional monitoring required.

Adverse events should be reported. For Great Britain and Northern Ireland, reporting forms and information can be found at www.mhra. gov.uk/yellowcard/ or via the Yellow Card app (download from the Apple App Store or Google Play Store). Adverse events should be reported to Gilead (safety_FC@gilead.com) or +44 (0) 1223 897500.

Adverse events should be reported. For Ireland, reporting forms and information can be found at www.hpra.ie and can be reported to HPRA on +353 1 6764971. Adverse events should be reported to Gilead (safety_FC@gilead.com) or +44 (0) 1223 897500.

End of Year Review: IPHA

Safeguarding Medicine Innovator Gains

In recent months, tax receipts from some of the country’s most important industrial sectors - biopharmaceuticals and technology, among themdemonstrate the importance of foreign direct investment. In our industry, many of the world’s largest players have commercial, manufacturing and, sometimes, research operations here, employing tens of thousands of people and generating billions in value-added for the economy. These companies’ productivity outputs are helping the Government to respond to cost-ofliving challenges and, before that, to the pandemic. The medicines they make are helping people, in Ireland and globally, to live better for longer. This impact is keenly felt in communities and in families. What medicines innovators do matters economically, socially and in healthcare terms.

It would be a mistake, though, to believe that the continued growth of the biopharmaceutical industry is inevitable. Like other industries, we are buffeted by international policy developments and geopolitical events. The global economic outlook is uncertain, especially with inflation, war in Europe and the ongoing impact of Covid-19.

Product life cycles, industry consolidation patterns, the draw of emerging markets, skills readiness and sub-optimal speeds of adoption of new medicines in the health services combine to create headwinds that could decelerate the pace at which the industry scales in Ireland into the future.

Ireland needs to improve our attractiveness for clinical trials, build our scientific research base, and position as a destination for production and supply chain investments in ATMPs, including cell and gene therapies, as well as their reimbursement for patients. It makes no sense that Ireland has scale when it comes to the biopharmaceutical manufacturing footprint but not speed when it comes to reimbursing new medicines in the health system. The Government has invested close to ¤100 million in new medicines in the past three Budgets. But an inefficient reimbursement process means we are still among the slowest countries in western Europe to make them available to patients.

The way to improve all this is through structured dialogue between policymakers, in Dublin and Brussels, and our industry. We can work on shared solutions. Together, we should identify how to yield growth opportunities for the country, as well as de-risking an environment that could make a loss of competitiveness or a diminution in standards of care entirely possible.

A recent study by consultants Charles River Associates for EFPIA, the industry’s representative organisation in Europe, urges steps to boost competitiveness so that Europe is less likely to lose out to the US and Asia for new investments in biopharmaceutical research and in production. The study, called ‘Factors Affecting the Location of Biopharmaceutical Investments and Implications for European Policy Priorities’, illustrates our industry’s declining competitiveness in Europe, with the global share of research and development investments, clinical trials and manufacturing output all waning. The study finds that a key driver of most new investments is the location and performance of existing research and development or manufacturing footprint.

That is positive for Ireland. Recent investments in production sites across the country are based, in part, on an already-established performance culture built over decades. This performance has been backed by sensible and stable Government policy, with IDA Ireland leading the effort to attract foreign direct investment.

But the study reveals trends all of us should heed. In 2002, the US spent $2 billion more than Europe on research and development. Today, that figure is $20 billion - a rise of 1000%. Of the total research and development investments made in the US, Europe, China and Japan, only 31% occurs in Europe. This has declined steadily from 41% in 2001. China has grown its share from 1% to 8%.

Clinical trial activity for ATMPs is twice as high in the US and almost three times as high in China than in Europe. Cell and gene therapies are usually one-time treatments that can add months, sometimes years, to a patient’s life, replacing a

lifetime of treatment. In cancer, haemophilia, SMA Type 1 and ocular diseases, cell and gene therapies can be game-changers. The number of trials for these treatments conducted in the US and Asia-Pacific region grew by 70% and 67%, respectively, between 2014 and 2021 while Europe remained stagnant. Europe accounted for a 19.3% share of global clinical trials activity in 2020, a drop of 6.3%, compared with a 25.6% average over the past 10 years.

ATMPs are the therapies of the future, with 804 next-generation biotherapeutics, including cell and gene therapies and mRNA technology, in a global pipeline of over 8,000 new medicines. The US has half the world’s ATMP manufacturing facilities. Asia is fast becoming the most competitive region for attracting ATMP clinical trials (255 in 2021), with Europe in decline (89 in 2021). For Europe to compete more effectively, it must recognise the complexity of these new technologies and build the interconnected ecosystem needed to develop them. We have argued for Ireland to aspire to be a centre for ATMP supply chain and production, and to adopt a national policy for adopting ATMPs affordably and fast in the health system. The EU should take a more proactive role in fostering the growth of emerging ATMP clusters, providing support across the ecosystem of research and development, manufacturing and clinical trials. The old approach of siloed policymaking focused on innovation, manufacturing and healthcare sustainability does not work.

The study finds that global research and development is expected to grow at a rate of 4.2% annually to $233 billion in 2026.

The problem is that it is moving out of the EU. While world-leading hubs like Boston, San Francisco and the UK’s ‘Golden Triangle’ get significant policy focus and strategic funding, European research funding is more uniform across countries. The countries with the highest EU research

spend per population are not the centres of innovation. This is a weak strategy. The European Commission should consider more strategic allocation of resources to foster the growth of world-leading research centres.

The European Commission is reviewing the operating environment for medicines innovation as part of the EU Pharmaceutical Strategy. A legislative proposal is due to be published early next year. Our Government, and our MEPs, should adopt a position that backs innovation and supportive intellectual property rights. That means making Europe more competitive for jobs and investments in biopharmaceuticals, accelerating patients’ access to affordable medicines, investing in research for unmet medical needs and making regulatory pathways more agile and efficient. It does not mean curtailing intellectual property rights or linking them to medicines access.

Our industry’s local brand purpose is ‘innovate for life’. Although it is the name of our flagship, multiaward-winning film-led digital campaign, it is much more than a slogan. It means our work changes lives for the better - and that innovation is a life-long endeavour. Covid-19 has shown the value of partnership. It should not take a crisis for us to work together.

Closer collaboration between industry and policy leaders, especially when healthcare outcomes and investments are at stake, makes sense. We should build a permanent bridge, through regular strategic dialogue, that cements the interdependency between citizens, policymakers and industry.

Written by Bernard Mallee, Director of Communications and Advocacy at the Irish Pharmaceutical Healthcare Association

Medicines innovators’ impact is keenly felt but we must safeguard the gains and tackle the gaps

End of Year Review: Thrombosis Ireland

disability and death

Blood Clots

Venous thromboembolism (VTE) compromising deep vein thrombosis (DVT) and Pulmonary embolism (PE) is the leading cause of death and disability worldwide. In Ireland, VTE remains the leading cause of maternal mortality. Globally, two thirds of all cases of VTE are hospital acquired, meaning that they occur either during a patient’s hospital stay or within 90 days of discharge. In majority of patients, such events are preventable through timeous risk assessment, initiation of appropriate prophylaxis and patient education. In many cases, VTE is treatable, but if undetected, can be potentially fatal.

Written by Ann Marie O’Neill, Patient Founder, Thrombosis Ireland

• You have heart lung or inflammatory disease

• You are over 60 years of age or are overweight.

• You have varicose veins that become red and sore.

patient with respects to VTE risk factors, early warning signs to watch for and the importance of seeking medical attention if they suspect a blood clot.

to reduce hospital acquired VTE. Preventing Blood Clots in Hospitals 3

Blood Clots do not discriminate. One collaborative study by the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) study found that at least 1 in 12 middle-aged adults will develop venous thromboembolism in their remaining lifetime. They can happen to anyone. Male or female, young or old. Blood clots are more likely to occur in a person with two or more risk factors at any given point in time.

You may be at higher risk of a blood clot if:

• You are admitted to hospital and for 90 days after you go home.

• You have active cancer or are receiving cancer treatment.

• You are pregnant or have had a baby less than 6 weeks ago.

• You have recently been immobile for a prolonged period (more than 3 days in bed/ travel non-stop for 6 hours/ lower limb injury or in a leg cast)

Your risk my increase further if:

• You or a close relative had a previous blood clot.

• You have had surgery in the last 90 days.

• You have thrombophilia (blood clotting condition)

• You are taking the combined oral contraceptive pill or HRT.

Thrombosis Ireland was established in 2016 to address the lack of awareness and education programs for both patients and health care professionals regarding VTE and the complexities of its prevention and management. Through education campaigns and hospital drives, we aim to increase VTE risk awareness amongst health care providers and users, empowering clinicians, and patients to spot the signs early. In addition, we are strong advocates for the establishment of a coordinated rehabilitation program to support VTE patients during their recovery period and hope to work alongside hospitals in the future to develop such initiatives.

Our first initiative was to produce a wallet sized, laminated Blood Clot Alert, card which would provide all the necessary information to a

In 2017, Thrombosis Ireland participated in the HSE VTE Collaborative, an initiative led by Ms Ciara Kirke and the HSE Medication Safety Improvement Program. From this collaborative effort in 2018, a number of HSE VTE Safety recommendations were developed.

Preventing Blood Clots in Hospitals (hse.ie)

This report summarises the learning from the collaboration and provides a toolkit to facilitate hospitals with further improvement, including patient alert cards which have been provided to all hospitals.

Hospitals Must Ensure that:

• Oversight for monitoring and improving VTE prevention is assigned to the appropriate governance committee and is an agenda item at meetings at least twice a year.

• An adequately resourced multidisciplinary team is supported to carry out quality improvement

• A VTE prevention protocol is in place, accessible and staff are aware of it.

• The protocol is followed for each in-patient as soon as possible after the decision to admit is made, and correct prophylaxis received asap and within 24 hours.

• Tools and processes which have been found to be effective are in place, e.g. independent check(s) of prophylaxis, education for staff and patients and prompts/alerts, e.g. pre-printed prescriptions.

• Each in-patient receives information about any VTE prophylaxis they are receiving, their risk of VTE for 90 days after hospitalisation, the signs and symptoms of VTE and what to do if they occur, facilitated by providing the Patient Alert Card.

• Responsibilities are assigned for, following the VTE prevention protocol and prescribing prophylaxis, independently checking prophylaxis and ensuring patients receive information prior to discharge.

What is the leading cause of PREVENTABLE

in your hospital?

• Monitoring of key metrics takes place at least quarterly and is reviewed at the appropriate governance committee. This includes a new national key performance indicator, together with measuring the percentage of patients with appropriate prophylaxis and monitoring whether patients are receiving alert cards.

• Hospital-acquired VTE is reported and managed in accordance with the HSE Incident Management Framework, including open disclosure.

• Hospital-acquired VTE is listed as a risk on the hospital’s risk register.

As a patient led organisation, we have worked hard to encourage and drive the implementation of these recommendations to ensure that patient’s receives the best possible standardised care.

It has been truly uplifting to witness various hospitals implement safety initiatives to improve VTE awareness, prevention and management throughout their hospitals and communities at large. This year for World Thrombosis Day 2022 we provided VTE awareness event kits for 35 of our acute hospitals, our National Ambulance Service and Lifeline Ambulance service along with Blood Clot Alert Cards for hundreds of Community Pharmacies. We also ran a VTE coffee cup awareness campaign and distributed 100,000 recyclable/compostable cups through many community coffee outlets, hospital coffee shops and canteens and UCD and NUIG while running a national radio advertising campaign on Newstalk and Today FM.

The movement of change has been growing year on year and we have a mechanism for monitoring, acknowledging and thanking all those who are helping us to make a difference through our ‘ Thrombosis Ireland VTE Exemplar Awards’. Our 2022 winners are as follows:-

Best Hospital Group: Ireland East Hospital Group

Best Hospital: Cork University Hospital, Cork.

Best Maternity Hospital: Rotunda Hospital, Dublin

VTE Scientific Advancement: The Mater Misericordiae University Hospital

VTE Quality Improvement: Tallaght University Hospital, Dublin

VTE Quality Improvement

Maternity Hospital: Our Lady of Lourdes Maternity Hospital, Co. Louth

VTE Warrior Awards: Katherine Quinn, Anticoagulation Nurse Specialist, Tallaght Hospital, Dublin.

Therese O’Brien, Anticoagulaton Nurse Manager, Portiuncula University Hospital, Galway

Dr. Su Maung, Haematologist, Our Lady’s Hospital, Navan, Co. Meath

Lidhy Solomon, VTE Clinical Nurse Manager, Mater Misericordiae University Hospital, Dublin

Prof. Fionnuala Ni Ainle, Consultant Haematologist, Mater Misericordiae University Hospital, Dublin

Our 2022 VTE Champion’s Award went to: Mullingar Regional Hospital for their Patient Safety Initiative – DOAC Dosing Quick Guide.

We were responsible for lighting up many national monument and public buildings throughout

the country on October 13th to highlight World Thrombosis Day and link with all of our other VTE Awareness initiatives.

Looking to the future, what we require is a strong national direction for the prevention and management of VTE in Ireland. We are so much closer to having this. In October this year, the HSE

WTD22 VTE Awareness Event at the Mater Misercordiae Hospital, Dublin

appointed Prof. Fionnuala Ni Ainle as the HSE National VTE Lead with Miriam Kennedy as the National Program Manager. We are hopeful that the passion and momentum of this team will shine a new light for VTE in Ireland. In the meantime, I would appeal to each hospital group and individual hospital, to ensure that all HSE VTE Collaborative recommendations are imbedded into daily practice in your organisation, and in particular, the VTE Risk Assessment for every person who presents at your hospital, not just those admitted and direct your blood clot patients to Thrombosis Ireland education and support services through our website www.thrombosis.ie. Together we are so much stronger.

#Spot the Signs #Save a life

Dr. Su Maung, Haematologist, Our Lady’s Hospital Navan & Mater University Hospital receiving her Thrombosis Ireland VTE Warrior Award from Patient Founder, Thrombosis Ireland

STIs, HIV and Effective Screening

An

Sexually transmitted infections (STIs) are a major public health concern, and an increasing cause of ill health globally. STIs are spread through intimate sexual contact, including unprotected vaginal, anal and oral sex with an infected partner. Even protected sex can be a risk of contracting some sexually transmitted infections.

We spoke with Theresa Lowry Lehnen, RGN, RNP, BSc, MSc, PG. Dip. Ed, M. Ed, PhD Clinical Nurse Practitioner and Associate Lecturer South East Technological University to find out more about sexually transmitted infections and their associated screening.

STIs usually affect the genitals, anus, or mouth, but can also affect other areas of the body. Many STIs have no signs and symptoms and if left untreated have the potential to cause significant morbidity in women and men, including infertility, ectopic pregnancy and other medical conditions, which is why STI screening is so important.

“Some activities pose higher risk than others including unprotected sex with casual partners, multiple partners, with a partner who has taken risks - had unprotected sex with casual partners or with a partner who has injected drugs. Men who have unprotected anal sex with other men (MSM) are also at higher risk,” says Theresa.

Chlamydia trachomatis (CT, chlamydia) is the most commonly diagnosed bacterial sexually transmitted infection (STI) in Ireland, and most cases occur in young people under the age of 25. Theresa explains, “Often asymptomatic in both males and females, symptoms in males can include dysuria and a urethral discharge, and in women, vaginal discharge, intermenstrual bleeding and post coital bleeding. Infection

can lead to epididymitis in males and Pelvic Inflammatory Disease (PID) in females. PID is associated with an increased risk of tubal factor infertility, ectopic pregnancy and chronic pelvic pain. Diagnosis can be made on first void urine in males and vulvovaginal or endocervical swab (less sensitive) in females. Vulvovaginal swabs can be provider or self-taken. In MSM, as well as first void urine, pharyngeal and rectal sites should also be tested.”

Gonorrhoea (Neisseria gonorrhoeae) is the second most common bacterial sexually transmitted infection in Ireland, and is found most frequently in young people under the age of 25 and in men who have sex with men (MSM). Infection may involve the genitals, mouth, or rectum. Infected men may experience pain or burning with urination, discharge from the penis, testicular pain and epididymitis.

Symptoms in women can include vaginal discharge, intermenstrual bleeding, post coital bleeding and PID. Rectal infection can lead to proctitis. Diagnosis can be made on first void urine in males and vulvovaginal or endocervical swab in females. Vulvovaginal swabs can be provider or self-taken. In MSM, pharyngeal and rectal sites should also be tested. Gonorrhoea is a notifiable disease.

Theresa continues, “The Nucleic Acid Amplification Test (NAATs)/ PCR is the gold standard for chlamydia and gonorrhoea testing. The type of test may vary at different laboratories.”

Genital herpes is a viral infection caused by the herpes simplex virus (HSV). There are two types: HSV-1 and HSV-2. “Type 2 is most commonly associated with genital infection. Type 1 has also been

found to cause genital infection but is more commonly associated with oral herpes (cold sores). Genital herpes is common in Ireland, and is mostly diagnosed in young women.

“The diagnosis can be made clinically but should be confirmed with a HSV NAAT swab of the lesions to determine if HSV-1 or HSV-2.”

Turning to Hepatitis B, a viral infection that infects the liver and is a major cause of serious liver disease, Theresa notes, “Hepatitis B affects millions of people worldwide. It is vaccine preventable. Hepatitis C is a viral infection that can cause long-term liver disease, such as liver cirrhosis and liver cancer. There is currently no vaccination against hepatitis C. Most cases of hepatitis C are found in people who inject drugs, however, the number of cases of sexually transmitted hepatitis C diagnosed in men who have sex with men (MSM) in Ireland, has increased.

“Many cases have been in MSM who are also infected with HIV.

“Hepatitis C testing (HCV) should be considered part of routine sexual health screening for MSM; people living with HIV; commercial sex workers and people who inject drugs (PWID). Partners should also be considered for HCV testing. Trichomoniasis (TV) is a sexually transmitted infection (STI) caused by a protozoan-Trichomonas vaginalis. Most cases are found in women, and although it can affect both men and women, infection in men is uncommon. TV can infect the vagina and cervix in women, and the urethra and underneath the foreskin in men.

“In women it usually presents with a vaginal discharge which may be offensive with an associated vulvitis /vaginitis. Men usually present as sexual contacts of women with infection, and may present with symptoms of urethritis including dysuria and urethral discharge. Trichomoniasis is a notifiable disease.”

Syphilis is a sexually transmitted infection caused by a bacterium called Treponema pallidum. There were 611 cases reported in Ireland in 2020. The highest rate in males and females was in the 30-34year age group, 75.6 per 100,000 population and 6.9 per 100,000 population, respectively. Most new cases of syphilis are among men who have sex with men.

While the number of STI notifications decreased in Ireland in 2020, most likely due to the impact of the COVID-19 pandemic, early infectious syphilis (EIS) is on the increase, with a 43% increase (498 cases) reported by HPSC in 2021 between 01/01/2021 and 21/08/2021, compared to the same time- period in 2020 (349 cases).

She adds, “Human Immunodeficiency Virus (HIV) is a virus that attacks the human immune system and weakens its ability to fight infection and disease. Over 6,000 people are estimated to be living with HIV in Ireland and approximately 15% of people with HIV in Ireland are unaware they have the condition, because they have either not been tested, or developed HIV since their last test.

“Approximately half of new cases of HIV in Ireland are among men who have sex with men (MSM), the other half being mostly heterosexual men and women, and people who inject drug. HIV is diagnosed with a blood test. HIV testing is available in many health care settings including STI clinics, GPs and student health clinics. Many NGOs offer HIV testing in Ireland, including rapid HIV testing in community venues. HIV is a notifiable disease.”

HIV Prevention: PrEP and PEP/PEPSE Pre-exposure prophylaxis (PrEP) is the use of oral antiretroviral therapy in HIV negative people to reduce the risk of HIV infection. Theresa told us, “PrEP is taken by HIV negative people prophylactically before having sex (pre-exposure) and after sex, to prevent HIV. The window period for HIV is 45 days. PrEP is available free of charge through the HSE to people who meet the clinical eligibility criteria and who are deemed to be at substantial risk of acquiring HIV.

“Post-exposure prophylaxis (PEP) is short-term antiretroviral treatment to reduce the likelihood of HIV infection after potential exposure, either occupationally or through sexual intercourse. PEP may prevent infection with HIV developing. A full course of PEP (two or three antiretroviral HIV drugs) is for 28 days (4 weeks). The medication must be started within 72 hours of possible exposure to HIV infection to be effective. The term PEPSE is sometimes used, and stands for PEP after Sexual Exposure.”

interview with Theresa Lowry Lehnen (PhD), Clinical Nurse Practitioner and Associate Lecturer South East Technological University

Make Doravirine a Part of Every Day For treatment of HIV-1

DELSTRIGO® is indicated for the treatment of adults infected with HIV-1 without past or present evidence of resistance to the NNRTI class, lamivudine, or tenofovir. Delstrigo is also indicated for the treatment of adolescents aged 12 years and older weighing at least 35kg who are infected with HIV-1 without past or present evidence of resistance to the NNRTI class, lamivudine, or tenofovir and who have experienced toxicities which preclude the use of other regimens that do not contain tenofovir disoproxil.1

PIFELTRO® is indicated, in combination with other antiretroviral medicinal products, for the treatment of adults, and adolescents aged 12 years and older weighing at least 35kg infected with HIV-1 without past or present evidence of resistance to the NNRTI class.2 This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.

INDICATIONS Pifeltro: For use in combination with other antiretrovirals, for the treatment of HIV-1 without past or present evidence of resistance to non-nucleoside reverse transcriptase inhibitors (NNRTI). Delstrigo: For the treatment of HIV-1 without past or present evidence of resistance to NNRTIs, lamivudine or tenofovir. For the treatment of adolescents aged 12 years and older weighing at least 35 kg who are infected with HIV-1 without past or present evidence of resistance to the NNRTI class, lamivudine, or tenofovir and who have experienced toxicities which preclude the use of other regimens that do not contain tenofovir disoproxil. DOSAGE AND ADMINISTRATION Therapy should be initiated by a physician experienced in HIV infection management. Pifeltro: One 100 mg tablet once daily. Delstrigo: One 100/300/245 mg tablet once daily. Pifeltro and Delstrigo: If co-administered with rifabutin or other moderate CYP3A inducers, increase doravirine dose to 100 mg twice daily (12 hours apart). Pifeltro: Elderly: No dose adjustment necessary. Renal impairment: No dose adjustment necessary. Hepatic impairment: mild to moderate: no dosage adjustment required; severe: use with caution. Delstrigo: Elderly: Special care advised. Renal impairment: estimated creatinine clearance (CrCl) ≥ 50 mL/min: no dose adjustment necessary; estimated CrCl <50 mL/min: not recommended. Hepatic impairment: mild to moderate: no adjustment required; severe hepatic: use with caution. CONTRAINDICATIONS Hyper sensitivity to the active substance or excipients. Co-administration with strong CYP3A inducers. PRECAUTIONS AND WARNINGS A residual risk of sexual transmission of HIV-1 cannot be excluded and precautions should be taken in accordance with national guidelines. Use with CYP3A inducers may reduce the exposure of doravirine. Autoimmune disorders (such as autoimmune hepatitis) and immune reactivation syndrome have been reported in patients treated with combination antiretroviral therapy which may require investigation and treatment. Contains lactose monohydrate. Delstrigo: Post-treatment exacerbation of HBV (including hepatic decompensation and liver failure) have been reported in patients co-infected with HIV-1 and HBV following discontinuation of lamivudine or tenofovir disproxil. Monitor patients co-infected with HIV-1 and HBV after discontinuation of Delstrigo and if appropriate initiate anti-HBV therapy. Renal impairment, including acute renal failure and Fanconi syndrome have been reported with tenofovir disoproxil. Assess estimated CrCl prior to initiation and during therapy. In patients at risk of renal dysfunction, serum phosphorus, urine glu cose, and urine protein should also be assessed. Discontinue therapy if estimated CrCl declines below 50 mL/min. Avoid with concurrent or recent use of nephrotoxic medicinal products (e.g. high-dose or multiple NSAIDs). Evaluation of renal function is recommended for persistent or worsening bone pain, pain in extremities, fractures, and/or muscular pain or weakness. Assessment of bone mineral density should be considered for patients who have a history of pathologic bone fracture or other risk factors for osteoporosis or bone loss. Hypophosphatemia and osteomalacia secondary to proximal renal tubulopathy should be considered in patients at risk of renal dysfunction who present with persistent or worsening bone or muscle symptoms.

Doravirine/lamivudine/tenofovir disoproxil must not be co-administered with other medicinal products containing lamivudine, tenofovir disoproxil, or tenofovir alafenamide or with adefovir dipivoxil. Doravirine/lamivudine/tenofovir disoproxil should not be administered with doravirine unless needed for dose adjustment (e.g. co-administered with rifabutin). Drug interactions: Refer to SmPC for full information on drug interactions.

have a narrow therapeutic window (e.g., midazolam, tacrolimus and sirolimus). Delstrigo: Do not administer with other antiretroviral medicinal products. Co-administration of doravir ine/lamivudine/tenofovir disoproxil with medicinal products that reduce renal function or compete for active tubular secretion may increase serum concentrations of lamivudine. Co-administration of doravirine/lamivudine/tenofovir disoproxil with medicinal products that reduce renal function or compete for active tubular secretion via OAT1, OAT3 or MRP4 may increase serum concentrations of tenofovir. Avoid with concurrent or recent use of nephrotoxic medicinal products. Pregnancy and Lactation: Pifeltro and Delstrigo: Avoid use during pregnancy. An Antiretroviral Pregnancy Registry has been established. Breastfeeding is not recommended. SIDE EFFECTS Refer to SmPC for complete information on side-effects. Pifeltro and Delstrigo: Common: abnormal dreams, insomnia, headache, dizziness, somnolence, nausea, diarrhoea, abdominal pain, flatulence, vomiting, rash, fatigue alanine aminotransferase increased. Uncommon: hypophosphataemia, nightmare, depression, suicidal ideation, paraes thesia, asthenia. Rare: hypomagnesaemia, blood creatine phosphokinase increased. Delstrigo: Common: cough, nasal symptoms, alopecia, muscle disorders, fever. Uncommon: neutropenia, anaemia, thrombocytopenia, pancreatitis, rhabdomyolysis, proximal renal tubulopathy (including Fanconi syndrome), aspartate aminotransferase increased. Rare: lactic acidosis, hepatitis, angioedema, myopathy, acute renal failure, renal failure, acute tubular necrosis, nephritis (including acute interstitial) and nephrogenic diabetes insipidus. Very Rare: pure red cell aplasia, peripheral neu ropathy (or paraesthesia). Lactic acidosis Cases of lactic acidosis have been reported with tenofovir disoproxil alone or in combination with other antiretrovirals. Patients with predisposing factors such as patients with decompensated liver disease, or patients receiving concomitant medications known to induce lactic acidosis are at increased risk of experiencing severe lactic acidosis during tenofovir disoproxil treatment, including fatal outcomes.

PIFELTRO® ▼ (Doravirine)

DELSTRIGO® ▼ (Doravirine/Lamivudine/Tenofovir disproxil fumarate)

Pifeltro and Delstrigo: Doravirine is metabolized primarily by CYP3A. Do not co-administer with strong CYP3A enzyme inducers. If co-administra tion with rifabutin or other moderate CYP3A inducers cannot be avoided, increase doravirine dose to 100 mg twice daily (taken 12 hours apart). Use with caution when co-administering doravirine with medicinal products that are sensitive CYP3A substrates that

Who is eligible for free PrEP?

HIV negative individuals who are aged 17 years or older, have a PPSN and fall into one of the categories set out below:

1. Men who have sex with men or transgender women who have sex with men who are:

Sexually active with likelihood of remaining sexually active in the next 3 months AND one of the following:

Reported condomless anal sex with at least two partners over the last 6 months

Episode of documented or reported acute STI over the last 12 months

Documented or reported use of HIV post-exposure prophylaxis following sexual exposure (PEPSE) over the last 12 months

Reported engagement in chemsex over the last 6 months

2. Individuals having condomless sex with a HIV positive person who is not suitably suppressed on antiretroviral therapy specifically:

Where the person living with HIV is not on antiretroviral therapy 

Where the person living with HIV has initiated antiretroviral therapy but has not yet achieved virological suppression 

Where the person living with HIV has loss of virological control on antiretroviral therapy and the risk of HIV transmission has been deemed by a consultant physician specialising in HIV Medicine to be substantial and warrant PrEP for the HIV-negative partner

3. Other heterosexual men, heterosexual women considered by a senior clinician specialising in HIV Medicine to be at substantial risk for sexual acquisition of HIV

HIV can be treated effectively with antiretroviral medications which stops HIV reproducing in the body. When taken properly, HIV treatment reduces the chance of a person living with HIV passing it on to someone else. When a person living with HIV is on treatment and the viral load in the body is 'undetectable', HIV cannot be transmitted to sexual partners. This is known as 'undetectable' equals 'un-transmittable' (U=U).

Current Situation and Outlook

Theresa concludes, “The timeliness of treatment for STIs can have consequences for the individual and increase the likelihood of

infecting others. Given the high burden of STIs, and the risk of medical complications associated with these infections, screening, accurate diagnosis, and timely and appropriate treatment are critical. The testing and treatment of sexual partners is important in preventing the spread of STIs, decreasing the rate of reinfection, and preventing medical complications of asymptomatic infections.

“The continuing rise in STIs annually in Ireland is a worrying trend. The key message from the HSE HPSC is for people to get tested regularly, use condoms for vaginal, oral and anal sex and reduce the number of partners

and overlapping partners. People should get tested for STIs if they have symptoms of an STI, change their sexual partner, have multiple or overlapping partners or their partner has an STI.

“Stigma causes many people to avoid seeking STIrelated services because of negative experiences such as discrimination, indifference, and overt hostility in health care settings. In addition to effective public health infrastructures and the technologies needed for diagnosis and treatment, global STI prevention and control efforts require renewed commitment to systematic programmatic

Table 1: Eligibility for PrEP (HIV Pre Exposure Prophylaxis in Ireland) (HSE Guidance)2

Breast Reconstruction Awareness Day

The Breast Reconstruction Awareness Day (BRA Day) this year was organised jointly by the Plastic Surgery Department of The Mater Misericordiae University Hospital, Dublin, and the Marie Keating Foundation. This year’s event was sponsored by Pfizer and held at the Clayton Airport. The free of charge event offered a unique combination of education, support, and connection for breast cancer patients and for those patients who are contemplating risk reducing surgery and breast reconstruction as a result of e.g., a BRCA gene mutation (which predisposes them to develop breast cancer).

This event is unparalleled and has become an annual event in the Marie Keating Foundation’s October event calendar. The seminar not only brings together a host of speakers from different supportive fields but also offers breast cancer patients and their families an opportunity to network and connect with both experts and others sharing a similar journey.

As centres of excellence in breast cancer care and reconstruction, the teams at the Mater Hospital, Beaumont, St. Vincent’s, and St James, strive to always provide a world class level of holistic care for every patient that is tailored to the specific needs of each woman. It

was with this in mind that the event aimed to feature specialists from as many of these hospitals as possible.

Speaking about the event Professor Robert H Caulfield, Consultant Plastic Surgeon, Mater Misericordiae University Hospital said, “We are delighted to be able to hold this event again after the 2-year hiatus caused by the COVID pandemic. This year we have expanded the day to include other plastic surgery and breast surgery units from all areas of Dublin, including Beaumont Hospital, St Vincent’s Hospital and St James’ Hospital. We have also expanded the range and type of healthcare practitioners

approaches to prevent or reduce STI-related stigma.”

The HSE, SHCPP’s Sexual Health Promotion Training Strategy 2019-2029, directs the activities and funding of the SHCPP, and aims to address the training of professionals enabling them to respond to the sexual health education and information needs of their service users. The strategy enables the integration of sexual health promotion into core support services within health, social care, education, community and youth work so that service users can be supported to make good sexual health choices.

She adds, “Sexual health is an essential component of overall health. Effective STI prevention and control emerges from a holistic, sexual health perspective involving many levels of society and a variety of approaches. An integrated approach is required that involves taking action throughout the entire population and at all levels of the prevention and care continua. Further advancement in technology, specifically the development of rapid, sensitive and specific point-of-care testing, will provide additional tools for STI diagnosis and control. These actions can lead to better prevention, screening, and treatment.”

involved to include breast care nurses, physiotherapists, psychologists, 3D nipple reconstruction specialists and surgeons. However, ultimately, the most important people involved today, are of course, the patients themselves. The aim of an event like this is to provide all patients with all the necessary information and advice about their reconstructive journey. As with all areas of medicine, diagnosis, investigation, and management, both surgical and medical, continues to progress and develop year by year and so too must any educational and informative event such as BRA Day.”

DURABLE AND ROBUST 2,3

GROWING ORAL REGIMEN FOR PLHIV 1*

DOVATO

PART OF HEALTHY LIVING WITH HIV WITHOUT TDF, TAF AND ABC

DOVATO is indicated for the treatment of HIV-1 in adults and adolescents above 12 years weighing at least 40 kg, with no known or suspected resistance to the integrase inhibitor class, or lamivudine.

Abridged Prescribing Information

Dovato (dolutegravir 50mg/lamivudine 300mg) tablets

See Summary of Product Characteristics (SmPC) before prescribing.

Presentation: Film-coated tablet containing dolutegravir sodium equivalent to 50 mg dolutegravir and 300 mg lamivudine debossed with “SV-137” on one face. Indication: HIV-1 in adults & adolescents above 12 years of age weighing >40kg, with no known or suspected resistance to the integrase inhibitor class, or lamivudine. Dosing: One tablet once daily with or without food. Use an additional 50mg tablet of dolutegravir approximately 12 hours after the dose of Dovato when co-administered with efavirenz, nevirapine, tipranavir/ritonavir, etravirine (without boosted PI), carbamazepine, oxcarbazepine, phenytoin, phenobarbital, St John’s Wort or rifampicin. Elderly: Limited data in 65+ yrs. Renal impairment: Not recommended in patients with creatinine clearance < 30 mL/min. For patients with a sustained creatinine clearance between 30 and 49 mL/min see SmPC section 4.4. Hepatic impairment: Caution in severe hepatic impairment (Child-Pugh grade C). Contraindications: Hypersensitivity to any ingredient. Co-administration with substrates of OCT-2 with narrow therapeutic windows, such as fampridine. Special warnings/precautions: Risk of hypersensitivity reactions. Discontinue dolutegravir and other suspect agents immediately. Risks of osteonecrosis, immune reactivation syndrome. Monitor LFTs in Hepatitis B/C co-infection and ensure effective Hepatitis B therapy. Caution with metformin: monitor renal function and consider metformin dose adjustment. Use with etravirine requires boosted PI or increased dose of dolutegravir. Use with Mg/Al-containing antacids requires dosage separation. Use with calcium, multivitamins or iron also requires dosage separation if not taken at the same time with food. Use with cladribine or emtricitabine not recommended. When possible, avoid chronic co-administration of sorbitol or other osmotic acting alcohols (see SmPC

section 4.5). If unavoidable, consider more frequent viral load monitoring. Fertility, pregnancy and lactation: Human fertility - no data; animal fertility - studies indicate no effects. Women of childbearing potential (WOCBP) should be counselled about the potential risk of neural tube defects including consideration of effective contraceptive measures. If a woman plans pregnancy, the benefits and the risks of continuing treatment should be discussed with the patient. The safety and efficacy of a duel regime has not been studied in pregnancy. If a pregnancy is confirmed in the first trimester while on Dovato, the benefits and risks of continuing Dovato versus switching to another antiretroviral regimen should be discussed with the patient taking the gestational age and the critical time period of neural tube defect development into account (see SmPC section 4.6). There have been reports of mitochondrial dysfunction in HIV-negative infants exposed in utero and/or post-natally to nucleoside analogues. Do not breast-feed. Side effects: See SmPC for full details. Headache, GI disturbance, insomnia, abnormal dreams, depression, anxiety, dizziness, somnolence, rash, pruritus, alopecia, fatigue, arthralgia, myalgia, hypersensitivity, completed suicide, suicidal ideation or suicide attempt, panic attack, hepatitis, blood dyscrasias, acute hepatic failure, pancreatitis, angioedema, rhabdomyolysis, lactic acidosis, peripheral neuropathy. Elevations of bilirubin, ALT, AST and CPK. MA Nr: EU/1/19/1370/001. MA holder: ViiV Healthcare BV, Van Asch van Wijckstraat 55H, 3811 LP Amersfoort, Netherlands. Legal Category: POM A. Date of preparation of API: February 2022. Code: PI-6305. Further information available from GlaxoSmithKline, 12 Riverwalk, Citywest, Business Campus, Dublin 24. Tel: 01-4955000.

Adverse events should be reported directly to the Health Products Regulatory Authority (HPRA) on their website: www.hpra.ie. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255.

*From November 2020 through October 2021, over 39 markets and territories with data sources available.

References: 1. Data on file. Regimen market share growth November 2020-October 2021. REF-146400. ViiV Healthcare group of companies. Research Triangle Park, NC. 2. Cahn P, Sierra Madero J, Arribas JR, et al. Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral treatment-naïve adults with HIV-1 infection. AIDS. 2022;36(1): 39-48. doi:10.1097/QAD.0000000000003070

3. Osiyemi O, De Wit S, Ajana F, et al. Efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) versus continuing a tenofovir alafenamide-based 3- or 4-drug regimen for maintenance of virologic suppression in adults living with HIV-1: results through week 144 from the phase 3, non-inferiority TANGO randomized trial. Clin Infect Dis. 2022;ciac036 and suppl 1-18. doi:10.1093/cid/ciac036

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Prostate Cancer

Inflammation and Prostate Cancer: A Multidisciplinary Approach to Identifying Opportunities for Treatment and Prevention

Written by Lanshan Huang1, 2, Melissa J. LaBonte1, Stephanie G. Craig1, Stephen P Finn3, Emma H Allott1, 3

1Patrick G. Johnston

Centre

for Cancer Research, Queen’s University Belfast, Belfast BT9 7AE, UK

2Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China

3Department of Histopathology and Morbid Anatomy, Trinity Translational Medicine Institute, Trinity College Dublin, D08 HD53 Dublin, Ireland

Abstract: Prostate cancer is a major cause of disease for men globally. Inflammation, an established hallmark of cancer, is frequently observed in the prostate, though its contribution to prostate cancer risks and outcomes is not fully understood. Prostate cancer is biologically and clinically heterogeneous, and there is now evidence that inflammation and immunological characteristics vary by the genomic and mutational landscape of the tumor. Moreover, it is now recognized that risk factor profiles vary between tumor subgroups, as defined by histopathological and molecular features. Here, we provide a review centered around the relationship between inflammation and prostate cancer, with a consideration of molecular tumor features and a particular focus on the advanced and lethal stages of disease. The authors summarized findings from epidemiological studies of the etiology and role of inflammation in prostate cancer. Here we offer a simple summary overview of the paper, which can be viewed in full at: https://www.mdpi.com/2072-6694/14/6/1367/htm

Infections in Prostate Cancer Etiology

An infectious etiology for prostate cancer has been put forward, supported by evidence from questionnaire-based and sero/ urinary-epidemiological studies. The inflammatory response within the prostate could be induced by systemic dissemination or an organ-restricted infection. Sexually transmitted infections (STIs) have been studied as an etiologic factor. A meta-analysis, which included 47 studies published between 1971 and 2011, showed that men who reported a history of any STI had a 49% higher total prostate cancer risk.16

Prostate cancer is a major cause of disease among men, notable for its geographic variation, ranking the second most common men’s cancer for incidence and the fifth for mortality globally, with 1,414,259 new cases and 375,304 deaths estimated in 2020.1 Prostate cancer is biologically and clinically heterogeneous, and a major challenge lies in identifying, at the time of diagnosis, which cancers will be lethal. As such, there is an unmet need to understand the biology of lethal prostate cancer in order to inform prevention efforts and treatment strategies.

