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HPN April 2016

Issue 26

HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication

IN THIS ISSUE: NEWS: St James’s Hospital launch kidney disease tool Page 4

S TA N D A R D S O L U T I O N S

AMPOULES FOR SMART AND NEEDLE-FREE HANDLING

Products Sodium Chloride 9mg/ml (0.9%)

PROFILE: New IMO President Dr John Duddy Page 9

Water for Injection

Ampoule sizes 20ml

REPORT: Improving the Diagnosis of Gestational Diabetes Mellitus Page 22

10ml 5ml

CPD: Relapsed Mantle Cell Lymphoma Page 23 AWARDS: Launch of the 2016 Hospital Professional Awards Page 28

Fresenius Kabi Ltd Unit 3B Fingal Bay Business Park Balbriggan, Co. Dublin T: +353 (0)1 841 3030 F: +353 (0)1 849 6949 www.fresenius-kabi.ie

FEATURE: Allergic Rhinitis & Asthma Page 37


STILL EXPLORING

34.7 median OS1

MO N T H S

94.9%

of patients treated with ZYTIGA® plus low-dose prednisolone did not experience grade 3 or 4 corticosteroidassociated adverse event2

reduction in the risk of

48% radiographic progression3 WITH

of median follow up

YEARS

ZYTIGA maintains a favourable safety profile and is generally well-tolerated1

4+

ZYTIGA® ▼ 250 mg Tablets PRESCRIBING INFORMATION. ACTIVE INGREDIENT(S): Abiraterone acetate. Please refer to Summary of Product Characteristics (SmPC) before prescribing. INDICATION(S): Taken with prednisone or prednisolone for the treatment of metastatic castration resistant prostate cancer in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated. The treatment of metastatic castration resistant prostate cancer in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen. DOSAGE & ADMINISTRATION: Adults: 1000 mg (4 tablets) single daily dose. Not with food as this increases the systemic exposure (take dose at least two hours after eating; no food for at least one hour post-dose). Swallow whole with water. Take with recommended dose of prednisone or prednisolone of 10 mg daily. Medical castration with LHRH analogue should be continued during treatment in patients not surgically castrated. Children: No relevant use. Hypokalaemia: In patients with pre-existing, or who develop hypokalaemia during treatment with Zytiga, consider maintaining potassium level at ≥4.0 mM. Patients who develop Grade ≥ 3 toxicities (hypertension, hypokalaemia, oedema and other non-mineralocorticoid toxicities) stop treatment and start appropriate medical management. Do not restart Zytiga until symptoms of the toxicity have resolved to Grade 1 or baseline. Renal impairment: No dose adjustment, however no experience in patients with prostate cancer and severe renal impairment; caution advised. Hepatotoxicity: If hepatotoxicity develops (ALT or AST >5x upper limit of normal - ULN), stop treatment immediately until liver function returns to baseline; restart Zytiga at 500 mg (2 tablets) once daily and monitor serum transaminases at least every 2 weeks for 3 months and monthly thereafter (see Special warnings & precautions). If hepatotoxicity recurs on reduced dose, stop treatment. If severe hepatotoxicity develops (ALT or AST 20xULN), discontinue Zytiga and do not restart. Hepatic impairment: Mild (Child-Pugh class A) - no dose adjustment required. Moderate (Child-Pugh class B) approximately 4x increased systemic exposure after single oral doses of 1,000 mg. Moderate/Severe (Child-Pugh class B or C) – no clinical data for multiple doses. Use with caution in moderate impairment, benefit should clearly outweigh risk. CONTRAINDICATIONS: Pregnancy or potential to be pregnant. Hypersensitivity to active substance or any excipients. Severe hepatic impairment (Child-Pugh Class C). SPECIAL WARNINGS & PRECAUTIONS: Zytiga may cause hypertension, hypokalaemia and fluid retention due to increased mineralocorticoid levels. Cardiovascular: Caution in patients with history of cardiovascular disease. In patients with a significant risk for congestive heart failure (history of cardiac failure, uncontrolled hypertension, ischaemic heart disease) consider an assessment of cardiac function before treating (echocardiogram). Safety not established in patients with left ventricular ejection fraction < 50% or NYHA Class II to IV (pre-chemotherapy) and III or IV (post-chemotherapy) heart failure. Before treatment cardiac failure should be treated and cardiac function optimised. Correct and control Hypertension, hypokalaemia and fluid retention pretreatment. Caution in patients whose medical conditions might be compromised by hypertension, hypokalaemia or fluid retention e.g. heart failure, severe or unstable angina pectoris, recent myocardial infarction or ventricular arrhythmia, severe renal impairment. Monitor blood pressure, serum potassium and fluid retention and other signs and symptoms of congestive heart failure before treatment, then every two weeks for 3 months, and monthly thereafter. QT prolongation observed in patients experiencing hypokalaemia with Zytiga treatment. Consider discontinuation if there is a clinically significant decrease in cardiac function. Hepatotoxicity & hepatic impairment: Measure serum transaminases pre-treatment and every two weeks for first three months, then monthly. If symptoms/signs suggest hepatotoxicity, immediately measure serum transaminases. If ALT or AST > 5x ULN, stop treatment and monitor liver function. Restart treatment after liver function returns to baseline; use reduced dose (see dosage and administration). No clinical data in patients with active or symptomatic viral hepatitis. Rare reports of acute liver failure and hepatitis fulminant, some fatal. Corticosteroid withdrawal: Monitor for adrenocortical insufficiency if prednisone or prednisolone is withdrawn. Monitor for mineralocorticoid excess if Zytiga continued after corticosteroids withdrawn. Bone density: Decreased bone density may be accentuated by Zytiga plus glucocorticoid. Prior use of ketoconazole: Lower response rates may occur in patients previously treated with ketoconazole for prostate cancer. Hyperglycaemia: Use of glucocorticoids could increase hyperglycaemia, measure blood sugar frequently in patients with diabetes. Use with chemotherapy: Safety and efficacy of concomitant use of Zytiga with cytotoxic chemotherapy not established. Intolerance to excipients: Not to be taken by patients with galactose intolerance, Lapp lactase deficiency or glucosegalactose malabsorption. Take sodium content into account for those on controlled sodium diet. Potential risks: Anaemia and sexual dysfunction may occur in men with metastatic castration resistant prostate cancer including those