There is a large body of evidence supporting inflammation as a hallmark of cancer.2 Inflammation is frequently observed in the prostate microenvironment, and has been hypothesized to

be involved in prostate cancer initiation and progression.3

Epidemiological studies assessing histological inflammation using hematoxylin and eosin (H&E)stained tissues have reported both positive and inverse associations with prostate cancer risks4,5,6 and outcomes.7,8,9,10 However, the histological assessment of inflammation is a relatively crude measure, as inflammation is a complex and heterogeneous phenotype. Various technologies exist for determining the phenotype and activation status of immune cells, and their suitability for use in epidemiological studies depends on their compatibility with tissue preservation methods, the scalability of the technology for profiling sufficient numbers of individuals for a well-powered

statistical analysis, and the desire to preserve spatial context. From a clinical perspective, it is intriguing that a relatively low proportion of patients achieve a response from currently available immunotherapies, 11,12,13 suggesting that much of prostate cancer is likely to be immunologically “cold”. This could be characterized by lack of T-cells within tumor, or failed T-cell priming, such as ineffective antigen presentation.14 Understanding the immune microenvironment across histological and molecular subgroups of prostate cancer may identify patients that could benefit from immunotherapy, as well as informing our understanding of lethal prostate cancer etiology to identify lifestyle interventions and prevention strategies.

Subgroup analyses within the above-mentioned meta-analysis showed a 20% higher total prostate cancer risk in those reporting a history of Neisseria gonorrhoeae.16 Few studies have separated prostate cancer into histological subgroups. A population-based case-control study in Mexico reported higher odds of prostate cancer in men with a history of gonorrhea, relative to those without (OR 3.04; 95% CI 1.99–4.64), with similar estimates when stratified by the Gleason score, <7 vs. ≥7.17 An analysis within the prospective Health Professionals Follow-Up Study reported no association between gonorrhea and the total prostate cancer risk (RR 1.04; 95% CI 0.79–1.36), but found a suggestion of a positive association for advanced (stage 3b or higher) (RR 1.37; 95% CI 0.64–2.95), relative to organ-confined (RR 0.99; 95% CI 0.71–1.38), prostate cancer risk, although there were no differences in Gleason scores (<7 vs. ≥7).18 Therefore, while there is evidence supporting a higher risk

cancer (mHSPC)

with metastatic hormone-sensitive

androgen deprivation therapy. The treatment of adult men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC). The treatment of adult men with metastatic CRPC who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated. The treatment of adult men with metastatic CRPC whose disease has progressed on or after docetaxel therapy. Posology and administration: Treatment with enzalutamide should be initiated and supervised by specialist physicians experienced in the medical treatment of prostate cancer. The recommended dose is 160 mg enzalutamide (four 40 mg film-coated tablets) as a single oral daily dose. The tablets should be swallowed whole with water, and can be taken with or without food. Medical castration with a luteinising hormone-releasing hormone (LHRH) analogue should be continued during treatment of patients not surgically castrated. If a patient experiences a ≥ Grade 3 toxicity or an intolerable adverse reaction, dosing should be withheld for one week or until symptoms improve to ≤ Grade 2, then resumed at the same or a reduced dose (120 mg or 80 mg) if warranted. Contraindications: Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of the SPC. Women who are or may become pregnant. Special warnings and precautions for use: Risk of seizure: Use of enzalutamide has been associated with seizure. The decision to continue treatment in patients who develop seizures should be taken case by case. Posterior reversible encephalopathy syndrome: There have been rare reports of posterior reversible encephalopathy syndrome (PRES) in patients receiving XTANDI. PRES is a rare, reversible, neurological disorder which can present with rapidly evolving symptoms including seizure, headache, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). Discontinuation of XTANDI in patients who develop PRES is recommended. Second Primary Malignancies: Cases of second primary malignancies have been reported in patients treated with enzalutamide in clinical studies. In phase 3 clinical studies, the most frequently reported events in enzalutamide treated patients, and greater than placebo, were bladder cancer (0.3%), adenocarcinoma of the colon (0.2%), transitional cell carcinoma (0.2%) and bladder transitional cell carcinoma (0.1%). Patients should be advised to promptly seek the attention of their physician if they notice signs of gastrointestinal bleeding, macroscopic haematuria, or other symptoms such as dysuria or urinary urgency develop during treatment with enzalutamide. Concomitant use with other medicinal products: Enzalutamide is a potent enzyme inducer and may lead to loss of efficacy of many commonly used medicinal products. A review of concomitant medicinal products should therefore be conducted when initiating enzalutamide treatment. Concomitant use of enzalutamide with medicinal products that are sensitive substrates of many metabolising enzymes or transporters should generally be avoided if their therapeutic effect is of large importance to the patient, and if dose adjustments cannot easily be performed based on monitoring of efficacy or plasma concentrations. Co-administration with warfarin and coumarin-like anticoagulants should be avoided. If XTANDI is co-administered with an anticoagulant metabolised by CYP2C9 (such as warfarin or acenocoumarol), additional International Normalised Ratio (INR) monitoring should be conducted. Renal impairment: Caution is required in patients with severe renal impairment as enzalutamide has not been studied in this patient population. Severe hepatic impairment: An increased half-life of enzalutamide has been observed in patients with severe hepatic impairment, possibly related to increased tissue distribution. The clinical relevance of this observation remains unknown. A prolonged time to reach steady state concentrations is however anticipated, and the time to maximum pharmacological effect as well as time for onset and decline of enzyme induction may be increased. Recent cardiovascular disease: The phase 3 studies excluded patients with recent myocardial infarction (in the past 6 months) or unstable angina (in the past 3 months), New York Heart Association Class (NYHA) III or IV heart failure except if Left Ventricular Ejection Fraction (LVEF) ≥ 45%, bradycardia or uncontrolled hypertension. This should be taken into account if XTANDI is prescribed in these patients. Androgen deprivation therapy may prolong the QT interval: In patients with a history of or risk factors for QT prolongation and in patients receiving concomitant medicinal products that might prolong the QT interval physicians should assess the benefit risk ratio including the potential for Torsade de pointes prior to initiating XTANDI. Use with chemotherapy: The safety and efficacy of concomitant use of XTANDI with cytotoxic chemotherapy has not been established. Co-administration of enzalutamide has no clinically relevant effect on the pharmacokinetics of intravenous docetaxel; however, an increase in the occurrence of docetaxel-induced neutropenia cannot be excluded. Hypersensitivity reactions: Hypersensitivity reactions manifested by symptoms including, but not limited to, rash, or face, tongue, lip, or pharyngeal oedema have been observed with enzalutamide. Severe cutaneous adverse reactions (SCARs) have been reported with enzalutamide. At the time of prescription patients should be advised of the signs and symptoms and monitored closely for skin reactions.

Excipients: This medicine contains less than 1 mmol sodium (less than 23 mg) per

film-coated tablet, that is to say essentially ‘sodium-free’. Interactions: Potential for other medicinal products to affect enzalutamide exposures: CYP2C8 plays an important role in the elimination of enzalutamide and in the formation of its active metabolite. Strong inhibitors (e.g. gemfibrozil) of CYP2C8 are to be avoided or used with caution during enzalutamide treatment. If patients must be co-administered a strong CYP2C8 inhibitor, the dose of enzalutamide should be reduced to 80 mg once daily. No dose adjustment is necessary when XTANDI is co-administered with inducers of CYP2C8. CYP3A4 plays a minor role in the metabolism of enzalutamide. No dose adjustment is necessary when XTANDI is co-administered with inhibitors or inducers of CYP3A4. Potential for enzalutamide to affect exposures to other medicinal products: Enzalutamide is a potent enzyme inducer and increases the synthesis of many enzymes and transporters; therefore, interaction with many common medicinal products that are substrates of enzymes or transporters is expected. Enzymes that may be induced include CYP3A in the liver and gut, CYP2B6, CYP2C9, CYP2C19, and uridine 5’-diphospho-glucuronosyltransferase (UGTs - glucuronide conjugating enzymes). Some transporters may also be induced, e.g. multidrug resistanceassociated protein 2 (MRP2) and the organic anion transporting polypeptide 1B1 (OATP1B1). In vivo studies have shown that enzalutamide is a strong inducer of CYP3A4 and a moderate inducer of CYP2C9 and CYP2C19. The full induction potential of enzalutamide may not occur until approximately 1 month after the start of treatment, when steady-state plasma concentrations of enzalutamide are reached, although some induction effects may be apparent earlier. Patients taking medicinal products that are substrates of CYP2B6, CYP3A4, CYP2C9, CYP2C19 or UGT1A1 should be evaluated for possible loss of pharmacological effects (or increase in effects in cases where active metabolites are formed) during the first month of enzalutamide treatment, and dose adjustment should be considered as appropriate. In consideration of the long half-life of enzalutamide (5.8 days), effects on enzymes may persist for one month or longer after stopping enzalutamide. A gradual dose reduction of the concomitant medicinal product may be necessary when stopping enzalutamide treatment. In vitro data indicate that enzalutamide may be an inhibitor of the efflux transporter P-gp. A mild inhibitory effect of enzalutamide, at steadystate, on P-gp was observed in a study in patients with prostate cancer that received a single oral dose of the probe P-gp substrate digoxin before and concomitantly with enzalutamide (concomitant administration followed at least 55 days of once daily dosing of 160 mg enzalutamide). The AUC and Cmax of digoxin increased by 33% and 17%, respectively. Medicinal products with a narrow therapeutic range that are substrates for P-gp (e.g. colchicine, dabigatran etexilate, digoxin) should be used with caution when administered concomitantly with XTANDI and may require dose adjustment to maintain optimal plasma concentrations. At steady state, enzalutamide did not cause a clinically meaningful change in exposure to the probe breast cancer resistance protein (BCRP) substrate rosuvastatin in patients with prostate cancer that received a single oral dose of rosuvastatin before and concomitantly with enzalutamide (concomitant administration followed at least 55 days of once daily dosing of 160 mg enzalutamide). The AUC of rosuvastatin decreased by 14% while Cmax increased by 6%. No dose adjustment is necessary when a BCRP substrate is co administered with XTANDI. Based on in vitro data, inhibition of MRP2 (in the intestine), as well as organic anion transporter 3 (OAT3) and organic cation transporter 1 (OCT1) (systemically) cannot be excluded. Theoretically, induction of these transporters is also possible, and the net effect is presently unknown. Since androgen deprivation treatment may prolong the QT interval, the concomitant use of XTANDI with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de pointes should be carefully evaluated. Fertility, pregnancy and lactation: There are no human data on the use of XTANDI in pregnancy and this medicinal product is not for use in women of childbearing potential. This medicine may cause harm to the unborn child or potential loss of pregnancy if taken by women who are pregnant. It is not known whether enzalutamide or its metabolites are present in semen. A condom is required during and for 3 months after treatment with enzalutamide if the patient is engaged in sexual activity with a pregnant woman. If the patient engages in sexual intercourse with a woman of childbearing potential a condom and another form of birth control must be used during and for 3 months after treatment. Enzalutamide is not for use in women. Enzalutamide is contraindicated in women who are, or who may become, pregnant. It is not known if enzalutamide is present in human milk. Enzalutamide and/or its metabolites are secreted in rat milk. Animal studies showed that enzalutamide affected the reproductive system in male rats and dogs. Effects on ability to drive and use machines: XTANDI may have a moderate influence on the ability to drive and use machines as psychiatric and neurologic events including seizure have been reported. Patients should be advised of the potential risk of experiencing a psychiatric or neurological event while driving or operating machines. Undesirable effects: Summary of the safety profile: The most common adverse reactions are asthenia/ fatigue, hot flush, hypertension, fractures, and fall. Other important adverse reactions include ischemic heart disease and seizure. Seizure occurred in 0.5% of enzalutamidetreated patients, 0.2% of placebo-treated patients, and 0.3% in bicalutamide-treated patients. Rare cases of posterior reversible encephalopathy syndrome have been reported in enzalutamide-treated patients. Adverse reactions observed during clinical studies are listed below by frequency category. Frequency categories are defined as follows: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥

XTANDI™ is indicated for the treatment of adult men with metastatic castrationresistant prostate cancer who are asymptomatic or mildly symptomatic after failure of androgendeprivation therapy, in whom chemotherapy is not yet clinically indicated.1

XTANDI is also indicated for the treatment of adult men with metastatic castration – resistant prostate cancer whose disease has progressed on or after Docetaxel.1

1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000); very rare (< 1/10,000); not known (cannot be estimated from the available data). Adverse reactions are presented according to Medical Dictionary for Regulatory Activities (MedDRA) system organ classification and within each frequency grouping they are presented in order of decreasing seriousness. Adverse reactions identified in controlled clinical trials and post-marketing: Blood and lymphatic system disorders: Uncommon: leucopenia, neutropenia; Not known*: thrombocytopenia. Immune system disorders: Not known*: face oedema, tongue oedema, lip oedema, pharyngeal oedema Psychiatric disorders: Common: anxiety; Uncommon: visual hallucination. Nervous system disorders: Common: headache, memory impairment, amnesia, disturbance in attention, dysgeusia, restless legs syndrome; Uncommon: cognitive disorder, seizure Not known*: posterior reversible encephalopathy syndrome. Cardiac disorders: Common: ischemic heart disease†; Not known*: QT-prolongation. Vascular disorders: Very common: hot flush, hypertension. Gastrointestinal disorders: Not known*: nausea, vomiting, diarrhoea. Skin and subcutaneous tissue disorders: Common: dry skin, pruritus; Not known*: erythema multiforme, rash. Musculoskeletal and connective tissue disorders: Very common: fractures‡; Not known*: myalgia, muscle spasms, muscular weakness, back pain. Reproductive system and breast disorder: Common: gynaecomastia. General disorders and administration site conditions: Very common: asthenia, fatigue. Injury, poisoning and procedural complications: Very common: fall. * Spontaneous reports from post-marketing experience. As evaluated by narrow Standardised MedDRA Queries (SMQs) of ‘Convulsions’ including convulsion, grand mal convulsion, complex partial seizures, partial seizures and status epilepticus. This includes rare cases of seizure with complications leading to death. † As evaluated by narrow SMQs of ‘Myocardial Infarction’ and ‘Other Ischemic Heart Disease’ including the following preferred terms observed in at least two patients in randomized placebo-controlled phase 3 studies: angina pectoris, coronary artery disease, myocardial infarctions, acute myocardial infarction, acute coronary syndrome, angina unstable, myocardial ischaemia and arteriosclerosis coronary artery. ‡ Includes all preferred terms with the word ‘fracture’ in bones. Description of selected adverse reactions: Seizure: In controlled clinical studies, 24 patients (0.5%) experienced a seizure out of 4403 patients treated with a daily dose of 160 mg enzalutamide, whereas four patients (0.2%) receiving placebo and one patient (0.3%) receiving bicalutamide experienced a seizure. Dose appears to be an important predictor of the risk of seizure, as reflected by preclinical data, and data from a dose-escalation study. In the controlled clinical studies, patients with prior seizure or risk factors for seizure were excluded. In the 9785 CL 0403 (UPWARD) single-arm trial to assess incidence of seizure in patients with predisposing factors for seizure (whereof 1.6% had a history of seizures), 8 of 366 (2.2%) patients treated with enzalutamide experienced a seizure. The median duration of treatment was 9.3 months. The mechanism by which enzalutamide may lower the seizure threshold is not known but could be related to data from in vitro studies showing that enzalutamide and its active metabolite bind to and can inhibit the activity of the GABA-gated chloride channel. Ischemic Heart Disease: In randomized placebocontrolled clinical studies, ischemic heart disease occurred in 3.9% of patients treated with enzalutamide plus ADT compared to 1.5% patients treated with placebo plus ADT. Fifteen (0.4%) patients treated with enzalutamide and 2 (0.1%) patients treated with placebo had an ischemic heart disease event that led to death. Prescribers should consult the full SPC in relation to other adverse reactions. Overdose: There is no antidote for enzalutamide. In the event of an overdose, treatment with enzalutamide should be stopped and general supportive measures initiated taking into consideration the half-life of 5.8 days. Patients may be at increased risk of seizures following an overdose. Cost (excluding VAT): XTANDI 40 mg film-coated tablets x 112: Ireland: POA. Northern Ireland: £2,734.67. Legal classification: Ireland: POM/ S1A. Northern Ireland: POM. Marketing Authorisation number: XTANDI 40 mg filmcoated tablets: EU/1/13/846/002 Marketing Authorisation Holder: Astellas Pharma Europe B.V., Sylviusweg 62, 2333 BE Leiden, The Netherlands. Date of preparation of Prescribing Information: April 2022 Job number: XTD_2022_0079_IE Further information is available on request from: Ireland: Astellas Pharma Co. Ltd., 5 Waterside, Citywest Business Campus, Dublin 24. Tel.: +353 1 467 1555. Northern Ireland: Astellas Pharma Ltd, Medical Information 0800 783 5018. For full prescribing information, refer to the SPCs, which may be found at www.medicines.ie (Ireland) and https://www.emcmedicines.com/en-GB/northernireland/ (Northern Ireland).

Adverse events should be reported. For Ireland, Healthcare professionals are asked to report any suspected adverse reactions via: HPRA Pharmacovigilance, Website: www.hpra.ie or Astellas Pharma Co. Ltd. Tel: +353 1 467 1555, E-mail: irishdrugsafety@astellas.com

Adverse events should be reported. For Northern Ireland, reporting forms and information can be found at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store. Adverse events should also be reported to Astellas Pharma Ltd on 0800 783 5018.

The hyperlinks on this page will take you to non-Astellas websites. Astellas does not endorse or accept liability for sites controlled by third-parties.

Ireland and Northern Ireland Abbreviated Prescribing Information: XTANDITM (enzalutamide) 40 mg film-coated tablets. For full prescribing information, refer to the Summary of Product Characteristics (SPC). Presentation: 40 mg film-coated tablets each containing 40 mg of enzalutamide. Indications: The treatment of adult men

prostate

in combination with

Prostate Cancer

of a total prostate cancer risk in men with a history of gonorrhoeae infection, additional studies that focus on advanced and lethal diseases are needed.

In summary, genital infections with Neisseria gonorrhoeae, Mycoplasma/Ureaplasma, and BKV appear to be modestly associated with increased rates of prostate cancer. It should be addressed that we need to note the research methods and exposure assessment approaches when interpreting these results. If the epidemiological evidence arises from studies with a case-control design, the interpretation should take potential confounding into consideration, which can be caused by selection bias, recall bias, or detection bias. When considering studies using tissue analyses, we should be aware that the infections detected in the prostate cancer tissue may be acquired before, or after, the initiation of cancer. The consideration of these methodological challenges is needed when designing future studies to understand the role of infections by microbial species in aggressive, particularly lethal, prostate cancer, as well as the mechanisms contributing to these associations.

Histopathological Inflammation in Prostate Cancer

While the prostate may be exposed to a variety of microorganisms, inflammation in the prostate can also appear without a dominant infection and can present as histological prostatitis (i.e., asymptomatic prostatic inflammation). The cause of prostatic inflammation, in most cases, is indistinct, and it tends to be, incidentally, identified post-prostate biopsy or resection due to other certain prostate diseases, such as prostate cancer. Potential sources are postulated for the initial initiating event, including a direct infection as discussed above, chemical, and physical trauma induced by urine reflux, diet, estrogens, or a combination of two or more of these factors.39 Different degrees of chronic or acute inflammation and inflammation-associated lesions are frequently observed in histological specimens of prostate tissue. The prevalence of chronic histological inflammation in prostate biopsies that are negative for cancer is high, reported at 78% in the PCPT,5 and 77% in the REduction by DUtasteride

of PCa Events (REDUCE) trial.6 It should be noted that there is an early histologic alteration induced by inflammation, called proliferative inflammatory atrophy, characterized by prostatic epithelia proliferation accompanied with atrophy, surrounded by inflammatory cell infiltration.40 It shares many of the genomic and protein alterations that are exhibited by high grade-prostatic intraepithelial neoplasia and prostate cancer, such as ERG fusion and a lower expression of NKX3.1, strongly suggesting a potential preneoplastic transition and indicating an association between inflammation with the progression to prostate cancer.41,42 A consensus of the histopathological classification system for prostatic inflammation, featuring the location of inflammatory infiltrates, as well as their extent and grade, has been proposed and applied in the cases using prostate biopsies, the transurethral resection of the prostate (TURP), or prostatectomy specimens (Figure 1).43

Studies assessing histological inflammation using H&E-stained tissues have reported contrasting associations with prostate cancer risk. Two studies by Platz et al. within the PCPT indicated that benign tissue inflammation was positively associated with the presence of prostate cancer, especially high-grade.4,5 In their results, men with inflammation in benign regions of prostate biopsy tissue showed 1.78-times higher odds of being positive for prostate cancer, compared with cases without inflammation. The association was stronger for those with the more aggressive disease, defined as a Gleason score of 7–10, which had 2.24-times higher odds compared with cases with a lower Gleason score. In contrast, Moreira et al. found that the presence of acute and chronic inflammation in baseline negative prostate biopsies were

both independently associated with lower odds of prostate cancer upon a subsequent biopsy in the REDUCE study.6 To date, few studies have explored the association between histological inflammation at the time of prostate cancer diagnosis and prostate cancer outcomes.7,8,9,10 An analysis of data from the Health Professionals FollowUp Study showed an inverse association between the presence of histological inflammation in resected tumors, the adjacent normal prostate tissue, and the progression to lethal prostate cancer.10 In contrast, a Swedish case-control study, where cases were early-stage prostate cancer patients receiving TURP, revealed a weak positive association between chronic histological inflammation and prostate cancer-specific mortality.8 Klink et al. reported that prostate tumor inflammation was positively associated with biochemical recurrence in a subgroup of men treated with radical prostatectomy, but the association was no longer statistically significant after adjusting for pathologic features.9

Overall, histological inflammation in prostate tissue is common, and its association with either the prostate cancer risks, or outcomes, could not be simply concluded based on current evidence. It is noteworthy that how the study population is selected might affect the findings. In countries with PSA screening, if men selected into the study were

biopsied due to a high PSA and the cause of the elevated PSA was inflammation and not cancer, then the study may find that inflammation is inversely related to the presence of cancer, perhaps artificially. An explanation for these findings is the collider stratification bias, a form of selection bias occurring in studies where the study population is stratified or restricted by a collider—i.e., a shared effect of both the exposure and the outcome of interest. In this case, the PSA concentration is elevated in prostate inflammation as well as in prostate cancer.44 More investigations of inflammation and prostate cancer risk, in the context of clinical studies with for-cause biopsies, will likely be subject to the same bias. Hence, it is worth considering other methods to assess prostate inflammation to reduce this issue. Non-invasive approaches, which do not require tissue sampling, may be good alternatives, and there is preliminary evidence that an imaging-based assessment of prostate inflammation may be feasible.45 More investigations are still warranted to further clarify histological inflammation associations with prostate cancer risks and outcomes, particularly in the advanced/lethal disease.

Strategies for Measuring Prostatic Inflammation

Studies have used a variety of techniques and data sources, both experimental and computational, to estimate the TIME status

in past years. Most early data sources are based on tissue sections and tissue microarrays. The microscopic examination of H&E-stained slides provide a direct view of immune cells, with primary morphologic information of the cell amount, location, and tissue structure, but it lacks immuno-labeling to identify specific immune cell subsets. Immunohistochemistry and immunofluorescence techniques help to further differentiate immune cell populations based on immunophenotypes, and provide qualitative and quantitative results. These conventional approaches are usually limited to a low number of markers that can be assessed simultaneously. The development of multiplex methods allows more markers to be evaluated on the same tissue section, particularly in the area of immunofluorescence. For instance, a six-color multiplex immunofluorescence panel of CD4, CD8, FOXP3, Ki67, PanCK, and PD-L1 has been applied to assess immune-cell infiltrates in formalinfixed paraffin-embedded sections from prostate biopsies and radical prostatectomy specimens.85 With advances in machine learning, the automated digital image analysis presents advantages in the quantification of target objects with high accuracy and reproducibility, compared to the manual examination of a section under a microscope.86 As an example, TILs could be quantified on images scanned from H&E slides,87 or those processed after immunohistochemistry or immunofluorescence.88,89 An iterative chromogenic-based multiplex immunohistochemistry has been applied to quantify the densities of eight T-cell phenotypes separately in the tumor epithelial and stromal regions of prostate cancer, using a whole slide image analysis.90 Since most epidemiological studies have a limited access to sufficient tissue sections for immunohistochemistry or immunofluorescence, especially biopsy specimens with a low volume of tissue, a digital image analysis demonstrates one use for scanned archival H&E images to gain insights into the TIME.

Flow cytometry is another tool that enables a more precise view of the immune cells from not only blood and bone marrow but also solid tissues that can be dissociated into single cells. Various populations can be identified simultaneously using fluorescentlabeled antibodies on each cell from prostate cancer tissues,91,92

though the necessity for fresh prostate specimens may hinder its application within the context of epidemiological studies. Mass cytometry, or CyTOF, is a variant platform from flow cytometry in which antibodies are labeled with heavy metal ion tags and then quantified by time-of-flight mass spectrometry. It allows for up to 40 markers to be measured in a single sample at a rate of 1,000 cells per second. Another advantage of this method is that it could enable the investigation of cell identity and behaviors at the protein level, including posttranslational modifications and proteolysis products, capturing diverse aspects of biological processes.93

A total of 57 phenotypically-distinct immune cell types were found in the benign human prostate by mass cytometry, with the abundance of specific immune cell clusters varying considerably between patients,94 highlighting the feasibility to phenotype the immune compartment of prostate cancer.

Computational techniques, such as XCell,95 MCPcounter,96 CIBERSORT,97 and TIMER,98 using gene expression data from tissues, can estimate the abundance of the immune infiltrate into the tumor more precisely, and can present more functional characteristics. More recently, next-generation technologies on the basis of high-resolution data contribute much to the improvement of TIME classifications and uncovering immune heterogeneity, which reveals the deeper knowledge of immunotherapy responses and encourages the discovery of new immunotherapy strategies.61 For example, aiming at characterizing the phenotypic heterogeneity and spatial distribution of target cells, NanoString digital spatial profiling technology, a combination of techniques for the “highresolution” profiling of immune cells alongside preserving spatial information, was explored. This technology has been used to quantify transcript and protein levels in formalin-fixed tumor specimens from multiple prostate cancer metastatic sites, demonstrating the utility for accurately assessing tumor heterogeneity and identifying aspects of tumor biology involving the immunological composition of metastases.99

Prospectively, a growing number of studies seeks to better demonstrate the immune landscape in prostate cancer through these new approaches.

Clinical Treatment/Lifestyle Intervention Relevant to Inflammation

Mounting evidence for a link between TIME and prostate cancer have led to a number of immuno-oncology clinical trials, which are based on strategies of single agents or synergistic combinations, via various immune approaches, including vaccines, checkpoint inhibitors, adoptive T-cell therapy, and monoclonal antibodies. Men with asymptomatic or minimally symptomatic mCRPC may consider immunotherapy in clinical trials according to the American National Comprehensive Cancer Network (NCCN) guidelines. Sipuleucel-T, a dendritic cell-based vaccine targeting PAP, is the only therapeutic vaccine approved to treat advanced prostate cancer so far, which has presented a promising result in the registration trial. The median survival in the vaccine group was 25.8 months, compared to 21.7 months in the control group, and this treatment constituted a 22% reduction in mortality risk.108 Pembrolizumab (anti-PD-1) and Ipilimumab (antiCTLA4) checkpoint blockades, targeting inhibitory molecules at the surface of Tregs, have already been applied for the treatment of several cancer types, but not specifically to prostate cancer. Clinical trials of these treatments in advanced prostate cancer have been carried out. In the nonrandomized phase Ib KEYNOTE-028 trial of Pembrolizumab, 23 patients with advanced prostate cancer were enrolled. Four patients confirmed partial responses and eight patients had a stable disease within this cohort.109 In a phase III trial of Ipilimumab in the firstline treatment of patients with chemotherapy-naïve mCRPC, no significant difference was found between the Ipilimumab group and the placebo group in terms of overall survival, but an improvement in progressionfree survival (median 5.6 vs. 3.8 months; HR 0.67; 95% CI, 0.55 to 0.81) and PSA responses were identified.13 Recently, Pembrolizumab was supported by the NCCN panel to be used in patients with microsatellite instability-high- or mismatch repair deficiency-mCRPC. It was reported that androgen deprivation therapy could increase both the number of CD8+ T-cells and Tregs, as well as selectively targeting immunosuppressive cell populations, which may be essential for maximizing the

immunogenicity of neoadjuvant therapy, providing the potential of combining androgen deprivation therapy with Treg-depleting agents, or a vaccine-based approach in the treatment of prostate cancer.110 Immunotherapy has gained less therapeutic efficacy in patients with prostate cancer than expected, despite promising advances in other solid tumors, such as melanomas and nonsmall-cell lung cancer. High tumor PD-L1 expression or alterations in homologous recombination pathway genes, such as CDK12, may be potentially predictive of responses to immune checkpoint inhibitors for prostate cancer patients.111 Whether there is a role for immunotherapy in prostate cancer, the questions of which patient subgroups are ideal for this approach, and how to improve the treatment strategies and protocols, still require more investigations.

Conclusions

In conclusion, we provide an insight into the relationship between inflammation and prostate cancer. Current evidence on the microorganism infections and histopathological characteristics of prostatic inflammation were summarized. The clinical and molecular heterogeneity of prostate cancer makes it challenging to predict the relationship of the immune contexture with outcomes. Therefore, characterizing the different immune phenotypes associated with key genomic alterations and subtypes in prostate cancer will form the foundation for understanding the proposed link between inflammation and prostate cancer. Additional work needs to be done to determine the epidemiological association of inflammation with advanced/lethal prostate cancer and to develop strategies for lethal prostate cancer prevention. Sustained investigation is required to establish whether there is a role for immunotherapy in prostate cancer, and there is scope for additional research on identifying patients who may benefit from diet and lifestyle interventions to target inflammation. Future research should aim to understand the immunological cell types, their spatial distribution, and their function within the prostate cancer TIME, in order to uncover new perspectives on prostate carcinogenesis and reveal novel targets for prevention and treatment.

References available on request

Clonmel Lecigon Meeting Report

A new paradigm for Parkinson’s treatment in Ireland

Despite decades of advances in the treatment of Parkinson’s disease, there remains a high unmet need among patients. It is thought that there are around 12,000 people living with Parkinson's disease in Ireland, with this figure projected to reach 20,000 over the next 15-20 years.

The RCPI on Kildare Street was the venue for the eagerly-awaited launch of the first triple fixed combination therapy gel for the treatment of Parkinson’s disease, Lecigon. Incorporating levodopa, entacapone, and carbidopa in the form of an intestinal gel, Lecigon is indicated for the treatment of advanced Parkinson’s disease with severe motor fluctuations

and hyperkinesia or dyskinesia when available oral combinations of Parkinson’s medicinal products have not given satisfactory results.

The launch event was chaired by Professor Tim Lynch, Clinical Director of The Dublin Neurological Institute at the Mater Misericordiae University Hospital in Dublin. Prof Lynch told the audience of clinicians, nurses, and other healthcare professionals that levodopa therapy is a mainstay of Parkinson’s management and is “phenomenal”, but there are problems with its absorption for some patients. Complex therapies are increasingly being used, as are dual therapies, he noted. Meanwhile, the cutting edge

treatment of deep brain stimulation (DBS) is now available in Ireland but not everyone will be suitable for this treatment.

“A new intestinal gel in the form of levo-carbidopa with entacapone is very welcome,” commented the professor. “I can certainly see a role for it, and it will be important to see how it fits into the treatment paradigm.”

an introduction to the

There are currently a total of 659 patients on the treatment worldwide, 337 of which were added during 2022. As this number increases, real world data is being gathered in the form of a large pan-European non-interventional study (ELEGANCE); this is currently in

Robert Wood, the general manager of Britannia Pharmaceuticals Ltd, offered

therapy.

the recruitment phase

Professor Tim Lynch, Clinical Director Dublin Neurological Institute, Mater Hospital chairing the Lecigon launch

Vasiliki Papachristopolou, International Product Manager Britannia Pharmaceuticals, Robert Wood, Managing Director Britannia Pharmaceuticals, Martin Gallagher, Director of Marketing Clonmel Healthcare, Niall Smith, Medical Affairs Manager Britannia Pharmaceuticals, Samantha Doundoulakis, Marketing Manager Rx Clonmel Healthcare

Clonmel Healthcare Senior Management Team; Martin Gallagher, Simon McGowan, Tome Farell, Barry Fitzpatrick and Jim Hanlon

Robert Wood, Managing Director Britannia Pharmaceuticals presenting at the Lecigon launch

and enrolment will commence in Ireland in November 2022. “The key message is not to delay when it comes to advanced therapies,” Wood stated.

Developments in levodopa infusion therapies were covered by Professor Dag Nyholm of the Department of Medical Sciences/Neurology Uppsala University, Uppsala University Hospital, Sweden.

The Dutch experience of treatment transition to Lecigon was outlined by Professor Teus van Laar, who is

Medical Director

Lecigon is now available in Ireland and reimbursed on the high-tech scheme.

of the Parkinson Expertise Centre at the University of Groningen in the Netherlands.

Helen Martin, Senior Product Specialist, Denise O'Brien, Therapy Support and MSL Manager and Anne O'Reilly, Patient Service Manager with Lecigon Pump

Martin Gallagher, Robert Wood, Professor Tim Lynch, Clinical Director Dublin Neurological Institute and Jim Hanlon, CEO Clonmel Healthcare

Martin Gallagher greeting guests

The first and only treatment indicated to reduce: • all-cause mortality • frequency of CV-related hospitalisations in patients with wild-type or hereditary ATTR-CM.1

ATTR-CM=transthyretin amyloid cardiomyopathy; CV=cardiovascular.

References: 1. Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016.

2. VYNDAQEL Summary of Product Characteristics. Vyndaqelq 61 mg soft capsules (tafamidis) Prescribing Information: Before prescribing Vyndaqel please refer to the full Summary of Product Characteristics. Presentation: Vyndaqel 61 mg soft capsules. Each soft capsule contains 61 mg tafamidis. Uses: Vyndaqel is indicated for the treatment of wild-type or hereditary transthyretin amyloidosis in adult patients with cardiomyopathy (ATTR-CM). Dosage: Treatment should be initiated under the supervision of a physician knowledgeable in the management of patients with amyloidosis or cardiomyopathy. When there is a suspicion in patients presenting with specific medical history or signs of heart failure or cardiomyopathy, etiologic diagnosis must be done by a physician knowledgeable in the management of amyloidosis or cardiomyopathy to confirm ATTR-CM and exclude AL amyloidosis before starting Vyndaqel, using appropriate assessment tools such as: bone scintigraphy and blood/urine assessment, and/or histological assessment by biopsy, and transthyretin (TTR) genotyping to characterise as wild-type or hereditary. The recommended dose is one capsule of Vyndaqel 61 mg (tafamidis) orally once daily. Vyndaqel 61 mg (tafamidis) corresponds to 80 mg tafamidis meglumine, tafamidis and tafamidis meglumine are not interchangeable on a per mg basis. Vyndaqel should be started as early as possible in the disease course when the clinical benefit on disease progression could be more evident. Conversely, when amyoid-related cardiac damage is more advanced, such as in NYHA Class III, the decision to start or maintain treatment should be taken at the discretion of a physician knowledgeable in the management of patients with amyloidosis or cardiomyopathy. There are limited clinical data in patients with NYHA Class IV. If vomiting occurs after dosing, and the intact Vyndaqel capsule is identified, then an additional dose of Vyndaqel should be administered if possible. If no capsule is identified, then no additional dose is necessary, with resumption of dosing the next day as usual. There are no recommended dosage adjustments for elderly patients or patients with renal or mild and moderate hepatic impairment. Limited data are available in patients with severe renal impairment (creatinine clearance less than or equal to 30 mL/min). Tafamidis has not been studied in patients with severe hepatic impairment and caution is recommended. There is no relevant use of tafamidis in the paediatric population. Method of Administration: The soft capsules should be swallowed whole and not crushed or cut. Vyndaqel may be taken with or without food. Contra-indications: Hypersensitivity to the active substance or to any of the excipients as listed in section 6.1 of SPC. Warnings and Precautions: Contraceptive measures should be used by women of childbearing potential during treatment with tafamidis and for one month after stopping treatment. Tafamidis should be added to the standard of care for the treatment of patients with transthyretin amyloidosis. Physicians should monitor patients and continue to assess the need for other therapy, including the need for organ transplantation, as part of this standard of care. As there are no data available regarding the use of tafamidis in organ transplantation, tafamidis should be discontinued in patients who undergo organ transplantation. Increase in liver function tests and decrease in thyroxine may occur. This medicinal product contains no more than 44 mg sorbitol in each capsule. Sorbitol is a source of fructose. The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of

Further information available upon request.

PP-VYN-IRL-0159. Date of Preparation: September 2022. © 2022 Pfizer Inc.

sorbitol (or fructose) should be taken into account. The content of sorbitol in medicinal products for oral use may affect the bioavailability of other medicinal products for oral use administered concomitantly. Pregnancy and Lactation: Tafamidis is not recommended during pregnancy and in women of childbearing potential not using contraception.Available data in animals have shown excretion of tafamidis in milk.A risk to the newborns/infants cannot be excluded. Vyndaqel should not be used during breastfeeding. Interactions: In a clinical study in healthy volunteers, 20 mg tafamidis meglumine did not induce or inhibit the cytochrome P450 enzyme CYP3A4. In vitro tafamidis inhibits the efflux transporter BCRP (breast cancer resistant protein) at the 61 mg/day tafamidis dose with IC50=1.16 μM and may cause drug-drug interactions at clinically relevant concentrations with substrates of this transporter (e.g. methotrexate, rosuvastatin, imatinib). In a clinical study in healthy participants, the exposure of the BCRP substrate rosuvastatin increased approximately 2-fold following multiple doses of Page 2 of 2 2020-0065522 61 mg tafamidis daily dosing. Likewise, tafamidis inhibits the uptake transporters OAT1 and OAT3 (organic anion transporters) with IC50=2.9 μM and IC50=2.36 μM,respectively,and may cause drug-drug interactions at clinically relevant concentrations with substrates of these transporters (e.g. non-steroidal anti-inflammatory drugs, bumetanide, furosemide, lamivudine, methotrexate, oseltamivir, tenofovir, ganciclovir, adefovir, cidofovir, zidovudine, zalcitabine). Based on in vitro data, the maximal predicted changes in AUC of OAT1 and OAT3 substrates were determined to be less than 1.25 for the tafamidis 61 mg dose, therefore, inhibition of OAT1 or OAT3 transporters by tafamidis is not expected to result in clinically significant interactions. No interaction studies have been performed evaluating the effect of other medicinal products on tafamidis. Undesirable Effects: The following adverse events were reported more often in 176 ATTR-CM patients treated with tafamidis meglumine 80 mg compared to placebo: flatulence [8 patients (4.5%) versus 3 patients (1.7%)] and liver function test increased [6 patients (3.4%) versus 2 patients (1.1%)]. A causal relationship has not been established. Safety data for tafamidis 61 mg are not available as this formulation was not evaluated in the double-blind, placebo-controlled, randomised phase 3 study. Legal category: S1A. Marketing Authorisation Numbers: EU/1/11/717/003– 61mg (30 capsules). Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at EUMEDINFO@pfizer.com. For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 4676500. Last revised: 04/2021

q This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions.