taking Zytiga. Skeletal muscle effects: Cases of myopathy reported. Some patients had rhabdomyolysis with renal failure. Caution is recommended in patients concomitantly treated with drugs known to be associated with myopathy/ rhabdomyolysis. SIDE EFFECTS: Very common: urinary tract infection, hypokalaemia, hypertension, diarrhoea, peripheral oedema. Common: sepsis, hypertriglyceridaemia, cardiac failure (including congestive heart failure, left ventricular dysfunction and decreased ejection fraction), angina pectoris, arrhythmia, atrial fibrillation, tachycardia, dyspepsia, increased alanine aminotransferase, increased aspartate aminotransferase, rash, haematuria, fractures (includes all fractures with the exception of pathological fracture). Other side effects: adrenal insufficiency, myocardial infarction, QT prolongation, hepatitis fulminant, acute hepatic failure, myopathy, rhabdomyolysis. Refer to SmPC for other side effects. FERTILITY/PREGNANCY/LACTATION: Not for use in women. Not known whether abiraterone or its metabolites are present in semen. A condom is required if the patient is engaged in sexual activity with a pregnant woman. If the patient is engaged in sexual activity with a woman of childbearing potential, a condom is required along with another effective contraceptive method. Studies have shown that abiraterone affected fertility in male and female rats, but these effects were fully reversible. INTERACTIONS: Caution with drugs activated by or metabolised by CYP2D6 particularly when there is a narrow therapeutic index e.g. metoprolol, propranolol, desipramine, venlafaxine, haloperidol, risperidone, propafenone, flecanide, codeine, oxycodone and tramadol. Avoid strong inducers of CYP3A4 (e.g. phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital, St John’s wort). Zytiga is a CYP2C8 inhibitor (in vitro data). Examples of medicinal products metabolised by CYP2C8 incl paclitaxel, repaglinide. No clinical data are available on the use of Zytiga with CYP2C8 substrates. May increase concentrations of drugs eliminated by OATP1B1. Food (see Dosage & Administration). Caution with medicines known to prolong QT interval or induce Torsade de pointes e.g. quinidine, disopyramide, amiodarone, sotalol, dofetilide, ibutilide, antiarrhythmic medicinal products, methadone, moxifloxacin and antipsychotics. Refer to SmPC for full details of interactions. LEGAL CATEGORY: Prescription only medicine. PRESENTATIONS, PACK SIZES & MARKETING AUTHORISATION NUMBERS: Bottle, 120 tablets, EU/1/11/714/001. MARKETING AUTHORISATION HOLDER: JANSSEN-CILAG INTERNATIONAL NV, Turnhoutseweg 30, B-2340 Beerse, Belgium. FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG, UK. Prescribing information last revised: February 2016 Adverse events should be reported. ▼ This medicinal product is subject to additional monitoring and it is therefore important to report any suspected adverse events related to this medicinal product. Healthcare professionals are asked to report any suspected adverse events via: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, Website: www.hpra.ie, E-mail: medsafety@hpra.ie. Adverse events should also be reported to Janssen-Cilag Limited on +44 1494 567447 or at dsafety@its.jnj.com. © Janssen-Cilag Limited 2016 References: 1. Ryan CJ, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapynaive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo controlled phase 3 study. Lancet Oncol 2015; 16: 152–60. 2. Fizazi, K., et al (2015). ASCO GU 2015 (abstract 169). 3. Rathkopf, DE et al. Updated Interim Efficacy Analysis and Long-term Safety of Abiraterone Acetate in Metastatic Castration-resistant Prostate Cancer Patients Without Prior Chemotherapy (COUAA-302). Eur Urol (2014), http://dx.doi.org/10.1016/j. eururo.2014.02.056. Date of Preparation: March 2016 | PHIR/ZYT/1014/0004(3)


3

HPN April 2016 Issue 26

Contents

Foreword

EAHP Congress coverage P5

Editor

Kelly Jo Eastwood

HIQA’s Report on infection control P6 St Patrick’s Mental Health Services and RCSI MMoU P8

6

Building a system that works for everyone. A sentiment that is bound to be at the fore front of many hospital professional minds. But this was also the theme of the 12th National Health Summit which took place in the Crowne Plaza Hotel last month, drawing with it, interest from a plethora of high profile health strategists, economists, medical professionals and healthcare companies across Ireland. The summit featured a vast array of speakers who advised on how to systematically improve the Irish healthcare sector in a variety of different and explorative new ways.

Polypharmacy ‘commonplace’ findings P12

At the Summit, Matt Aiello, Urgent and Acute Workforce Transformation Specialist at Health Education West Midlands, UK, gave a talk about how he and his team had prepared and delivered a portfolio of pilot projects in the UK.

IMO accuses HSE over abuse of power claims P22

Interestingly, the results of the pilot projects uncovered a need for a potential new advanced clinical pharmacist role in the primary care setting.

8

Regulars

Speaking at the conference, Aiello explained how he and his team built a workforce transformation programme for Pharmacy essentially from scratch and he provided insight into how they intended to take steps towards expanding the role of the pharmacist both in the hospital and community setting.

Feature: Crohn’s & Colitis P20 CPD: Relapsed Mantle Cell Lymphoma P23 12

Feature: Current management updates in Hay Fever P37

“Originally, one of our Chief Pharmacists coined the term ‘generalist specialist pharmacist’ and that was the first time we started thinking about a specialist role, an allied health professional role,” he explained. “Nurses have been doing it for years but we hadn’t really taken anything from that. Healthcare professionals don’t just have to do one thing. When you have a specialty, you have your specialty practice area but there could be more you could do, you could be more effective. It is only through that realisation that we can work towards a more integrated workforce.”

Feature: Prostate Cancer P42 Clinical Profiles P46

You can read the full report on page 20. 22

In other news, this issue sees the launch of the 2016 Hospital Professional Awards. The fourth annual Hospital Professional Awards will be held on September 17th, 2016 in the Hilton DoubleTree Hotel, Dublin.

Hospital Pharmacy News is Circulated to all independent, multiple and hospital pharmacist, pre reg pharmacists, students pharmacy student’s offi cial bodies, government officials and departments, Pharmacy Managers, Manufactures, Wholesalers. Buyers of pharmacy groups and healthcare outlets. Circulation is free to all pharmacists Subscription rate for Hospital Pharmacy News ¤60 plus vat per year

Once again hosted by RTE current affairs broadcaster Miriam O’Callaghan, the Hospital Professional Awards have rapidly become recognised as Ireland’s leading platform to recognise the excellent work carried out by Hospital professionals and their teams.

All rights reserved by Hospital Pharmacy News. All material published in Hospital Pharmacy 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. Pharmacy Communication Ireland 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.

The Awards have been met with great enthusiasm from suppliers, healthcare professionals including Consultants and Pharmacists. They have raised the profile of the industry within Ireland. Our sponsors are amongst the elite of the industry, all of whom see the awards as the perfect vehicle to show their support in this arena.

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

We have an exciting selection of award categories for this year, turn to page 28 for all the details.

MANAGING DIRECTOR Natalie Maginnis n-maginnis@btconnect.com EDITOR Kelly Jo Eastwood kjeastwood@hotmail.com 00447876548989 ACCOUNTS Jennifer Dunseath cs.ipn@btconnect.com

COMMERCIAL MANAGER Ingrid Lyons Ingrid@ipnirishpharmacynews.ie + 353 1 669 0562 + 353 87 777 0480 CONTRIBUTORS Aisling Kennedy | M. Dreyling C. Geisler | O. Hermine H. C. Kluin-Nelemans | S. Rule S. Le Gouill | O. Shpilberg J. Walewski | M. Ladetto DESIGN DIRECTOR Ian Stoddart Design Visual Communications www.pharmacynewsireland.com www.facebook.com/ HospitalProfessionalNews

Further updates and details to follow in next month’s issue but in the meantime you can contact me for your entry form at Kelly@ipnirishpharmacynews.ie or by giving me a call on 0044 78765478989 – Good luck and we look forward to receiving your submissions.

HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication HPN • April 2016


4 News

St James’s Hospital new tool for Chronic Kidney Disease patients St James’s Hospital has announced, on World Kidney Day, its plans to develop an innovative digital tool with the input of patients from the hospital’s Acute Renal Unit. The planned digital platform will enable patients living with kidney disease to manage their care and access important information on a day to day basis, therefore having a positive impact on a wide range of symptoms and complications. Speaking about the plans, Consultant in Nephrology at St James’s Hospital, Professor George Mellotte, said, “Approximately 12% of Ireland’s population are living with chronic kidney disease and that number is growing, especially amongst younger cohorts. Preventing the progression of chronic kidney disease has been shown to significantly improve patient survival.”

“The digital platform that St James’s Hospital is currently developing aims to give chronic kidney disease patients the tools to help manage their treatment and symptoms in order to slow progression and ensure the best clinical outcome for all patients.” St James’s Hospital is an acute dialysis centre, currently treating approximately 450 patients ranging from stages 3 to 5 of chronic kidney disease. Two-thirds of all chronic kidney disease cases are caused by either diabetes or high blood pressure, while heart disease is the major cause of death for chronic kidney disease patients. Chronic kidney disease is staged, with stage 1 being the mildest and usually causing few symptoms to stage 5 or end-stage kidney disease which is a severe illness with reduced poor life expectancy. The number of patients in Ireland

requiring kidney dialysis or a transplant is approximately 4,400. The symptoms associated with chronic kidney disease are often vague and attributed to agerelated frailty and as a result chronic kidney disease often

remains undiagnosed until the condition is advanced. Chronic kidney disease results in a wide range of complications including hypertension, hyperparathyroidism, anaemia, vascular calcification and accelerated cardiovascular disease.

HPRA strategic plan for 2016-2020 HPRA Chief Executive, Ms Lorraine Nolan

Plan sets out the strategic direction that will guide the health products regulator over five-year period The Health Products Regulatory Authority (HPRA) has launched its Strategic Plan 2016-2020 which outlines its goals, objectives and high level strategic actions for the next five years. The plan has been prepared in consultation with staff and a range of external stakeholders including those who use health products, and in line with Department of Health priorities. The HPRA’s five core strategic goals which incorporate 17 high level actions are: April 2016 • HPN

Strategic Goal 1 – Optimised Regulatory Systems: The HPRA is committed to appropriate regulation of all health products. To ensure that the regulatory system keeps pace with developments in health products, it will continue to place an emphasis on effective collaboration with colleagues at European as well as international levels. We will also work in partnership with other national agencies to develop and deliver on government policies. Strategic Goal 2 – Better Informed Users: Healthcare professionals and the public need access to clear, readily available, high-quality information on which to base their health decisions. The HPRA

will make use of all appropriate channels to communicate comprehensively and effectively with health product users and other key audiences. Strategic Goal 3 – Access to Health Products: The HPRA is committed to working with all stakeholders to enhance access to health products; this includes working on measures to reduce medicine shortages and, when they occur, managing those shortages better. Maintaining access to current and future health products whilst also protecting the integrity of the supply chain to avoid illegal products reaching patients, are significant areas of focus in the HPRA’s five year plan. Strategic Goal 4 – Supporting Innovation: Ireland has a substantial and growing lifesciences industry. The HPRA aims to strengthen its capabilities in providing regulatory assistance to companies developing new products. In addition, new developments taking place in research centres will point to the technologies that the HPRA will need to regulate in the future. Strategic Goal 5 – Internal Capabilities: The HPRA will

continue to invest in and develop its internal expertise. Appropriate systems and resources to manage all aspects of the business will be enhanced, so that the HPRA meets the opportunities and challenges presented by external developments. According to Chief Executive, Ms Lorraine Nolan, “The actions and activities identified in our strategic plan provide a clear roadmap for the future focus and development of the HPRA. It involved an extensive consultation process where we gained valuable and important insight and feedback. Our final plan published today reflects the key issues and work areas highlighted during that process where we engaged with our expert staff as well as healthcare professionals, government agencies, patient advocacy groups and the large and vibrant health products sector in Ireland. We welcome the opportunity to work in collaboration with all our stakeholders to deliver on our plan in the years ahead.”