Ref: VY 61MG 2_0

Continuing Professional Development

CPD

Written by

CPD

60 Second Summary

Atrial Fibrillation (AF) is the commonest cardiac arrhythmia affecting at least 3% of Irish adults over 60 and 6 % over 70. The worldwide prevalence has been rising and is approximately 600 in men and 375 in women per 100,000 population.

While much progress has been made in the last 10 years in particular with collaborative interdisciplinary working and research between cardiologists and stroke physicians, nevertheless there are many unanswered questions and dilemmas in AF.

AUTHORS: Professor Rónán Collins, consultant physician in geriatric and stroke medicine and Associate Clinical Professor in Gerontology Trinity College Dublin.

!! : A trial Fibrillation and Stroke

Professor Collins is Clinical lead National Stroke Programme, Member of the British and Irish Stroke Physicians (BIASP), Fellow of European Stroke Organsiation (FESO), Steering group member for EHRA-PATHS and member of the EHRA writing group for Practical guide to anticoagulation with NOACS in non-vavlulat atrial fribrillation.

1. REFLECT Before reading this module, consider the following: Will this clinical area be relevant to my practice?

2. IDENTIFY If the answer is no, I may still be interested in the area but the article may not contribute towards my continuing professional development (CPD). If the answer is yes, I should identify any knowledge gaps in the clinical area. 3. PLAN If I have identified a

knowledge gap - will this article satisfy those needs - or will more reading be required? 4. EVALUATE Did this article meet my learning needs - and how has my practise changed as a result?Have I identified further learning needs? 5. WHAT NEXT At this time you may like to record your learning for future use or assessment. Follow the

4 previous steps, log and record your findings.

Published by HPN. Copies can be downloaded from www.irishpharmacytraining.ie

in our understanding of the pathophysiology of AF as a truly systemic condition and its association with risk of stroke and other illnesses. AF is associated with a 2 3.5 fold increase in mortality, impaired left ventricular dysfunction in 20 30% of cases, a hazard ratio of 1.6 for the development of dementia independent of previous stroke and associated with an impaired quality of life in almost 60% cases and a hospitalisation rate of 10 40% annually [3]

One in Three!! : Atrial Fibrillation and Stroke

While much progress has been made in the last 10 years in particular with collaborative interdisciplinary working and research between cardiologists and stroke physicians, nevertheless there are many unanswered questions and dilemmas in AF.

Screening for AF has huge potential benefits not least in preventing stroke, development of AF associated symptoms or preventing irreversible remodelling of the atrium and associated atrial or ventricular tachycardia associated cardiomyopathy.

In recent years international guidelines have correctly focused more on stroke prevention as the priority in the management of AF. In their “Atrial Fibrillation Better Care (ABC)” approach to AF the latest ESC guidelines on the management of AF stress the ‘A’ -to Avoid stroke / Anticoagulation as the prime issue of concern before addressing ‘B’ – better symptom control and ‘C’ optimisation of cardiovascular comorbidity and other risk factors.’

Table 1: Original Wilson and Jungner

Atrial Fibrillation (AF) is the commonest cardiac arrhythmia affecting at least 3% of Irish adults over 60 and 6 % over 70.1 The worldwide prevalence has been rising and is approximately 600 in men and 375 in women per 100,000 population.2 The lifetime risk of developing atrial fibrillation is almost 1 in 3 and it is estimated there may be as many as 18 million people with AF in the EU by 2060.

Principles for screening

other illnesses. AF is associated with a 2-3.5 fold increase in mortality, impaired left ventricular dysfunction in 20-30% of cases, a hazard ratio of 1.6 for the development of dementia independent of previous stroke and associated with an impaired quality of life in almost 60% cases and a hospitalisation rate of 10-40% annually.3

unanswered questions and dilemmas in AF.

Much attention has focused on the potential to screen for AF given it fulfils many of the original Wilson and Jungner criteria adopted by the WHO for a disease condition which would be amenable to a screening programme (see table 1.) and more specifically that the condition is common, detectable, associated with serious disease (stroke) which is preventable (with anticoagulation) [4].

Much attention has focused on the potential to screen for AF given it fulfils many of the original Wilson and Jungner criteria adopted by the WHO for a disease condition which would be amenable to a screening programme (see table 1.) and more specifically that the condition is common, detectable, associated with serious disease (stroke) which is preventable (with anticoagulation).4

Table 1: Original Wilson and Jungner Principles for screening

WILSON AND JUNGNER PRINCIPLES FOR SCREENING (1968)

• The condition sought should be an important health problem.

Both biomarkers and echocardiographic variable have been shown to independently predict risk of stroke and may well improve upon the accuracy of the CHA2DS2-VASC score. Secondary prevention for the AF stroke patient is of prime importance and applies to both stroke due to ischaemia and probably surprisingly also in cases of stroke due intracerebral haemorrhage.

ESC guidelines promote an integrated management to the AF patient and in their ‘circle of ideal integration’ list the importance of access to a many specialty model with the patient at the centre of decision making.

• There should be an accepted treatment for patients with recognized disease.

• Facilities for diagnosis and treatment should be available.

• There should be a recognizable latent or early symptomatic stage.

• There should be a suitable test or examination.

• The test should be acceptable to the population.

• The natural history of the condition, including development from latent to declared disease, should be adequately understood.

• There should be an agreed policy on whom to treat as patients.

• The cost of case finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole.

• Case finding should be a continuing process and not a ‘once and for all’ project.

94 98% 76 95% Smartphone devices /watches 91 99% 84 100%

• Adapted from Hindricks G et al. European Heart Journal 2021;42(5):373 498

Adapted from Hindricks G et al. European Heart Journal 2021;42(5):373–498

Given those facts the national clinical programmes for stroke and chronic disease management in Ireland have introduced case finding as part of the primary care contract to opportunistically pulse check for AF in an older population. The advent of personal digital devices with the potential to detect irregularities of heart rhythm has expanded this potential to detect AF.

Stroke and AF

At present despite a growing body of evidence for use of digital devices, there is no evidence to suggest more strokes would be prevented adopting such strategies over opportunistic screening by pulse checking in high- risk groups. An overview of reported specificities and sensitivities of various detection approaches is outlined below in table 2. All suspected AF must be confirmed by a 12 lead ECG or a 30 second single lead strip read by a physician experienced in AF diagnosis.

Sum Zero game: The Low CHA2DS2-VASC patient

Stroke and AF

tool for risk assessment, there are concerns that it performs modestly and has relatively poor validity (C-statistic of 0.64 at best) and that the emphasis should perhaps be on a positive bias for anticoagulation than not. This author still regularly sees cases of stroke due to atrial fibrillation in people with seemingly low risk as indicated by a CHA2DS2-VASC score of 0 or 1 (for female sex) who are on aspirin or nothing rather than an anticoagulant and this approach is not necessarily at odds with current guidelines.

In recent years international guidelines have correctly focused more on stroke prevention as the priority in the management of AF [7]. In their “Atrial Fibrillation Better Care (ABC)” approach to AF the latest ESC guidelines on the management of AF stress the ‘A’ to Avoid stroke / Anticoagulation as the prime issue of concern before addressing ‘B’ – better symptom control and ‘C’ optimisation of cardiovascular comorbidity and other risk factors.’

A proof of concept study using apples i-phone and watch for example found a positive predictive value 0.84 when a notification was received of an irregular pulse.5 The recently published ‘Smartphonebased screening for atrial fibrillation: a pragmatic randomised clinical trial (eBrave)’ showed a doubling of detection of clinically relevant atrial fibrillation in a cohort of older people who owned a smartphone in both phases of the crossover design.6

disease, obstructive sleep apnoea etc. though these variables are often closely related to the CHA2DS2-VASC risk factors themselves and their inclusion does not seem to improve score predictability. It is unknown as to whether including factors such co-existent malignancy, smoking or obesity would improve reliability. Then as we age, we must recognise that the risk of stroke with AF is a continuum and likely to increase with the duration of AF as the atrium becomes increasingly dilated and dysfunctional with chronic fibrillation.

In addition, many more people now have implantable pacemaker and ICD devices capable of detecting AF if interrogated for same and there is increasing use of implantable recorders in patients with a high index of suspicion for AF. Many such devices pick up brief runs of AF or Atrial High-Rate Episodes (AHREs)that may suggest a risk of developing AF though it is not proven that anticoagulation in such cases would prevent more stroke.

Screening for AF has huge potential benefits not least in preventing stroke, development of AF associated symptoms or preventing irreversible remodelling of the atrium and associated atrial or ventricular tachycardia associated cardiomyopathy. It can also however create unnecessary anxiety, lead to over diagnosis and treatment with anticoagulation or even potentially lead to further invasive investigations that may have associated risks and be unnecessary.

In recent years international guidelines have correctly focused more on stroke prevention as the priority in the management of AF.7 In their “Atrial Fibrillation Better Care (ABC)” approach to AF the latest ESC guidelines on the management of AF stress the ‘A’ -to Avoid stroke / Anticoagulation as the prime issue of concern before addressing ‘B’ – better symptom control and ‘C’ optimisation of cardiovascular comorbidity and other risk factors.’

Sum Zero game: The Low CHA2DS2-VASC patient

While at higher scores the CHA2DS2-VASC performs modestly it does seem to perform more consistently when the a score is low and the incidence of stroke seems < 1% consistently in those with a score of 0 or 1 (for female sex). However, it is increasingly recognised that some populations with low CHA2DS2 VASC scores of 0 or 1 may have appreciably higher risk of stroke than previously thought, (e.g up to 2% risk per annum) and that this risk seems greater in studies of Asian populations and perhaps in other groups too.8,9

For all these reasons it is good practice that people with a low CHA2DS2-VASC score where there may be doubt about initiating anticoagulation, should be referred for a specialist opinion and a thorough assessment of risk.

While the CHA2DS2 VASC score has remained the standard tool for risk assessment, there are concerns that it performs modestly and has relatively poor validity (C statistic of 0.64 at best) and that the emphasis should perhaps be on a positive bias for anticoagulation than not. This author still regularly

This may include assessment of biomarkers such as D-Dimer, Troponin, NT ProBNP, IL-6 and CRP among others, many of which have been shown to independently improve upon the risk stratification of CHA2DS2-VASC alone.

There is no role for aspirin or clopidogrel therapy in the prevention of stroke in AF and indeed it may just increase risk of bleeding without benefit.

While the CHA2DS2-VASC score has remained the standard

A limitation of CHA2DS2-VASC is that it does not include other variables such as chronic kidney

Echocardiographic evaluation of the left atrium to look for dilatation, spontaneous contrast or thrombus in the left atrial appendage, low atrial appendage exit velocity

Suggested best Practice for the CHA2 DS2 VASC = 0 (or 1 for female sex) patient?

• ESC advises no anticoagulation may be reasonable in this population BUT to reassess regularly

• Risk of stroke is < 1% but it is not zero and catastrophic strokes do occur in this population

• Lifestyle advice, weight loss and BP control may reduce burden of Paroxysmal AF

• Seek specialist opinion from an AF service to further assess risk - specific echocardiography evaluation biomarkers e.g Troponin, Pro BNP, D Dimer, CRP IL 6 etc

• Discuss in full with the patient, explain and document indicative risk of stroke and risk of bleeding (HAS BLED score)

• Give your opinion on management when asked – you’re their doctor!

The AF patient with stroke

A third of our strokes in Ireland are associated with AF and AF is a strong predictor of recurrent events Secondary prevention for the AF stroke patient is of prime importance and applies to both stroke due to ischaemia and probably surprisingly also in cases of stroke due intracerebral haemorrhage.

Post stroke AF patient with cerebral infarction

Stroke recurrence is an early risk in AF. A significant decision is when to anticoagulate the AF stroke patient after a stroke due to infarction. This is generally a specialist decision made with the benefit of

Table 2 Reported reliabilities of methods of AF detection

and measurement of Total atrial conduction time (PA-TDI) may also be useful in individual risk stratification.10 MR imaging is another growing area of interest in assessing left atrial function.

Both biomarkers and echocardiographic variable have been shown to independently predict risk of stroke and may well improve upon the accuracy of the CHA2DS2-VASC score. A number of more complex risk scores such as Garfield-AF, Anticoagulation and Risk factors in Atrial Fibrillation (ATRIA) and ABC-stroke have been shown to modestly improve upon CHA2DS2-VASC though a pragmatic balance must also be struck between the time involved to use such tools in clinical practice and added expenses of additional measurements versus accruing benefit. At least one biomarker-based risk stratification tools is currently undergoing evaluation in a RCT (ABC-AF Study NCT 03753490).

While acknowledging the ESC guidelines it is important to remember that, as pointed out in the preamble, that a guideline does not robustly cover every situation where there is a paucity of evidence and is not a substitute for physician-based judgement of their individual patient. In discussing the uncertainty of apparent low risk of stroke with patients it is my personal practice to advise anticoagulation in patients with low CHA2DS2-VASC scores (i.e 0 or 1 for female sex alone) with elevated biomarkers or possibly ‘risky’ echocardiographic measurements. All other patients need to understand that the risk of stroke is not Zero, that the risk of stroke in AF is a continuum and unless there is a high risk of bleeding, that anticoagulation may be the best strategy especially where the risk of bleeding is low. Where a decision is made not to anti-coagulate in the CHA2DS2 VASC =0 or 1 (for female sex) patient, this should be reviewed regularly with reassessment of risk factors. Almost 15% of new AF cases will have one new non sex CHA2DS2-VASC risk factor detected at one year the majority of new comorbidities detected within 5 months after diagnosis.11

There is no role for aspirin or clopidogrel therapy in the

prevention of stroke in AF and indeed it may just increase risk of bleeding without benefit.

The AF patient with stroke

A third of our strokes in Ireland are associated with AF and AF is a strong predictor of recurrent events. Secondary prevention for the AF stroke patient is of prime importance and applies to both stroke due to ischaemia and probably surprisingly also in cases of stroke due intracerebral haemorrhage.

Post-stroke AF patient with cerebral infarction

Stroke recurrence is an early risk in AF. A significant decision is when to anticoagulate the AF stroke patient after a stroke due to infarction. This is generally a specialist decision made with the benefit of repeated neuroimaging and assessment of infarct size and the presence or absence of significant haemorrhagic transformation. A traditional role of thumb, largely dictated by concern for haemorrhagic transformation in the era of Warfarin, had been to start anticoagulation in the post-stroke AF patient on the same day -2 days for TIA small infarcts, 4-7 days for moderate sized infarcts and 10-14 days for large volume infarcts. This was always a judgement based

on expert consensus rather than expert science.

More recently the TIMING study published in Circulation,12 showed that it was safe to start anticoagulation with a NOAC in the AF patient with cerebral infarction < 5 days (early) compared to starting > 5 days (delayed). ‘Early’ initiation was not inferior to ‘Delayed’ initiation with a NOAC and though, perhaps not surprisingly, it was associated with less recurrent events numerically, it was not found to be superior. A caveat to the trial was the incidence of intracerebral haemorrhage was very low (only 3 cases and not symptomatic) compared to anticipated 3-4% incidence from previous studies in a warfarin era, and the median NIHSS was only 4 suggesting mainly milder and perhaps lower volume infractions, thought the latter was not detailed. A previous small study initiating rivaroxaban or warfarin within 5 days of infarction showed no difference in rates of recurrence or bleeding on neuroimaging at 4 weeks and the AREST study comparing early initiation with apixaban within 5 days versus delayed initiation with warfarin showed a 2.1 % incidence of haemorrhagic transformation in

the warfarin group versus non with apixaban.13,14

Three further RCTs (OPTIMAS NCT 03759938, ELAN NCT 03148457 and START NCT 03021928) aim to examine the issue of superiority of an early versus delayed strategy to initiation of anticoagulation with a NOAC in the post-stroke AF patient, but the tide is moving to earlier initiation of anticoagulation for AF patients post stroke due to infarction and with a NOAC as the safest option.

The Post stroke AF patient with intracerebral haemorrhage

It seems counter-intuitive and perhaps even dangerous to be considering anticoagulation in the AF patient who has suffered an intracerebral haemorrhage (ICH), but good longitudinal data shows that the AF patient who has suffered a stroke due to ICH does better in terms of recurrent stroke events (both ischemic and haemorrhagic) if started on anticoagulation than not.15,16 A number of caveats need to be stated here, the initiation needs careful risk assessment by a stroke specialist with repeated neuroimaging to ensure the volume of ICH is stable and resolving, that the patient does not have underlying cerebral

Table 3 Modified EHRA symptom score for AF

Table 3 Modified EHRA symptom score for AF

mEHRA score symptoms description

1

No symtoms 2a Mild

Mild. Daily activity not affected and symptoms not troublesome to the patient 2b Moderate Moderate. Daily activity not affected but symptoms troublesome to the patient 3 Severe Normal daily activity affected 4 Disabling Normal daily activity discontinued

Adapted from Wynn GJ et al. EP Europace, 2014:16(7):965–972, https://doi.org/10.1093/europace/eut395

amyloid angiopathy and that underlying anatomical risks such as aneurysm or AV malformation have been adequately addressed and treated and that blood pressure control is good.

(e.g using the lower dose of dabigatran if on higher dose). In general, a period of 4-8 weeks has been suggested with repeated neuroimaging before restarting anticoagulation in the AF patient who has suffered stroke due to ICH.

The frequency of return assessments at an AF service is largely determined by patients’ symptoms and uncontrolled co morbidities such as hypertension which can increase risk of bleeding, or the presence of troublesome bleeding itself. In all other cases a good rule of thumb is to see the patient a month after initiation of oral anticoagulation and thereafter at monthly intervals suggested by the simple formula of [19]

If the ICH had occurred in the AF patient on an anticoagulant already, then it is important to undertake an assessment of pre-morbid drug adherence; review the time in therapeutic range (TTR) if on warfarin; ensure correct dose of NOAC adjusted for creatinine clearance, age and weight (where indicated); conduct a review of the full prescription for other drugs that increase haemorrhagic risk (e.g concomitant antiplatelet use which may no longer be needed).

Ongoing Management of Atrial Fibrillation

Interval of Routine follow up in months = creatinine clearance (Cockroft Gault) 10

in gerontology and it is intuitive that a properly constructed integrated model of care that includes cardiology, gerontology / strokeneurology , advanced nurse practitioners, clinical pharmacy and clinical nutrition would improve on patient education, medication adherence, better decision making re stroke prevention, AF symptom management, reduced drug errors or unnecessary prescription and reduced burden of AF and symptoms. It is important at each visit that the patients’ CHA2DS2-VASC, HAS-BLED, creatinne clearance as calculated by the Cockroft -Gault equation and the European Heart Rhythm Association (EHRA) Symptom Score (table 3).18

In such cases where the AF patient had been on an oral anticoagulant before the ICH, then consideration should be given to switching from warfarin to a NOAC in all cases (unless patient has true valvular AF* or a mechanical heart valve) as NOACS are associated with a 50% lower risk of intracranial haemorrhage and in vent of iCH outcomes are better on NOACS than Vitamin K antagonists.17 If the patient had been on a NOAC pre-ICH consider switching agent or lowering the dose of anticoagulant where appropriate

ESC guidelines promote an integrated management to the AF patient and in their ‘circle of ideal integration’ list the importance of access to a many speciality model with the patient at the centre of decision making. A criticism personally would be the very obvious glaring omission of geriatric medicine, given that AF is primarily a disease of later life and that many patients with AF have significant comorbidities, polypharmacy, frailty syndromes and may have already had a stroke, be suffering with cognitive impairment and pose some of the more difficult decisions when deciding to initiate anticoagulation and its subsequent management.

While the available research on models of integrated care for AF have had mixed results the components of such care have been heterogenous, none have included a specialist

The frequency of return assessments at an AF service is largely determined by patients’ symptoms and uncontrolled co-morbidities such as hypertension which can increase risk of bleeding, or the presence of troublesome bleeding itself. In all other cases a good rule of thumb is to see the patient a month after initiation of oral anticoagulation and thereafter at monthly intervals suggested by the simple formula of:19 Interval of Routine follow up in months = creatinine clearance (Cockroft Gault)

Many older patients with AF have significant co morbidities such as cancer, hypertension , dementia, polypharmacy or are trauma patients or awaiting surgery . Management of AF within this context can be challenging as oral anticoagulation can pose a risk . The EHRA PATHS project funded by Horizon 2020 aims to address the need for a more holistic approach to the older patient with AF through development of pathways of care that trigger both actions and KPIs for the domains of detected / suspected co morbidity [20]. It is planned to do a RCT on the new proposed pathways of care and you can read more about this important project in the management of AF at https://ehra paths.eu/

Many older patients with AF have significant co-morbidities such as cancer, hypertension , dementia, polypharmacy or are trauma patients or awaiting surgery . Management of AF within this context can be challenging as oral anticoagulation can pose a risk . The EHRA-PATHS project funded by Horizon 2020 aims to address the need for a more holistic approach to the older patient with AF through development of pathways of care that trigger both actions and KPIs for the domains of detected / suspected co-morbidity.20 It is planned to do a RCT on the new proposed pathways of care and you can read more about this important project in the management of AF at https://ehra-paths.eu/

References available on request

AND SAFETY?

Choose both efficacy and safety with ELIQUIS®

ELIQUIS is a factor Xa inhibitor that offers superior risk reduction in stroke and systemic embolism, with significantly less major bleeding vs. warfarin in non-valvular AF patients.1,*

• Superiority demonstrated on stroke / systemic embolism vs. warfarin 1 • Superiority demonstrated on major bleeding vs. warfarin 1

AND ADMINISTRATION (SPC section 4.2): Oral. Taken with water, with or without food. Prevention of stroke and systemic embolism in patients with NVAF: The recommended dose is 5 mg twice a day. In patients who meet at least two of the following criteria: serum creatinine ≥ 1.5 mg/dL (133 micromole/L), age ≥ 80 years, or body weight ≤ 60 kg the recommended dose is Eliquis, 2.5 mg twice daily. Patients with severe renal impairment (creatinine clearance 15-29 ml/min) should receive Eliquis 2.5 mg twice daily. Therapy should be continued long term. Treatment of DVT, treatment of PE and prevention of recurrent DVT and PE (VTEt): The recommended dose for the treatment of acute DVT and treatment of PE is 10 mg twice daily for the first 7 days followed by 5 mg twice daily. As per available medical guidelines, short duration of treatment (at least 3 months) should be based on transient risk factors (e.g. recent surgery, trauma, immobilisation). The recommended dose for the prevention of recurrent DVT and PE is 2.5 mg twice daily. When prevention of recurrent DVT and PE is indicated, the 2.5 mg twice daily dose should be initiated following completion of 6 months of treatment with Eliquis 5 mg twice daily or with another anticoagulant. The duration of overall therapy should be individualised after careful assessment of the treatment benefit against the risk for bleeding. Prevention of VTE (VTEp): elective hip or knee replacement surgery: The recommended dose is 2.5 mg twice a day. The initial dose should be taken 12 to 24 hours after surgery. Hip replacement surgery, the recommended duration of treatment is 32 to 38 days. Knee replacement surgery, the recommended duration of treatment is 10 to 14 days. Missed Dose for All Indications: If a dose is missed, Eliquis should be taken immediately and then continue with twice daily dose as before. Switching: Switching treatment from parenteral anticoagulants to Eliquis (and vice versa) can be done at the next scheduled dose. These medicinal products should not be administered simultaneously. Switching treatment from VKA therapy to Eliquis: Warfarin or other VKA therapy should be discontinued and Eliquis started when the international normalized ratio (INR) is < 2. Switching treatment from Eliquis to VKA therapy: Administration of Eliquis should be continued for at least 2 days after beginning VKA therapy. After 2 days of co- administration of Eliquis with VKA therapy, an INR should be obtained prior to next scheduled dose of Eliquis. Co-administration of Eliquis and VKA therapy should be continued until the INR is ≥2. Renal Impairment - mild or moderate renal impairment: For the prevention of VTE in elective hip or knee replacement surgery (VTEp), for the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE (VTEt), no dose adjustment is necessary. For the prevention of stroke and systemic embolism in patients with NVAF and serum creatinine ≥ 1.5 mg/dL (133 micromole/L) associated with age ≥ 80 years or body weight ≤ 60 kg, a dose reduction is necessary. In the absence of other criteria for dose reduction (age, body weight), no dose adjustment is necessary. Severe renal impairment (creatinine clearance 15-29 mL/min): For the prevention of VTE in elective hip or knee replacement surgery (VTEp), for the treatment of DVT, treatment of PE and prevention of recurrent DVT and PE (VTEt), Eliquis is to be used with caution. For the prevention of stroke and systemic embolism in patients with NVAF, patients should receive the lower dose of Eliquis 2.5mg twice daily. In patients with creatinine clearance < 15 mL/min, or in patients undergoing dialysis, there is no clinical experience therefore Eliquis is not recommended. See SmPC for further details. Hepatic impairment: Contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk. Not recommended in patients with severe hepatic impairment. Use with caution in patients with mild or moderate hepatic impairment (Child Pugh A or B). No dose adjustment is required in patients with mild or moderate hepatic impairment. Use with caution in patients with elevated liver enzymes (ALT/AST >2 x ULN) or total bilirubin ≥ 1.5 x ULN. Prior to initiating Eliquis, liver function testing should be performed. Catheter ablation (NVAF): Patients can continue Eliquis use while undergoing catheter ablation. Cardioversion (NVAF): Eliquis can be initiated or continued in NVAF patients who may require cardioversion. See SmPC for further details. Patients with NVAF and acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI): There is limited experience of treatment with apixaban at the recommended dose for NVAF patients when used in combination with antiplatelet agents in patients with ACS and/or undergoing PCI after haemostasis is achieved. See SmPC for further details. Paediatric population: Eliquis is not recommended in children and adolescents below the age of 18. CONTRAINDICATIONS (SPC section 4.3): Hypersensitivity to active substance or to excipients, active clinically significant bleeding, hepatic disease associated with coagulopathy and clinically relevant bleeding risk, lesion or condition if considered a significant risk factor for major bleeding, see SmPC for further details. Concomitant treatment with any other anticoagulant agent except under specific circumstances of switching anticoagulant therapy or when unfractionated heparin (UFH) is given at doses necessary to maintain an open central venous or arterial catheter or when UFH is given during catheter ablation for atrial fibrillation, see SmPC for further details. WARNINGS AND PRECAUTIONS (SPC section 4.4): Haemorrhage risk: Carefully observe for signs of bleeding. Use with caution in conditions with increased risk of haemorrhage. Discontinue administration if severe haemorrhage occurs. An agent to reverse the anti-factor Xa activity of apixaban is available. For information on reversal and managing bleeding, see SmPC for further details. Interaction with other medicinal products affecting haemostasis: Concomitant treatment with any other anticoagulant is contraindicated (see contraindications). Concomitant use of Eliquis with antiplatelet agents increases the risk of bleeding. Care with concomitant SSRIs, SNRIs or NSAIDs, including acetylsalicylic acid. Following surgery, other platelet aggregation inhibitors are not recommended concomitantly with Eliquis. In patients with atrial fibrillation and conditions that warrant mono or dual antiplatelet therapy, a careful assessment of the potential benefits against the potential risks should be made before combining this therapy with Eliquis. A clinical trial enrolled patients with atrial fibrillation with ACS and/or undergoing PCI and a planned treatment period with a P2Y12 inhibitor, with or without ASA, and oral anticoagulant (either apixaban or VKA) for 6 months. Concomitant use of ASA increased the risk of ISTH (International Society on Thrombosis and Hemostasis) major or CRNM (Clinically Relevant Non-Major) bleeding in apixaban-treated subjects. See SmPC for further details. Use of thrombolytic agents for the treatment of acute ischemic stroke: Limited experience. Patients with prosthetic heart valves: safety and efficacy of Eliquis have not been studied in patients with prosthetic heart valves, with or without atrial fibrillation. Therefore, the use of Eliquis is not recommended in this setting. Patients with antiphospholipid syndrome: Direct acting Oral Anticoagulants (DOACs), including Eliquis, are not recommended for patients with a history of thrombosis who are diagnosed with antiphospholipid syndrome (see SmPC for further details). Surgery and invasive procedures: Discontinue at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of bleeding. Discontinue at least 24 hours prior to elective surgery or invasive procedures with a low risk of bleeding. If surgery or invasive procedures cannot be delayed, appropriate caution should be exercised, taking into consideration an increased risk of bleeding. Eliquis should be restarted after the invasive procedure or surgical intervention as soon as possible provided the clinical situation allows and adequate haemostasis has been established. For patients undergoing catheter ablation for atrial fibrillation, Eliquis treatment does not need to be interrupted. Temporary discontinuation: Discontinuing anticoagulants, including Eliquis, for active bleeding, elective surgery, or invasive procedures places patients at an increased risk of thrombosis. Lapses in therapy should be avoided and if anticoagulation with Eliquis must be temporarily discontinued for any reason, therapy should be restarted as soon as possible. Spinal/ epidural anaesthesia or puncture Patients treated with antithrombotic agents for prevention of thromboembolic complications are at risk of developing an epidural or spinal haematoma which can result in long- term or permanent paralysis. The risk of these events may be increased by the post- operative use of indwelling epidural catheters or the concomitant use of medicinal products affecting haemostasis. Indwelling epidural or intrathecal catheters must be removed at least 5 hours prior to the first dose of Eliquis. The risk may also be increased by traumatic or repeated epidural or spinal puncture. Patients are to be frequently monitored for signs and symptoms of neurological impairment (e.g., numbness or weakness of the legs, bowel or bladder dysfunction). If neurological compromise is noted, urgent diagnosis and treatment is necessary. Prior to neuraxial intervention the physician should consider the potential benefit versus the risk in anticoagulated patients or in patients to be anticoagulated for thromboprophylaxis. There is no clinical experience with the use of Eliquis with indwelling intrathecal or epidural catheters. See SmPC for further details. Haemodynamically unstable PE patients or patients who require thrombolysis or pulmonary embolectomy: Eliquis is not recommended as an alternative to unfractionated heparin in patients with pulmonary embolism who are haemodynamically unstable or may receive thrombolysis or pulmonary embolectomy since the safety and efficacy of Eliquis have not been established. Patients with active cancer: Patients with active cancer can be at high risk of both venous thromboembolism and bleeding events. When apixaban is considered for DVT or PE treatment in cancer patients, a careful assessment of the benefits against the risks should be made. Renal impairment: see dosage and administration section. Elderly patients: Increasing age may increase haemorrhagic risk. Also, the co-administration of Eliquis with ASA in elderly patients should be used cautiously because of a potentially higher bleeding risk. Body weight: Low body weight (< 60 kg) may increase haemorrhagic risk. Hepatic impairment: see dosage and administration section. Interaction with Inhibitors of CYP3A4 and P-gp: Not recommended with strong inhibitors of both CYP3A4 and P-gp. These medicinal products may increase Eliquis exposure by 2-fold or greater in the presence of additional factors that increase Eliquis exposure (e.g. severe renal impairment) see SmPC for further details. Interaction with Inducers of CYP3A4 and P-gp: Eliquis should not be used for the treatment of DVT and PE in patients receiving concomitant systemic treatment with strong inducers of both CYP3A4 and P-gp since efficacy may be compromised. Concomitant systemic treatment with strong inducers of both CYP3A4 and P-gp, Eliquis should be used with caution for the prevention of VTE in elective hip or knee replacement surgery, for the prevention of stroke and systemic embolism in patients with NVAF and for the prevention of recurrent DVT and PE, though no dose adjustment for Eliquis is required during concomitant therapy with such medicinal products. Hip fracture surgery: Eliquis has not been studied in clinical trials in patients undergoing hip fracture surgery. Therefore, it is not recommended in these patients. Laboratory parameters Clotting tests (PT, INR, and aPTT) are affected by the mechanism of action of apixaban. Changes observed at the expected therapeutic dose are small and subject to a high degree of variability, see SmPC for further details. Information about excipients: Eliquis contains lactose. Patients with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take Eliquis. DRUG INTERACTIONS (SPC Section 4.5): Eliquis should be used with caution when co-administered with SSRIs/SNRIs, NSAIDs, ASA and/or P2Y12 inhibitors because these medicinal products typically increase the bleeding risk. There is limited experience of co-administration with other platelet aggregation inhibitors (such as GPIIb/IIIa receptor antagonists, dipyridamole, dextran or sulfinpyrazone) or thrombolytic agents. As such agents increase the bleeding risk, co-administration of these products with Eliquis is not recommended. See SmPC for further details.Due to an increased bleeding risk, concomitant treatment with any other anticoagulants is contraindicated, except under specific circumstances of switching anticoagulant therapy, when UFH is given at doses necessary to maintain an open central venous or arterial catheter or when UFH is given during catheter ablation for atrial fibrillation. Administration of activated charcoal reduces Eliquis exposure. Also see contraindications and special warnings and precautions section; Consult SmPC (contraindications, special warnings and precautions and drug interactions) for full details on interactions. PREGNANCY AND LACTATION (SPC section 4.6): Pregnancy: As a precautionary measure, it is preferable to avoid the use of apixaban during pregnancy. Breastfeeding A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from apixaban therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. UNDESIRABLE EFFECTS (SPC section 4.8): Increased risk of occult or overt bleeding from any tissue or organ, which may result in post haemorrhagic

(cannot be

haematoma*; nausea; contusion. Uncommon: thrombocytopenia*; epistaxis*; haematochezia*; liver function test abnormal (including blood bilirubin increased*); haematuria*; specific haemorrhage such as gastrointestinal*, abnormal vaginal*, urogenital*, post procedural*, wound secretion*, incision site*, operative*. Rare: hypersensitivity*; anaphylaxis*; haemoptysis*; gingival bleeding*; specific haemorrhage such as eye (including conjunctival)*, rectal*, muscle*. Not known: angioedema*; specific haemorrhage such as brain (encompassing intracranial, intraspinal)*, intra-abdominal*, respiratory tract*, haemorrhoidal*, mouth*, retroperitoneal*, traumatic*, erythema multiforme*. Prevention of stroke and systemic embolism in adult patients with NVAF, with one or more risk factors (NVAF): Common: anaemia; haemorrhage*; haematoma*; hypotension (including procedural hypotension); epistaxis*; nausea; gingival bleeding*; gamma-glutamyltransferase increased; haematuria*; contusion; specific haemorrhage such as eye (including conjunctival)*, gastrointestinal*, rectal*. Uncommon: thrombocytopenia*; hypersensitivity*; anaphylaxis*; haemoptysis*; haematochezia*; liver function test abnormal (including blood bilirubin increased*); specific haemorrhage such as brain (encompassing intracranial, intraspinal)*, intra-abdominal*, haemorrhoidal*, mouth*, abnormal vaginal*, urogenital*, post procedural*, wound secretion*, incision site*, operative*, traumatic*. Rare: specific haemorrhage such as respiratory tract*, retroperitoneal*, muscle*. Very Rare: erythema multiforme*. Not known: angioedema*. Treatment of DVT and PE, and prevention of recurrent DVT and PE (VTEt): Common: anaemia; thrombocytopenia*; haemorrhage*; haematoma*; epistaxis*; nausea; gingival bleeding*; gamma-glutamyltransferase increased; alanine aminotransferase increased; skin rash; haematuria*; contusion; specific haemorrhage such as gastrointestinal*, mouth*, rectal*, abnormal vaginal*, urogenital*. Uncommon: hypersensitivity*; anaphylaxis*; haemoptysis*; haematochezia*; liver function test abnormal (including blood bilirubin

Significant skin clearance at week 12, with sustained control at week 481,5

Rapid itch relief, superior to dupilumab + TCS at week 2 for CIBINQO 200 mg + TCS, with significant results as early as day 41,6

A once-daily pill available in multiple doses that can be used with or without medicated topical therapies so you can tailor treatment to meet the individual needs of your patients1-3,7,8

CONSISTENT SAFETY PROFILE: Rigorously studied in >3100 patients across 7 clinical trials, including one ongoing LTE 9

PRESCRIBING INFORMATION CIBINQO® ▼ (ABROCITINIB)

Please refer to full Summary of Product Characteristics (SmPC) before prescribing Cibinqo®.