5

Hospital pharmacy driving change The theme of hospital pharmacists as leaders was thoroughly explored during a packed threeday EAHP Congress in Vienna 16th to 18th March 2016. Hospital pharmacists as the driver for change in such areas as patient empowerment, combatting antimicrobial resistance, the enhancement of multi-disciplinary teams, and the introduction of new technologies was examined in speeches, seminars and workshops. The Congress opened on the theme of patient empowerment, with a duet of a hospital pharmacist and a patient presenting further developments in the model of patient centred care that has taken place in Canada. Marie-Claude Vanier (hospital pharmacist) and Vincent Dumez (chronic disease patient) outlined how much healthcare professionals can learn from listening to the experiences of patients, as they are the health system experts on living with an illness. A Synergy Satellite highlighted the role of hospital pharmacists in educating fellow healthcare professionals, payers and patients about biological interchangeability. With many new biosimilars coming

Joan Peppard, President, EAHP

to market in the future it is the expertise of the pharmacist as a source of reliable advice that will make the difference. Elsewhere, a record number of students registered for the Congress and took part in a dedicated programme on pharmaceutical care. Another Synergy Satellite examined the role of Ready to Use Drugs as a useful option for patient safety. At the end of the Congress Armando Alcobia Martins from Portugal was awarded the 1st prize for poster submissions for his work on 'Double checking

manipulations for complex and/or high risk preparations'. The EAHPEPSA Student Science Award was presented to Slovenian Rok Barle for his manuscript on the control of chemotherapy-induced nausea and vomiting in patients with gastrointestinal tumours.

another top class event covering so many issues of high public interest, such as combatting antimicrobial resistance, introducing new technologies, and fostering truly better partnerships with patients and other healthcare professionals.

Speaking after the Congress, EAHP President Joan Peppard remarked, "With 3,500 attendees from 73 countries registered for the event, the EAHP Congress is firmly established as the leading educational congress for hospital pharmacists in Europe. Our Scientific Committee has overseen

â&#x20AC;&#x153;The leadership message came across loud and clear and as we all return to our places of practice, the onus is on our profession to take up these challenges and for health system managers to support these improvements."

PSI and Medical Council Working Group A working group with relevant members of the Medical Council and the Pharmaceutical Society of Ireland has been established to examine patient safety matters of mutual concern and particularly focusing on safe prescribing and dispensing. The aim of this is

to make sure that pharmacists, doctors and members of the public receive clear information on agreed best practice for both professions. This positive initiative aims to explore how the two regulators can work together to support the existing collaborative

practice between medical doctors and pharmacists, in the shared care of patients in the broader multidisciplinary team. Some of the areas being examined relate to the prescribing and dispensing of controlled drugs and

the care of patients in particular care settings. This work will be progressed on a phased basis throughout 2016, and both professions will continue to be updated.

UCC MSc in Clinical Pharmacy 2016 Applications are invited for this two-year (part-time) distance learning Masters Degree offered by the School of Pharmacy, University College Cork course, commencing in September 2016. The course is structured to provide specialist training to enable pharmacists working in hospital and community pharmacies, extend their professional role within the evolving clinical healthcare system. The course will develop a greater understanding of the major pharmacotherapeutic issues of various disease states in order to develop a greater understanding of the particular needs of patients with these diseases. Closing date for applications: Friday, 29th July 2016. Applicants must apply online at www.pac.ie/ucc. Full details of the applicant procedure are available on this website.

HPN â&#x20AC;˘ April 2016


6 News

HIQA Overview of infection prevention The HSE has welcomed the publication of HIQA’s Report ‘Overview of HIQA unannounced infection prevention and control inspections 2015’. The HSE says it remains fully committed to ensuring that national standards for Healthcare Associated Infections (HCAI) and Antimicrobial Resistance (AMR) are implemented and that hospitals are in full compliance. The report provides a much welcome focus on key aspects of infection prevention and control and addresses wider aspects of practice including the use of care bundles. Significant progress has been made over recent years. Compliance with HSE Hand Hygiene targets has progressively improved with an average hand hygiene compliance rate of 89.2% achieved by hospitals in 2015. The national target remains 90%. HIQA also noted that hospitals were committed to achieving and embedding good hand hygiene practices at all levels within their organisation.

All hospitals inspected throughout 2015 have already received copies of their individual reports and have agreed plans with HIQA to address any areas requiring greater effort and attention. The HSE acknowledge that significant improvement is required in some areas and is committed to ensuring that the necessary improvement plans are implemented. The relevant hospitals continue to work on these improvement areas with the support of their respective Hospital Groups. Key priorities identified for 2016 and contained in the HSE National Service Plan include reviewing the organisational approach to HCAI and Antimicrobial Resistance to ensure that every healthcare worker across the healthcare system recognises that infection prevention is a key element of all aspects of clinical work. The HSE has established a National Taskforce to direct and coordinate an effective systemwide response to the issue of HCAI/AMR. This is a multidisciplinary high-level group

that will oversee and ensure the following aims are achieved:  Ensure rational antimicrobial use across all healthcare settings  Effective diagnostic support for infection  Reduce incidence of Multi Drug Resistant Organisms (MDROs)  Decrease incidence of Healthcare Associated Infections (HCAIs)  Improve professional education, training and public engagement to promote wider understanding of the need for appropriate use of antibiotics  Compliance with HIQA Standards for Prevention of HCAI across all healthcare settings

to ensure that these practices highlighted in the reports are addressed. The report also notes that new buildings, refurbishments and upgrade programmes in the planning stages, or commenced during 2015, will address some of the infrastructural and environmental deficiencies identified and assist in meeting compliance requirements. The HSE acknowledge that ongoing targeted investment is required to address deficiencies in hospital infrastructure and is committed to supporting refurbishment programmes in our hospitals within allocated resources. In order to address high risk areas, Hospital Groups are required to quantify the cost of required improvements over the next five years.