Presentation: Film-coated tablets containing 50 mg, 100 mg, or 200 mg abrocitinib. Each tablet contains 1.37 mg, 2.73 mg, and 5.46 mg of lactose monohydrate, respectively. Indications: For the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy. Dosage: Treatment should be initiated and supervised by a healthcare professional experienced in the diagnosis and treatment of atopic dermatitis. Posology: The recommended starting dose is 200 mg once daily. A starting dose of 100 mg once daily is recommended for patients ≥ 65 years of age. For other patients who may benefit from a starting dose of 100 mg, see sections 4.4 and 4.8 of the SmPC. During treatment, the dose may be decreased or increased based on tolerability and e cacy. The lowest e ective dose for maintenance should be considered. The maximum daily dose is 200 mg. Can be used with or without medicated topical therapies for atopic dermatitis. Discontinuation of treatment should be considered in patients who show no evidence of therapeutic benefit after 24 weeks. Treatment initiation: Treatment should not be initiated in patients with a platelet count < 150 × 103/mm3, an absolute lymphocyte count (ALC) < 0.5 × 103/mm3, an absolute neutrophil count (ANC) < 1.2 × 103/mm3 or who have a haemoglobin value < 10 g/dL. Dose interruption: If a patient develops a serious infection, sepsis or opportunistic infection, dose interruption should be considered until the infection is controlled. Interruption of dosing may be needed for management of laboratory abnormalities. Missed doses: If a dose is missed, patients should be advised to take the dose as soon as possible unless it is less than 12 hours before the next dose, in which case the patient should not take the missed dose. Thereafter, dosing should be resumed at the regular scheduled time. Interactions: In patients receiving dual strong inhibitors of cytochrome CYP2C19 and moderate inhibitors of CYP2C9, or strong inhibitors of CYP2C19 alone (e.g., fluvoxamine, fluconazole, fluoxetine and ticlopidine), the recommended starting dose of Cibinqo should be reduced by half to 100 mg or 50 mg once daily. Treatment is not recommended concomitantly with moderate or strong inducers of CYP2C19/CYP2C9 enzymes (e.g., rifampicin, apalutamide, efavirenz, enzalutamide, phenytoin). In patients receiving acid reducing agents (e.g. antacids, proton pump inhibitors and H2 receptor antagonists), 200 mg once daily dose of abrocitinib should be considered (see section 4.5). Renal impairment: No dose adjustment is required in patients with mild renal impairment, i.e., estimated glomerular filtration rate (eGFR) of 60 to < 90 mL/min. In patients with moderate (eGFR 30 to < 60 mL/min) renal impairment, the recommended dose of Cibinqo should be reduced by half to 100 mg or 50 mg once daily. In patients with severe (eGFR < 30 mL/min) renal impairment, 50 mg once daily is the recommended starting dose. The maximum daily dose is 100 mg. Cibinqo has not been studied in patients with end-stage renal disease (ESRD) on renal replacement therapy. Hepatic impairment: No dose adjustment is required in patients with mild (Child Pugh A) or moderate (Child Pugh B) hepatic impairment. Cibinqo must not be used in patients with severe (Child Pugh C) hepatic impairment. Elderly: The recommended starting dose for patients aged 65 years or more 100 mg once daily. Paediatric population: The safety and e cacy of Cibinqo in children under 12 years of age have not yet been established. No data are available. Cibinqo has been studied in adolescents 12 to < 18 years of age. However, because of bone findings in juvenile rats (comparable to a 3 month old human), additional long-term data in growing adolescents is needed to conclude that the benefits outweigh the risks. Method of administration: This medicinal product is to be taken orally once daily with or without food at approximately the same time each day. In patients who experience nausea, taking Cibinqo with food may improve nausea. Tablets should be swallowed whole with water and should not be split, crushed, or chewed because these methods have not been studied in clinical trials. Contra-indications: Hypersensitivity to the active substance or to any of the excipients. Active serious systemic infections, including tuberculosis (TB), severe hepatic impairment, pregnancy, and breast-feeding. Warnings and Precautions: Serious infections: Serious infections have been reported in patients receiving Cibinqo. The most frequent serious infections in clinical studies were herpes simplex, herpes zoster and pneumonia. Treatment must not be initiated in patients with an active, serious systemic infection. Risks and benefits of treatment prior to initiating Cibinqo should be considered. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with abrocitinib. A patient who develops a new infection during treatment should undergo prompt and complete diagnostic testing and appropriate antimicrobial therapy should be initiated. The patient should be closely monitored, and therapy should be temporarily interrupted if the patient is not responding to standard therapy. Tuberculosis: Tuberculosis was observed in clinical studies with abrocitinib. Patients should be screened for TB before starting treatment and yearly screening for patients in highly endemic areas for TB should be considered. Abrocitinib must not be given to patients with active TB. For patients with a new diagnosis of latent TB or prior untreated latent TB, preventive therapy for latent TB should be started prior to initiation of treatment. Viral reactivation: Viral reactivation, including herpes virus reactivation (e.g., herpes zoster, herpes simplex), was reported in clinical studies. The rate of herpes zoster infections was higher in patients who were treated with 200 mg, 65 years of age and older, with a medical history of herpes zoster, with a confirmed ALC < 1 × 103/mm3 prior to the event and patients with severe atopic dermatitis at baseline. If a patient develops herpes zoster, temporary interruption of treatment should be considered until the episode resolves. Screening for viral hepatitis should be performed in accordance with clinical guidelines before starting therapy and during therapy. Patients with evidence of active hepatitis B or hepatitis C (positive hepatitis C PCR) infection were excluded from clinical studies. Patients who were hepatitis B surface antigen negative, hepatitis B core antibody positive, and hepatitis B surface antibody positive had testing for hepatitis B virus (HBV) DNA. Patients who had HBV DNA above the lower limit of quantification (LLQ) were excluded. Patients who had HBV DNA negative or below LLQ could initiate treatment; such patients had HBV DNA monitored. If HBV DNA is detected, a liver specialist should be consulted. Vaccination: No data are available on the response to vaccination in patients receiving Cibinqo. Use of live, attenuated vaccines should be avoided during or immediately prior to treatment. Prior to initiating treatment with this medicinal product, it is recommended that patients be brought up to date with all immunisations, including prophylactic herpes zoster vaccinations, in agreement with current immunisation guidelines. Thrombotic events including pulmonary embolism: Events of deep venous thrombosis (DVT) and pulmonary embolism (PE) have been reported in patients receiving abrocitinib. Cibinqo should be used with caution in patients at high risk for DVT/PE. Risk factors that should be considered in determining the patient’s risk for DVT/PE include older age, obesity, a medical history of DVT/PE, prothrombotic disorder, use of combined hormonal contraceptives or hormone replacement therapy, patients undergoing major surgery or prolonged immobilisation. If clinical features of DVT/PE occur, treatment should be discontinued and patients should be evaluated promptly, followed by appropriate treatment. Malignancy (including non-melanoma skin cancers): Malignancies, including

non-melanoma skin cancer (NMSC), were observed in clinical studies with abrocitinib. Clinical data are insu cient to assess the potential relationship of exposure to abrocitinib and the development of malignancies. Long-term safety evaluations are ongoing. The risks and benefits of Cibinqo treatment should be considered prior to initiating in patients with a known malignancy other than a successfully treated NMSC or cervical cancer in situ or when considering continuing Cibinqo therapy in patients who develop a malignancy. Periodic skin examination is recommended for patients who are at increased risk for skin cancer. Haematologic abnormalities: Confirmed ALC < 0.5 × 103/mm3 and platelet count < 50 × 103/mm3 were observed in less than 0.5% of patients in clinical studies. Treatment with abrocitinib should not be initiated in patients with a platelet count < 150 × 103 mm3, an ALC < 0.5 × 103/mm3, an ANC < 1.2 × 103/mm3 or who have a haemoglobin value < 10 g/dL. Complete blood count should be monitored 4 weeks after initiation of therapy and thereafter according to routine patient management. Lipids: Dose dependent increases in blood lipid parameters were reported in patients treated with abrocitinib compared to placebo. Lipid parameters should be assessed approximately 4 weeks following initiation of therapy and thereafter according to the patient’s risk for cardiovascular disease. The e ect of these lipid parameter elevations on cardiovascular morbidity and mortality has not been determined. Patients with abnormal lipid parameters should be further monitored and managed according to clinical guidelines, due to the known cardiovascular risks associated with hyperlipidaemia. In patients with a high burden of cardiovascular risk factors, the risks, and benefits of abrocitinib compared to that of other available therapies for atopic dermatitis should be considered. If abrocitinib is chosen, interventions to manage lipid concentrations should be implemented according to clinical guidelines. Elderly: The safety profile observed in elderly patients was similar to that of the adult population with the following exceptions: a higher proportion of patients 65 years of age and older discontinued from clinical studies and were more likely to have serious adverse reactions compared to younger patients; patients 65 years and older were more likely to develop low platelet and ALC values; the incidence rate of herpes zoster in patients 65 years of age and older was higher than that of younger patients. There are limited data in patients above 75 years of age. Immunosuppressive conditions or medicinal products: Patients with immunodeficiency disorders or a first-degree relative with a hereditary immunodeficiency were excluded from clinical studies and no information on these patients is available. Combination with biologic immunomodulators, potent immunosuppressants such as ciclosporin or other Janus kinase (JAK) inhibitors has not been studied. Their concomitant use with abrocitinib is not recommended as a risk of additive immunosuppression cannot be excluded. Lactose: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. Drug Interactions: Potential for other medicines to a ect pharmacokinetics of abrocitinib: Abrocitinib is metabolised predominantly by CYP2C19 and CYP2C9 enzymes, and to a lesser extent by CYP3A4 and CYP2B6 enzymes, and its active metabolites are renally excreted and are substrates of the organic anion transporter 3 (OAT3). Therefore, exposures of abrocitinib and/or its active metabolites may be a ected by medicinal products that strongly inhibit or induce theses enzymes and transporter. Dose adjustments, as appropriate, may be required. Coadministration with products which increase gastric pH: When abrocitinib 200 mg was administered concomitantly with famotidine 40 mg, an H2-receptor antagonist, abrocitinib active moiety exposures decreased by approximately 35%. The e ect of elevating gastric pH with antacids, or proton pump inhibitors (omeprazole) on the pharmacokinetics of abrocitinib has not been studied and may be similar to that seen with famotidine. The higher 200 mg daily dose should be considered for patients treated concomitantly with products which increase gastric pH, as they may reduce the e cacy of abrocitinib. Potential for Cibinqo to a ect pharmacokinetics of other medicinal products: No clinically significant e ects of Cibinqo were observed in drug interaction studies with oral contraceptives. Caution should be exercised for concomitant use of abrocitinib with dabigatran. Caution should be exercised as the levels of P-gp substrates with a narrow therapeutic index, such as digoxin, may increase. Caution should be exercised when using abrocitinib concomitantly with narrow therapeutic index medicines that are primarily metabolised by CYP2C19 enzyme (e.g. S mephenytoin and clopidogrel). Dose adjustment may be required for other medicines primarily metabolised by CYP2C19 enzyme in accordance with their product information (e.g. citalopram, clobazam, escitalopram and selumetinib). Fertility, pregnancy, and lactation: Women of childbearing potential: Women of reproductive potential should be advised to use e ective contraception during treatment and for 1 month following the final dose of Cibinqo. Pregnancy planning and prevention for females of reproductive potential should be encouraged. Pregnancy: There are no or limited amount of data on the use of abrocitinib in pregnant women. Studies in animals have shown reproductive toxicity. Abrocitinib has been shown to cause embryo-foetal lethality in pregnant rats and rabbits, skeletal variations in the foetuses of pregnant rats and rabbits and to a ect parturition and peri/postnatal development in rats. Cibinqo is contraindicated during pregnancy. Breast-feeding: There are no data on the presence of abrocitinib in human milk, the e ects on the breast fed infant, or the e ects on milk production. Abrocitinib was secreted in milk of lactating rats. A risk to newborns/infants cannot be excluded and Cibinqo is contraindicated during breast feeding. Fertility: Based on the findings in rats, oral administration of Cibinqo may result in temporary reduced fertility in females of reproductive potential. The e ects on female rat fertility were reversible 1 month after cessation of abrocitinib oral administration. Driving and operating machinery: Cibinqo has no e ect on the ability to drive or use machines. Side E ects: The most commonly reported adverse reactions are nausea (15.1%), headache (7.9%), acne (4.8%), herpes simplex (4.2%), blood creatine phosphokinase increased (3.8%), vomiting (3.5%), dizziness (3.4%) and abdominal pain upper (2.2%). The most frequent serious adverse reactions are infections (0.3%) including herpes simplex, herpes zoster, and pneumonia. Refer to SmPC for further information on side e ects. Legal Category: S1A. Marketing Authorisation Numbers: EU/1/21/1593/002 - Cibinqo 50 mg (28 film-coated tablets), EU/1/21/1593/007 - Cibinqo 100 mg (28 film-coated tablets); EU/1/21/1593/012 - Cibinqo 200 mg (28 film-coated tablets). Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com. For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 4676500. ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions.

Last revised: 10/2022. Ref: CQ 4_0 IE.

References: 1. Bieber T, Simpson EL, Silverberg JI, et al. N Engl J Med. 2021;384(12):1101-1112. 2. Simpson EL, Sinclair R, Forman S, et al. Lancet. 2020;396(10246):255-266. 3. Silverberg JI, Simpson EL, Thyssen JP, et al. JAMA Dermatol 2020;156(8):863-873. 4. Boeri M, Sutphin J, Hauber B, et al. J Dermatolog Treat. 2020 Nov 2:1-10. doi:10.1080/09546634.1832185. 5. Reich K, Silverberg JI, Papp K, et al. Presented at the Revolutionizing Atopic Dermatitis Virtual Conference; 13 June 2021. 6. Ständer S, Yosipovitch G, Simpson EL, et al. Presented at the American Academy of Dermatology Virtual Meeting Experience 2021; 23-25 April 2021. 7. Cibinqo Summary of Product Characteristics.

8. Blauvelt A, Silverberg JI, Lynde CW, et al. J Am Acad Dermatol. Published online 17 August 2021. doi: 10.1016/j.jaad.2021.05.075. 9. Cork MJ, Deleuran MS, Geng B, et al. Presented at the European Academy of Dermatology and Venereology Virtual Congress 2021; 29 September-2 October 2021.

Although some clinical trials included adolescents, please note that CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis in adults who are candidates for systemic therapy.

TCS includes low- to medium-potency topical corticosteroids, topical calcineurin inhibitors, or topical phosphodiesterase 4 inhibitors, per protocol guidance in JADE COMPARE. Nonmedicated topicals were also required.1 AD=atopic dermatitis; JAK=Janus kinase; LTE=long-term extension.

reserved. November 2022. PP-CIB-IRL-0070

CIBINQO is a convenient once-daily oral JAK1 inhibitor for moderate-to-severe atopic dermatitis (AD) that o ers1-4

Whether your patients’ moderate-to-severe AD is FIERCE or TAMER,

Asthma

Can Asthma be Prevented?

The pulmonary system has been studied since antiquity. For the first time, bronchial asthma was mentioned in Homer's “Iliad”, in which one of the characters, the doctor Machaon, periodically suffered from asthma attacks. Herodotus believed that there is a relationship between asthma attacks and the seasons of the year. Hippocrates in his work "Corpus Hippocraticum" described a disease of the respiratory tract with chronic attacks of suffocation and viscous sputum and called it "asthma". Also, Hippocrates introduced the term orthopnea (orthopnoea; Greek orthos straight, vertical + pnoē breathing) - the forced position of a person sitting or standing to facilitate breathing in a difficult prone position. Hippocrates called cold and dampness to be the cause of orthopnea. Areteus of Cappadocia, an ancient physician and philosopher, in his essay “The Causes and Symptoms of Acute and Chronic Diseases”, described orthopnea as a disease which occurs when inhaling moist cold air and attributed it to the lung diseases. Galen, Avicenna, the ancient Indian doctors also majorly contributed to the study of asthma. The English physician John Floyer, in his “Treatise of the Asthma” (1698), noted: "I have assign' d the immediate Cause

of the Asthma, to the Straitness, Compression, or Constriction of the Bronchia...” Floyer himself suffered from asthma. His research is still relevant and is of interest in the study of bronchial asthma. In the middle of the 18th century, German scientists Kurshman and Leiden singled out asthma as a separate disease. In 1860, Henry Hyde Salter, a physician at the Charing Cross Hospital in London, in his Treatise On Asthma: Its Pathology and Treatment, described “a peculiar paroxysmal character of dyspnea with intervals of healthy breathing between attacks” and suggested that asthma is allergic in nature and can give hyperreactivity to the cold air.

Scientists from all over the world have been studying bronchial asthma. In recent decades, bronchial asthma (BA) has been one of the most common chronic diseases, especially among children. It ranks 5th after the diseases of the cardiovascular system, oncology and diabetes. The reasons for the rapid increase in the incidence of bronchial asthma, scientists believe are the deterioration of the environment across the globe, especially in large cities. Asthma affects more than 300 million (about 6-7% of children and 3-4% of adults)

Written by Written by Tatiana Larmak – http://orcid. org/0000-0001-5371-2958. Lecturer of the Department of Advanced Training of Junior Medical Specialists at the Municipal Health Care Institution 'Kharkiv Regional Medical Vocational College', Kharkiv, Ukraine. An independent trainer, consultant to medical facilities and non-medical facilities to instruct medical staff on how to safely provide services to patients/clients.

Corresponding Author details: iarmak.tat@gmail.com

people in the world, and by 2025 the number may increase up to 400 million or more. The number of patients suffering from asthma increases by 1.5 times every 10 years. Asthma can lead to disability which significantly reduces the quality of life and also causes great economic and social damage to countries. More than 180,000 people die from asthma every year in the world; and there is a negative trend in mortality, especially in countries with low

living standards, where detection and treatment are insufficiently provided. People can get sick with asthma, regardless of age, profession, country, nationality or race (WHO data).

Such international programs as International Study Asthma and Allergies in Childhood (ISAAC) and the European Community Respiratory Health Survey (ECRHS) have been studying asthma. The ECRHS, conducted in 56 countries among children and in 22 countries among adults, found that the prevalence of asthma depends on climate and geography: higher in Englishspeaking countries - the UK, Ireland, USA and lower in the Mediterranean and Eastern European countries; the frequency of manifestations varies which is associated with environmental factors. In addition, the prevalence of asthma in highly developed countries is higher among urban residents than among the rural residents. Studies by American scientists at George Washington University have shown that the atmospheric air of megacities is heavily polluted with car exhaust gases which annually provokes the incidence of bronchial asthma in the world. In recent years, there has been a tendency to increase and spread the incidence of bronchial asthma.

Bronchial asthma is a noninfectious chronic inflammatory disease, allergic in nature and genetically (hereditary) predisposed, which affects

the

“Prevention is so much better than healing because it saves the labor of being sick.” Tom Adams

Asthma

respiratory system, in particular the bronchi, characterized by the periodic attacks in a form of a severe cough, dyspnea, shortness of breath and alternating periods of remission and exacerbation. Every tenth inhabitant in the world will suffer from allergies by 2030 (WHO forecast). The factors which cause attacks and exacerbation of asthma are divided into external and internal. External include a large number of allergens: flowering plants, tobacco smoke, pet hair, especially cats, household chemicals, cold air, food products, bad ecology and much more which can cause inflammation of the bronchial mucosa, their hypersensitivity. Internal factors include hereditary (genetic) predisposition, in other words, the likelihood of getting sick is higher if there are patients with bronchial asthma in the family. Various concomitant diseases of the respiratory system also exacerbate the process. The professional activity of a person, associated with harmful factors plays an important role: grain, wood, metal dust; wool, animal biological substrates; adhesives, resins, latex, etc. Strong emotions and stress can also provoke an attack.

The season plays a key role for people with asthma. Winter is the most provocative season. In winter, the likelihood of exacerbations of bronchial asthma increases.

Cold frosty air, fluctuations in temperature and humidity, icy wind and possible frequent respiratory infections exacerbate the condition of asthmatics, most of whom react to the change of seasons but feel worse, namely, in cold winter weather. A sharp change in temperature can lead to a narrowing of the airways - cold bronchospasm, for example, when leaving a warm room in the cold which leads to an asthma attack. If you cover your nose and mouth with a scarf or a glove for a short time when going outside, the cold air will warm up and the irritation of the respiratory tract will not occur. However, breathing into a scarf or other warm clothes for a long time is not recommended, since the warm air which appears from breathing moistens the fabric in which the pathogens of various respiratory infections easily multiply and the resulting condensate mixed with cold air outside causes irritation of the bronchi and may provoke an asthma attack. Modern thermal masks with a special mesh which protects against temperature changes allow people with asthma to be safe in the frosty air. The increased sensitivity of the bronchi to respiratory infections is also manifested by bronchospasm and leads to an attack, so it is advisable to avoid crowded places during the seasonal rise in respiratory diseases. It is

necessary to prescribe antipyretic, analgesic drugs, antibiotics for respiratory infections with a great care as they can cause an asthma attack in a patient with asthma and even lead to death. The air, especially in megacities, is polluted with various harmful substances (smog - exhaust gases, waste, etc.). When inhaling not just cold, but polluted cold air, the sensitivity of the mucous membrane of the upper respiratory tract increases which causes an asthmatic attack, so it is recommended that asthma patients always have an inhaler with them.

The nose plays a fundamental role in protecting the respiratory organs from various harmful effects. A huge number of functions that the nose performs - respiratory, protective, speech, information, calorific, olfactory, excretory, suction, aesthetic are so closely interconnected that a violation of the process of one affects all the others. The respiratory function is the main function of the nose. Violation of the respiratory function worsens the functioning of the lungs, the cardiovascular system and increases intracranial pressure. Each person has two lungs: the right and the left and two nasal passages: right and left (nostrils). The right nasal passage is responsible for the work of the right lung, the left - for the left. Therefore, the closedness

or congestion of one nostril leads to oxygen starvation of the corresponding lung and the breathing process is carried out by only one functioning nostril. The main protective barrier against environmental factors is the nasal mucosa. The flow of the inhaled air, passing through the nasal cavity is moistened and heated from + 25 ° C to + 35 ° C, so the cold air does not enter the lower respiratory tract. Also, there are cilia (hair) in the nose which do not let various harmful air components into the respiratory tract: dust, dirt and other small particles. Violation of the nasal breathing is one of the main causes of rhinitis. In the cold, it is difficult to breathe through the nose as the lumen of the nasal passages narrows due to the swelling of the vessels of the nasal mucosa, the blood flow worsens and the air does not have time to heat up. Various allergens, for instance, dust, plants, tobacco smoke, chemicals, polluted air, especially cold air and others, entering the nasal cavity, cause sensitization of the body, i.e. the body becomes sensitive to foreign agents (antigens-AG), for which the immune system produces protective antibodies - immunoglobulins E (Ig E). With repeated exposure of AG to the nasal mucosa, the amount of Ig E in the blood increases which causes an allergic reactionhypersensitivity of the immediate

type - allergic rhinitis. A direct link between allergic rhinitis and bronchial asthma is maintained by inflammation of the mucous membrane of the nasal cavity and bronchi. With bronchial asthma, a person is often forced to breathe through the mouth which aggravates one’s condition. When walking, especially fast, running, exercising in the fresh air at low temperatures of -10 ° C and below, asthma attacks may occur as breathing becomes faster during exercise and a large amount of cold air enters the respiratory tract. However, physical activity is necessary to strengthen the immune system and maintain a human health. For an asthmatic, as for all the people, movement is life. Children and adults who are overweight or obese are at risk for developing asthma. Short-term (15 - 20 min.) physical activity of moderate intensity in frosty weather (-5 ° C) improves blood circulation, oxygen supply to all organs and tissues of the human body which contributes to the good functioning of the cardiovascular, respiratory and other systems and is the prevention of many diseases, particularly, asthma.

The problem of non-communicable diseases (NCDs), leading to disability and death, has remained relevant for all countries of the world over the past three decades.

Bronchial asthma is included in the list of non-communicable diseases (NCDs) of the WHO Global Action Plan for the Prevention and Control of NCDs until 2030. One of the main points of the plan is “Prevention must be a central component of the response to NCDs.” According to the UN Sustainable Development Agenda, the goal is to achieve the NCD prevention and control the targets which will improve the air quality of the cities, especially in megacities, for the safety of people's lives.

“By adopting the 2030 Agenda for Sustainable Development, all governments – not just ministries of health – have committed to support the national responses to NCDs.” Founded in 2009, the Global Alliance for Chronic Respiratory Diseases (GARD), a community of more than 2,000 nongovernmental organizations (NGOs) in 170 countries, works with WHO on NCD prevention and advocates for people at risk of developing NCDs or suffering from NCDs. In 1993, The Global Initiative for Asthma (GINA) was launched in collaboration with the National Heart, Lung, and Blood Institute, National Institutes of Health, USA, and the World Health Organization. Since 1998, at the initiative of GINA, the World Asthma Day has been celebrated every first Tuesday of May in order to inform the population of all countries of the world about the incidence of asthma and its prevention. In 2006, WHO defined A European Strategy for the Prevention and Control Noncommunicable Diseases aiming at strengthening the health system for better prevention and control of NCDs and set out on a course to recovery.

To date, the treatment of bronchial asthma has not given a complete recovery to patients, but can maintain a long-term remission. The scientists from the USA,

Canada, Ireland, Germany have discovered a substanceitaconate which is produced by the immune cells of the human body - macrophages. With the help of itaconate, the immune response can be regulated. Itaconate has an anti-inflammatory effect which will allow the treatment of various diseases with severe inflammatory processes, such as bronchial asthma. Research by Professor in the Department of Biochemistry, Trinity College School of Biochemistry and Immunology, Trinity Institute of Biomedical Sciences, Dublin, Ireland, Luke A. J. O'Neill, showed the effectiveness of itaconate in laboratory models of bronchial asthma. A drug made on the basis of itaconate can change the quality of life of people suffering from bronchial asthma.

Prevention is necessary for any process that negatively affects human health and is aimed at preventing the onset of the disease. It is much easier to prevent any process than to deal with it. Prevention of bronchial asthma is multicomponent. It includes the prevention of: a) allergies – a complete exclusion or minimization of contact with allergens, for example, dust, animals, tobacco, cigarette smoke, drugs, especially aspirin and others; b) chronic respiratory diseases such as bronchitis, pneumonia, bronchiectasis, etc.; c) respiratory infections: influenza, adenovirus, rhinovirus, respiratory syncytial, etc. Airing, wet cleaning of premises, personal hygiene rules, walks in the fresh air, a balanced fortified diet - more vitamins, vegetables and fruits; hardening, regular breathing and physical exercises, strengthen the immune system, protect the human body from the onset and illness of bronchial asthma and allergies. In addition, the results of a study by the scientists of

the Johns Hopkins University School of Medicine in Baltimore, USA showed that the intake of foods containing vitamin D, for example, fish oil, seafood, egg yolk and others, reduces the risk of developing allergies and asthma, especially in obese children living in air polluted areas. Children with a genetic predisposition to the disease should be breastfed for up to 12 months to strengthen the immune system and maintain normal intestinal microflora. It is advisable to introduce additional nutrition for breastfeeding no earlier than 6 months of the first year of life without the content of allergenic products: citrus fruits, red apples, carrots, etc.; also prevent the occurrence of respiratory diseases - rhinitis, sinusitis, laryngitis, tracheitis, bronchitis; adenoid formation. Adults with a genetic predisposition are recommended to take a course of prophylactic treatment with antihistamines - anti-allergy drugs. To prevent exacerbations and alleviate the condition of patients suffering from allergies or asthma, an elimination regime is created - a complete exclusion or reduction of contact with an allergen which causes allergy or an asthma attack.

Conclusions

Bronchial asthma is a big problem for all countries of the world. Timely early diagnosis and a wellorganized prophylaxis in bronchial asthma prevents its occurrence and the identification of the risk factors will allow targeted preventive measures. Prevention is often much more effective than cure. High-quality preventive measures will significantly reduce the incidence and the prevalence of bronchial asthma among adults and, especially, children. It is much easier to prevent morbidity than to deal with it.

News - Calls to address Waiting Lists

“It is vital that the public and private systems work together to form a long-term partnership to meaningfully tackle waiting lists. Much more can be done to draw on the capacity of our Members nationwide than is currently the case and Members have put forward a range of solutions and options to the Department of Health and the HSE on how we can assist. As we now grapple with the “Cost of Living Crisis” PHA Members stand ready to once again demonstrate the efficiency, value and quality of private healthcare in supporting the public system in reducing waiting lists.”

Frank Feighan TD, Minister of State with responsibility for Public Health, Well Being and National Drugs Strategy recently opened the Private Hospitals Association Conference at Croke Park which is being attended by over 200 delegates from across the healthcare sector and sees the return of the first in-person conference since 2019. The theme of today’s Conference is “Partnership and Quality”.

PHA Chair – Bill Maher told the conference, “The last few years has been extraordinary for us all as a country, as citizens, health sector workers and organisations and together we have fought hard to combat Covid-19. We now find ourselves in the midst of a “Cost of Living Crisis” and a very challenging healthcare landscape. I believe those challenges can be overcome by working together as one healthcare system. Throughout the Covid-19 crises we came together to work collectively in partnership in ways that might previously have been unimaginable. That partnership should continue beyond the Covid crisis.”

Dr Naomi Algeo, St James’s Hospital Dublin

Dr Naomi sits on the World Health Organisation Development Group for Cancer Rehabilitation. She specialises in cancer survivorship, with a focus on employment reintegration post-cancer diagnosis, cancer-related fatigue, and cancer-related brain fog. In 2022, she was jointly awarded the Irish Cancer Society Allied Health Professional Cancer Research Award to explore the unmet needs of Adolescents and Young Adults (AYAs) with cancer, in the context of reintegration into education and employment. She will act as Clinical Lead alongside Prof. Deirdre Connolly (Discipline of Occupational Therapy, Trinity College Dublin) as Academic Lead.

Ahmad Bahlool, PhD Scholar, Royal College of Surgeons in Ireland

Ahmad Bahlool is a pharmacist currently undertaking a PhD in translational drug delivery at the Royal College of Surgeons in Ireland. He is interested in developing inhalable targeted nanomedicines for treatment of tuberculosis. This year he received the DDL Career Development Grant - Glad to receive the DDL Career Development Grant by Drug Delivery to the Lungs (DDL) to support his career development and the late stages of my ongoing PhD work on developing inhalable ATRA-loaded nanoparticles as host directed immunotherapy for tuberculosis.

Professor Andrew Bowie, Trinity Biomedical Sciences Institute

Professor Bowie has featured on the 2022 annual Highly Cited Researchers™ list from Clarivate, which identifies researchers who have demonstrated significant influence in their chosen field or fields through the publication of multiple highly cited papers during the past decade.

Andrew is Professor of Innate Immunology in Trinity’s School of Biochemistry and Immunology, based in the Trinity Biomedical Sciences Instutute (TBSI).

Dr Alex Boychak, St Lukes Radiation Oncology Network

Dr Boychak, a Consultant Radiation Oncologist responded to the war in Ukraine by setting up an initiative to help send medical supplies to Ukraine - he and colleagues have set up a website, medicalhelpukraine.com, to send medical supplies. It is accepting donations of money and supplies. Already a number of ambulances carrying supplies have been sent. Their cargos have been guided by what medics on the ground say they need: painkillers, bandages, crutches, creams and antibiotics, as well as surgical supplies.

The initiative has the support of the Ukrainian embassy in Dublin and Ukraine’s department of health.

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

Professor Donal Brennan, University College Dublin

Professor Brennan is the Head of ThisIsGo.ie, a new platform which offers a one-stop shop for helpful resources and advice on cervical cancer. Professor Donal Brennan is Professor for Gynaecological Oncology at UCD and Academic Lead of the UCD Gynaecological Oncology group, the Mater Misericordiae and St Vincent’s University Hospitals. He has multiple research interests in gynaecological oncology and has led the Irish Cancer Society Women's Health Initiative at UCD which is focused on improving care for women after cancer. He is also a Principal Investigator at Systems Biology Ireland where he leads a number of clinical and translational research projects.

Dr Jonathan Briody, University of Medicine of Medicine and Health Sciences, RCSI

Dr Briody has demonstrated passion for driving secondary care excellence across Ireland, dedicating extracurricular time to refereeing journals in health, meeting prospective health-services PhD students and writing non-specialist scientific articles on health for a wider audience, such as an editor-invited piece for a national health professional magazine and a research brief aimed at diabetic patients for Diabetes Ireland. Seeking innovative healthcare concepts, he contributes to a worldwide network of experts (SMDM, ISPOR, IHEA, HEAI, EUHEA, etc.), recently contributing a health economics competency framework and, subsequently, applying emergent theories to healthcare projects at RCSI.

Jennifer Brown, Mater Misericoridae University Hospital

Jennifer was appointed into her current position, the Clinical Directorate Lead within the Pharmacy & Medicines Optimisation (PAMO) Directorate, and the Head of Pharmacy Services in the MMUH, in June 2020. Leading the directorate during the COVID-19 pandemic presented substantial clinical, financial, safety and human resource challenges. Jennifer has overall responsibility for maintaining continuity of drug supply to the hospital, including the largest critical care complex in Ireland. She oversaw Pharmacy involvement in COVID-related clinical trials and was instrumental in the MMUH COVID-19 vaccine programme. Jennifer also introduced a weekend pharmacy drug supply service during COVID-19 and this service continues. Jennifer other professional responsibilities as Head of Pharmacy Services include her active roles with the MMUH Drugs and Therapeutics, Drug Safety, Quality and Patient Safety and Drug Expenditure and Reimbursement Monitoring Committees. Her commitment to clinical excellence has resulted in expansion of the MMUH Pharmacist-led Medicines Reconciliation team, the introduction of a Frailty-Intervention team pharmacist, a Cancer Services Clinical Pharmacy Lead as well as ongoing efforts to support pharmacy staff retention and recruitment.

Dr Joseph Byrne, NUI Galway

In 2022 Dr Byrne established the SUGARCOAT project, investigating how attaching sugar molecules to plastics could help prevent and detect bacterial infections in medical devices (e.g. urinary catheters, endotracheal tubes). Coating medical devices with these plastics would result in “smart” devices, giving doctors and nurses tools to reduce risks of infection, bring down healthcare costs and decrease the need for antibiotic use in hospitals. He has been awarded ¤193,000 to spearhead the project alongside Dr Matthew Whlie from Queen’s University in Belfast. This project is part of the North-South Research Programme, announced by An Taoiseach Micheál Martin TD on 2 March 2022, as part of the Shared Island Fund.

Legal Category: S1A. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com

Professor Karen Cadoo, St James’s Hospital, Dublin

Professor Cadoo is a recipient of the 2022 Irish Cancer Society’s Clinical Research Leadership Award. Professor Cadoo of St James’s Hospital has dedicated her research to helping people understand this risk and the steps they can take to reduce this, or catch the signs of cancer early. She would like to pilot a range of initiatives including a rapid access clinic for those concerned about their genetic risk of cancer, and a nurse phone line that people can get in touch with to ask questions, with a view to proving their value on a national scale in future.

Professor Ronan Cahill, Mater Misericordiae University Hospital

Professor Cahill has pioneered the development of translational surgical research programmes including in digital surgery using artificial intelligence methods such as computer vision for the discrimination of malignant tissue and personalised navigation systems during minimally invasive surgery for cancer in Ireland. These programmes involve high level cross-disciplinary working with national and international clinical, academic and industry partners across the fields of anatomy, chemistry, mechanical and fluid engineering, mathematics and computer sciences and include postgraduate and phd students as well as research and clinical fellows. In Ireland, the clinical work is centred at the Mater Misericordiae University Hospital which has established a Digital Surgery Unit and there is a formal academic centre now too for this work with UCD (the UCD Centre for Precision Surgery).

Professor Matthew Campbell, Smurfit Institute of Genetics, Trinity College Dublin

Professor Campbell leads the EYE-D research project into degenerative retinal diseases. In September of this year it was announced that the project has received €3.2 million in funding under the Science Foundation Ireland (SFI) Strategic Partnership Programme. “We are excited about the potential developments that will emerge from this funding,” says Prof Campbell. “The budget of €3.2 million will allow us to make a big impact on the international stage of vision research. In addition, our research endeavours put us in a perfect position to identify the cause of some of the most common forms of blindness”.

Jun is a change-maker and an exceptional leader with a keen interest in making things better for patients and staff. She is constantly questioning the status quo and striving for quality care. She was the recipient of a ‘Think Different Grant’ from TUH in October 2019. She has developed and submitted 4 successful business cases in the last 3 years which have helped change practice and improve efficiency in the Oncology Day Ward. Jun introduced a virtual clinic for cancer patients receiving oral anticancer therapy during Covid19, this was the first clinic of its kind in an Irish setting. She is currently working on projects with the TUH Lab Medicine Innovation Hub to improve safe practice and the quality of blood samples.

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

Jun Cao, Tallaght University Hospital

Keith Cassidy, Smarmore Castle Clinic

Keith is the Manager at Smarmore Castle Clinic, which earlier this year was awarded a major international accreditation recognising Excellence in International Best Practice, Legislation and Regulatory Standards.

Located in a 13th century castle, and surrounded by 15 acres of gardens, Smarmore Castle Clinic offers an unrivalled environment in which patients can take the first steps on the road to recovery from addiction. News of the recognition comes as the Health Service Executive (HSE) has entered into an agreement with Smarmore Castle Clinic to provide public funding for patients in need of inpatient detox and rehab from alcohol and drugs.

Sarah Chambers, Irish Institute of Pharmacy

In July of 2022 Sarah was appointed as the Operations Director of the IIOP. Sarah has been working in the IIOP since March 2018. In this time, she has led a range of projects including statutory requirements such as ePortfolio Review and Practice Review as well as managing specific projects that focus on the development of pharmacists. In October 2021, the IIOP Mentoring Programme was launched with Sarah as the Mentoring Programme Lead. The programme has gone on to successfully run for a third cohort, connecting another cohort of thriving mentors and mentees. The IIOP mentoring programme works to build the belief in the understanding of mentoring across the profession and to drive a culture of self-leadership and leading others. It has gone on to win the EMCC Global Mentoring Award in 2021 and was shortlisted for the IITD Best Coaching & Mentoring Initiative in 2022.

Dr Melissa Conroy is a Principal Investigator and Course Coordinator in the School of Medicine at Trinity College Dublin where she leads biomedical research and teaching activities. She is Group Lead of the Cancer Immunology Research Group and currently supervises 3 PhD students. Dr Conroy’s patient-oriented research focuses on identifying and developing new immunotherapeutic approaches for poor prognosis cancers, inflammation and neurological disorders. In 2022, Dr Conroy was awarded the Breakthrough Cancer Research/5ForTheFight Cancer Immunology Research Fellowship. This prestigious award will allow Dr Conroy’s team to progress their crucial research focussed on reinvigorating the anti-cancer immune response in oesophageal cancer.

Legal Category: S1A. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com

Dr Melissa Conroy, Trinity College Dublin

Dr Michael Crotty, My Best Weight

Dr Crotty has launched my Best Weight - a dedicated medical weight management clinic which has opened in Dublin. This team of internationally accredited doctors and experts provide an innovative approach using the most up to date scientific research. Employing a collaborative approach with the person being treated. They explore the underlying reasons for issues with weight and assess the impact that this may have on health. An individualised, long term treatment plan may include medication therapy, behavioural supports, medical nutrition and exercise therapy. My Best Weight has been recognised by the European Association for the Study of Obesity as a leading obesity management centre in Europe. It becomes the first non-hospital based accredited centre in Ireland.

Professor John Cryan, APC Microbiome Ireland, University College Cork

Professor Cryan was recently awarded ¤1.2 million towards an Irish/UK research study to examine middle age health. APC Microbiome Ireland, the SFI Research Centre at University College Cork (UCC) together with King's College London have been awarded research funding to investigate how exercise impacts gut microbiota and brain health in middle age. This project seeks to provide new knowledge about the relationship between the brain, the gut microbiota and exercise by identifying a gut-to-brain pathway, which may offer individualised therapy for changes in memory and mood as we age. Middle-age is an understudied time window across the lifecourse. Moreover, recent exciting evidence from APC Microbiome Ireland shows that the microbiome may be a suitable target to promote healthy ageing.

Dr Noelle Cullinan, Irish Cancer Society

Dedicated cancer genetics programme for children with cancer, Dr Cullinan was recently awarded funding through the Irish Cancer Society. This funding has facilitated her appointment as a Consultant Paediatric Oncologist with a Special Interest in Cancer Genetics. Since her appointment, significant progress has been made in establishing and developing a dedicated cancer genetics service for children, working closely with haematology, oncology, and clinical genetics health professionals. “I am now accepting referrals from my colleagues in the Department of Clinical Genetics for children with a confirmed cancer predisposition syndrome who are anticipated to have a high risk of developing cancer in childhood. Once a referral has been received, children with a confirmed cancer predisposition syndrome are now being invited to attend a dedicated clinic for clinical evaluation and disease surveillance, following evidence-based international recommendations,” Dr. Cullinan explains.

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

Audrey Cunningham, Irish Institute of Pharmacy

Audrey Cunningham works as a CPD Operations Coordinator in the Irish Institute of Pharmacy. A pharmacy technician by training, Audrey joined the IIOP in March 2020, just as the country went into lockdown. She led the implementation of a new online format for events for the IIOP during COVID, supporting the establishment and implementation of the IIOP “In Conversation With” webinar series. This series has been maintained post-COVID due to its popularity amongst pharmacists, providing a platform for connection for the profession where contemporaneous pharmacy issues can be discussed. Audrey is instrumental in the Peer Support agenda in the IIOP, and managed the IIOP Peer Support Event in October 2022, a forum which enabled pharmacists to contribute to the future of the peer support agenda for Irish pharmacists. She contributes to a range of ongoing IIOP projects and agendas, where her understanding of, and commitment to the pharmacy profession is always evident.

Dr Annie Curtis, Royal College of Surgeons in Ireland

Dr Curtis was the lead author on a study which discovered a new link between a disrupted body clock and inflammatory diseases - Dr Curtis, Senior Lecturer at RCSI School of Pharmacy and Biomolecular Sciences says, "This study also shows that anything which negatively impacts on our body clocks, such as insufficient sleep and not enough daylight, can impact on the ability of our immune system to work effectively." Dr Curtis is a strong advocate for Women in STEM and was awarded a L’Oreal Women in Science Fellowship. In addition to her position in the Molecular and Cellular Therapeutics (MCT) Department, she is a Principal Investigator of the Tissue Engineering Research Group (TERG) at RCSI and also a funded investigator of the SFI Funded AMBER centre. Anne also serves on the Executive Committee for the Irish Society for Immunology.