Ensuring medicines are managed safely and securely throughout Irish hospitals is a key patient safety objective. This includes handling of all IV preparations (preparation, labelling and storage). Quality Improvement Programmes are in place for the relevant hospitals

New Neurology Research & Assessment Unit for Tallaght Tallaght Hospital’s Raymond P Murphy Neurology Assessment & Research Unit was officially opened at the end of last month. The new room will offer enhanced space to review patients with neurological diseases and was officially opened by recently retired Dr Raymond Murphy, a former neurologist at Tallaght Hospital and the Adelaide Hospital. This new facility incorporates a research unit which forms part of the Trinity College Academic Unit of Neurology. Guests attended the official opening at the Ruttle Ward in Tallaght Hospital where they had the opportunity to view the new room. The unit has been equipped with an ocular coherence tomography machine, making the Department of Neurology in Tallaght Hospital the only unit in the country with dedicated access to this technology. While Tallaght Hospital provides services for chronic neurological disease in a catchment area of over 500,000 people, it has not previously had a dedicated space April 2016 • HPN

Dr Raymond Murphy, former Neurologist, Tallaght Hospital and Adelaide Hospital

to cater for such patients. The new room has three fully equipped examination bays, two comfortable armchairs for patients requiring prolonged periods of observation or administration of treatments. In addition, nurse specialists will be in a position to provide education to patients and for a Research Fellow in Ataxia and Movement disorders.

Dr Richard Walsh, Consultant Neurologist, Tallaght Hospital said, “We are extremely proud to be opening this dedicated unit today. This facility will undoubtedly further enhance our ability to provide care to our patients in an efficient manner and in a comfortable environment. It is also fitting that this important unit is named after Dr Raymond Murphy who gave many years of service

to neurology in Tallaght Hospital, which is now reflected throughout the country where his influence continues in the many neurologists he trained during his career. I am delighted that he is here with his family today to officially open the unit. I must also thank the Meath Foundation and Novartis who have provided all the funding to make this project possible.”


No w that I HAVE YOUR

Attention The Boehringer Ingelheim and Lilly Diabetes Alliance are proud to introduce ABASAGLAR®

The efficacy and safety you would expect from glargine, but supported with a patient initiative that focuses on the person not just the patient. ABASAGLAR® is indicated for the treatment of diabetes mellitus in adults, adolescents and children 2 years and above.1 ABASAGLAR®

CARTRIDGE and KWIKPEN™ ABBREVIATED PRESCRIBING INFORMATION ABASAGLAR IS INSULIN GLARGINE (human insulin analogue)

Presentation Abasaglar is a clear, colourless, sterile solution of 100 units/ml (equivalent to 3.64mg) insulin glargine (rDNA origin), available as either 3ml cartridge or 3ml KwikPen. Each cartridge/pen contains 300 units of insulin glargine in 3ml solution. Uses Treatment of diabetes mellitus in adults, adolescents, and children aged 2 years and above. Dosage and Administration The dose regimen (dose and timing) should be individually adjusted. In patients with Type 2 diabetes mellitus, Abasaglar can also be given together with orally active antidiabetic medication. Abasaglar has a prolonged duration of action, and should be administered once daily at any time, but at the same time each day. It should only be given by subcutaneous injection and should not be administered intravenously. Injection sites must be rotated within a given injection area from one injection to the next. Abasaglar must not be mixed with any other insulin or diluted. When changing from another intermediate or long-acting insulin treatment regimen to Abasaglar, a change of the dose of the basal insulin may be required and the concomitant antidiabetic treatment may need to be adjusted (dose and timing of additional regular insulins or fast-acting insulin analogues, or the dose of oral antidiabetic medicinal products). Contraindications Hypersensitivity to insulin glargine or any of the excipients. Warnings and Special Precautions Abasaglar is not the insulin of choice for the treatment of diabetic ketoacidosis. In case of insufficient glucose control, or tendency to hyper- or hypoglycaemic episodes, other relevant factors must be reviewed before dose adjustment is considered. Transferring a patient to another type or brand of insulin should be done under strict medical supervision. Changes in strength, brand, type, origin, and/or method of manufacture may result in the need for a change in dose. In rare cases, insulin antibodies may necessitate dose adjustment. The time of occurrence of hypoglycaemia may change when the insulin regimen is changed, depending on the action profile of the insulins used. Caution and intensified glucose monitoring are advised in patients for whom

hypoglycaemia might be of particular clinical relevance. Patients should be aware that warning symptoms of hypoglycaemia may be changed, less pronounced, or absent in certain circumstances, including: markedly improved glycaemic control; when hypoglycaemia develops gradually; in the elderly; after transfer from animal to human insulin; autonomic neuropathy; long history of diabetes; psychiatric illness; use of certain medications such as beta-blockers. This may result in severe hypoglycaemia. The prolonged effect of insulin glargine may delay recovery from hypoglycaemia. If HbA1c is low, consider possibility of recurrent, unrecognised hypoglycaemia. Adherence of the patient to the dose and dietary regimen, correct insulin administration, and awareness of hypoglycaemia symptoms are essential to reduce risk of hypoglycaemia. Factors increasing risk of hypoglycaemia require particularly close monitoring and may necessitate dose adjustment. Intercurrent illness requires intensified monitoring. Testing for ketones and dose adjustment may be necessary. Patients with Type 1 diabetes must continue to consume at least small amounts of carbohydrate and must never omit insulin entirely. The cartridges should only be used in a pen recommended for the use with Lilly insulin cartridges. The insulin label must always be checked before each injection to avoid medication errors. Cases of cardiac failure have been reported when pioglitazone was used in combination with insulin. If the combination is used, patients should be observed for signs and symptoms of heart failure and pioglitazone discontinued if any deterioration occurs. Pregnancy and Lactation No clinical data from controlled studies are available. Data from >1,000 pregnancy outcomes indicate no specific adverse effects of insulin glargine on pregnancy and no specific malformative nor feto/neonatal toxicity. The use of Abasaglar may be considered during pregnancy, if necessary. Insulin requirements may decrease during the first trimester and generally increase during the second and third trimesters. Immediately after delivery, insulin