Professor Kieran Dalton, University College Cork

In the past year, Professor Dalton has been a champion in providing a greater voice to pharmacists in Ireland through his research. He has showcased how the COVID-19 pandemic and other recent pharmacy practice changes have impacted on community pharmacies and the pharmacists themselves. Notably, he has published research highlighting the effect that COVID-19 had on community pharmacy practice and pharmacist wellbeing, as well as how both the introduction of electronic prescription transfer via Healthmail and the Falsified Medicines Directive have affected community pharmacies. Kieran has also continued his ongoing work to help the advancement of the pharmacist profession by publishing his findings on pharmacists’ views of pharmacist prescribing in hospital settings, which he hopes will contribute to enhancing the scope of pharmacist roles in Ireland and improve the delivery of patient care. Additionally, Kieran has recently supervised a pharmacist-led project in an Irish hospital that has demonstrated important findings involving a significant reduction in errors with pharmacist prescribing versus medical prescribing for chemotherapy regimens, associated with cost savings.

Legal Category: S1A. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com

DURABLE RESPONSE

Median PFS1 (Primary Endpoint n=792) 26.3 months vs Rd 17.6 months

(HR 0.69,95% CI:0.57-0.83; 1-sided p<0.0001) Median follow-up 32 months

DEEP RESPONSE ORR1,2 (Secondary Endpoint) 87.1% vs Rd 66.7%

3.47, 95% CI: 2.41-5.00;

0.67-0.95;

p<0.0045)

Results are from ITT population (1-3 prior lines of treatment).

with lenalidomide and dexamethasone or with dexamethasone alone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. Dosage and Administration: Intravenous (iv) infusion on two consecutive days each week for 3 weeks (days 1, 2, 8, 9, 15 and 16), followed by a 12 day rest period. Each 28-day period is considered one treatment cycle. Kyprolis in combination with lenalidomide and dexamethasone (KRd): Infuse over 10 minutes at a starting dose of 20mg/m2 (max dose 44mg) on days 1 & 2 of cycle 1. If tolerated, increase dose to 27mg/m2 (max dose 60mg) on day 8 of cycle 1. From cycle 13, omit doses on day 8 & 9 of each cycle. In combination with Kyprolis, lenalidomide is administered as 25 mg orally on days 1–21 and dexamethasone is administered as 40 mg orally or iv on days 1, 8, 15, and 22 of the 28 day cycles. Continue treatment until disease progression or until unacceptable toxicity occurs; treatment beyond 18 cycles should be based on an individual bene t:risk assessment as data are limited. Consider appropriate dose reduction for lenalidomide according to the current lenalidomide SmPC. Kyprolis in combination with dexamethasone (Kd): Infuse over 30 minutes at a starting dose of 20 mg/m2 (max dose 44 mg) on days 1 and 2 of cycle 1. If tolerated, increase dose to 56 mg/m2 (max dose 123 mg) on day 8 of cycle 1. Dexamethasone is administered as 20 mg orally or iv on days 1, 2, 8, 9, 15, 16, 22, and 23 of the 28 day cycles. Continue treatment until disease progression or until unacceptable toxicity occurs. Kyprolis in combination with daratumumab and dexamethasone (KdD): Infuse over 30 minutes at a starting dose of 20mg/m2 (max dose 44mg) on days 1 & 2 of cycle 1. If tolerated, increase dose to 56mg/m2 (max dose 123mg) on day 8 of cycle 1. If given intravenously, daratumumab is administered at 8mg/kg on days 1 & 2 of cycle 1, then 16mg/kg weekly from day 8 for cycles 1&2, then every 2 weeks for cycles 3-6, and every 4 weeks thereafter . If given subcutaneously, daratumumab is administered at 1800mg weekly from day 1 of cycles 1&2, then every 2 weeks for cycles 3-6, and every 4 weeks thereafter. Administer preinfusion medication to reduce risk of infusion-related reactions with daratumumab. Dexamethasone is administered as 20 mg orally or iv on days 1, 2, 8, 9, 15, & 16, then 40mg on day 22 of each cycle. For patients > 75 years of age, dexamethasone is administered as 20 mg orally or intravenously weekly after the rst week. Order of administration on days when more than one medicine is administered: dexamethasone, preinfusion medication for daratumumab, car lzomib, daratumumab, post infusion medication for daratumumab. Continue treatment until disease progression or until unacceptable toxicity occurs. Refer to the current daratumumab SmPC for additional detail regarding concomitant medication and appropriate dose reduction for daratumumab. All regimens: Modify dosing based on haematologic, renal and other non-haematologic toxicity as de ned in the SmPC. Consider antiviral prophylaxis in patients treated with Kyprolis to decrease the risk of herpes zoster reactivation. Monitor platelet counts frequently. Thromboprophylaxis is recommended based on an individual bene t:risk assessment. Adequate hydration is required before Kyprolis administration in cycle 1, especially in patients at high risk of tumour lysis syndrome or renal toxicity, give additional uids after Kyprolis administration in cycle 1 as needed. Monitor all patients for evidence of volume overload and tailor uid requirements to individual patient needs. Oral and/or intravenous hydration is not required on days when intravenous daratumumab is dosed in the KdD regimen. Monitor serum potassium monthly or more frequently as clinically indicated. Assess renal function at treatment initiation and monitor at least monthly, particularly in patients with lower baseline creatinine clearance (CrCL < 30 mL/min) for whom there are limited ef cacy and safety data. Assess liver enzymes and bilirubin at treatment initiation and monitor monthly during treatment, regardless of baseline values; pay special attention to patients with moderate and severe hepatic impairment for whom there are very limited ef cacy and safety data. Contraindications: Hypersensitivity to the active substance or to any of the excipients; women who are breast-feeding. Refer to relevant SmPC for contraindications, special warnings and precautions for products used in combination with Kyprolis. Special Warnings and Precautions: For patients who experience grade 3 or 4 cardiac events or dyspnoea, or pulmonary toxicities/hypertension or hypertensive crisis, stop Kyprolis until recovery and consider whether to restart Kyprolis at 1 dose level reduction based on a bene t/risk assessment. Cardiac disorders: New or worsening cardiac failure, myocardial ischaemia and infarction have occurred, including fatal outcomes. The risk of cardiac failure is increased in elderly (≥ 75 years) and Asian patients. A thorough assessment for cardiovascular risk factors prior to starting treatment is recommended. Patients with signs or symptoms of NYHA Class III or IV cardiac failure, recent history of myocardial infarction (in the last 4 months), and in patients with uncontrolled angina or arrhythmias should have a comprehensive cardiological assessment prior to starting treatment. Electrocardiographic changes: Cases of QT interval prolongation and of ventricular tachycardia have been reported. Pulmonary toxicity: Acute respiratory distress syndrome (ARDS), acute respiratory failure, and acute diffuse in ltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred, some events have been fatal. Pulmonary hypertension: Pulmonary hypertension has been reported, some events have been fatal. Dyspnoea: Evaluate dyspnoea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Hypertension: Hypertension, including hypertensive crisis and hypertensive emergency, has been observed, some events have been fatal. Control hypertension prior to starting and during treatment. Evaluate all patients for hypertension during treatment. If hypertension cannot be controlled, reduce dose. Acute renal failure: Cases of acute renal failure have been reported, some of these events have been fatal. Tumour lysis syndrome (TLS): Cases of TLS, including with fatal outcome, have been reported. Consider patients with a high tumour burden at greater risk. Ensure patients are well hydrated before Kyprolis administration in cycle 1 and subsequent cycles as needed. Consider uric acid lowering medicinal products in patients at high risk for TLS. Monitor for evidence of TLS during treatment. Stop Kyprolis until TLS is resolved. Infusion reactions: Infusion reactions, including life-threatening reactions, have been reported in patients who received Kyprolis. Reactions can occur immediately following or up to 24 hours after administration of Kyprolis. Dexamethasone should be administered prior to Kyprolis to reduce the incidence and severity of reactions. Haemorrhage and thrombocytopenia: Haemorrhage, often associated with thrombocytopenia has been reported; some events have been fatal. Venous thromboembolic events: Events, including deep vein thrombosis and pulmonary embolism with fatal outcomes, have been reported. Closely monitor patients with known risk factors for thromboembolism, minimise all modi able risk factors (e.g. smoking, hypertension and hyperlipidaemia), and administer other agents that may increase the risk of thrombosis with caution (e.g. erythropoietic agents or hormone replacement therapy). Hepatic toxicity: Cases of hepatic failure, including fatal cases, have been reported. Thrombotic

KRd was generally well tolerated. For full details of the Kyprolis safety pro le, please refer to the Summary of Product Characteristics (SPC) available online at www.medicines.ie/medicines/kyprolis-32623/spc.

KRd

KYPROLIS® in combination with lenalidomide and dexamethasone (KRd) is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.4

microangiopathy: Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome (TTP/HUS) have been reported, some events have been fatal. Monitor for signs and symptoms of TTP/HUS and stop treatment if suspected. Once excluded, Kyprolis can be restarted. The safety of reinitiating Kyprolis in patients previously experiencing TTP/HUS is unknown. Posterior reversible encephalopathy syndrome (PRES): Cases of PRES have been reported. Kyprolis should be discontinued if PRES is suspected. The safety of reinitiating Kyprolis therapy in patients previously experiencing PRES is not known. Hepatitis B Virus (HBV) reactivation: Cases of HBV reactivation have been reported. Patients should be screened for HBV before initiation of treatment. For patients with positive HBV serology, consider prophylaxis with antivirals. Monitor for clinical and laboratory signs of HBV reactivation during and after the end of treatment. The safety of resuming car lzomib after HBV is adequately controlled is not known. Resumption of therapy should be discussed with experts in managing HBV. Progressive Multifocal Leukoencephalopathy (PML): Cases of PML have been reported in patients receiving car lzomib who have had prior or concurrent immunosuppressive therapy. Patients should be monitored for any new of worsening neurological, cognitive or behavioural signs and symptoms that may be suggestive of PML. If PML is suspected, further administration must be suspended until PML has been excluded by a specialist with appropriate diagnostic testing. If PML is con rmed, car lzomib must be discontinued. Contraception: Female patients of child bearing potential (and/or their partners) must use effective contraception measures during and for one month following treatment. Kyprolis may decrease the ef cacy or oral contraceptives. Patients using oral contraceptives or hormonal contraception associated with a risk of thrombosis should switch to an alternative method. Male patients must use effective contraception measures during and for 3 months following treatment if their partner is pregnant or of childbearing potential not using effective contraception. Sodium content: Each 10mg, 30mg and 60mg vial contains 37, 109 and 216 mg sodium, respectively. Cyclodextrin content: Each 10mg, 30mg and 60mg contains 500, 1500 and 3000 mg of cyclodextrin (betadex sulfobutyl ether sodium), respectively. Interactions: Caution should be observed when car lzomib is combined with medicinal products that are substrates of CYP1A2, 2C8, 2C9, 2C19 and 2B6 (e.g. oral contraceptives), or with substrates of P-gp (e.g. digoxin, colchicine). Fertility, pregnancy and lactation: No available data on use of Kyprolis in pregnant women; should not be used during pregnancy unless the potential bene t outweighs the potential risk to the foetus. Breast-feeding is contra-indicated during and for at least 2 days after treatment with Kyprolis. No fertility studies have been performed. Undesirable Effects: Adverse reactions in patients receiving Kyprolis: very common (≥ 1/10) pneumonia, respiratory tract infection, thrombocytopenia, neutropenia, anaemia, lymphopenia, leukopenia, hypokalaemia, decreased appetite, insomnia, dizziness, peripheral neuropathy, headache, hypertension, dyspnoea, cough, vomiting, diarrhoea, constipation, abdominal pain, nausea, back pain, arthralgia, pain in extremity, muscle spasms, increased blood creatinine, pyrexia, peripheral oedema, asthenia, fatigue, chills; common (≥ 1/100 to < 1/10) sepsis, lung infection, in uenza, herpes zoster, urinary tract infection, bronchitis, gastroenteritis, viral infection, nasopharyngitis, rhinitis, febrile neutropenia, dehydration, hyperkalaemia, hypomagnesaemia, hyponatraemia, hypercalcaemia, hypocalcaemia, hypophosphataemia, hyperuricaemia, hypoalbuminaemia, hyperglycaemia, anxiety, confusional state, paraesthesia, hypoaesthesia, cataract, blurred vision, tinnitus, cardiac failure, myocardial infarction, atrial brillation, tachycardia, ejection fraction decreased, palpitations, deep vein thrombosis, hypotension, ushing, pulmonary embolism, pulmonary oedema, epistaxis, oropharyngeal pain, dysphonia,wheezing, pulmonary hypertension, gastrointestinal haemorrhage, dyspepsia, toothache, increased alanine aminotransferase, increased aspartate aminotransferase, increased gammaglutamyltransferase, hyperbilirubinaemia, rash, pruritus, erythema, hyperhidrosis, musculoskeletal pain, musculoskeletal chest pain, bone pain, myalgia, muscular weakness, acute kidney injury, renal failure, renal impairment, decreased creatinine renal clearance, chest pain, pain, infusion site reactions, in uenza-like illness, malaise, increased c-reactive protein, increased blood uric acid, infusion related reaction; uncommon (≥ 1/1,000 to < 1/100) clostridium dif cile colitis, cytomegalovirus infection, hepatitis B virus reactivation, drug hypersensitivity, HUS, TTP, tumour lysis syndrome, intracranial haemorrhage, cerebrovascular accident, PRES, cardiac arrest, cardiomyopathy, myocardial ischaemia, pericarditis, pericardial effusion, ventricular tachycardia, hypertensive crisis, haemorrhage, ARDS, acute respiratory failure, pulmonary haemorrhage, interstitial lung disease, pneumonitis, gastrointestinal perforation, acute pancreatitis, hepatic failure, cholestasis, multi-organ dysfunction syndrome. In a phase III study comparing KdD with Kd, secondary primary malignancies were reported (1.9% in KdD; 1.3% in Kd arm). Please consult the Summary of Product Characteristics for a full description of adverse reactions. Pharmaceutical Precautions: Do not mix or administer as an infusion with other medicinal products. Store at 2°C to 8°C (in a refrigerator). Do not freeze. Store in original carton to protect from light. Reconstitute with sterile water for injections. Reconstituted solutions in the vial, syringe, or intravenous bag may be stored at 2°C – 8°C for up to 24 hours or at 25°C for up to 4 hours. Inspect visually before administration;

Amgen Ireland Limited 21 Northwood Court, Santry, Dublin 9

Loretta

Dignam, Founder/CEO,

The Menopause Hub

Loretta is a pioneer in the menopause revolution throughout Ireland, having set up Ireland’s first dedicated menopause clinic in Mount Merrion. Loretta and her team are the only dedicated multidisciplinary menopause clinic in Ireland, offering evidenced-based treatment. The move to digital healthcare during Covid-19 has allowed them to offer easier access to treatment and care for all. For World Menopause Day this year they opened their second clinic in North Dublin to better service the Northeast community of women. To date they have seen well over 6,000 patients in the clinic.

In addition, Loretta has been an advocate for menopausal women for the past 3 and a half years, with key stakeholders, such as Government, politicians, the Department of Health, the medical profession, the pharmacy profession, with members bodies like the INMO, media and consumers.

Professor Sarah Doyle, Trinity Institute of Neurosciences

Professor Doyle leads the EYE-D research project into degenerative retinal diseases. In September of this year it was announced that the project has received ¤3.2 million in funding under the Science Foundation Ireland (SFI) Strategic Partnership Programme. Professor Doyle said: “This funding will allow us to build on the major successes our group has had in understanding degenerative eye diseases. Added to this, we can now recruit the most talented group of scientists internationally and place Ireland at the forefront of vision research.”

Professor Trevor Duffy, Hermitage Clinic

Professor Duffy is the new Director of Healthcare leadership with the Royal College of Physicians Ireland. This new role has been established as part of a new Strategic Framework for 2021-2024. The purpose of the role will be to lead RCPI activity in the area of healthcare delivery and professional practice, working with internal and external stakeholders to promote excellence in patient care.

As a member of the Senior Management Team, Prof Duffy will oversee existing activities in the area of healthcare policy and delivery, developing new initiatives in agreement with the Executive Board and Council. Consultant Rheumatologist at the Connolly Hospital Blanchardstown and the Hermitage Medical Clinic and is Honorary Clinical Associate Professor at RCSI. Following specialist training in Ireland he was a Rheumatology Fellow at the Hospital Universitaire Cantonal de Geneve where he subsequently became a Chef de Clinique.

Caitriona Duggan, Portiuncula Hospital

Through a ¤160,000 Cancer Nursing Research Award made available by the Irish Cancer Society Caitriona Duggan and Dr Peter Carr are trialling using portable ultrasound machines to give a more accurate reading of the vein location, which they hope will remove much unnecessary stress and anxiety for patients who are already going through a difficult enough time with their cancer treatment. The ultrasound technology will provide important data on everything from vein size, quality and blood flow so that in time they can improve insertion success and reduce complications with infusion treatment, in what would be a combined win for all of cancer and patient care, nursing, and vascular access science.

Legal Category: S1A. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions.

Dr Waleed Faisal, School of Pharmacy, University College Cork

Dr Faisal and his team recently won the SSPC Commercial Activity of the Year Award. The award, presented at the SSPC 2022 Centre Symposium held on the 31st of September, recognised Faisal and his team behind the patent platform microneedle technology, Array Patch, for their outstanding contribution to knowledge transfer and commercialisation activities. Enterprise Ireland (EI) recently awarded the team a second commercialization fund to develop a medicated 'band-aid' to treat fungal infections of the fingernails and toenails (onychomycosis).

Foley, Chief Pharmacist, Hermitage Clinic

Patrick Foley leads the pharmacy team at Blackrock Health Hermitage Clinic. Through hard work and careful planning, they have become one of the first hospitals in Ireland to provide a ‘TTO’ discharge medication service. This service now mean patients can have their medicines provided to them at the bedside at the point of discharge. The service involves the clinical pharmacist screening of a discharge prescription and the subsequent provision of medication to the patient. This service represents a significant improvement in medication safety as well as patient experience. As the patient’s biochemistry data is available on the ward, highly trained clinical pharmacists can make key clinical interventions at the point of prescribing. Another tremendous benefit of the service to the patient is its convenience. Patrick continues to drive forward innovative improvements within his department and wider organisation that affect medication safety, patient experience and quality of service.

Professor Gallagher is a Professor of Cancer Biology in the UCD School of Biomolecular & Biomedical Science and Former Director of the UCD Conway Institute of Biomolecular and Biomedical Research. He is co-lead of an emerging virtual institute (All-Island Cancer Research Institute) that aims to bring together cancer researchers across the island of Ireland within an overarching research programme. More recently, he assumed the role of Deputy Director of Precision Oncology Ireland (www.precisiononcology. ie; 2019-2024), a nationwide Strategic Research Partnership funded by Science Foundation Ireland focused on developing better treatment strategies and diagnostics

patients.

Patrick

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

for cancer

Professor William Gallagher, University College Dublin

Professor Subrata Ghosh, University College Cork

Prestigious science foundation Ireland research professorship award - An Indian-origin professor Subrata Ghosh, a Cork-based global leader in research into Crohn’s disease and ulcerative colitis, has been awarded ¤5.6 million in funding to establish a world-leading research lab at University College Cork (UCC). Professor Ghosh works at Increasing the efficacy of currently used targeted therapies and minimising adverse events through modulation of the gut microbiome may have a major impact on the life of the sufferers and address the economic burden of expensive therapies that prove to be ineffective.

Patricia Ging, Mater Misericordiae University Hospital

The corner stone to the success of the lung transplant programme is the collaborative approach to patient care. Patricia Ging invokes a patient centred approach with on-going commitment to lung transplant service and improvements in patient care. She is internationally recognised contributor to excellence in research and clinical practice. In recognition of Patricia’s current post and academic attainments and her sustained and valued contribution to RCSI, Patricia Ging, was promoted to Honorary Clinical Associate Professor by the RCSI. As a member of the leadership advisory forum for the International Society of Heart and Lung Transplant, Patricia is a leader in innovation of specialist services and healthcare transformation with a strong academic and research focus. She demonstrates consistent efficiencies and quality care improvements and delivering excellence in care.

Dr Siobhan Glavey, Beaumont Hospital/Royal College of Surgeons in Ireland

Dr Glavey is the Principal Investigator for a new project research study that aims to advance predictive tests for multiple myeloma, which is the second most common blood cancer in Ireland.

The study, which combines genomic testing and next-generation sequencing technology, will be carried out at Beaumont Hospital in Dublin, and will be run through Blood Cancer Network Ireland, with several other cancer hospitals in Ireland participating.

Dzana Hadzic, Mater Misericoridae University Hospital

In October 2020, Dzana was appointed as the critical care pharmacist in the largest, most demanding critical care unit in the country. Taking up this role in the midst of a pandemic, she demonstrated efficiency, commitment, and dedication by quickly reacting to and problem-solving emerging medication management issues. Her main research centred around optimising the safety and quality of the dedicated pharmacist-led Medicines Reconciliation service by streamlining current processes, improving efficiency and resource-allocation. Dzana took on additional management responsibilities when she was appointed into the Deputy Clinical Pharmacy Service Manager role in 2022. Here, she helps oversee service provision, contributes to service optimisation and provides essential support to clinical pharmacists.

Legal Category: S1A. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions.

Dr Aamir Hameed, Trinity Centre for Biomedical Engineering

Dr Hameed recently launched lab with TERG on development of the new generation cardio devices and therapeutics - Dr Aamir Hameed’s lab within the Tissue Engineering Research Group (TERG) at RCSI focuses on the development of new generation cardiovascular devices and therapeutics.

TERG-CarDevT lab spinout startup, Pumpinheart, was awarded the TERMIS-AM Annual Conference and Exhibition Business Plan Competition. Donald Hickey, Co-founder and CEO presented the Pumpinheart pitch deck to an audience of tissue engineering researchers and businesses attending the conference.

Dr Hameed’s current interest is in tissue engineering and minimally invasive medical devices innovation research, especially in the domain of cardiovascular diseases. Tissue-engineered biomaterials coupled with a minimally invasive delivery system could contribute in structural improvement and function of the repaired organs and hence may provide revolutionary therapeutic opportunities.

Professor Orla Hardiman, Trinity College Dublin/SFI Precision ALS

In November of this year, Professor Hardiman received the Provost Innovation Award for her innovative research at the 2022 Trinity Innovation Awards. Professor Hardiman, Head of the Academic Unit of Neurology in Trinity and leader of the SFI Precision ALS Spoke, is also a PI at the SFI FutureNeuro and ADAPT Research Centres. She is founder and director of the National ALS/MND Clinical and Research Programme, and the HSE National Clinical Lead for Neurology.

An exceptional clinician scientist and an established world authority on the causes, diagnosis and treatment of Motor Neuron Disease, she has established the world’s longest-running ALS register in Trinity, co-founded TRICALS and transformed understanding of the genetic causes of ALS.

Bernadetta Higgins, Department of Public Health Mid-West

Bernadetta has won an award in recognition of their innovative idea to collect urine samples in a cleaner way in order to improve diagnosis rates of infections, with the aid of a special app named 'Wee Catch It'. Collecting a clean, accurate midstream urine in babies, children and adults with incontinence in an efficient and hygienic way is challenging, this can lead to contamination of samples and often results in unnecessary antibiotic prescribing and costly unplanned hospital admissions. Necessity being the mother of invention, Bernadette came up with a solution to improve the ‘clean catch’ urine samples.

‘Wee Catch It’ is currently in prototype development phase, and the nurses will now work towards developing the unique product and software for national and international use.

Moninne Howlett, Children’s Health Ireland

Dr Howlett is Ireland’s first Chief Pharmacy Information Officer and has just been granted a FulbrightTechImpact Scholar Award to visit St Jude’s Children’s Research Hospital in Memphis, Tennessee, and learn more about pharmacy informatics and their medication systems. Dr Howlett has implemented a closed-loop medication management in Ireland’s new children’s hospital involving an electronic health organisation and a number of auxiliary interfaced systems. The Fulbright Commission in Ireland is in charge of awarding grants each year for Irish citizens to study, research, or teach in the US and for Americans to do the same in Ireland. Since its formation, more than 2,500 postgraduate students, scholars, professionals and teachers across all disciplines have participated in the programme between the two countries.

Dr

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

Barry Jones, Hermitage Clinic

Mr Barry Jones was recently designated the first GreenLight™ Expert User in Dublin. This Award showcases Mr Jones’ expertise in delivering effective, long-lasting therapy to men suffering from benign prostatic enlargement. He is among the first urology consultants in Europe to receive this accolade.

The GreenLight XPS™ Laser Therapy System is a 180W, 532nm wavelength laser for the treatment of benign prostatic hyperplasia (BPH). It’s redefining the standard of care for BPH.

Mr Jones is a Consultant Urologist at The Hermitage Clinic.

Professor Brendan Kelly, Trinity College Dublin

Professor Brendan Kelly is Professor of Psychiatry at Trinity College Dublin, Consultant Psychiatrist at Tallaght University Hospital, and UCD Visiting Full Clinical Professor at UCD School of Medicine. He has authored and co-authored over 300 publications in peer-reviewed journals, over 600 non-peer-reviewed publications, 21 book chapters and book contributions, and 16 books (10 as sole author). Brendan’s recent books include ‘The Science of Happiness: The Six Principles of a Happy Life and the Seven Strategies for Achieving It’ (2021) and ‘In Search of Madness: A Psychiatrist’s Travels Through the History of Mental Illness’ (2022). Brendan is a Fellow of the Royal College of Psychiatrists, the Royal College of Physicians of Ireland, and Trinity College Dublin. In 2017, he became Editor-in-Chief of the International Journal of Law and Psychiatry and in 2020 was elected as Dun’s Librarian at the Royal College of Physicians of Ireland. He contributes frequently to print and broadcast media, especially Newstalk radio, and writes regularly for the medical press.

Since his return from the prestigious Hospital for Sick Children, Toronto in July 2020 to take up a post as a paediatric and adolescent urological surgeon in the private sector, A/Professor O’Kelly has remained both clinical and academically prolific. With >75 publications, 6 European Panel memberships including the Guidelines Panel for paediatric urology and a panel-writer with the Joint Committee on Intercollegiate Examinations in the UK and Ireland, continues to work with the European Association of Urology to develop guidelines on transitional and adult congenital care for urological patients and hopes to create a public sector program for this in Ireland. He continues to collaborate with colleagues in North America and Europe, and has started to introduce business and medical law teaching to postgraduate training in surgery to prepare future surgical consultants for practice. During COVID, he completed an advanced diploma in medical law through Kings Inns, as well as an executive MBA through Smurfit Business School, and in 2022 was shortlisted for the world AMBA student of the year.

Dr Ina Kelly, Irish Medical Organisation

Dr Kelly, Chair of Public Health Committee, was appointed IMO President at the IMO AGM. Dr Kelly said: “I am honoured to take on the role of IMO President for what I know will be a challenging year for doctors and patients across the health system.” She added that it was crucial that any barriers that stop women reaching their full potential in their careers, particularly during their training years, are acknowledged and fixed. “We have many extraordinary women in leadership positions in medicine but we want to see more of our colleagues being supported and having their voices heard.”

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

Assistant Professor Fardod Kelly, Beacon hospital/UPMC/Kildare, Royal College of Surgeons in Ireland/University College Dublin

Mary-Claire Kennedy, Irish Institute of Pharmacy

In October 2022, Mary-Claire Kennedy joined the Irish Institute of Pharmacy team as a Quality Assurance Pharmacist. Mary-Claire has been a Peer Support Pharmacist with the IIOP since 2013, supporting Practice Review, the delivery of Introduction to CPD and ePortfolio Review webinars. Most recently she has been responsible for hosting and sourcing a range of subject matter experts to feature on the IIOP “In Conversation With…” webinar series. She was awarded her PhD from the School of Pharmacy and Pharmaceutical Sciences, Trinity College Dublin in 2015. Mary-Claire has worked as a community pharmacist and also completed a Post-Graduate Diploma in Statistics in Trinity College while completing her PhD research.

Mariosa Kieran, Mater Misericordiae University Hospital

Maríosa was appointed into the MMUH Clinical Director of Operations, Pharmacy and Medicines Optimisation (PAMO) Directorate and the Pharmacy Head of Operations position in 2020. Mariosa provides high-level expertise to senior hospital management regarding pharmacy involvement in patient care, clinical excellence, drug storage and utilisation. She oversees staff recruitment as well as on-going review, improvement and strategic planning for MMUH Pharmacy services. Maríosa is a valued member of the MMUH Drugs and Therapeutics Committee and manages development, review and update of MMUH pharmacy and drug protocols, policies, procedures and guidelines as well as review and update of the MMUH drug formulary. Mariosa also supports the financial performance of the MMUH through her involvement in the Drug Expenditure Monitoring Review Committee with associated actions and has progressed recent drug procurement tenders. Maríosa has a keen interest in pharmacy educations. Maríosa successfully completed a MSc in Healthcare Management in 2021 and continued her interest in education in 2022 having completed the HSE / DELL Diploma in Digital Futures in Healthcare to upskill in application of digital solutions in healthcare.

As Chief Pharmacist for the Acute Hospital Drug Management Programme, Fionnuala provides leadership and strategic direction for a team whose work has provided enormous support to acute hospital pharmacy departments. AHDMP has undertaken significant work evaluating supply chain resilience and drug stock planning, developing the national COVID Therapeutics guidance documents and advisory statements, and supporting implementation of the COVID-19 vaccination programme initially in acute hospitals and subsequently in the Centralised Vaccination Centres. Fionnuala’s work on the business case and early development of Trackvax, the vaccine tracking system for COIVD 19 vaccination centres ensured the HSE got a safe and efficient solution to track the vaccine at such a crucial time. Fionnuala’s efforts to progress the Hospital Medicines Management System (HMMS) brings closer the delivery of efficient and reliable technology for hospital pharmacies. HMMS will be implemented as a single, centrally-deployed, national ICT system to support the information and technology requirements of hospitals’ pharmacy services to replace the currently deployed hospital pharmacy software.

Professor Brian Kirby, St Vincent’s University Hospital

Professor Brian Kirby features in the podcast series, Let’s Talk Psoriasis - the first series of its kind designed to bridge the gap in support for people awaiting specialist care, by providing access to expert guidance from leading Irish dermatologists to help people manage their psoriasis. Professor Kirby is a Consultant Dermatologist at St Vincent’s University Hospital in Dublin, Ireland, and a Full Clinical Professor of Dermatology and Principal Investigator at the Charles Institute of Dermatology, University College Dublin.

He has published more than 250 PubMed-cited publications, the majority of which are on psoriasis. He is a member of the steering committee of the British Association of Dermatologists, Biologics and Immunomodulator Registry, and a member of the International Psoriasis Council. He is an Associate Editor of British Journal of Dermatology and the journal Dermatology.

Legal Category: S1A. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com

Fionnuala King, Chief Pharmacist, HSE

Professor Veronica Lambert, Dublin City University

Professor Veronica Lambert, is a Professor of Children and Family Nursing/Health at Dublin City University’s School of Nursing, Psychotherapy and Community Health. This year, in a competitive funding call, Prof Lambert acted as a role model for peers and colleagues, by leading through invitation, a successful Higher Education Authority North South Research Programme Award in collaboration with Queen’s University Belfast, for a project entitled “the all-island CO-DECIDE Study: Co-production of a decision-making framework for planning the place of end-of-life care for children, young people and their families on the island of Ireland”. Over the next two years, Professor Lambert will work with research peers and colleagues at DCU and QUB to advance this collaborative and capacity building research through four incremental stages across the island of Ireland. This will result in the development of a novel shared decision-making framework which will improve the lives of families receiving end-of-life care for children with life-limiting and life-threatening conditions on the island of Ireland.

Professor Robert Landers, University Hospital Waterford

In 2022, Professor Landers was appointed President of the Irish Hospital Consultants Association. Since then he has campaigned on behalf of the organisation in advocating for timely, quality care for patients and the essential resources needed for the Consultants who treat them. He has urged Government to deliver on its Budget promises by providing the necessary resources, capacity and hospital professionals to assess and treat patients.

Professor Landers is a Consultant Histopathologist at the University Hospital Waterford.

Professor Aoife Lowery, National University Galway

Professor Lowery, Associate Professor and Consultant Surgeon recently received an Irish Cancer Society Clinician Research Leadership Award. All too often, cancer surgeon Professor Aoife Lowery sees the underappreciated impact that the side effects from treatment can have on patients. As the outcomes and survival for patients with breast cancer continue to improve, she feels that survivorship issues such as the side effects of cancer treatment are becoming increasingly recognised. A key focus of Professor Lowery’s increased time commitment to research, which is made possible by Irish Cancer Society award, will be on issues faced by patients arising from treatment, with a focus on reducing the burden of cancer treatment for these patients by identifying ways to prevent or minimise associated side effects.

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

Theresa Lowry-Lehnen, South-East Technological University

Theresa has 40 years clinical nursing experience in primary and secondary care, and currently runs a nurse led medical centre for a population of over 10,500 patients. She developed and delivers a successful on-site smoking cessation service for her patient cohort. She is an active social prescriber, involved in providing people with non-medical sources of support and interventions within the community to improve their physical, emotional and mental wellbeing. To date, Theresa has written five nursing, health and psychology books, and has had over 140 academic articles published in medical, nursing and pharmacological journals. Some of her academic work has been used to create CPD modules for Nurses and Doctors and pharmacy team’s continuous education and professional development. This year she carried out research on antimicrobial stewardship and CRP POCT testing to guide clinician’s antibiotic prescribing decisions for RTIs. Theresa is a contributor to local radio where she provides updates for the community on health-related matters. She also produces podcasts and health related videos and presentations on a wide variety of medical/health related topics, including a series of men’s health related presentation/ videos during men's health week 2022. This year she also provided a wellness week, and health checks for SETU staff.

Maria Macken, Mater

Misericordiae

Beacon Hospital together with Professor Jonathan Lyne, Director of Electrophysiology, announced earlier this year that they have been selected as one of only 12 cardiac centres of excellence in the world to take part in a ground-breaking clinical trial. Beacon Hospital the only centre in Ireland to be selected. The other 11 selected centres are located in the USA and the UK. The trial is working on a new type of Cardiac Resynchronisation Therapy (CRT) for heart failure patients. This technique utilises the hearts own electrical wiring system known as conduction system pacing. Congratulations to Prof Lyne and all in Beacon Hospital’s Cath Lab, Clinical Trials and Research Institute teams.

University Hospital

Maria has played a consequential role for the fairly new Physician Associate (PA) profession in Ireland. Maria was part of the first cohort of the RCSI Physician Associates Studies Programme. There were only six in this cohort and Maria was also the class rep. Upon graduation, Maria was awarded “The Physician Associate Gold Medal” for the top performance across the two years of the PA master’s programme. Maria works at the Mater Hospital in the National Spinal Injuries Unit. as a clinic Physician Associate and was the first PA to work in the Mater (there are now 4 PAs working in the Mater). Her responsibilities include caring for patients on the ward, assisting in theatre, and in the clinic. On any given day, she would be reviewing patients on the wards, following their laboratory and imaging investigations, assisting with patient care technical procedures, discuss patient findings with consultants and members of the team. Marias activities related to the theatre include listing patients, conduct pre-operative assessments, and assist in surgery. Specific responsibilities related to spinal patients include arranging transfer to and from National Spinal Injuries Unit (NSIU). She served as President for two years which she played a major part in ISPA policy, scope of practice documents and liaising with Consultants and other hospitals in regards to PA employment. Legal Category: S1A. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com

Dr Jonathan Lyne, Beacon Hospital

Ellen Martin, HSE National Antimicrobial Resistance Infection Control Team

Ellen has been instrumental in the creation and development of the Pharmacist Antimicrobial Stewardship Network (PAMS-Net) this year. This forum is the result of a collaboration between the HSE Antimicrobial Resistance and Infection Control (AMRIC) team and the Irish Institute of Pharmacy. The network aims to support pharmacists across all sectors in their role as antimicrobial stewards. The network provides a discussion forum and regular educational events for members and facilitates the sharing of knowledge and information in relation to antimicrobial stewardship across the pharmacy profession. It also aims to foster creativity and innovation in antimicrobial stewardship. Ellen chairs the PAMS-net working group which brings together pharmacists from a range of professional backgrounds to inform and advise on the continuous development of the network. Ellen was a member of the Antimicrobial Stewardship Guidance Working Group for the recently published HSE Antimicrobial Stewardship Guidance for all healthcare settings.

Professor Oliver McElvaney, Beaumont Hospital/Royal College of Surgeons in Ireland

In March of this year Professor McElvaney carried out a clinical trial which indicated an effective treatment for critically ill Covid-19 patients. The study investigates the effects of using an antiinflammatory protein, alpha-1 antitryspin (AAT), to treat COVID-19 patients who have progressed to acute respiratory distress syndrome (ARDS). Professor McElvaney is from the RCSI Department of Medicine and Beaumont Hospital. He commented: “These early results are encouraging, and will we hope form the basis for a larger trial to see how much of an effect reducing inflammation using AAT has on clinical outcomes such as mortality.”

Professor McGee, Deputy Vice Chancellor for Academic Affairs at RCSI, was formally admitted as a member of the RIA at a ceremony in Dublin recently. Professor McGee is a distinguished scholar in psychology, specifically psychosocial aspects of health. Committed to translational research, Professor McGee has been Principal Investigator on many national interdisciplinary health-related projects, earning almost ¤17 million in peer-reviewed grant income. Within RCSI, she has fostered collaboration across cognate disciplines since she joined in 1987. As RCSI’s Deputy Vice Chancellor for Academic Affairs, Professor McGee is responsible for the quality of degree-awarding activities in RCSI’s campuses in Dublin, Bahrain, Dubai and Malaysia.

Professor Hannah McGee, Royal College of Surgeons in Ireland

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

Professor Patrick McGorey, Royal College of Surgeons

Development and scaling up of early intervention and youth mental health servicesThe RCSI Honorary Doctorate was awarded to Professor Patrick McGorry, an Irishborn, Australian psychiatrist known worldwide for his development and scaling up of early intervention and youth mental health services, and for mental health innovation, advocacy and reform. - https://www.rcsi.com/dublin/news-and-events/news/newsarticle/2022/06/healthcare-and-research-professionals-graduate

Niamh McMahon, St James’s Hospital Dublin/Trinity College Dublin

Course Director for the MSc in Hospital Pharmacy, Trinity College Dublin, and Chief 2 Pharmacist in the Medicine for the Elderly Directorate, St. James’s hospital, this year Niamh successfully completed Consultant Pharmacist Credentialing through the Royal Pharmaceutical Society of Great Britain –becoming the first pharmacist based in the Republic of Ireland to be awarded this status. This provides formal recognition for her expert level of pharmacist practice across five domains: person-centred care and collaboration, professional practice, leadership and management, education, and research. In particular, it recognises Niamh’s clinical knowledge, expertise and leadership in the profession of pharmacy, delivering person-centred care and driving change across the healthcare system, in her chosen specialty, Care of Older Persons. She is Lead Pharmacist to the National Integrated Care Programme for Older Persons, and Chairperson of the Hospital Pharmacists’ Association of Ireland, Special Interest Group for the Care of Older People.