requirements decline rapidly. Careful monitoring of glucose control is essential. Driving, etc The patient’s ability to concentrate and react may be impaired as a result of hypo- or hyperglycaemia, or visual impairment. This may constitute a risk in situations where these abilities are of special importance (eg, driving a car or operating machines). Undesirable Effects Hypoglycaemia is very common. Injection site reactions and lipohypertrophy are common. Immediate-type allergic reactions are rare, but may be life-threatening. For full details of these and other side-effects, please see the Summary of Product Characteristics, which is available at http://www.medicines.ie/. Legal Category POM Marketing Authorisation Numbers and Holder EU/1/14/944/003 EU/1/14/944/007 Eli Lilly Regional Operations GmbH Kölblgasse 8-10 1030 Vienna Austria Date of Preparation or Last Review May 2015 Full Prescribing Information is Available From Eli Lilly and Company Limited, Lilly House, Priestley Road, Basingstoke, Hampshire, RG24 9NL. Telephone: Basingstoke (01256) 315 000. E-mail: ukmedinfo@lilly. com or Eli Lilly and Company (Ireland) Limited, Hyde House, 65 Adelaide Road, Dublin 2, Republic of Ireland. Telephone: Dublin (01) 661 4377, E-mail: ukmedinfo@lilly. com. ABASAGLAR® (insulin glargine) is a registered trademark of Eli Lilly and Company. KWIKPEN™ is a trademark of Eli Lilly and Company. October 2015 IE/aba/00027b 1. ABASAGLAR® Summary of Product Characteristics. December 2014. Adverse events and product complaints should be reported. To report an adverse event or a product complaint about a Lilly medicine, please call Lilly on: 01 664 0446. Adverse events and product complaints may also be reported to the Health Products Regulatory Authority. Reporting forms and information can be found at www.hpra.ie. This medicinal product is subject to additional monitoring.


8 News

Formal agreement to benefit mental health services St Patrick’s Mental Health Services are delighted to announce the establishment of a formal agreement that will enable the Hospital to grant clinical facilities and facilitate the clinical training of undergraduate medical students from the Royal College of Surgeons in Ireland (RCSI). The Memorandum of Agreement was signed this morning in the Board Room of St Patrick’s University Hospital by CEO Paul Gilligan on behalf of St Patrick’s Mental Health Services, and by Professor Hannah McGee, Dean of the Faculty of Medicine and Health Sciences on behalf of RCSI. As Ireland’s largest centre for postgraduate training of mental health professionals in Ireland, St Patrick’s Mental Health Services have a long-established commitment to training and education. St Patrick’s Mental Health Services, CEO Paul Gilligan, said, “At this time, there is a substantial need to advance education in mental health and to promote clinical education where possible. We have a long standing relationship with other colleges and welcome the opportunity to expand our offering to another educational institution by becoming formally involved in their teaching programme.” Speaking on the signing, Professor Hannah McGee Dean of the Faculty of Medicine & Health Sciences, RCSI said, “I am delighted to sign this agreement

Back Row: Tom Maher, Director of Services, St Patrick’s Mental Health Services; Prof. Kieran C. Murphy, Vice-Dean for Professionalism & Chairman, Dept of Psychiatry, RCSI; Prof. James Lucey, Medical Director, St Patrick’s Mental Health Services. Front Row: Prof. Hannah McGee, Dean of the Faculty of Medicine & Health Sciences and Paul Gilligan, CEO, St Patrick’s Mental Health Services. with St Patrick’s Mental Health Services to advance the clinical training and rich learning experience for our students. RCSI aims to provide our students with excellence in education and central to this is the provision of a high

quality learning environment for our students to receive their clinical training and this collaboration with St Patrick’s Mental Health Services is testament to that goal.” The memorandum of agreement

will be actualised in October of 2016, at the start of the next academic year, when undergraduate students will be invited into St Edmundsbury Hospital in Lucan for their first series of lectures.

EMA Reaffirms Positive Benefit-Risk Balance of rivaroxaban for Stroke Prevention in Patients with Atrial Fibrillation' The European Medicines Agency (EMA) has reaffirmed the positive benefit-risk balance of Bayer’s Xarelto® for stroke prevention in patients with atrial fibrillation. This outcome concludes a CHMP (Committee for Medicinal Products for Human Use) procedure that was initiated to assess whether a potential malfunctioning of the INR device used in the ROCKET AF trial had any impact on the study results. Bayer and its development partner Janssen have undertaken thorough analyses, which were shared with Health Authorities, in particular EMA and the FDA. Separately, the re-analysis conducted by the ROCKET AF Executive Committee, who ran the ROCKET AF trial, was recently published online in the New England Journal of Medicine. April 2016 • HPN

The EMA has concluded that a defect with the INR device used in the ROCKET study does not change its conclusions on the overall safety or benefit-risk balance of Xarelto (rivaroxaban). In particular, the EMA in their announcement states that “after further analyses of the ROCKET study data taking into account the defect in the INR device, EMA’s Committee for Medicinal Products for Human Use (CHMP) concluded that any incorrect measurements obtained with the defective device would have had only a marginal effect on the study results, and the safety of Xarelto remains unchanged. In addition, data from other large studies confirmed the comparative safety of the medicine and showed similar rates of bleeding in their warfarin groups.” The EMA therefore states: “This

means that Xarelto can continue to be used as before, in line with the current prescribing information.” “As a member of the ROCKET AF Executive Committee but equally important as a physician the re-analysis provides me with additional confidence in the strength and robustness of the ROCKET AF trial. It is valuable to be able to provide reassurance to my fellow colleagues but also to our patients and their carers about the evidence for the benefits of rivaroxaban in protecting people with atrial fibrillation from the risk of a stroke,” said Professor Keith A. A. Fox, Duke of Edinburgh Emeritus Professor of Cardiology of the University of Edinburgh, Scotland and Member of the ROCKET AF Executive Committee.