Professor Deborah McNamara, Royal College of Surgeons in Ireland

Newly elected vice- president of RCSI, over the last decade, Professor McNamara has focused on healthcare quality improvement, obtaining post-graduate qualifications in quality improvement and implementation science. She founded the better beaumont quality improvement learning collaborative in 2014, a group that she co-leads with Consultant Microbiologist Dr Fidelma Fitzpatrick, to support a range of hospitalbased improvement activities. At a national level, her work with the National Clinical Programme in Surgery focuses on helping colleagues in all surgical specialties to publish implementable evidence-based policies and care pathways that will improve the delivery of surgical care in Ireland.

Professor Zena Moore, Royal College of Surgeons in Ireland

Professor Moore was awarded the Life Achievement Award from the World Union of Wound Healing Societies - Commitment to wound care. Furthermore she is progressing the education provided by the School of Nursing & Midwifery at RCSI, is to be commended. Her work has greatly advanced the way wounds are cared for, thereby improving the lives of patients across the world. Director of the Skin Wounds and Trauma (SWaT) Research Centre is leading cutting-edge research in the field of wound healing and tissue repair, with a specific emphasis on pressure ulcer prevention and management. The Centre aims to translate evidence into contemporary clinical decision-making, and to provide a platform for outcome-focused healthcare practice.

Mary Mullen, Mater Misericordiae University Hospital

Mary commenced her current post in the Mater Misericordiae University Hospital (MMUH) in September 2018 and is one of the few Registered Advanced Nurse Practitioners in Ortho-Geriatrics in the country. To date she has pioneered and championed hip fracture care for older adults within the MMUH advocating the national key performance indicators within hip fracture care, positively impacting on patient’s outcomes and health related quality of life for older adults. This is demonstrated and reflected in the MMUH hip fracture data for 2021 showing the greatest improvements for patients within this hip fracture pathway. She is a passionate inspirational leader acting as a catalyst in initiating change and driving quality improvements within the hip fracture population. This was recognised earlier this year by the National Office of Clinical Audit (NOCA) where Mary and the local hip fracture governance committee won the Quality Improvement Champion Award for 2022 for reducing heel ulcers in hip fracture patients. She recently was nominated for the Fellowship of the Faculty of Nursing & Midwifery in the RCSI in recognition of her outstanding leadership, work and commitment as a nurse practitioner.

Dearbhla Murphy, Mater Misericordiae University Hospital

Dearbhla has been working at the Pharmacy Department of the Mater Misericordiae University Hospital (MMUH) since 2014. In January 2022, she was appointed into the new post of Cancer Services Clinical Pharmacy Lead. In the short time since taking up this post, Dearbhla has demonstrated her passion and motivation in the development and continued improvement of clinical pharmacy service provision for cancer patients. Dearbhla provides a ward based clinical pharmacy service for the Oncology/ Haematology inpatient ward, allowing for a senior level of clinical care and intervention for this patient cohort, and has established a Medicines Information enquiry answering service for the Cancer Service, enabling specialist review, oversight and review for opportunities for service changes based on the queries generated. Dearbhla is leading a number of initiatives in her new role including a review of human normal Immunoglobulin use in accordance with international evidence and national guidelines and is lead coordinator for MMUH access to cancer Managed Access Programmes (MAPs), to ensure that all terms of participation are agreeable for both the hospital and the patient.

Dr Eddie Murphy, St Vincent’s University Hospital

Dr Eddie Murphy is the psychologist on RTE’s Operation Transformation where his practical, respectful and hope orientated approach has opened the hidden doors of the therapy room to the public at large. He has contributed extensively to local and national media including RTE’s Marian Finucane show & The John Murray Show, The Irish Independent, Irish Daily Mail and RTE Guide. Dr Murphy is a clinical psychologist, mental health expert, author, teacher, & life coach.

He is a Head of Psychology / Principal Clinical Psychologist working in the HSE and is committed to providing professional psychology passionately and promoting successful outcomes using CBT, Mindfulness, Solution Focused therapies for children, adults, families, communities and organisations. He has a specialist interest in trauma and PTSD.

Anne recently received a top award in recognition of an innovative idea to collect urine samples in a cleaner way in order to improve diagnosis rates of infections, with the aid of a special app. Anne won the National Spark Ignite award and ¤3,000 seed funding for the ‘Wee Catch It’ innovation idea, at the annual Spark Innovation Programme conference in Dublin recently. ‘Wee Catch It’ is currently in prototype development phase, and the nurses will now work towards developing the unique product and software for national and international use.

Anne Murray, Department of Public Health Mid-West

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

Professor Jarushka Naidoo, Beaumont Hospital

Consultant Oncologist at Beaumont RCSI Cancer Centre (Beaumont Hospital and RCSI University of Health Sciences) Professor Naidoo has won a clinical Research Leadership Award for research which utilises immunotherapy by utilising a person’s own immune system against cancer. This award ‘buys out’ some of the time a practicing oncologist like Prof Naidoo would spend in hospital, providing cover to allow ambitious researchers like her to dedicate more time to working on innovative new breakthroughs that can help patients.

Eric Neville, Mater Private Network

In September of this year, Eric announced that the Mater Private Network has embarked on delivering Ireland’s most ambitious and comprehensive Electronic Health Record (EHR) platform, MEDITECH Expanse. Backed by an investment of ¤26m, Mater Private Network will integrate MEDITECH Expanse across its entire Irish network, including its flagship Dublin and Cork hospitals, the Mid-Western Radiation Oncology Centre, Limerick, both Day Hospitals and clinics in counties Limerick, Offaly, Meath and Louth.

Eric is Chief Information Officer with the Mater Private Network, and in outlining his vision said, “This significant investment in the latest EHR technology is a major leap forward in our Digital Transformation. Being a fully digital Network will be a gamechanger not only for us but for our patients and other healthcare institutions with which we collaborate.”

Aoife Ni Eochaidh, Bon Secours Consultants Clinic

Aoife has launched Home Pelvic Routines - an online digital product, which is a series of specific pelvic floor muscle exercises and routines developed by me that are provided in a step-by-step way, at the right pace, in a clear, concise, easy to follow way. They are affordable, discrete, and widely available on a smart phone, tablet, or PC, and can be used in comfort and privacy. Pelvic floor muscle tone is a really important function in managing Pregnancy, the Post Natal Period and for Menopause and its impact on body and functions. She has partnered with pharmacies and physiotherapy clinics in Ireland (Spectrum Health and Meagher’s Pharmacies and I have just launched them for sale too, in UK pharmacies online, (Weldrick’s).

Muireann

Ní Shúilleabháin,

Pharmaceutical Society of Ireland

Muireann was re-Appointed President of Pharmaceutical Society of Ireland. Her overall remit is in Medication Safety and she has been an active advocate for quality and safety in medicines management at a local and national level. Muireann has further experience in Healthcare Management, Clinical Governance, Clinical Pharmacy, Consultancy Pharmacy, Accreditation processes, Pharmacy Practice and Project Leadership. She has been in a Chief/ Superintendent role since 2001.

Legal Category: S1A. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions.

Oral solution containing tofacitinib citrate, equivalent to 1 mg/mL tofacitinib. Indications: Please note not all presentations are licensed for all indications, please see dosage section for details: In combination with methotrexate (MTX) for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs. Can be given as monotherapy in case of intolerance to MTX or when treatment with MTX is inappropriate. In combination with MTX for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an inadequate response or who have been intolerant to a prior disease modifying antirheumatic drug (DMARD) therapy. For the treatment of adult patients with active ankylosing spondylitis (AS) who have responded inadequately to conventional therapy. For the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent. For the treatment of active polyarticular juvenile idiopathic arthritis (JIA) (rheumatoid factor positive [RF+] or negative [RF-] polyarthritis, and extended oligoarthritis), and juvenile psoriatic arthritis in patients 2 years of age and older, who have responded inadequately to previous therapy with DMARDs. Can be given in combination with MTX or as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate. Dosage: Treatment should be initiated and supervised by specialist physicians experienced in the diagnosis and treatment of the condition for which tofacitinib is indicated. Tofacitinib is given orally, with or without food. RA, PsA and AS: The recommended dose is 5 mg twice daily or 11 mg once daily which should not be exceeded. Treatment with tofacitinib 5 mg film coated tablets twice daily and tofacitinib 11 mg prolonged release tablet once daily may be switched between each other on the day following the last dose of either tablet. Available data suggest that clinical improvement in AS is observed within 16 weeks of initiation of treatment. Continued therapy should be carefully reconsidered in AS patients exhibiting no clinical improvement within this timeframe. UC: The recommended dose is 10 mg twice daily for induction for 8 weeks. For patients who do not achieve adequate therapeutic benefit by week 8, the induction dose of 10 mg twice daily can be extended for an additional 8 weeks (16 weeks total), followed by 5 mg twice daily for maintenance. Tofacitinib induction therapy should be discontinued in any patient who shows no evidence of therapeutic benefit by week 16. The recommended dose for maintenance treatment is tofacitinib 5 mg twice daily. Tofacitinib 10 mg twice daily for maintenance treatment is not recommended in patients with UC who have known venous thromboembolism (VTE) risk factors, unless there is no suitable alternative treatment available. For patients with UC who are not at increased risk for VTE, tofacitinib 10 mg twice daily may be considered if the patient experiences a decrease in response on tofacitinib 5 mg twice daily and failed to respond to alternative treatment options for UC such as tumour necrosis factor (TNF) inhibitor treatment. Tofacitinib 10 mg twice daily for maintenance treatment should be used for the shortest duration possible. The lowest effective dose needed to maintain response should be used. Polyarticular JIA and juvenile PsA: The recommended dose in patients 2 years of age and older: 10 kg - < 20 kg: 3.2 mg (3.2 mL oral solution) twice daily, 20 kg - < 40 kg: 4 mg (4 mL oral solution) twice daily, and ≥ 40 kg 5 mg (5 mL oral solution or 5 mg tablet) twice daily. Patients ≥ 40 kg treated with tofacitinib 5 mL oral solution twice daily may be switched to tofacitinib 5 mg tablets twice daily. Available data suggest that clinical improvement is observed in paediatric patients within 18 weeks of initiation. Continued therapy should be carefully reconsidered in a paediatric patient exhibiting no clinical improvement within this timeframe. Dose interruption and adjustment:

Tofacitinib treatment should be interrupted if a patient develops a serious infection until the infection is controlled. Interruption of dosing may be needed for management of dose-related laboratory abnormalities including lymphopenia, neutropenia, and anaemia. It is recommended not to initiate dosing in patients with an absolute lymphocyte count (ALC) less than 0.75×10 /L, an absolute neutrophil count (ANC) less than 1×10 /L or with haemoglobin less than 9 g/dL. It is recommended not to initiate dosing in paediatric patients with an absolute neutrophil count (ANC) less than 1.2×109/L or with haemoglobin less than 10 g/dL. Renal impairment: No dose adjustment is required in patients with mild or moderate renal impairment. Patients with severe renal impairment the dose should be reduced to 5 mg once daily when the indicated dose in the presence of normal renal function is 5 mg twice daily or 11 mg prolonged-release tablet once daily. Dose should be reduced to 5 mg twice daily when the indicated dose in the presence of normal renal function is 10 mg twice daily. Patients with severe renal impairment should remain on a reduced dose even after haemodialysis. Hepatic impairment: No dose adjustment is required in patients with mild hepatic impairment. Patients with moderate hepatic impairment dose should be reduced to 5 mg once daily when the indicated dose in the presence of normal hepatic function is 5 mg twice daily or 11 mg prolonged-release tablet once daily. Dose should be reduced to 5 mg twice daily when the indicated dose in the presence of normal hepatic function is 10 mg twice daily. Tofacitinib should not be used in patients with severe hepatic impairment. Elderly: No dose adjustment is required in patients aged 65 years and older. Use with caution as increased risk and severity of adverse events. See also Warnings & Precautions for use in patients over 65 years of age. Paediatric population: The safety and efficacy of tofacitinib in children less than 2 years of age with polyarticular JIA and juvenile PsA has not been established. The safety and efficacy of tofacitinib in children less than 18 years of age with other indications (e.g. ulcerative colitis) has not been established. The safety and efficacy of tofacitinib prolonged-release formulation in children aged less than 18 years have not been established. Interactions: Tofacitinib total daily dose should be reduced by half in patients receiving potent inhibitors of cytochrome P450 (CYP) 3A4 (e.g. ketoconazole) and in patients receiving 1 or more products that result in both moderate inhibition of CYP3A4 and potent inhibition of CYP2C19 (e.g. fluconazole). Coadministration with potent CYP inducers (e.g. rifampicin) may result in a loss of or reduced clinical response. Coadministration with potent inducers of CYP3A4 is not recommended. Contraindications: Hypersensitivity to any of the ingredients, active tuberculosis (TB), serious infections such as sepsis, or opportunistic infections, severe hepatic impairment, pregnancy and lactation. Warnings and Precautions: Patients treated with tofacitinib should be given a patient alert card. Use in patients over 65 years of age: Considering the increased risk of serious infections, myocardial infarction, and malignancies with tofacitinib in patients over 65 years of age, tofacitinib should only be used in patients over 65 years of age if no suitable treatment alternatives are available. Combination with other therapies: There was a higher incidence of adverse events for the combination of tofacitinib with MTX versus tofacitinib as monotherapy in RA clinical studies. Tofacitinib should be avoided in combination with biologics and potent immunosuppressants such as azathioprine, 6-mercaptopurine, ciclosporin and tacrolimus. Venous thromboembolism (VTE): Serious VTE events including pulmonary embolism (PE), some of which were fatal, and deep vein thrombosis (DVT), have been observed in patients taking tofacitinib. In a randomised post authorisation safety study in patients with rheumatoid arthritis who were 50 years of age or older with at least one additional

a XELJANZ is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (rheumatoid factor positive [RF+] or negative [RF-] polyarthritis and extended oligoarthritis), and juvenile psoriatic arthritis (PsA) in patients 2 years of age and older, who have responded inadequately to previous therapy with disease modifying antirheumatic drugs (DMARDs). RA=rheumatoid arthritis; PsA=psoriatic arthritis; UC=ulcerative colitis; JAK= Janus kinase.

ORAL JAK INHIBITOR IDIOPATHIC ARTHRITIS (JIA)

XELJANZ has been prescribed to more than 362,000 patients across indications globally (RA,UC,PsA)5

cardiovascular risk factor, a dose dependent increased risk for VTE was observed with tofacitinib compared to TNF inhibitors. In a post hoc exploratory analysis within this study, in patients with known VTE risk factors, occurrences of subsequent VTEs were observed more frequently in tofacitinib-treated patients that, at 12 months treatment, had D-dimer level greater than or equal to twice the upper limit of normal (2×ULN) versus those with D-dimer level <2×ULN. For patients with RA with known risk factors for VTE, consider testing D-dimer levels after approximately 12 months of treatment. If D-dimer test result is ≥ 2×ULN, confirm that clinical benefits outweigh risks prior to a decision on treatment continuation with tofacitinib. Tofacitinib should be used with caution in patients with known risk factors for VTE, regardless of indication and dose. Tofacitinib 10 mg twice daily for maintenance treatment is not recommended in patients with UC who have known VTE risk factors, unless there is no suitable alternative treatment available. Promptly evaluate patients with signs and symptoms of VTE and discontinue tofacitinib in patients with suspected VTE, regardless of dose or indication. Retinal venous thrombosis (RVT): Patients experiencing symptoms suggestive of RVT should be advised to promptly seek medical care. Infections: Serious and sometimes fatal infections have been reported in patients administered tofacitinib. Rheumatoid arthritis patients taking corticosteroids may be predisposed to infection. Patients should be closely monitored for infections, with prompt diagnosis and treatment. Treatment should be interrupted if a serious infection develops. As there is a higher incidence of infections in the elderly and in the diabetic populations in general, caution should be used when treating the elderly and patients with diabetes. Tuberculosis: Patients should be evaluated for both active and latent TB prior to being treated with tofacitinib. Patients who test positive for latent TB should be treated with standard antimycobacterial therapy before administering tofacitinib. Viral Reactivation: Viral reactivation and cases of herpes zoster have been observed. Screening for viral hepatitis should be performed in accordance with clinical guidelines prior to starting therapy with tofacitinib. The impact on chronic viral hepatitis is not known. Major adverse cardiovascular events (MACE): MACE have been observed in patients taking tofacitinib. In a randomised post authorisation safety study in patients with RA who were 50 years of age or older with at least one additional cardiovascular risk factor, an increased incidence of myocardial infarctions was observed with tofacitinib compared to TNF inhibitors. In patients over 65 years of age, patients who are current or past smokers, and patients with other cardiovascular risk factors, tofacitinib should only be used if no suitable treatment alternatives are available.

Diabetes: Dose adjustment of anti-diabetic medication may be necessary in the event that hypoglycaemia occurs following initiation of tofacitinib. Vaccinations: Prior to initiating tofacitinib it is recommended that all patients, particularly pJIA and jPsA patients, be brought up to date with all immunisations in agreement with current immunisation guidelines. Live vaccines should not be given concurrently with tofacitinib. Malignancy and lymphoproliferative disorder: Tofacitinib may affect host defences against malignancies. In a randomised post authorisation safety study in patients with RA who were 50 years of age or older with at least one additional cardiovascular risk factor, an increased incidence of malignancies excluding non-melanoma skin cancer (NMSC), particularly lung cancer and lymphoma, was observed with tofacitinib compared to TNF inhibitors. Lung cancers and lymphoma in patients treated with tofacitinib have also been observed in other clinical studies and in the post marketing setting. Other malignancies in patients treated with tofacitinib were observed in clinical studies and the post marketing setting, including, but not limited

References:

1. XELJANZ Summary of Product Characteristics.

2. OLUMIANT (baracitinib) Summary of Product Characteristics. 3. RINVOQ (upadacitinib hemihydrate) Summary of Product Characteristics. 4. JYSELECA (fi lgotinib maleate) Summary of Product Characteristics. 5. Data on File, Pfi zer Inc, New York, NY.

to, breast cancer, melanoma, prostate cancer, and pancreatic cancer. In patients over 65 years of age, patients who are current or past smokers, and patients with other malignancy risk factors tofacitinib should only be used if no suitable treatment alternatives are available. NMSCs have been reported in patients treated with tofacitinib; the risk of NMSC may be higher in patients treated with tofacitinib 10 mg twice daily than in patients treated with 5 mg twice daily. Periodic skin examination is recommended in patients at increased risk for skin cancer. Interstitial lung disease: Caution is recommended in patients with a history of chronic lung disease as they may be more prone to infection. Asian patients are known to be at higher risk of ILD, caution should be exercised with these patients. Gastrointestinal perforations: Tofacitinib should be used with caution in patients who may be at increased risk, e.g. history of diverticulitis or concomitant use of corticosteroids or NSAIDs. Hypersensitivity: Cases of hypersensitivity associated with tofacitinib administration have been reported. Allergic reactions included angioedema and urticaria; serious reactions have occurred. If any serious allergic or anaphylactic reaction occurs, tofacitinib should be discontinued immediately. Laboratory Parameters: Increased incidence of lymphopenia and neutropenia have been reported, and decreases in haemoglobin, which should be monitored in accordance with the SmPC. Monitor ANC and haemoglobin at baseline, 4-8 weeks and 3 monthly, ALC at baseline and 3 monthly. Tofacitinib has been associated with increases in lipid parameters, maximal effects were observed within 6 weeks. Monitoring should be performed 8 weeks after initiation and managed according to hyperlipidaemia guidelines. Tofacitinib has been associated with liver enzyme elevations; use caution if initiating in patients with elevated liver enzymes particularly in combination with potentially hepatotoxic products. Routine monitoring of liver tests and prompt investigation of any observed liver enzyme elevations are recommended to identify potential cases of drug-induced liver injury. Gastrointestinal obstruction with a non-deformable prolonged-release formulation: Caution should be used when administering tofacitinib 11 mg prolonged release tablets to patients with pre-existing severe gastrointestinal narrowing (pathologic or iatrogenic). Pregnancy & Lactation: Use of tofacitinib during pregnancy and breast-feeding is contraindicated. Undesirable Effects: RA, PsA and A: The most common serious adverse reactions were serious infections; pneumonia, herpes zoster, UTIs, cellulitis, diverticulitis, appendicitis and opportunistic infections. The most commonly reported adverse reactions during the first 3 months in controlled clinical studies were headache, upper respiratory tract infections, diarrhoea, nausea and hypertension. UC: The most commonly reported adverse reactions in patients receiving tofacitinib 10 mg twice daily were headache, nasopharyngitis, nausea, and arthralgia. Commonly reported adverse reactions (>1/100 to <1/10) across all indications were pneumonia, influenza, herpes zoster, urinary tract infection, sinusitis, bronchitis, nasopharyngitis, pharyngitis, lymphopenia, anaemia, headache, hypertension, cough, abdominal pain, vomiting, diarrhoea, nausea, gastritis, dyspepsia, rash, arthralgia, peripheral oedema, increased creatine phosphokinase. Refer to section 4.8 of the SmPC for further information on side effects, including description of selected adverse reactions. Legal Category: S1A. Marketing Authorisation Number: EU/1/17/1178/003 – 5 mg (56 film-coated tablets); EU/1/17/1178/007 – 10 mg (56 filmcoated tablets); EU/1/17/1178/012 – 11 mg (28 prolonged-release tablets); EU/1/17/1178/015 1mg/mL oral solution. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@ pfizer.com For queries regarding product availability please contact: Pfizer Healthcare Ireland, 9 Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24, + 353 1 467 6500. Last revised: 09/2022. Ref: XJ 18_0.

Professor Alistair Nichol, University College Dublin

UCD Chair of Critical Care Medicine, Professor Alistair Nichol received a special commendation for his ‘exceptional contribution’ in the field of medical research, specifically in critical care clinical trials and especially in the global fight against the COVID-19 pandemic at the Irish Research Council, Research of the Year Awards.

Professor Nichol’s research foci are traumatic brain injury, acute respiratory distress syndrome, and sepsis. He has a particular interest in the ethical barriers to research in the critically ill.

Professor Yvonne Nolan, APC Microbiome Ireland, University College Cork

Professor Nolan was recently awarded ¤1.2 million for an Irish/UK research study to examine middle age health. APC Microbiome Ireland, the SFI Research Centre at University College Cork (UCC) together with King's College London have been awarded research funding to investigate how exercise impacts gut microbiota and brain health in middle age. The Reta Lila Weston Trust as part of their Brain Health and Microbiome programme awarded a ¤1.2 million collaboration project studying the role of gutmicrobiota in exercise-induced changes in cognitive function in middle age to Prof Yvonne Nolan and Prof John Cryan at UCC in collaboration with Prof Sandrine Thuret and Dr Brendon Stubbs at King’s College London.

Dr Lucy Norris, Trinity College Dublin

Dr Norris received Trinity College’s Dean's Research Award in 2022 to develop and validate a risk score for VTE in patients with gynecologic cancer and to test the predictive ability of the score following addition of procoagulant biomarker data. Dr Norris is the Principal Investigator of Coagulation Research group at the Department of obstetrics and Gynaecology and has over 25 years' experience in the area of haemostasis and thrombosis research. Her current research program focuses on the prediction of venous thrombosis in gynaecological cancer and the role of coagulation gene expression in the aetiology of ovarian cancer and has recieved independent funding from the HRB and the pharmaceutical industry.

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

Dr Barry O’Connell, St James’s Hospital, Dublin

Dr O’Connell undertook a collaborative project with Dr Una Kennedy and Medication Safety Facilitator, Eileen Relihan, all of St James’s Hospital, Dublin called the Medication Safety Minute. The project is the only European initiative to be awarded a ‘Cheers Award’ at the 24th annual awards ceremony. The Cheers Awards take place each year and seek to highlight institutions and individuals that ensure that the implementation of medication safety strategies stretch far beyond a few individuals or a single department and are fully integrated into their organisation’s culture and clinical practice.

The project resources are currently used by 24 hospitals in Ireland and by a number of university undergraduate and postgraduate programmes. The material has also been made available as a free online access resource in the form of a digital flipbook as well as being published weekly.

Dr Cathal O’Connor, University

Michael O’Connell, Country Director for Biogen and president of the Irish Pharmaceutical Healthcare Association (IPHA), the representative body for the research-based biopharmaceutical industry. Has worked with a focus on achieving a better environment for access, competitiveness and innovation. Has developed a new Framework Agreement for the Supply and Pricing of Medicines is improving Ireland’s capacity to deliver the latest treatments to patients.

College Cork

Professor Caitriona O’Driscoll, University College Cork

Professor O’Driscoll is the lead and Project Co-ordinator for a research project, led by the School of Pharmacy in partnership with APC Microbiome Ireland SFI Research Centre at University College Cork (UCC), that is seeking to revolutionise how Crohn’s disease is treated. This year she and her team were awarded €5.4 million in funding by the European Union (EU).

Now GENEGUT, a four-year research project funded by Horizon Europe, is to develop the first oral RNAbased therapy for ileal Crohn’s Disease. CD drastically impacts the quality of life of affected patients - and that of their families, friends, and caregivers.

Dr O’Connor is a is a PhD fellow with the prestigious Irish Clinical and Academic Training (ICAT) programme He is a Specialist Registrar in Dermatology with the Royal College of Physicians of Ireland (RCPI), and is dual training in general paediatrics. This year he has been chosen as an inaugural 'Future Leader' by the executive board of the European Society for Paediatric Dermatology for 2021-2024. The ESPD Future Leaders Programme is a highly competitive three-year rolling programme to attract and support the careers of trainee/resident doctors who are interested in Paediatric Dermatology. This year Cathal is also the recipient of the O’Connor scholarship in University College Cork. Cathal’s research on misinformation in dermatology and the burden of treatment in dermatology has recently won several awards, including the Martin Beare award for best paediatric research at the British Association of Dermatology meeting, and the Quality in Care Dermatology award. Legal Category: S1A. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this

Michael O’Connell

Professor Lorraine O’Driscoll, Trinity College Dublin

The International Society of Extracellular Vesicles (ISEV), a leading professional society for researchers and scientists involved in the study of microvesicles and exosomes, recently announced that ISEV Board Member Lorraine O’Driscoll, Professor of Pharmacology and Biomedicine at the School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, was inducted into the Royal Irish Academy on May 21. Professor O’Driscoll was honoured and recognised for her unique contributions to education and scientific research.

Fiona O’Hara, The Pharmaceutical Managers’ Institute

Fiona is the Vice-President of the Pharmaceuttical Managers’ Institute. During 2022 she has undertaken leadership of complex transformational global change programme transactions, divisional COO roles in industry and technology and leadership of inclusion and diversity for the UK and Ireland. During this year the PMI has hosted a number of health information events including the Women in Leadership series, the Pharma Manager series and the Pharma Summit.

Dr Grace O’Malley, Royal College of Surgeons in Ireland

Dr Grace O’Malley, leads the W82GO Child and Adolescent Weight Management Service delivering assessment and treatment for childhood obesity at Children’s Health Ireland at Temple Street and is committed to ensuring children and adolescents with obesity have equal access to evidence-based care.

Dr O’Malley was also the Inaugural Chair of theAssociation for the Study of Obesity on the Island of Ireland and participates in developing national programmes and strategies related to childhood obesity in Ireland. She is a member of the EASO Childhood Obesity Task Force and is committed to the provision of evidence-based high quality education for health professionals.

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

Professor Luke O’Neill, Trinity College Dublin

Professor O’Neill has been listed on the 2022 on the annual Highly Cited Researchers™ 2022 list from Clarivate, which identifies researchers who have demonstrated significant influence in their chosen field or fields through the publication of multiple highly cited papers during the last decade.

Professor O’Neill is Professor of Biochemistry in Trinity’s School of Biochemistry and Immunology, and founder and investigator at the Trinity Biomedical Sciences Institute. He is one of the world’s leading immunologists.

Rhona O’Neill, Health Services Executive

As Chief II Pharmacist, Rhona joined the COVID-19 Therapeutic Advisory Group (TAG) when it was founded by the Chief Clinical Officer in November 2021 as a subject matter expert in medicines and was subsequently invited to join the COVID-19 Therapeutic Guidelines (TGS) and Paediatric Subgroups which reported into the COVID-19 TAG. As well as being a subject matter expert, she acted as co-ordinator and secretariat to the TGS throughout the third wave of the COVID-19 pandemic (22/11/2020 onwards). Over the course of eight months she co-ordinated the group to respond to rapidly emerging and changing evidence to inform these clinical recommendations. The main piece of work was the development of the ‘HSE Interim Guidance for the Pharmacological Management of Patients with COVID-19’. Rhona was responsible for writing and updating this guideline as new recommendations were made by the TGS. This guideline is now in its fifth iteration.

The purpose of the Taskforce is to put in place sustainable workforce planning strategies and policies to improve the NCHD experience and to support present and future retention of NCHDs in Ireland. The Taskforce will seek to improve the NCHD experience/work-life balance through the development and implementation of improved NCHD structures and supports in hospital sites. It will aim to further develop and foster a culture of education and training at clinical site level and plan for future configuration of the medical workforce to support delivery of healthcare in Ireland.

Professor O’Regan is Consultant Respiratory Physician and Director of Postgraduate Clinical Education at the Saolta University Healthcare Group.

Dr Oisin O’Connell, Bon Secours Hospital, Cork

Dr O’Connell in conjunction with Health Innovation Hub Ireland and the MPS cofounded HOSPITALBUDDY an Irish Healthcare app dedicated to the improving the flow of doctors and healthcare professionals working throughout hospitals in Ireland. In the past 18 months over 1600 Hospital Doctors in Ireland are regularly using the HOSPITALBUDDY app and its associated website to track their internal CPD, uploading internal integrated hospital phone directory, uploading on-call clinical rosters and improving communication between medical HR depts and NCHD’s nationally through various dedicated private discussion forums. As a previous Vice-President of the IHCA and previous National Medical Director of he MMUH Heart and Lung Transplant program, Dr O’Connell has seen first hand the potential benefits of IT integration with healthcare in Ireland.

Legal Category: S1A. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com

▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions.

Professor O’Regan, Dean of the Institute of Medicine at the Royal College of Physicians of Ireland (RCPI) will Chair a new National Taskforce on the NCHD Workforce announced by the Minister for Health Stephen Donnelly this year.

Professor Anthony O’Regan, Royal College of Surgeons in Ireland

Dearbhla O’Sullivan, Regional Hospital Mullingar/ St Loman’s Hospital

Dearbhla has led the pharmacy department in the Regional Hospital Mullingar and St Loman’s Hospital since March 2020. Very shortly after taking up position, the Covid-19 pandemic unfolded, followed by the cyber-attack. These challenges were compounded in RHM by unprecedented pharmacist staffing challenges. As the only Chief Pharmacist, Dearbhla’s workload is immense and varied. RHM is a busy model 3 hospital with a 24/7 Emergency Department, Intensive Care Unit, multiple Medical and Surgical specialties, an Obstetric Unit and a Paediatric Unit, while St Loman’s is a psychiatric hospital on a separate site with a satellite pharmacy. Dearbhla’s pharmacy team also provide all pharmaceutical services to three HSE Care of the Elderly residential facilities in the region, as well as the national ambulance service, public health medicine and three out-of-hours GP services in the midlands.

Muriel

Pate, Health Services Executive

Muriel works tirelessly to support the provision of safe, effective and high quality medication services nationally. Over the past year, she has played a crucial role in providing extensive support to safely manage Covid vaccines and minimise multiple potential safety issues, in CVCs and community pharmacies. This includes developing guidance, training and TrackVax software development with NIO/GS1 and supporting shared learning between vaccinating staff, focussing on quality systems and risk reduction. She has supported the roll out of the PCRS to hospitals with the Office of the Chief Information Officer. This facilitates more effective and efficient medicines reconciliation by pharmacists at admission to hospital. Muriel contributed to the development of the ‘Medication without Harm’ elearning programme in collaboration with the Irish Institute of Pharmacy, and making it available on HSELanD. She has supported the Ukrainian Crisis Clinical Workstream 2022 in development of HSE micro-website, including Medicines Information resources to support clinicians. She contributes to eHealth developments including the development of the HSE National Medicinal Product Catalogue and the Hospital Medicines Management System.

Professor Patton commenced employment as Director of Nursing and Midwifery Research in the RCSI in 2014. Since then he has led many key successes for the School. In doing so he has become a role model for others in the school and an ambassador for nursing led research. Notable about Declan’s achievements is his inclusion of others, be that staff, patient groups or students. For example, Declan initiated the inclusion of multiple members of School staff in writing for publication. Even though Declan led many of these publications he involved others ensuring that their number of authorships also increased as well as them learning the skills of writing for publication. Declan also initiated a programme of writing for publication with students. Since 2020, over 50 publications have happened with students/ former students. His leadership has been further recognised by his appointment as Editor in Chief of the Journal of Tissue Viability, a Q1 international scientific wound care journal. Development of Hospital services / Impact as a healthcare professional.

Marie

HSE Antimicrobial Resistance and Infection Control

Marie Philbin is the first Chief Antimicrobial Pharmacist to be appointed to the HSE’s Antimicrobial Resistance and Infection Control (AMRIC) team. Marie has been a member of the AMRIC team since 2018. Her role involves monitoring the consumption of antimicrobials in all setting in Ireland and she is also involved in coordinating the National Annual Acute Hospital Point Prevalence Survey. Marie, together with her colleagues, has been involved in the delivery of a number of ‘IIOP In Conversation with…’ webinars and training programmes on HSE Land and the Irish Institute of Pharmacy. She has also been a driving force behind the creation of Pharmacist Antimicrobial Stewardship Network (PAMS-Net), a collaboration between the HSE Antimicrobial Resistance and Infection Control (AMRIC) team and IIOP. Marie chaired the inaugural PAMS-Net AMRIC educational event in September 2022, bringing together pharmacists, pharmacy students and other healthcare professionals to showcase all the good work that pharmacists are doing to support antimicrobial stewardship across a variety of settings.

Philbin,

Professor Declan Patton, Royal College of Surgeons in Ireland

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

Grainne Power, Healthcare Products Regulatory Authority

Grainne is Director of Compliance with the HPRA, which she joined in 2018 to lead the Human Products Authorisation and Registration Department where her responsibilities included the authorisation or registration of human medicines, together with clinical trials authorisation for the Irish market. In January 2022, Ms Power was appointed Director of the Compliance Department. Ms Power studied Biotechnology at Dublin City University and has worked in a number of Quality leadership roles within the Irish Pharma/ Biopharma manufacturing sectors over a period of 25 years before joining the HPRA.

Dr Rebecca Power, Nutrition Research Centre Ireland

Dr Power’s current project, the Cognitive impAiRmEnt Study (CARES), is investigating the role of nutrition supplementation on cognitive function among individuals with mild cognitive impairment in comparison to age-matched controls. This research is being performed under the supervision of Professor John Nolan, Professor Stephen Beatty and Professor Riona Mulcahy, and support from Dr Robert Coen.

Her research interests at the NRCI include the management and co-ordination of the re-MIND trial, as well as the design and implementation of the FortiXan trial. Dr Power has recently been awarded a Marie Sklodowska Curie Action Individual Fellowship to work with Professor Aron Barbey and his team and the University of Illinois at Urbana Champaign.

Purcell, St John of God Hospital

In September of this year, Audrey helped publish a new patient information booklet on lithium therapy, which is also aimed at healthcare professionals. The aim of the booklet is to promote safer lithium therapy and empower patients to engage more with healthcare professionals on all aspects of their treatment, including potential side-effects.

It contains important safety and clinical information, as well as a means of recording essential information on lithium levels and blood test results. Additional information is also provided on different lithium products on the market, as well how to recognise signs of lithium toxicity.

Assistant Professor Arman Rahman, University College Dublin

Dr Rahman was appointed as the Translational Researcher and Engagement manager (TREM) of POI. Since early 2022, he has also taken up a temporary role of a lecturer at the UCD School of Medicine. He has been pivotal to developing and leading the Tissue Imaging Platform and in recognition of his efforts in developing and establishing the Tissue Imaging Platform, he was named Senior Researcher of the Year 2020 by the Irish Cancer Society. Legal Category: S1A. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium.

Audrey

Dr Eileen Relihan, St James’s Hospital Dublin

Dr Relihan is the co-creator of the Medication Safety Minute - The Medication Safety Minute is an innovative education tool that has been developed to promote the safe prescription of medication to patients.

The project emerged from the review of real-world medication errors and discussions about how to optimally communicate the learning points to prescribers in the age of information overload.

She is currently the Medication Safety Facilitator in St James’s Hospital and a teaching fellow at Trinity College Dublin.

Aoife Sartini Bhreathnach, Mater Misericordiae University Hospital

Aoife Sartini Bhreathnach is part of the second cohort of the RCSI Physician Associates (PA) Studies Programme and graduated in 2019 with ten of her classmates. Aoife has been a member of the Irish Society of Physician Associate(ISPA) since it was established in 2019. She became a member of the ISPA Advocacy committee (sub-committee of ISPA) in 2021 and was elected then the President Elect (Vice President) of ISPA this year in June 2022. She plays a huge part in being an advocate for the PA profession and her involvement on the ISPA advocacy committee will help push the PA profession for regulation. Aoife was the second PA to be employed in the Mater Hospital in Dublin.

Dr Ingmar Schoen, Royal College of Surgeons in Ireland

Dr Schoen was, earlier this year, lead author of new blood clotting research, which indicates enhanced understanding of wound repair. The research, published in Science Advances, examines the behaviour of platelets at a wound site, specifically their ability to sense where within a blood clot they are and remodel their surroundings accordinglyThis new study indicates that platelets can also form a provisional fibron matrix in their surroundings, similar to what fibroblasts do in the later stages of wound healing. This has potential implications for how the integrity of blood clots might be maintained during vascular repair.

Professor Faisal Sharif, Galway University Hospital

Professor Sharif has introduced a new minimally invasive day case procedure to reduce blood pressure in patients. Galway University Hospitals (GUH) is the first hospital in the country to introduce a new minimally invasive day case procedure to reduce blood pressure in patients. This means that patients arrive in the hospital in the morning, have the procedure, and are able to return home the same day.

Professor Sharif is the Professor of Translational Cardiovascular Medicine and Innovation at National University of Ireland Galway and an Interventional Cardiologist at the Saolta Group, Galway University Hospital. He is also an Executive Director of BioInnovate Ireland, a multi disciplinary programme for novel medical device innovation. His research predominantly focuses on medical device innovation and clinical translation of novel medical devices and concepts for cardiovascular diseases.

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

Rose Shivmangal, St Columcille’s Hospital

During her time in Connolly Hospital as Head of Unscheduled Care, Rose was responsible for leading a team of 12 people before leaving to assume the role of General Manager of St. Columcille’s Hospital, Loughlinstown, Co. Dublin in February 2022. Rose was instrumental in establishing an innovative quality project in conjunction with the Dublin North City Centre (DNCC) General Manager for Older Persons Services in January 2020. Rose further established additional step-down facility beds for the hospital which has further enhanced the capacity and flow. Rose has also been the Operational Project Manager responsible for the building of a new Emergency Department Covid Resus from February 2021. In Loughlinstown, Rose is currently leading on a refurbishment of the Obesity Management Service inpatient beds, ensuring an accessible and appropriate environment is being created for future patients. Rose was influential in developing discharge pathways to ensure that the patient had the right care, at the right time and in the right place. This led to 4 patients on the delayed transfer of care database (DTOC) in January 2022 versus 36 patients in December 2019 in Connolly Hospital.