“We are very pleased with EMA’s assessment confirming the positive benefit-risk profile of Xarelto for stroke prevention in patients with atrial fibrillation,” said Dr. Michael Devoy, Head of Medical Affairs & Pharmacovigilance of Bayer AG’s Pharmaceuticals Division and Bayer Chief Medical Officer. “EMA’s assessment follows the conclusions from Bayer and Janssen and those from the independent ROCKET AF Executive Committee that the ROCKET AF data are robust. The re-analyses are reassuring and will provide physicians with additional confidence to prescribe Xarelto for their patients with atrial fibrillation at risk of stroke."


Profile

9

New IMO President makes Calls to Government Dr John Duddy, President, IMO

IMO Vice President and Chair of the NCHD Committee Dr John Duddy has recently taken over as President of the country’s largest representative body for medical practitioners at its AGM held in Sligo last month. The three-day AGM was held this year under the theme, ‘A New Prescription for Health’. Dr Duddy graduated from Trinity College Dublin in 2002 with a BA in Computational Chemistry. He then studied Medicine at UCC, graduating in 2008. He completed internship and basic surgical training at the Mercy University Hospital, Cork and Cork University Hospital. He then worked as a Neurosurgery Registrar at Beaumont Hospital and Children's University Hospital Temple Street, and obtained a Masters in Surgery at RCSI. He is now a Specialist Registrar in Neurosurgery and Lead NCHD at Beaumont Hospital.

The new President took over the reigns from Dr Ray Wallely, and kicked off his term with strong calls to the Government over funding, saying that any Programme for Government negotiated in the must ring-fence a realistic and fair budget for the health services for the coming five years. Speaking as he begins his term of office he strongly criticises the current budget process. “The current budget process for health is simply not credible,” he says. “Nobody really believes the figures when the budget is announced and within weeks stories are planted about potential overruns and problems. The process has no credibility largely because the figures proposed are insufficient to enable the health services to operate on an appropriate basis.” Dr Duddy says that there was significant concern in medical circles at the current political situation. “The recession cutbacks

fundamentally damaged our public health services and simultaneously caused a spike in demand for those same services. As a result we are in a continuous state of crisis management. There is an urgent need for investment and leadership if we are to stabilise the system. This will be challenging for any Government but there is a real concern that it will be beyond the scope of what is likely to be an unstable, short-term administration.”

Dr Duddy criticises recent political commentary which characterised health as a political problem. He says, “People try to objective health as if it’s some obscure issue that is distant from everyday life when in fact it is everything to do with real life. It’s about people receiving life changing treatments, people on trollies and on endless waiting lists for urgently needed surgery, people in emergency departments desperately waiting for attention and help.”

Dr Duddy highlighted the number of doctors now emigrating as a particularly urgent issue. “There is no greater evidence that our system is failing than the thousands of young, highly qualified and expensively trained doctors are choosing to emigrate rather than work here. Few patients can choose to travel for treatment but many doctors can choose to travel for work and they are doing so in every increasing numbers. This is a real threat to the future of the services here.”

The new President has also called on the HSE to take urgent action to tackle the low number of female doctors and consultants at senior levels in the health services. The low number of women in senior medical posts was a key structural weakness in the Irish health services, he says. “From a gender perspective, there has been enormous change in the health services over the past 50 years with increasing numbers of women qualifying as doctors but HPN • April 2016


10 Profile Dr John Duddy with outgoing President Dr Ray Wallely

AGM CALLS FOR A FIVE YEAR INVESTMENT PLAN The AGM of the Irish Medical Organisation (IMO) will heard strong criticism by doctors of  the impact of successive years of cuts on the public health services,a  falling morale amongst doctors leading to increased emigration

that is not being reflected at senior levels because so few women are progressing through to senior positions.” He continues that figures from the Medical Council showed that while there was little difference between the numbers of women and men qualifying from medical school, women account for just 29% of Hospital Consultants and significantly less in certain specialities. Dr Duddy has called for changes to medical training and to working hour regimes in order to make medical posts more attractive to female doctors; “Our current structures are antiquated and unsuitable and they reflect a traditionalist attitude that assumes participants are single-mindedly focused on their careers above all else. These are key factors in discouraging women from progressing their careers.” Dr Duddy says it was significant that few of the women who participated on medical and surgical training schemes progressed to consultant level; “clearly the hours that are required and the nature of the training – including the requirement for people to travel extensively to work for relatively short periods

Professor Pollyck and outgoing President Dr Ray Wallely

April 2016 • HPN

in different locations are totally unsuited to anyone who is interested in starting a family or taking a career break to raise children.” In other news, the IMO has said that the expected shortfall of half a billion euro in funding for the health services was proof that the health budget had been under resourced for the current year and confirmed the IMO contention at the time that the budget figures were not credible. Outgoing President Dr Ray Wallely told HPN that the organisation had warned at the time of the budget that the projected spending figure would be insufficient to cope with demands. He says, “We are looking at a massive shortfall simply because the budget did not provide adequate resources in the first place. The whole budget

process for health is farcical and makes this kind of budget crisis inevitable." He added, “The proposal by the outgoing Government that they will not countenance a supplementary budget and may curtail spending towards the end of the year would cause a major problem in hospital services in particular and is simply not realistic. Treating an overspend this year as a forward payment from next year’s budget is similarly impractical.” Dr Walley says that it was critical that any new Programme for Government would put forward practical, workable solutions to deal with the funding crisis and give certainty to health professionals that they will not be left without funds or resources at the end of the year.