Kashif Siddiqui, Hermitage Clinic

Consultant Urologist Mr Siddiqui was this year recognised as an Expert User of GreenLight XPS Laser Therapy System – demonstrating his expert knowledge in delivering effective, long lasting therapy to men suffering from benign prostatic enlargement. Mr Siddiqui graduated in 1993 and subsequently completed his basic surgical and urological training in Ireland before obtaining FRCS (Urol). He was conferred with Masters Med Sc in Urology from NUI Galway and Fellowship from European Board of Urology.

He completed his research fellowship from Sunnybrook Hospital Toronto in MRgUS treatment of localized prostate cancer. He worked as a consultant urologist in Oxford UK for a short time before returning to Ireland

Dubhfeasa Slattery, Children’s Health Ireland

Professor Slattery is a Consultant Respiratory and General Paediatrician in CHI at Temple St. Her work involves multiple pillars: clinical work, professionalism, education, training, research, quality, patient safety, risk, fundraising and leadership. In these areas she has demonstrated unique skills as a role model, ambassador, inspirational leader; has developed hospital services and impacted healthcare nationally and internationally. She enjoys research and how it improves clinical standards and care for children and young adults. Her research in Boston culminated in a PhD in Molecular Medicine. She has received significant independent grant funding and published multiple peer-reviewed publications across the areas of basic science, clinical, translational and educational research. Her research has won multiple prizes at national and international level.

Professor

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

Dr Stephen Tuoy, Galway Clinic

Dr Tuoy performed the first ventricular tachycardia ablation procedure in Ireland earlier in 2022. Dr Tuohy is Consultant Cardiologist & Electrophysiologist established a life-saving procedure against Ventricular tachycardia (VT), a life-threatening heart rhythm problem caused by irregular electrical signals in the lower chambers of the heart, which results in patients experiencing much faster heartbeats. This procedure marked an innovative first in the West of Ireland. Dr Tuohy is a graduate from the School of Medicine at National University of Ireland, Galway in 2009 and was the recipient of the gold medal in paediatrics. Dr Tuohy also holds Bachelor of Science from NUI Galway and a Master of Science in Clinical Research from NUI Galway.

Dr Damir Versilija, Royal College of Surgeons in Ireland

Led by Dr Versilijam researchers at RCSI and the Beaumont Hospital revealed a potential new way to treat secondary breast cancer that has spread to the brain, using existing drugs.

The RCSI study focused on genetically tracking the tumour evolution from diagnosis of primary breast to the metastatic spread in the brain in cancer patients. The researchers found that almost half of the tumours had changes in the way they repair their DNA, making these tumours vulnerable to an existing type of drug known as a PARP inhibitor. PARP inhibitor drugs work by preventing cancer cells to repair their DNA, which results in the cancer cells dying.

In September of this year Dr Vaughan published on the Role of Symbolic and Structural Violence in Ireland’s HIV Epidemic. She also spearheaded a survey earlier in the summer –Measuring HIV-related Stigma in Healthcare Settings: preliminary Results and Future Plans.

Dr Vaughan is a post-doctoral researcher in the Health Promotion Research Centre in NUI Galway. Her PhD research investigated HIV-related stigma in the Irish context. Specifically her work explored the relationship between media driven discourses of HIV and the embodied and enacted stigma experiences of people living with HIV in Ireland. Her research interests include HIV and sexual health, women and HIV, LGBT health, health related stigmas, and social and structural determinants of health.

Dr Elena Vaughan, NUI Galway

Professor Laura Viani, Royal College of Surgeons in Ireland

Professor Viani is the newly elected president of RCSI and Ireland’s first female otolaryngologist. As the first female Irish ENT surgeon, she founded the National Hearing Implant and Hearing Research centre in Ireland and established a National Cochlear Implant (CI) programme in 1995.

Professor Laura Viani is a consultant otolaryngologist and neurotologist at Beaumont Hospital and the Children’s University Hospital Temple Street. She is Director and Professor of the National Cochlear Implant Programme and Hearing Research Centre and is founder of this national specialty. She replaces outgoing President, Professor P. Ronan O’Connell.

Professor Leonie Young, Royal College of Surgeons in Ireland

Professor Young led a study which has revealed a potential new way to treat secondary breast cancer that has spread to the brain, using existing drugs.

The study was funded by Breast Cancer Ireland with support from Breast Cancer Now and Science Foundation Ireland.

The RCSI study focused on genetically tracking the tumour evolution from diagnosis of primary breast to the metastatic spread in the brain in cancer patients. The researchers found that almost half of the tumours had changes in the way they repair their DNA, making these tumours vulnerable to an existing type of drug known as a PARP inhibitor. PARP inhibitor drugs work by preventing cancer cells to repair their DNA, which results in the cancer cells dying.

Dominic Zerulla, University College Dublin

Professor Zerulla work has the potential to transform the understanding of processes such as cell signalling and cell proliferation in cancer has won this year’s NovaUCD Innovation Awards.

Professor Dominic Zerulla received the 2022 award in recognition for the development of a novel photonic chip which enables ultra-high spatial resolution at video rates in optical microscopy, far beyond the diffraction limit of visible light. This patented technology could aid early diagnostics and precision medicine, and help deliver improved drug treatments for patients facing a range of life-threatening diseases. His company PEARlabs, a spin-out from the UCD School of Physics, has been awarded over ¤700k in funding through the SFI Future Innovator Prize programme to further develop this technology.

Professor

CIBINQO is indicated for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy.

Kidney Disease

Management and Treatment of Chronic Kidney Disease

can drop so low that dialysis treatment or a kidney transplant will be required. This is known as End Stage Kidney Disease (ESKD).”

Cardiovascular disease is a leading cause of death in patients with chronic kidney disease, and is a major focus of preservative care in this population.

Theresa adds, “Diabetes, which affects more than 250, 000 people in Ireland, is one of the leading causes of CKD. Diabetes Ireland highlights the importance of screening for chronic kidney disease. Diabetes check-ups include the routine monitoring of kidney function so that changes can be detected early.

renal perfusion pressure; intrinsic renal - pathology of the vessels, glomeruli, or tubules-interstitium; or postrenal -obstructive.

Theresa continues, “Chronic prerenal disease occurs in patients with chronic heart failure or cirrhosis with persistently decreased renal perfusion, which increases the tendency for multiple episodes of an intrinsic kidney injury, such as acute tubular necrosis (ATN). This leads to progressive loss of renal function over time.

Chronic kidney disease (CKD) is a progressive renal disorder that commonly occurs in the adult population, especially in those with hypertension and diabetes. There is no cure, and the condition is associated with high morbidity and mortality rates.

Approximately 10% of adults globally are affected by some form of chronic kidney disease, which results in 1·2 million deaths and 28 million years of life lost annually.

We spoke with Theresa Lowry Lehnen, RGN, RNP, BSc, MSc, PG. Dip. Ed, M. Ed, PhD Clinical Nurse Practitioner and Associate Lecturer South East Technological University to find out more about the current management and treatment options available.

CKD affects 1:10 people in the whole population, and over 500 people in Ireland develop kidney failure every year. By 2040, it is estimated that chronic kidney disease will become the fifth leading cause of death globally.

Theresa begins by explaining, “CKD is defined as a reduction in kidney function, with estimated glomerular filtration rate (eGFR) of < 60 mL/min per 1·73 m2, or markers of kidney damage, such as albuminuria, haematuria, or abnormalities detected through laboratory testing or imaging, and that are present for at least 3 months.

“Chronic kidney disease is usually insidious, develops slowly over time and most people affected are asymptomatic until the disease becomes advanced (eGFR < 30

mL/min per 1·73 m2). The rate of kidney function loss varies by aetiology, exposures, and interventions but, in most cases, progression to kidney failure takes between months and decades to develop.”

Signs and symptoms of kidney failure result from progressive uraemia, anaemia, volume overload, electrolyte abnormalities, mineral and bone disorders, and acidaemia, and lead to death if left untreated.

Theresa adds, “Kidney function can decline gradually over several years, or rapidly over several months. In some people, function

“Diabetes Ireland urges all people with diabetes to attend for their routine diabetes checkups, have their kidney function monitored regularly and ensure that discussions on kidney health becomes an integral part of their review Risk factors for chronic kidney disease include older age (>50 years), low birth weight, obesity, smoking, high blood pressure, diabetes, a family history of kidney disease, being of African-American decent, and long-term use of over-thecounter medications.

“Both genomic and environmental factors contribute to this complex heterogeneous disease, and CKD heritability is estimated to be high at 30–75%. There is a higher incidence and prevalence in women than men, however, women have a lower risk of CKD progression, and men are more likely to develop end stage renal failure (ESRD).”

In addition to known causes, CKD can also be idiopathic, she adds. The most common causes of CKD are diabetes (type 1 and type 2) and hypertension. Other causes include primary glomerulonephritis, chronic tubulointerstitial nephritis; hereditary or cystic diseases, secondary glomerulonephritis or vasculitis and plasma cell dyscrasias or neoplasm.

“Autoimmune diseases such as lupus can damage blood vessels and can make antibodies against kidney tissue.”

CKD may result from disease processes in any of the three categories: prerenal - decreased

“Intrinsic occurs when direct damage to the kidneys causes a sudden loss in kidney function. The most common chronic renal vascular disease is nephrosclerosis, which causes chronic damage to blood vessels, glomeruli, and tubulointerstitium.

“The other renal vascular diseases are renal artery stenosis from atherosclerosis or fibro-muscular dysplasia which over months or years, cause ischemic nephropathy, characterised by glomerulosclerosis and tubulointerstitial fibrosis.

Chronic obstruction may be due to prostatic disease, nephrolithiasis or abdominal/pelvic tumour with mass effect on ureter(s). Retroperitoneal fibrosis is a rare cause of chronic ureteral obstruction.”

Signs and Symptoms

Kidney disease tends not to cause symptoms at the early stage, therefore routine screening using urine and blood tests is important. “Symptoms develop over time and can include weight loss, anorexia, oedema of the ankles, feet and hands, dyspnoea, fatigue, nocturia, haematuria, nausea, headaches, muscle cramps, headaches, and erectile dysfunction in men,” she says.

Diagnosis

A thorough medical history, physical examination and investigative tests are required to form a diagnosis for CKD. Early CKD stages are usually asymptomatic, and symptoms manifest in stages 4 or 5.

“Chronic kidney disease is typically identified through routine screening with blood serum chemistry profile (Serum creatinine concentration should be measured, allowing calculation of

An interview with Theresa Lowry Lehnen (PhD), Clinical Nurse Practitioner and Associate Lecturer South East Technological University

“The main goals of management of CKD are to reduce overall cardiovascular risk, delay progression to renal failure and avoid complications”

BRING PROTECTION TO LIFE

BY REDUCING THE RISK OF THE COMPOSITE OF DECLINING KIDNEY FUNCTION (BY ≥ 50%), ESKD, AND RENAL OR CV DEATH IN CONJUNCTION WITH OTHER CKD THERAPIES WHEN COMPARED TO PLACEBO*1

FORXIGA IS INDICATED IN ADULT PATIENTS FOR THE TREATMENT OF CKD.2

treatment

GFR mL/min/1.73m2

FORXIGA 10 mg Once daily

No titration required except in patients with severe hepatic impairment

Applicable for CKD, HFrEF, or T2D.2

*The DAPA-CKD study was an international, multicentre, randomised, double-blind, placebo-controlled study. In DAPA-CKD, the primary endpoint showed that FORXIGA in conjunction with other CKD therapies reduced the relative risk of the composite endpoint of ≥50% sustained decline in eGFR, reaching ESKD, and renal or CV death by 39% (5.3% ARR) vs placebo with other CKD therapies in 4304 adult patients with CKD with an eGFR of 75 to 25 mL/ min/1.73m2 and albuminuria (UACR ≥ 200 and ≤ 5000 mg/g) (median follow-up of 2.4 years; 9.2% vs 14.5%; HR 0.61; 95% CI (0.51 - 0.72; p<0.001).1 ESKD defined as sustained eGFR < 15 mL/min/1.73m2, chronic dialysis treatment or receiving a renal transplant. DAPA-CKD was stopped early due to efficacy benefit, because of the unplanned early stop, the secondary endpoints are considered nominally significant; Secondary endpoints showed that FORXIGA in conjunction with other CKD therapies reduced the relative risk of the composite of CV death or hHF by 29% (1.8% ARR: HR 0.71; 95% CI, 0.55 to 0.92; nominal p=0.009) and also reduced the relative risk of all-cause mortality by 31% (2.1% ARR; HR 0.69; 95% CI, 0.53 to 0.88; nominal p=0.004) vs placebo with other CKD therapies. There were comparable rates of the individual component of CV death, FORXIGA vs placebo (3.0% vs 3.7%; HR 0.81; 95% CI, 0.58, 1.12)1

The overall safety profile of dapagliflozin in patients with chronic kidney disease was consistent with the known safety profile of dapagliflozin.2 ©AstraZeneca 2022. All Rights Reserved.

ABRIDGED PRESCRIBING INFORMATION

FORXIGA® (dapagliflozin) 5MG & 10MG FILMCOATED TABLETS.

Consult Summary of Product Characteristics (SmPC) before prescribing.

Indications: Adults and children aged 10 years and above: Type 2 diabetes mellitus: For the treatment of insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise, as monotherapy when metformin is considered inappropriate due to intolerance, or in addition to other medicinal products for the treatment of type 2 diabetes. Adults: Heart Failure: Indicated in adults for the treatment of symptomatic chronic heart failure with reduced ejection fraction. Chronic kidney disease: Indicated in adults for the treatment of chronic kidney disease.

Presentation: Film-coated tablets. 5mg or 10mg of dapagliflozin (as propanediol monohydrate). Each 5mg tablet contains 25mg of lactose. Each 10mg tablet contains 50mg of lactose.

Dosage and Administration: Adults: Type 2 diabetes mellitus: The recommended dose is 10mg once daily. Consider a lower dose of insulin or insulin secretagogue such as a sulphonylurea when used in combination with dapagliflozin to reduce the risk of hypoglycaemia.

Children and adolescents: No dose adjustment in children aged 10 years and above. No safety and efficacy data available for children below 10 years of age. Heart Failure: The recommended dose is 10mg once daily. Chronic kidney disease: The recommended dose is 10 mg once daily. Children and adolescents: <18 years: Safety and efficacy not yet established. Elderly: ≥65 years: No dose adjustment is recommended based on age. Renal impairment: No dose adjustment is required based on renal function. Due to limited experience, it is not recommended to initiate treatment with dapagliflozin in patients with GFR < 25 mL/min. If GFR falls below 45 mL/min, additional glucose lowering treatment should be considered in patients with diabetes mellitus if further glycaemic control is needed. Mild or moderate hepatic impairment: No dose adjustment. Severe hepatic impairment: Starting dose of 5mg is recommended, if well tolerated, dose may be increased to 10mg. Method of administration: Forxiga can be taken orally at any time of day with or without food. Tablets should be swallowed whole.

Contraindications: Hypersensitivity to dapagliflozin, or excipients.

Warnings and Precautions: Renal impairment: Due to limited experience, it is not recommended to initiate treatment with dapagliflozin in patients with GFR < 25 mL/min. The glucose lowering efficacy of dapagliflozin is dependent on renal function, and is reduced in patients with GFR < 45 mL/min and is likely absent in patients with severe renal impairment. Hepatic impairment: Exposure is increased in patients with severe hepatic impairment. Use in patients at risk of volume depletion and/or hypotension: Dapagliflozin increases diuresis which may lead to a modest decrease in blood pressure, it may be more pronounced in patients with very high blood glucose concentrations. Exercise caution in patients for whom a dapagliflozin induced drop in blood pressure could pose a risk, such as patients on anti hypertensive therapy with a history of hypotension or elderly patients. Careful monitoring of volume status and electrolytes is recommended in conditions leading to volume depletion, such as acute gastrointestinal illness. In volume depleted patients temporary interruption of dapagliflozin is recommended until volume depletion is corrected. Diabetic ketoacidosis (DKA): Rare cases of DKA, including life-threatening and fatal cases, have been reported in patients treated with SGLT2 inhibitors, including dapagliflozin. In a

number of cases, the presentation of the condition was atypical with only moderately increased blood glucose values, below 14mmol/L (250mg/dL). The risk of DKA must be considered in the event of nonspecific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness. Patients should be assessed for ketoacidosis immediately if these symptoms occur, regardless of blood glucose level. In patients where DKA is suspected or diagnosed, dapagliflozin treatment should be stopped immediately. Treatment should be interrupted in patients who are hospitalised for major surgical procedures or acute serious medical illnesses. Monitoring of ketones is recommended in these patients. Measurement of blood ketone levels is preferred to urine. Treatment with dapagliflozin may be restarted when the ketone values are normal and the patient’s condition has stabilised. Before initiating dapagliflozin, factors in patient history that may predispose to ketoacidosis should be considered. Patients who may be at higher risk of DKA include patients with a low beta cell function reserve (e.g. patients with low C peptide or latent autoimmune diabetes in adults (LADA) or patients with a history of pancreatitis), patients with conditions that lead to restricted food intake or severe dehydration, patients for whom insulin doses are reduced and patients with increased insulin requirements due to acute medical illness, surgery or alcohol abuse. SGLT2 inhibitors should be used with caution in these patients. Restarting SGLT2 inhibitor treatment in patients experiencing a DKA while on SGLT2 inhibitor treatment is not recommended, unless another clear precipitating factor is identified and resolved. Dapagliflozin should not be used for treatment of patients with type 1 diabetes. Necrotising fasciitis of the perineum (Fournier’s gangrene): Postmarketing cases have been reported in female and male patients taking SGLT2 inhibitors. Urgent surgical intervention and antibiotic treatment is required. Advise patients to seek medical attention if they experience a combination of pain, tenderness, erythema, or swelling in the genital or perineal area, with fever or malaise. Either uro-genital infection or perineal abscess may precede necrotising fasciitis. If suspected, discontinue Forxiga and institute prompt treatment (including antibiotics and surgical debridement). Urinary tract infections: Temporary interruption of dapagliflozin should be considered when treating pyelonephritis or urosepsis. Elderly (≥65 years): Elderly patients are more likely to have impaired renal function, be treated with medicines such as anti-hypertensives or diuretics, and be at a greater risk of volume depletion. Cardiac failure: Experience with dapagliflozin in NYHA class IV is limited. Chronic kidney disease: There is no experience with dapagliflozin for the treatment of chronic kidney disease in patients without diabetes who do not have albuminuria. Patients with albuminuria may benefit more from treatment with dapagliflozin. Lower limb amputations: Counsel patients with diabetes on routine preventative foot care as an increase in cases of lower limb amputation (primarily of the toe) has been observed in long term, clinical studies in type 2 diabetes mellitus with SGLT2 inhibitors. Urine laboratory assessments: Patients will test positive for glucose in the urine due to mechanism of action. Lactose: Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take Forxiga.

Drug Interactions: Diuretics: Dapagliflozin may add to the diuretic effect of thiazide and loop diuretics and may increase the risk of dehydration and hypotension. Insulin and insulin secretagogues: Consider a lower dose of insulin or insulin secretagogue when used in combination with dapagliflozin to reduce the risk of hypoglycaemia. Interference with 1,5 AG assay: Monitoring glycaemic control with 1,5-AG assay is not recommended as measurements of 1,5 AG are

unreliable in assessing glycaemic control in patients taking SGLT2 inhibitors. Alternative methods should be used. Interference with lithium: Dapagliflozin may increase renal lithium excretion and the blood lithium levels may be decreased. Serum concentration of lithium should be monitored more frequently after dapagliflozin initiation and dose changes. Please refer the patient to the lithium prescribing doctor in order to monitor serum concentration of lithium. Pregnancy and Lactation: Not recommended during the second and third trimesters of pregnancy. Treatment should be discontinued when pregnancy is detected. Do not use whilst breast-feeding. Ability to Drive and Use Machines: Alert patients on the risk of hypoglycaemia when dapagliflozin is used in combination with a sulphonylurea or insulin.

Undesirable Events: Consult SmPC for full list of side effects. Very common (≥1/10): Hypoglycaemia (when used with SU or insulin). Common (≥1/100 to <1/10): Vulvovaginitis, balanitis and related genital infections, urinary tract infection, dizziness, rash, back pain, dysuria, polyuria, haematocrit increased, creatinine renal clearance decreased during initial treatment, dyslipidaemia. Uncommon (≥1/1,000 to < 1/100): Fungal infection, volume depletion, thirst, constipation, dry mouth, nocturia, vulvovaginal pruritus, pruritus genital, blood creatinine increased during initial treatment, blood urea increased, weight decreased. Rare (≥ 1/10,000 to < 1/1,000): Diabetic ketoacidosis (when used in type 2 diabetes mellitus). Very Rare (< 1/10,000): Angioedema, necrotising fasciitis of the perineum (Fournier’s gangrene), Tubulointerstitial nephritis.

Legal Category: Product subject to prescription which may be renewed (B).

Marketing Authorisation Number: EU/1/12/795/002; EU/1/12/795/007.

Marketing Authorisation Holder: AstraZeneca AB, SE-151 85 Södertälje, Sweden.

Further product information available on request from: AstraZeneca Pharmaceuticals (Ireland) DAC, College Business and Technology Park, Blanchardstown Road North, Dublin 15. Tel: +353 1 609 71 00.

FORXIGA is a trademark of the AstraZeneca group of companies.

Date of API preparation: 07/2022 Veeva ID: IE-4049

Adverse events should be reported directly to: HPRA Pharmacovigilance, Website: www.hpra.ie

Adverse events should also be reported to AstraZeneca Patient Safety on Freephone 1800 800 899

References:

1. Heerspink HJL et al. N Engl J Med. 2020;383(15):1436–1446.

2. FORXIGA 10 mg film-coated tablets. Summary of product characteristics.

ARR = absolute risk reduction; CKD = chronic kidney disease; CV = cardiovascular; DAPA-CKD = Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease; eGFR = estimated glomerular filtration rate; ESKD = end-stage kidney disease; hHF = hospitalisation for heart failure; HR = hazard ratio. HFrEF = heart failure with reduced ejection fraction; T2D = type 2 diabetes

Kidney Disease

eGFR) and urine studies (ACRalbumin: creatinine ratio) or as an incidental finding. Urine dipstick is first performed, and is a useful screening tool although it only provides a semi quantitative assessment of level of proteinuria, as the reported value can vary according to the hydration status of the patient.

“Spot urine sample is sent to the laboratory to measure Protein/ Albumin to Creatinine Ratio. This will detect even small levels of proteinuria and is essential for diagnosis, but is not useful for routine follow up of patients who already have established macroalbuminuria. At the same time, a midstream urine specimen (MSU) should be sent for culture to exclude urinary tract infection. The eGFR is a useful and accurate measure of renal function, and is calculated using serum creatinine as well as the variables of age, gender and race. In the following circumstances however, eGFR may not be accurate: acute renal failure; patients less than 18 years of age; patients with advanced muscle wasting and amputations; and pregnancy.”

Theresa goes to note that less commonly, patients may present with symptoms such as gross haematuria, foamy urine, nocturia, flank pain, or decreased urine output.

“If CKD is advanced, patients may report fatigue, poor appetite, nausea, vomiting, metallic taste, unintentional weight loss, pruritus, changes in mental status, dyspnoea, or peripheral oedema. In assessing a patient, additional symptoms that might suggest a systemic cause such as haemoptysis, rash, lymphadenopathy, hearing loss, neuropathy; or urinary obstruction such as hesitancy, urgency, frequency or incomplete bladder emptying should be enquired about.

“Patients should be assessed for risk factors of kidney disease including; prior exposure to potential nephrotoxins such as nonsteroidal anti-inflammatory drugs (NSAIDs); antibiotic therapies such as gentamicin and chemotherapies; history of nephrolithiasis or recurrent urinary tract infections; the presence of comorbidities; family history of kidney disease; and other known genetic risk factors.

“A detailed physical examination may provide additional information regarding the underlying cause of CKD. Signs of volume depletion may reflect poor oral intake, vomiting, diarrhoea, or over diuresis, whereas signs of volume overload may be due to decompensated heart failure, liver failure, or nephrotic syndrome. The presence of arterial-venous nicking or retinopathy on retinal examination suggests long-standing hypertension or diabetes. Patients with carotid or abdominal bruits may have renovascular disease. Flank pain or enlarged kidneys should prompt consideration of obstructive uropathy, nephrolithiasis, pyelonephritis, or polycystic kidney disease.

“Neuropathy may be due to diabetes or less commonly vasculitis, or amyloidosis. Skin findings may include rash, palpable purpura, telangiectasias, or extensive sclerosis. Patients with advanced CKD may exhibit pallor, skin excoriations, muscle wasting, asterixis, myoclonic jerks, altered mental status, and pericardial rub.

“Other diagnostic investigations carried out may include an ultrasound, MRI or CT scan and a biopsy. Once a diagnosis of CKD has been established, the next step is to determine staging.”

Stages and classification of CKD

The stages of CKD range from 1-5. Most patients who are diagnosed as having stage 1, 2 or 3, have mild to moderate kidney disease and usually do not progress to end stage kidney failure (ESKF). Once stage 4 is reached, damage is more severe and is usually not reversible. Dialysis or a kidney transplant may be required.

Theresa adds, “A patient is considered to have chronic kidney disease if they have abnormalities of kidney function or structure present for more than 3 months. The definition of CKD includes all individuals with markers of kidney damage or those with an eGFR of less than 60 ml/min/1.73m2 on at least two occasions, 90 days apart with or without markers of kidney damage. Markers of kidney disease may include: albuminuria (ACR > 3 mg/mmol), haematuria (presumed or confirmed renal origin), electrolyte abnormalities due to tubular disorders, renal histological abnormalities, structural abnormalities detected by imaging (e.g. polycystic kidneys, reflux nephropathy) or a history of kidney transplantation. CKD is classified based on the eGFR and the level of proteinuria and helps to risk stratify patients. Patients are classified as G1-G5, based on the eGFR, and A1A3 based on the ACR albumin: creatinine ratio.”

The stages include:

• G1: GFR 90 ml/min per 1.73 m2 and above

• G2: GFR 60 to 89 ml/min per 1.73 m2

• G3a: GFR 45 to 59 ml/min per 1.73 m2

• G3b: GFR 30 to 44 ml/min per 1.73 m2

• G4: GFR 15 to 29 ml/min per 1.73 m2

• G5: GFR < 15 ml/min per 1.73 m2 or treatment by dialysis

The 3 levels of albuminuria include albumin-creatinine ratio (ACR):

• A1: ACR less than 3 mg/mmol (normal to mild)

• A2: ACR 3 to 30 mg/mmol (moderately increased)

• A3: ACR greater than 30 mg/ mmol (severely increased)

Treatment and Management

Theresa concludes, “There is no cure for chronic kidney disease, but treatment and management can help relieve the symptoms and improve the patient’s quality of life. Treatment options and prognosis will depend on the stage of CKD. Lifestyle measures include, stopping smoking, a healthy diet, restricted salt intake of less than 6g.

“The main goals of management of CKD are to reduce overall cardiovascular risk, delay progression to renal failure and avoid complications. Regular reviews are recommended and should include blood pressure measurement, assessment of kidney function, review of all medications, and immunisation with Influenza vaccine and Pneumococcal vaccine, in addition to lifestyle advice regarding smoking, reduced salt intake and weight loss. Anaemia is common in more advanced disease and a target of 10–11.5gm/dL should be sought. If the Haemoglobin is low, nonrenal causes should be excluded. Management of “renal” anaemia can include the provision of iron and the use of erythropoiesis stimulating agents. Regular review of medication is important to minimise nephrotoxic drugs particularly NSAIDs, and ensure doses of others are appropriate to renal function. Metformin should be avoided in patients with CKD stage G4 and G5.”

Urinary Tract Infection

Urinary Tract Infection in Overactive Bladder: An Update on Pathophysiological Mechanisms

Kylie J Mansfield1, Zhuoran Chen2, Kate H Moore2 and Luke Grundy3,4

1 Illawarra Health and Medical Research Institute and School of Medicine, University of Wollongong, Wollongong, NSW, Australia

2 Department of Urogynaecology, St George Hospital, University of New South Wales, Kogarah, NSW, Australia

3 Visceral Pain Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI), Flinders University, Bedford Park, SA, Australia

4 Hopwood Centre for Neurobiology, Lifelong Health Theme, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia

This review summarises the key findings of recent laboratory and clinical studies which provide further insight into the relationship between chronic bacteriuria and associated inflammatory mediators in OAB patients.

Diagnosis, Treatment, and Pathophysiology of Overactive Bladder

In the typical clinical care pathway, patients presenting with symptoms of urinary urgency, urinary frequency and nocturia often undergo a diagnostic test involving filling the bladder with saline and observing the presence of spasms of the detrusor muscle (via intravesical manometry line), which is termed Detrusor

Overactivity. In the absence of organic disease, the condition is termed “Idiopathic,” which is predominant in women but quite uncommon in men. Therefore, while the pathophysiological consequence of the disease is defined by the cystometry testing (i.e. detrusor overactivity), the aetiology underlying this condition remains unknown.

As the chief symptoms of OAB are related to sensory dysfunction,

it is logical that the mechanisms underlying OAB are likely related to changes in neuronal excitability and/or exaggerated neuronal firing during bladder filling. This hypothesis is well supported by investigations conducted using animal models of bladder dysfunction (Yoshimura et al., 2014; Grundy et al., 2019). Despite this, OAB patients are initially treated with anticholinergic medications which reduce detrusor

muscle contractions and improve bladder capacity, thus lessening their incontinence/frequency/ urgency of micturition (Moore and Malykhina, 2014). Unsurprisingly, with little fundamental basis in pathophysiology, these treatments have only limited benefits over placebo and poor continuation rates (Wagg et al., 2012; Kim and Lee, 2016; Yeowell et al., 2018). Our longitudinal study revealed that after 8 years, only

20% of patients treated with antimuscarinic agents have longlasting improvement (Morris et al., 2008). Unfortunately, about 30%–40% of patients do not respond to these medicines at all. Such non-responsive patients are then denoted as having “Refractory OAB” (Moore and Malykhina, 2014). For these refractory patients, the absence of a defined pathology guarantees patients undergo a diagnostic odyssey, incorporating multiple invasive and non-invasive tests, and numerous prescriptions in an effort to exclude various pathophysiology (Gormley et al., 2015). Such “Refractory” patients may suffer lifelong debilitating symptoms, placing a significant burden on both the patient and the health system.

The large proportion of patients refractory to pharmacotherapy also supports an alternative pathophysiology to detrusor overactivity seen in OAB. Indeed, the relative success of neurotoxins that inhibit sensory nerve activity, such as resiniferatoxin and BOTOX (Guo et al., 2013; Hsieh et al., 2016; Cui et al., 2021), in relieving OAB symptoms refractory to pharmacotherapy suggests increased sensory outflow is responsible for the symptoms of urgency and urinary frequency. However, BOTOX treatment is invasive, has been associated with frequent side effects, and requires repeated doses at approximately 6 months intervals (Schurch et al., 2005; Apostolidis et al., 2009; Chen and Kuo, 2020) indicating the treatment is masking, rather than treating the underlying cause of bladder sensory neuron hypersensitivity. The initiating or contributing factors in the development of neuronal hypersensitivity in OAB remain to be determined. Numerous aetiologies have been proposed, including altered bladder permeability, inflammation, cross-organ sensitisation, and dysregulation of spinal and/ or cortical networks (de Groat et al., 2015; Grundy et al., 2018a). Amongst these potential mechanisms, there is mounting evidence that chronic bacterial infection of the bladder may contribute to the exacerbation of OAB symptoms in susceptible populations via direct or indirect sensitisation of sensory neurons (Moore et al., 2000; Walsh C et al., 2011; Brierley et al., 2020).

The Emerging Role of Urinary Tract Infection in Overactive Bladder

Bacteriuria in Overactive Bladder Even when using a conventional 105 CFU/ml MSU culture, 6%–17%

of women diagnosed with OAB have been found to have a UTI, compared to just 0.5%–2% of women from control groups (Moore et al., 2000; Khasriya et al., 2013; Gill et al., 2021). Similar results have been obtained from MSU samples taken specifically during symptom flares of refractory OAB patients, with 17% of patients versus 2% of the control group showing positive cultures at 105 CFU/ml (Walsh et al., 2011). Interestingly, when both standard (105 CFU/ml) and low-count criteria (102-3 CFU/ml) are used in samples from the same patient cohort, the proportion of those positive for bacteriuria increases (from 17% to 39%), compared to those of a control group (from 2% to 6%) (Walsh et al., 2011) showing that low-count MSU culture may reveal genuine infections in OAB patients that would otherwise be overlooked. Enhanced culture techniques have also revealed higher rates of infection that were previously missed by routine culture, identifying 23% of patients with OAB as positive for UTI, vs. 10% of controls, in a prospective blinded case control study (Khan et al., 2021).

Analysis of catheter (CSU), rather than mid-stream specimens of urine revealed similar results, with the proportion of OAB patients with positive cultures rising from 15% at 105 CFU/ml to 21% at 102 CFU/ml (Khasriya et al., 2010). Two additional studies support the concept that OAB patients have low-count bacteriuria but did not compare directly to an appropriate control group, including a follow up study that investigated catheter rather than MSU specimens from patients with refractory OAB (Walsh et al., 2013). Despite the lack of controls, these studies report similar proportions (27%–29%) of OAB patients with bacteriuria when using the lowcount threshold (Hessdoerfer et al., 2011; Walsh et al., 2013).

Intracellular Bacterial Colonies in Overactive Bladder

Whilst low-count bacteriuria can be quite easily identified by reducing the CFU threshold upon culture, a growing number of studies have shown that uropathogenic E. coli invade urothelial cells and form intracellular bacterial communities (IBC’s). A variety of studies have since identified large numbers of bacteria undetected in routine MSU or CSU specimens within cultures from bladder biopsies or shed urothelial cells from OAB patients examined by immunohistochemistry or confocal microscopy of centrifuged/ cytospin specimens (Rosen et al., 2007; Vijaya et al., 2013a;

Khasriya et al., 2013; Cheng et al., 2016; Gill et al., 2018). However, intracellular bacteria have also routinely been found in large numbers of asymptomatic, or control patients (Khasriya et al., 2013; Cheng et al., 2016), suggesting that the presence of IBC’s alone is not enough to accurately differentiate OAB and control patients. As such, it may not be the simple identification of IBC’s in urine, but a more nuanced diagnostic marker that reveals an accurate distinction between genuine and asymptomatic infection. Our own detailed analysis of exfoliated urothelial cell samples obtained from the urine of patients with OAB or controls revealed filamentous bacteria were significantly more common in patients with OAB (Cheng et al., 2016). Filamentous bacteria are associated with intracellular bacterial growth and bacteria fluxing out of the urothelial cells to recolonise the bladder (Justice et al., 2006). In this context, E. coli, the species of bacteria most commonly implicated in UTIs, was found more closely associated with urothelial cells from sediment cultures (via confocal microscopy) only in OAB patient samples (Khasriya et al., 2013). Similarly, our further study of urothelial cells obtained from OAB patients demonstrated that high- but not low-density intracellular bacteria correlate with OAB symptom severity, measured by leakage on pad test, leaks per day, and voids per day (Ognenovska et al., 2021).

The contribution of IBC’s to UTI pathophysiology is an emerging field of research. These initial reports suggest that IBC’s within the urothelium may also be an underappreciated component in the symptomology of OAB. Importantly, these bacteria are unlikely to be picked up by increasing the sensitivity of MSU or CSU culture, raising further questions as to the interpretation of urine culture as the gold standard for ruling out genuine UTI’s. The identification and classification of IBC’s is currently impractical for routine clinical practice. However, if the relevance of IBC’s in OAB is confirmed by additional high-quality studies, further urine analysis may be a useful tool in elucidating the pathophysiology underlying the symptoms for OAB patients refractory to traditional treatments.

Evidence and Implications for Clinical Practice

The information presented in this review poses a number of questions relating to the treatment and diagnosis of OAB. Chief amongst these include the potential use of antibiotics

and anti-inflammatory drugs in the treatment of subsets of OAB patients. And could the presence of specific inflammatory mediators or intracellular bacterial colonies in the urine be exploited as a novel diagnostic biomarker for identifying these otherwise overlooked patients?

Does Antibiotic Treatment of Urinary Tract Infections Relieve Overactive Bladder Symptoms?

There have been two prospective trials of rotating antibiotics for patients with OAB (Khasriya et al., 2011; Vijaya et al., 2013b). The first study demonstrated improvements in urinary leakage and urgency in women treated with prolonged courses of antibiotics in addition to standard anticholinergic therapy (Khasriya et al., 2011). This was followed by a second study confirming similar results in a more refractory OAB group (Vijaya et al., 2013b).

As a result of the promising outcome from the two prospective studies we conducted a placebo controlled randomised trial involving 6 weeks of antibiotics in addition to standard anticholinergic therapy in patients with refractory detrusor overactivity (Chen et al., 2021a). Microbiological data was collected throughout the trial with 10 samples per patient collected over 6 months. This phase IIb trial revealed that antibiotic therapy reduced UTI rates, and corresponded with a clinically significant reduction in urinary incontinence on 24 h pad test (pad weight reduced by 75 g, p < 0.008) at 6 months.

Improvements were also seen in measures of OAB symptoms such as leaks per day (1 less leak by 6 weeks and 2 less leaks per day by 6 months). In addition, patients who received antibiotics reported improvements on quality of life measures such as ICIQ, and OAB-q. Importantly, this improvement was sustained throughout the next 6 months [significant lower ICIQ score (Mean –5.57)], despite only 6 weeks of antibiotic therapy. Because of the robust collection and analysis of the relevant outcome measures, this study was able to provide objective evidence (i.e., reduced amount of leakage experienced in 24 h) of the biological effect of antibiotics in patients with OAB who were refractory to standard treatments. Based on these findings we concluded that lower rates of UTI experienced by OAB patients treated with antibiotics, and thus lower inflammation, may account for the increased response to anticholinergics in the subsequent months.

In addition to the findings described above, the longitudinal

Urinary Tract Infection

with symptom severity. For example, Pillalamarri et al. (2018) reported that the pro-inflammatory cytokine IL-1β expression was significantly associated with worsening OAB symptoms (Pillalamarri et al., 2018). A recent longitudinal study showed the anti-inflammatory cytokine IL-6 was found to be significantly higher in OAB patients when compared with controls, which also correlated with both bacterial growth and pyuria count over a 12 month period (Smelov et al., 2016). Another longitudinal study (conducted over 12–14 weeks) reported that at the initial visit MCP-1 levels correlated with symptom severity and that MCP-1 levels decreased in women who responded to treatment (Ghoniem et al., 2020).

nature of the trial also revealed UTI requiring antibiotic treatment in over 40% of the OAB women who were in the placebo arm. In addition, post antibiotic therapy, breakthrough infections were identified in almost 20% of the women in the antibiotic group. The high rates of symptomatic UTI in the refractory OAB cohort emphasises the importance of UTI to the aetiology of this condition, and supports the proposed paradigm of an infectious subgroup of OAB patients. The trial was halted after interim analysis, due to recruitment issues and ethical concerns raised by the high rates of UTI in these patients.

Does Antibiotic Treatment of Urinary Tract Infections Reduce Inflammation and Intracellular Bacterial Colonies?

Using samples collected as part of the phase IIb trial described above, we were able to investigate the mechanisms behind the improvement in outcomes in the OAB patients. Our followup analysis of the trial cohort revealed that cytokines associated with activation of the innate immune system are reduced by antibiotic therapy in women with OAB (Chen et al., 2021b). In particular, antibiotic treatment was associated with significant reductions of pro-inflammatory cytokines IL-1α, IL-1Ra, IL-6, IL-8, and CXCL-10 and the antiinflammatory cytokine IL-10, which are all cytokines typically present in UTIs (Sundac et al., 2016). The lower concentrations of the proinflammatory cytokines, especially CXCL-10, were associated with lower OAB symptom score, suggesting decreasing the inflammatory response leads to less urgency experienced by OAB patients treated with antibiotics. Other studies also support the hypothesis that changes in cytokine concentrations correlates

As well as affecting release of proinflammatory cytokines, antibiotic treatment was also found to significantly reduced high-density IBC’s in exfoliated urothelial cells from OAB patients (Ognenovska et al., 2021).

The decrease in high-density IBC’s significantly correlated with improved symptom scores (reduction in urinary incontinence, decreased leaks per day and decreased voids per day) (Ognenovska et al., 2021). Antibiotic therapy also significantly reduced the likelihood of identifying bacterial filaments in samples from women with OAB (Ognenovska et al., 2021). As mentioned previously, bacterial filaments are associated with intracellular growth of UPEC (Justice et al., 2006). In addition, antibiotic therapy increased the proportion of urothelial cells that were free of bacteria.

Thus, while antibiotic therapy appears to be effective in

relieving OAB symptoms, issues surrounding microbial resistance and breakthrough infection suggest that alternative treatments for UTI are warranted. Recently, anti-inflammatory agents such as ibuprofen and indomethacin have been shown to improve symptoms of acute UTI in patients without OAB (Gágyor et al., 2015; Kronenberg et al., 2017). Randomised trials have also shown that ibuprofen given to woman with suspected UTI can reduce dysuria and need for subsequent antibiotics (Moore et al., 2019). Interestingly, two small studies in the 1980s demonstrated that indomethacin significantly improved urge incontinence symptoms in women with OAB (Cardozo and Stanton, 1980; Delaere et al., 1981). However, due to limited understanding of the role of urinary tract infections in OAB at the time, no further studies using these therapies were undertaken.

The studies outlined above have determined that antibiotic therapy leads to improvement in OAB symptoms in women who are refractory to other standard treatments. This improvement in symptoms is associated with a decrease in the urine concentration of pro-inflammatory cytokines and a decrease in the presence of bacteria associated with the urothelium. Combined these studies provide evidence for an inflammatory/infectious aetiology of OAB in women who are refractory to standard therapy. We therefore hypothesise that in women who are refractory to standard therapy, UTI leads to intracellular colonisation of urothelial cells, triggering an inflammatory response (with release of cytokines) and an increase in urothelial permeability. This then sensitises

bladder sensory nerves so that they respond more easily to mechanical stretch of the bladder wall. This sensitisation then triggers the symptoms associated with OAB including urgency, frequency and nocturia.

Conclusion

There is accumulating evidence that we need to revisit the OAB phenotype given the association of the condition with bacterial colonisation of the urothelium. Multiple studies now implicate genuine UTI in the pathogenesis of OAB for a sub-group of patients who are refractory to standard therapy. The detection of bacterial invasion of urothelial cells, and subsequent inflammation, are shown to be key elements in prompting sensitisation of bladder-innervating sensory nerves to bladder distension, which would then evoke the symptoms of urgency, frequency, and nocturia. Small scale trials have shown antibiotics may be a useful tool to treat these patients, however, due to the growing risk of antibiotic resistance, prescription of antibiotics to large cohorts of patients is not desirable. As such, there is a need for alternative therapies to treat the infection and pro-inflammatory state that may include anti-inflammatory agents, or other treatments targeting the microbiome and urothelial environment. In addition, the methods used to diagnose UTI need to be improved. The current threshold values used to diagnose UTI are misleading and the culture techniques used often fail to detect the presence of bacteria. Improvements in our approaches for identifying the presence of bacteria in urine would greatly enhance our capacity to accurately diagnose UTI.

“Thus, while antibiotic therapy appears to be effective in relieving OAB symptoms, issues surrounding microbial resistance and breakthrough infection suggest that alternative treatments for UTI are warranted”

His 14th walk in

park

Prescribing Information: Please read the Summary of Product Characteristics (SPC) before prescribing. Presentation: Prolonged-release tablet, containing mirabegron 25mg/50mg. Indication: Symptomatic treatment of urgency, increased micturition frequency and/or urgency incontinence as may occur in adult patients with overactive bladder (OAB) syndrome. Posology and method of administration: The recommended dose is 50 mg once daily. A lower dose of 25mg is recommended for specific patient populations (renal and hepatic impairment) as well as in specific patient populations in combination with strong CYP3A inhibitors such as itraconazole, ketoconazole, ritonavir and clarithromycin. Renal impairment: End stage renal disease (GFR < 15 mL/min/1.73 m2 or patients requiring haemodialysis): Not recommended. Severe renal impairment (GFR 15 to 29 mL/min/1.73 m2): Reduce dose to 25 mg. Severe renal impairment and concomitant strong CYP3A inhibitors: Not recommended. Moderate renal impairment (GFR 30 to 59 mL/min/1.73 m2): 50 mg. Moderate renal impairment and concomitant strong CYP3A inhibitors: Reduce dose to 25 mg. Mild renal impairment (GFR 60 to 89 mL/min/1.73 m2): 50 mg. Mild renal impairment and concomitant strong CYP3A inhibitors: Reduce dose to 25 mg. Hepatic impairment: Severe hepatic impairment (Child-Pugh Class C): Not recommended. Moderate hepatic impairment (Child-Pugh B): Reduce dose to 25 mg. Moderate hepatic impairment and concomitant strong CYP3A inhibitors: Not recommended. Mild hepatic impairment (Child-Pugh A): 50 mg. Mild hepatic impairment and concomitant strong CYP3A inhibitors: Reduce dose to 25 mg. The tablet is to be taken once daily, with liquids, swallowed whole and is not to be chewed, divided, or crushed. It may be taken with or without food Contraindications: Hypersensitivity to the active substance or to any of the excipients (see the SPC for a list of excipients). Severe uncontrolled hypertension defined as systolic blood pressure ≥180 mm Hg and/or diastolic blood pressure ≥110 mm Hg. Special warnings and precautions for use: Renal impairment: Betmiga has not been studied in patients with end stage renal disease (GFR < 15 mL/min/1.73 m2 or patients requiring haemodialysis) and, therefore, it is not recommended for use in this patient population. Data are limited in patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2); based on a pharmacokinetic study a dose reduction to 25 mg is recommended in this population. This medicinal product is not recommended for use in patients with severe renal impairment (GFR 15 to 29 mL/min/1.73 m2) concomitantly receiving strong CYP3A inhibitors. Hepatic impairment: Betmiga has not been studied in patients with severe hepatic impairment (Child-Pugh Class C) and, therefore, it is not recommended for use in this patient population. This medicinal product is not recommended for use in patients with moderate hepatic impairment (Child-Pugh B) concomitantly receiving

Date of preparation:

strong CYP3A inhibitors. Hypertension: Mirabegron can increase blood pressure. Blood pressure should be measured at baseline and periodically during treatment with mirabegron, especially in hypertensive patients. Data are limited in patients with stage 2 hypertension (systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 100 mm Hg). Patients with congenital or acquired QT prolongation: Betmiga, at therapeutic doses, has not demonstrated clinically relevant QT prolongation in clinical studies. However, since patients with a known history of QT prolongation or patients who are taking medicinal products known to prolong the QT interval were not included in these studies, the effects of mirabegron in these patients is unknown. Caution should be exercised when administering mirabegron in these patients. Patients with bladder outlet obstruction and patients taking antimuscarinic medicinal products for OAB: Urinary retention in patients with bladder outlet obstruction (BOO) and in patients taking antimuscarinic medicinal products for the treatment of OAB has been reported in postmarketing experience in patients taking mirabegron. A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in patients treated with Betmiga; however, Betmiga should be administered with caution to patients with clinically significant BOO. Betmiga should also be administered with caution to patients taking antimuscarinic medicinal products for the treatment of OAB. Interactions: Pharmacokinetic interactions: Mirabegron is a substrate for CYP3A4, CYP2D6, butyrylcholinesterase, uridine diphosphoglucuronosyltransferases (UGT), the efflux transporter P-glycoprotein (P-gp) and the influx organic cation transporters (OCT) OCT1, OCT2, and OCT3. Pharmacokinetic interactions involving the potential for other medicinal products to affect mirabegron exposures: Increases in mirabegron exposure due to drug-drug interactions may be associated with increases in pulse rate. Strong CYP3A inhibitors See Posology and administration above for dose adjustments recommended during concomitant use of strong CYP3A inhibitors in patients with renal or hepatic impairment. Mirabegron exposure (AUC) was increased 1.8-fold in the presence of the strong inhibitor of CYP3A/P-gp ketoconazole. CYP2D6 inhibitors: No dose adjustment is needed for mirabegron when administered with CYP2D6 inhibitors (or in patients who are CYP2D6 poor metabolisers). Inducers: Inducers of CYP3A (such as rifampicin) or P-gp may decrease the plasma concentrations of mirabegron. No dose adjustment of mirabegron is required as this effect is not expected to be clinically relevant. Pharmacokinetic interactions involving the potential for mirabegron to affect exposures to other medicinal products: Inhibition of CYP2D6: Moderate and time dependent inhibition of CYP2D6 by mirabegron may result in clinically relevant drug interactions. CYP2D6 activity recovers within 15 days after discontinuation of mirabegron. Caution is advised if mirabegron is co-administered with medicinal

products metabolized by CYP2D6 with a narrow therapeutic index such as thioridazine, Type 1C antiarrhythmics (e.g.flecainide, propafenone) and tricyclic antidepressants (e.g., imipramine, desipramine). Caution is also advised if mirabegron is co-administered with CYP2D6 substrates that are individually dose titrated. Inhibition of P-gp: Mirabegron is a weak inhibitor of P-gp. For patients who are initiating a combination of Betmiga and digoxin, the lowest dose for digoxin should be prescribed initially. Serum digoxin concentrations should be monitored and used for titration of the digoxin dose to obtain the desired clinical effect. The potential for inhibition of P-gp by mirabegron should be considered when Betmiga is combined with sensitive P-gp substrates e.g. dabigatran. Fertility, pregnancy and lactation: The effect of mirabegron on human fertility has not been established. Betmiga is not recommended during pregnancy and in women of child-bearing potential not using contraception. Mirabegron should not be administered during breast feeding. Refer to SPC for full guidance. Driving and use of machines: Betmiga has no or negligible influence on the ability to drive and use machines.

Undesirable effects: Summary of the Safety Profile: the safety of Betmiga was evaluated in 8433 patients with OAB, of which 5648 received at least one dose of mirabegron in the phase 2/3 clinical program, and 622 patients received Betmiga for at least 1 year (365 days). In the three 12-week phase 3 double blind, placebo controlled studies, 88% of the patients completed treatment with this medicinal product, and 4% of the patients discontinued due to adverse events. Most adverse reactions were mild to moderate in severity. The most common adverse reactions reported for patients treated with Betmiga 50 mg during the three 12-week phase 3 double blind, placebo controlled studies are tachycardia and urinary tract infections. The frequency of tachycardia was 1.2% in patients receiving Betmiga 50 mg. Tachycardia led to discontinuation in 0.1% patients receiving Betmiga 50 mg. The frequency of urinary tract infections was 2.9% in patients receiving Betmiga 50 mg. Urinary tract infections led to discontinuation in none of the patients receiving Betmiga 50 mg. Serious adverse reactions included atrial fibrillation (0.2%). Adverse reactions observed during the 1-year (long term) active controlled (muscarinic antagonist) study were similar in type and severity to those observed in the three 12-week phase 3 double blind, placebo controlled studies. The following adverse reactions were observed with mirabegron in the three 12-week phase 3 double blind, placebo controlled studies. The frequency of adverse reactions is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be established from the available data) Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The adverse events

2019 References: 1. Freeman R, et al. Current Medical Research and Opinion 2017. https://doi.org/10.1080/03007995.2017.1419170.

are grouped by MedDRA system organ class. Infections and infestations: Common: urinary tract infection Uncommon: vaginal infection, cystitis Psychiatric disorders: Not known: Insomnia*, confusional state* Nervous system disorders: Common: headache* dizziness* Eye disorders: Rare: eyelid oedema Cardiac disorders: Common: tachycardia Uncommon: palpitation, atrial fibrillation Vascular disorders: Very rare: Hypertensive crisis* Gastrointestinal disorders: Common: nausea*, constipation*, diarrhoea* Uncommon: dyspepsia, gastritis Rare: lip oedema Skin and subcutaneous tissue disorders: Uncommon: urticaria, rash, rash macular, rash papular, pruritus Rare: leukocytoclastic vasculitis, purpura, angioedema* Musculoskeletal and connective tissue disorders: Uncommon: joint swelling Renal and urinary disorders: Rare: urinary retention* Reproductive system and breast disorders: Uncommon: vulvovaginal pruritus Investigations Uncommon: blood pressure increased, GGT increased, AST increased, ALT increased (*observed during post-marketing experience) Reporting of suspected adverse reactions: see below. Legal category: POM (S1B) Marketing Authorisation number: EU/1/12/809/003 - 25mg EU/1/12/809/010 - 50mg. Marketing

the

since the day he started BETMIGA1

RCSI COLLABORATES WITH 3M TO ADVANCE INITIATIVES IN GLOBAL SURGERY

RCSI University of Medicine and Health Sciences has partnered with science-based technology company 3M to provide support for two projects run by the RCSI Institute of Global Surgery.

3M Impact is an international programme that gives employees from the science-based technology company the opportunity to work overseas on a two-week volunteering project.

As part of the 3M Impact programme, six 3M employees from the US, Costa Rica, Mexico, Malaysia and the United Arab Emirates supported the development of an e-learning strategy to improve and expand training programmes for young healthcare professionals in subSaharan Africa.

Lack of access to safe surgical care is a silent killer in this area, and many minor injuries and conditions, which are dealt with through routine treatment in high income countries, often end in severe and sometimes catastrophic outcomes. To address this, RCSI supports a network of postgraduate training Colleges in the East, Central and Southern Africa region to train surgeons, anaesthesiologists, obstetrician/gynaecologists and peri-operative nurses. The College of Anaesthesiologists of Ireland and the Institute of Obstetricians and Gynaecologists in the Royal College of Physicians of Ireland also contribute to this work, which is funded by Irish Aid.

Delivering a standardised training experience across such a vast and varied region is challenging, so e-learning has played a vital role, particularly during the Covid-19 pandemic. The 3M consultants developed a strategy and roadmap which will help RCSI and partners deliver a coordinated e-learning training programme for the 1,500 doctors and nurses currently enrolled in training programmes.

A second project was to develop a student engagement plan for the RCSI Institute of Global Surgery (IGS). The Institute works primarily with partners in sub-Saharan Africa to improve surgical services for many communities lacking access to essential surgical care.

Every year, RCSI students with a passion for global health and surgery volunteer to support its work through a range of short- or medium-term research assignments. Until now, IGS lacked a formal programme of student engagement, with no standardised approach to

supporting and training the volunteers, or for communicating about their valuable work internally and externally.

The brief set for the project was to develop a plan for community engagement. communication and organisational strategies to benefit both the academic community at RCSI as well as current and future students. The work will also contribute to the university’s wider efforts to increase engagement with students, improve their learning experience and help to secure internal funding.

June Ryan, Country Leader for 3M, which has its Ireland operations in Dublin and Athlone, Co. Westmeath, said: “3M Impact has been running since 2017 and we are delighted that the programme has come to Ireland this year to support organisations working on the ground to help disadvantaged communities and advance equality.

“RCSI was chosen as a recipient of the programme for the valuable role it plays supporting healthcare professionals around the globe and its pioneering research in the health sciences. In 2020, the 3M Foundation awarded RCSI a philanthropic grant of $480,000 to support Covid-19 research, so the 3M Impact project has strengthened our relationship and ongoing collaboration.

“As well as providing a tangible benefit for RCSI, the pro bono support provided by the 3M consultants has advanced their knowledge and expertise and helped meet their personal development goals.”

Haematology Ruth Clifford, Nurse Practitioner Fidelma Hackett, and Senior Medical Scientist Ailín McMahon.

The video explains how the development of new treatments helped Geoffrey resume his active lifestyle. For the Limerick-based sailing enthusiast, the availability of innovative medicines meant he achieved remission and a break from the disease.

The video, which has been supported by the biopharmaceutical company AbbVie, is one of a series created by the Irish Pharmaceutical Healthcare Association (IPHA). The film also features two AbbVie employees from the company’s plants in Sligo and Cork who support the creation and availability of medicines used to treat blood cancer around the world.

the diseases we all know about. Medicines innovation is a lot closer to Irish public than many people may suspect.”

“In that context, it is important that we continue to protect intellectual property as the formula for the invention of new medicines. Innovate For Life, in capturing so cinematically the impact of innovation, is a way for us of us to engage with science for the public good.”

[i] Irish exports surge to ¤306bn as pandemic spurs trade in IT and pharma: https://www.irishtimes.com/business/ economy/irish-exports-surge-to306bn-as-pandemic-spurs-trade-in-itand-pharma-1.4754080 last accessed 12.9.2022

IRISH ONCOLOGY CARE PLATFORM ANNOUNCES COLLABORATION

AbbVie has participated in a new national campaign highlighting how scientific innovation is improving standards of care and offering Irish haematology patients increased treatment opportunities.

Retired engineer Geoffrey McDonald (81) outlines his fourteen-year journey with leukaemia in the ‘Six Degrees of Innovation’ video initiative.

The short film explains the purpose of new medicines creation. It also highlights the close connections that exist between a wide variety of workers in Ireland who are creating new treatments and helping bring them to those in medical need.

Geoffrey has successfully battled illness with the help of his medical team, who also appear in the video. They include Professor of

The video was distributed on social media channels to mark September’s Blood Cancer Awareness month. Across the overall campaign, a total cast of 26 participate including doctors, patients, scientists, and ordinary people whose lives have been touched by innovation.

With record exports, jobs and tax revenues, the biopharmaceutical industry is a major engine of Irish economic growth. The industry has shown leadership during Covid-19, with vaccines and treatments helping to turn the tide on the disease.[i]

IPHA’s Director of Communications and Advocacy, Bernard Mallee, said: “In human health, the industry continues to innovate for solutions for unmet medical needs and for

The Irish-founded oncology software company, ONCOassist, has announced a new agreement with The National Comprehensive Cancer Network® (NCCN®). The collaboration will focus on integrating NCCN Content to create a digital tool that will help oncology professionals around the world stay up to date with relevant clinical content about cancer care.

ONCOassist is a CE-approved decision support app for oncology professionals around the world. It is currently the only oncology app on the market with regulatory approval for use in a hospital setting.

ONCOassist hosts tools and content specific to oncology and is used by more than 73,000 professionals across 150+ countries. It is estimated that 40

LIMERICK-BASED HAEMATOLOGY TEAM PARTICIPATE IN NEW CAMPAIGN HIGHLIGHTING THE PATIENT BENEFITS OF MEDICAL INNOVATION

percent of oncology healthcare professionals (HCPs) globally use ONCOassist. ONCOassist is revolutionizing the delivery of global cancer care and aiding in reaching the goal of improving the quality of patient care globally.

NCCN is a not-for-profit alliance of 32 leading cancer centres devoted to patient care, research, and education. NCCN is dedicated to improving and facilitating quality, effective, equitable, and accessible cancer care so all patients can live better lives.

By joining forces, NCCN enables ONCOassist to make key decision support information available to their users around the world, advancing their mission of helping HCPs make more-informed oncology decisions. The new agreement will allow oncology clinicians to access relevant, up-to-date tools and content at their fingertips on the ONCOassist smartphone app. ONCOassist and NCCN are working together to bring their content to oncology clinicians around the world, irrespective of their resources. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the healthcare delivery system.

According to the Irish Cancer Society, there are around 45,000 new cancer cases in Ireland every year. Globally, 18,094,716 million cases of cancer were diagnosed in 2020 alone according to the World Cancer Research International Fund. With that in mind, figures from the HSE showed that the number of suspected cancer cases in Ireland referred by them through the Healthlink e-referral system has dropped by over 50 percent in 2020. This indicates that COVID-19 may have impacted and prevented patients from being diagnosed early on. ONCOassist aims to make life easier for both oncology professionals as well as patients themselves.

When speaking about the agreement, Co-founder and CEO of ONCOassist, Eoin O’Carroll said, “We are thrilled to announce this opportunity to collaborate with the NCCN. This project has been in the pipeline for some time and we are very much looking forward to working together. This is an exciting step forward for ONCOassist for our work in cancer care and goal to facilitate healthcare professionals by gaining access to the right information and delivering better care to patients.”

UPS HEALTHCARE ANNOUNCES EXPANSION IN IRISH MARKET

UPS has announced the launch of a first-of-its-kind healthcare facility in Dublin. Opening in late 2023, the new facility will boast nearly 6,000 m2 of healthcare-dedicated space to connect Ireland’s growing pharmaceutical and medical technology industries to UPS’s smart global logistics network that serves customers in over 220 countries and territories.

UPS Healthcare’s Dublin facility will support Ireland’s pharmaceutical and medical device industries in delivering next generation biologics, critical vaccines and vital healthcare equipment to patients around the world. The facility will create 30 jobs initially, and the investment demonstrates UPS commitment to the Irish market and support for its long-term export growth.

The announcement comes at a time when 80% of pharmaceutical drugs in the European Union require cold-chain logistical support and temperaturecontrolled transportation. More than 50% of all new drugs in the global pharmaceutical pipeline are cutting edge biomedical drugssuch as vaccines - that tend to be temperature-sensitive.

Speaking ahead of the announcement, Cathy O’Brien, UPS Healthcare’s Vice President for International Sales, said: “This is a significant investment by UPS in Ireland and a demonstration of our commitment to enabling truly global healthcare supply chains. Our new facility supports the quality and regulatory needs of manufacturers, many of whom are providing critical upstream activity, and we provide them with resiliency and scale. UPS Healthcare is now offering the first truly dedicated freight, small parcel and logistics offering in Ireland, including cold chain management services. Ireland is a world leader in research, biologics and healthcare innovation, and we are confident that our clinical to commercial service offering will drive value for the Irish healthcare and economic ecosystem in the years to come.”

Commenting on the announcement Martin Shanahan, CEO, IDA Ireland said “This is a welcome development from UPS which will support the thriving, export led life science sector here which supplies lifesaving medicines to patients all over the world. I wish the company well with this new initiative.”

UPS recently announced its planned acquisition of the Bomi Group, which has temperaturecontrolled facilities in 14 countries

in Europe and Latin America and will add nearly 3,000 highly skilled Bomi team members. With the approved completion of this acquisition by 2023, UPS Healthcare will have more than doubled the footprint of its facilities since 2020.

UPS is also investing in the next generation of products, including the launch and expansion of UPS Premier, a technology-enabled express delivery service, that upgrades small packages with advanced sensor technology as well as ensuring a priority lane in UPS’s global network. Earlier this year, UPS Healthcare expanded its specialized temperature-controlled fleet across Benelux and Italy. This expansion adds to existing cold chain transport services in Italy, Hungary, the UK, and Poland.

TAKEDA CELEBRATES 25 YEARS OF BUSINESS IN IRELAND

Takeda in Ireland, a subsidiary of Takeda headquartered in Tokyo, Japan, celebrated 25 years of business in Ireland with an anniversary event at their Bray site recently. Since first establishing this manufacturing facility in 1997, the company has developed three other locations in Ireland – Baggot Street, Citywest and Grange Castle – which collectively employ over 900 people and have been certified as a global and Irish Top Employer for the last five years. The sites provide innovative medicines to patients in more than 60 international markets. This milestone event was attended by more than 1,000 people, with the Bray facility proudly opening its doors to its employees and their families, guests including Japanese Ambassador to Ireland Mitsuru Kitano, public representatives, local schools and Takeda partners such as IDA Ireland and the International Society for Pharmaceutical Engineering (ISPE). This is a significant milestone for

Takeda in Ireland, and particularly for its Bray facility. In the last 25 years, the company has gone from strength to strength, and, notably, the Takeda facility in Bray has seen significant growth in its production portfolio, with the addition of a new oncology production suite inaugurated in 2020.

The site plans on continuing this growth while meeting ambitious environmental goals that build on the site's existing use of 100% renewable electricity. Being carbon neutral today, we set ourselves a more aspiring goal. We aim to become carbon net-zero across our value chain by 2040 and lead the way in our industry. Our holistic environmental program includes natural resource conservation initiatives and sustainable waste management. Since 2019, Bray has diverted 100 percent of our waste-to-landfill.

Commenting on the milestone, Minister for Health, Stephen Donnelly TD, said: “Congratulations to Takeda Ireland on 25 years of success in Ireland. The company has been a much-valued presence within the Irish health and pharmaceutical landscape. Since then, Takeda Ireland has gone from strength to strength, creating a valued bond with the local community here in Bray, Co. Wicklow and right across the east of the country through their Dublin facilities. I wish them continued success in the future.”

In celebration of the 25thanniversary milestone, Takeda’s Bray facility is launching a partnership with local schools, where primary and secondary school students will be offered the opportunity to visit the site and learn about the innovative work the company carries out.

Japanese Ambassador to Ireland Mitsuru Kitano and James Dinniss, Site Head at Takeda Bray. (Photo: Maxwell Photography)

James Dinniss, Bray Site Head, said: “As an active participant in our local communities, we are keen to open our doors – figuratively and literally – to the next generation of engineers, scientists, lab technicians and others, to demystify the work we do. It is hoped that this initiative will help to inspire the young people who will pave the way forward for the business in Ireland over the next 25 years and beyond.”

Mitsuru Kitano, Japanese Ambassador to Ireland, stated: “Takeda Ireland is one of Japan’s largest and longest-running investments in Ireland with its twenty-five-year history. Its achievement is substantial, to maintain and expand the foreign direct investments over such a long time. It is attributed to Takeda's ability to adapt to the changing internal and external environment, to capitalise on the sustained strength of Japan and Ireland in the pharmaceutical sector, and, most importantly, to the strong commitment of all those involved.”

Martin Shanahan, CEO IDA Ireland, stated: “I want to congratulate Takeda on this really important milestone of 25 years in Ireland. Takeda has played an important role in the development of Ireland’s life science ecosystem by employing over 900 people across 4 sites in the provision of innovative medicines for the treatment of disease. I wish the entire team continued success”

PRESTIGIOUS AWARD FOR UCD TEAM

A baby is stillborn every 16 seconds, leading to heartbreak for more than two million families worldwide per year. Despite advances in care for babies after birth, progress towards reducing the number of stillbirths is lagging behind. Over 50 per cent of stillbirths are associated with a reduction in the baby’s movements in the womb but there is currently no way to track a baby’s movements at home.

A team of biomedical engineers and clinicians in University College Dublin (UCD) and Imperial College London has developed a unique, wearable baby movement monitoring system, which they hope will address the urgent need to enable monitoring of babies’ movements in the womb at home, and dramatically reduce stillbirths globally.

The expert team has been awarded a contract as part of Wellcome Leap’s In Utero programme, which aims to create the scalable capacity to measure, model and predict gestational development with a primary goal to reduce

stillbirth rates by half. Wellcome Leap is a non-profit organisation founded by the Wellcome Trust to accelerate and increase the number of breakthroughs in human health globally. The team aims to determine how their monitor (called the FM monitor) can be used to measure a baby’s health in the womb. The FM monitor could potentially identify babies who are at risk of stillbirth and will also offer reassurance when the baby is healthy, thereby decreasing the rates of unnecessary induction of labour and early delivery.

Principal Investigator (PI) for the team, from UCD School of Mechanical and Materials Engineering and the UCD Conway Institute, Prof Niamh Nowlan said: “We are thrilled to have been selected for funding by the Wellcome Leap ‘In Utero’ programme. The funding will enable us to further develop our device by engaging with pregnant people and their midwives and doctors, by testing the monitor at home and in hospital, and - we believe- will lead to our device being adopted globally to reduce stillbirth rates worldwide. The unique aspect of the Wellcome Leap ‘In Utero’ programme is that it funds international multidisciplinary teams of experts. Our team is made up of biomedical engineers and clinicians from Ireland, the UK and Bangladesh, and together we can work to make ground-breaking advances towards cutting stillbirth rates by half.”

Co-PI from UCD School of Medicine and the National Maternity Hospital, Dublin, Prof Fionnuala McAuliffe said: “Every stillbirth is a tragedy for the parents and family but the majority of stillbirths occur when there are no obvious risk factors. New technologies such as baby movement monitoring will offer a crucial advance towards preventing stillbirth.”

ACCORD SUPPORT CHRISTMAS SHOEBOX APPEAL

Pictured above are members of the Accord Healthcare Ireland Team who have filled shoe boxes for the Team Hope Christmas shoebox appeal.

Team Hope’s Christmas Shoebox Appeal is an annual campaign that delivers gifts straight into the hands of children affected by poverty. Often these shoebox gifts are the only gift that a child will receive at Christmas and the joy that they bring is incredible. Since 2010, they have delivered over 2.1 million Shoebox gifts to Vulnerable Children across the world.

EXPERTS HIGHLIGHT IMPORTANCE OF VACCINATION IN PROTECTING PEOPLE AND HEALTH SYSTEMS AGAINST IMPACT OF RESPIRATORY DISEASE THIS WINTER

New research published by Pfizer shows an overall positive public attitude to vaccination in Ireland but varying levels of concern for

different respiratory diseases. The research was launched as Irish and European experts on immunisation and respiratory disease came together to examine the potential impact that diseases such as COVID-19, seasonal flu, and pneumonia may have on health systems and how routine adult vaccination is a key instrument in protecting lives and reducing the burden on health services.

The event, moderated by Gary Finnegan, Vaccines Today, titled Adult Vaccination and Healthy Ageing – An Opportunity to Build a Strong Future for Ireland, saw a wide group of stakeholders gather to discuss the societal and economic benefits of a healthy ageing population.

The research, conducted by Behaviour & Attitudes for Pfizer Healthcare Ireland, confirms a high uptake of the COVID-19 vaccination programme in Ireland, with 94% of respondents confirming they have received at least one dose of a COVID-19 vaccine to date. Overall attitude towards vaccination is positive, with only 24% stating that they will not get any vaccination (COVID-19, seasonal flu, or pneumococcal) this winter. However, only 22% of people surveyed plan to get a pneumococcal vaccination, despite the high numbers of pneumonia-related hospitalisations seen in Ireland each year.

Orlaith Gavan, Country Medical Director, Pfizer Healthcare Ireland, said: “Vaccination is an integral part of preventative healthcare and as we move into winter, we encourage those who are at an increased risk of catching respiratory diseases such as seasonal flu and pneumonia to speak to their healthcare provider about vaccination. While Ireland’s rate of COVID-19 vaccination has been among the best in the world, we are now seeing some decline in those presenting for their boosters. It is critical that those at higher risk from COVID-19 and other respiratory disease ensure that they are fully vaccinated.”

The research findings also revealed people’s thoughts on ageing and their future health. Perhaps unsurprisingly, ill health is the biggest cause of worry when people think about the next ten years with 54% of respondents aged over 50 saying it is their number one concern. When asked what steps they would take to future-proof their health in later life, the top three steps were exercise (82%), vaccination for preventable diseases such as flu and pneumonia (62%), and attend screening appointments (53%).

The research also found that

respiratory disease is top of mind for the public as we move into winter. When asked about their attitudes to vaccination and respiratory diseases in light of the COVID-19 pandemic, more than half (54%) of respondents said they were more concerned about respiratory diseases, 79% said they want to protect themselves from disease as they age, and 58% said they would be open to receiving vaccinations for other diseases if available.

Clare Fitzell, Head of Professional Services, Irish Pharmacy Union, added: “Seasonal flu and pneumonia are serious threats to our vulnerable communities and a strain on the health service year on year. Community pharmacists are well placed to offer vaccine protection in their local communities throughout the winter months to help reduce this burden. To date, community pharmacists have administered over 1.1 million COVID-19 vaccinations, and it is wonderful to see in this research that people have found the convenience of that service helpful.”

ACCORD HEALTHCARE WINS FOUR AWARDS AT THE GLOBAL GENERICS BIOSIMILAR AWARDS 2022

Accord Healthcare took home four awards including Company of the Year at the Global Generics and Biosimilars Awards, held in Frankfurt, Germany on November 2nd.

The company also won the Biosimilar Initiative of the Year, Value Added Medicine Initiative of the Year and Regulatory Achievement of the Year.

Speaking after the success, Paul Tredwell, EVP, EMENA says: “Year after year we are continuously recognised at these prestigious awards and that a is testament to our people, our culture and our

drive to make it better and the innovations we invest in.

“To be named Company of the Year, take the award for Biosimilar Initiative of the Year, Value Added Medicine Initiative of the Year, and Regulatory Achievement of the Year is a real accomplishment for everyone here at Accord and a real achievement to be awarded four in a highly competitive ceremony.”

THE LAUNCH OF SOLFEROL CAPSULES, A PRESCRIPTION RANGE OF VITAMIN D3 MEDICINES.

Windzor Pharma Ireland Ltd is please to announce the launch of SOLFEROL Softgel Capsules, a range of Vitamin D3 medicines, for the treatment of Vitamin D deficiency.

This brand offers the widest range of presentations on the market 5 different strengths, including two unique strengths, 400iu for the treatment of pregnant and breast feeding women, and 20,000iu for patients who are severely deficient in Vitamin D3.

The demand for Vitamin D3 has grown strongly in recent years due to the Covid pandemic and the need for bone health in elderly patients.

Solferol Softgel Capsules were developed in Ireland and are sold all across Europe.

The product range is now available in all pharma wholesalers and listed on all software prescribing systems nationally.

All five presentations are available on the reimbursement schemes, with a better price for all pack sizes.

The full range is as follows:

SOLFEROL Softgel Capsules 400iu x 90

SOLFEROL Softgel Capsules 800iu x 30

SOLFEROL Softgel Capsules 800iu x 90

SOLFEROL Softgel Capsules 1000iu x 28

SOLFEROL Softgel Capsules 20000iu x 4.

Full prescribing information available on www.windzorpharma.com.

NEW INTERIM DATA SHOW SHINGRIX CAN PROVIDE UP TO 10 YEARS OF PROTECTION AGAINST SHINGLES IN ADULTS AGED 50 YEARS AND OVER

New data published on 23 October 2022 in the Open Forum Infectious Diseases (OFID) by GSK plc (LSE/ NYSE: GSK), show positive interim results from the ZOSTER-049 extension study demonstrating that overall Shingrix (herpes zoster vaccine, recombinant) can provide up to a decade of protection against shingles (herpes zoster) after initial vaccination.i

These results come from ZOSTER-049 (ZOE-LTFU), an extension from two phase III clinical trials1 ZOE-50 and ZOE-70. From those trials, vaccine efficacy was 97%ii in adults 50 years and above and 91%iii in adults 70 years and above over a follow-up period of approximately four years.1 The ZOE-LTFU study, which follows participants from the ZOE-50 and ZOE-70 clinical trials for an additional six years, is ongoing and will continue to evaluate the longerterm efficacy, immunogenicity and safety of the vaccine.

Dr Eavan Daly (PhD), Director of Medical Affairs, GSK Ireland, said: “Shingles is a painful disease that one in three adults will develop in their lifetime. iv We can now – for the first time – confirm that the clinical benefit of the Recombinant Zoster Vaccine continues for up to 10 years after vaccination, giving patients and their healthcare professionals peace of mind about the duration of protection against shingles.”

Sabine Luik, Chief Medical Officer & SVP Global Medical Regulatory & Quality, GSK, said: “We are delighted to see the continuing longevity of protection from our shingles vaccine. The findings from ZOE-LTFU demonstrate that it can provide a decade of protection against the pain, debilitating impact, and potentially severe complications that shingles can cause in people aged 50 and over. These data significantly add to, and complement, the existing body of evidence demonstrating the long-term benefit of the vaccine, and we look forward to seeing additional results from this ongoing study.”

Shingles is caused by the reactivation of the varicella zoster virus (VZV), the same virus that causes chicken pox.ii iv,vi As people age, the immune system loses the ability to mount a strong and effective immune response, increasing the risk of developing shingles.iv,v,vi

The disease can cause unbearable pain and, in some cases, intense pain continues after the shingles rash fades, that nerve pain (called post-herpetic neuralgia [PHN]) can last for months or even years.iv

The Recombinant Zoster Vaccine (RZV) is the first approved shingles vaccine to combine a non-live antigen with GSK’s adjuvant and may help overcome the natural age-related decline in immunity that contributes to the challenge of protecting adults aged 50 years and above from this disease. vii,viii

About ZOSTER-049i

ZOSTER-049 is an open-label, long-term follow-up (LTFU) study from two pivotal phase III randomised clinical trials (ZOE-50, ZOE-70). The study is evaluating the efficacy, safety and immunogenicity for six additional years after completion of the ZOE-50 and ZOE-70 studies. In the interim analysis conducted over the >4 years of longterm follow-up, representing up to 10 years since immunisation (mean: from 5.6 (±0.3) to 9.6 (±0.3) years postvaccination), vaccine efficacy was 81.6%.

From 1 month post-second dose in those initial studies up to year 10 post-vaccination (mean: 9.6 (±0.3) years post-vaccination), vaccine efficacy was 89.0%. The safety profile observed in this extension study is consistent with the established safety profile of the vaccine. No new safety concerns were identified. The incidence of serious adverse events was consistent with the age of the study population. No deaths or other Safety Adverse Events (SAE) considered related to vaccination were reported. Five cases of HZ-related complications (PHN - 3 cases and HZ disseminated disease - 2 cases) were reported. A total of 7,413 participants were enrolled in the study’s Safety cohort. The participants were 60.7% female and 39.3% male.

Participants were 76.0% WhiteCaucasian/European heritage, 18.7% Asian and 5.3% Other.

ZOSTER-049 is being conducted in 18 countries/regions including Australia, Brazil, Canada, Czech Republic, Estonia, Finland, France, Germany, Hong Kong, Italy, Japan, Republic of Korea, Mexico, Spain, Sweden, Taiwan, the United Kingdom and the United States.

INDIC A T E D FOR

RA

UC

PsA | JIA | AS

Legal Category: S1A. Marketing Authorisation Holder: Pfizer Europe MA EEIG, Boulevard de la Plaine 17, 1050 Bruxelles, Belgium. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at medical.information@pfizer.com

XELJANZ is indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent.

XELJANZ in combination with methotrexate (MTX) is indicated for the treatment of moderate to severe active rheumatoid arthritis (RA) in adult patients who have responded inadequately to, or who are intolerant to one or more disease-modifying antirheumatic drugs.

XELJANZ in combination with MTX is indicated for the treatment of active psoriatic arthritis (PsA) in adult patients who have had an

inadequate response or who have been intolerant to a prior diseasemodifying antirheumatic drug (DMARD) therapy.

XELJANZ is indicated for the treatment of adult patients with active ankylosing spondylitis (AS) who have responded inadequately to conventional therapy.

XELJANZ is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (rheumatoid factor positive [RF+] or negative [RF-] polyarthritis and extended oligoarthritis), and juvenile psoriatic arthritis (PsA) in patients 2 years of age and older, who have responded inadequately to previous therapy with DMARDs.