Dr Walley, said that the conference took place at a critical time as various wouldbe participants in Government were considering alternative Programmes for Government for the coming years. He said in his opening address, “We want to ensure that the next Government puts the crisis in our health services centre stage and takes urgent steps to deal with the legacy of years of austerity. We have to put an end to elderly patients lying on trollies for days, young doctors leaving the country rather than practice here and a GP service that cannot meet demand.” The AGM also heard demands that the Departments of Health and Public Expenditure and Reform commit to a five-year investment programme for the health services to redress the effects of the cuts of recent years that have resulted in huge damage to health services and a capacity crisis in hospitals in particular. The AGM heard debates on a range of motions including:  The inadequacy of planned health funding given the effects of the cuts of recent years and the rapidly increasingly elderly population  Worsening conditions in acute hospitals including the need for increased bed capacity, measures to deal with the crisis in emergency departments and the need for structured admission pathways for non emergency patients  The need for proper resourcing of general practice to deliver a modern GP service with the priority being chronic care.  An end to any expansion of the GMS system until existing patients receive a full service under a long overdue new contract


News 11 Hospital awarded for innovation in blood clot prevention The Rotunda Hospital has been awarded an ‘Honourable Mention’ by the U.S. Centres for Disease Control and Prevention (CDC) Healthcare-Associated Venous Thromboembolism (HA-VTE) Prevention Challenge, for its electronic tool, Thrombocalc, which helps to identify women who are at risk of pregnancy associated blood clots. It is the only hospital or medical facility outside of the United States to have been recognised by the CDC. Fellow winners include some of the largest health systems in the USA including the Mayo Clinic. The accolade was awarded by a team of six judges from across the Department of Health and Human Services in the United States. The U.S Centre for Disease Control and Prevention stated “Out of the many outstanding submissions received, the Rotunda Hospital’s submission was chosen as one of four to be awarded Honourable Mention for the innovative and unique approach to prevention of blood clots in special populations and settings.”

Professor Fergal Malone, Master of the Rotunda Hospital

Thrombocalc was developed by a multidisciplinary team in the Rotunda Hospital, and was introduced into clinical practice in late 2014. Thrombocalc is an easy to use electronic tool which allows rapid, accurate assessment of each woman’s risk of blood clots after delivery. The tool has been demonstrated to be highly effective in facilitating the performance and recording of this essential risk assessment. In the last quarter of 2015, the tool was used to assess the risk of blood

clots in 92% of women delivering in the Rotunda Hospital. An online version was developed in collaboration with MEG Clinical Support Tools, an Irish health technology company, and the Thrombocalc team is currently collaborating with other healthcare institutions throughout Ireland on strategies to improve risk assessment methods and expand the use of Thrombocalc in the prevention of pregnancy associated clots.

Professor Fergal Malone, Master of the Rotunda Hospital said, “I would like to congratulate all those involved in the development and implementation of Thrombocalc on receiving an Honourable Mention. I am delighted that the innovation and hard work demonstrated by the team, and the midwives and nursing staff, who have incorporated this risk assessment tool as part of their standard of care, are being given prestigious international recognition by CDC.”

HPRA Workshops The Health Products Regulatory Authority (HPRA) is to host workshops in May to facilitate pharmaceutical manufacturers meet a new EU Directive on the mandatory implementation of safety features on outer packaging of specified medicines, which include a requirement for a unique identifier. The EU Falsified Medicines Directive (FMD) 2011/62/EU introduces the requirement for manufacturers or Marketing Authorisation Holders (MAHs) to add safety features to the outer packaging of specified medicines for human use and to fund a Europe-wide verification system that will enable the authentication of medicines before the unique identifier is decommissioned and the pack is dispensed to a patient. On the aims of the workshop, the HPRA said now that the Delegated Regulation had been published, the Authority would like to provide the industry and healthcare sectors with specific opportunities to engage with it in relation to the implementation of these systems. This will include workshop sessions in the Sheraton Hotel, in Athlone on May 3 and in the Clarion Hotel, Cork on May 4. A similar event will be held at the HPRA Offices on May 5 and 6.

Large variance in hospitals Clinical decision-making has been confirmed as a factor behind major variations in hospitals’ admission patterns, with Letterkenny, for example, having a propensity to admit 40% of patients from EDs, the HSE National Director for Acute Hospitals has revealed. Liam Woods told a seminar in Dublin recently that this compared with a rate of 27% nationally to admit patients from EDs. The admissions rate varied widely: from as low as 9% for children to between 55-60 % for those aged over 85, he noted.

In part, Woods said the reasons were geographic, but clinical decision making was also a factor.

junior clinicians”, according to Woods, and thus a “higher propensity to admit patients”.

In Letterkenny, where patients were potentially more likely to be admitted, the hinterland population was distributed across remote areas and patients were likely to have seen their GPs before attending hospital.

Letterkenny opened 10 additional beds over the recent winter to support the hospital’s emergency department. Trolley numbers then dropped significantly, Woods told a recent health seminar in Dublin.

It may also be the case that in a hospital such as Letterkenny, that struggles to attract and retain senior clinicians, “there may be a higher degree of caution among

Meanwhile, the Executive now knew what its real costs were, Woods said. In developing activitybased funding, the HSE studied the cost of all procedures on a diagnostic-related groups (DRG)

basis and this system went ‘live’ in January. The budget for all hospitals was ¤5.1 billion and ¤3.2 billion of this – related to day case and inpatients – was now covered by activitybased funding, he explained. Costs per case per hospital had now been calculated and the hospitals were aware of these, he added.

HPN • April 2016


12 News

Polypharmacy Commonplace for Older People with Intellectual Disability New findings from Trinity College Dublin’s IDS-TILDA study highlights that polypharmacy is commonplace among older adults with intellectual disabilities. The team’s research discovered that:  People with intellectual disabilities are likely to be exposed to multiple medicines (polypharmacy) to treat a multiple chronic conditions – 20% of participants used 10 or more medicines; over 30% used between five and nine.  While polypharmacy, when used appropriately, plays a critical role in maintaining health, there is clear evidence that it is also associated with increased prescribing errors, and a higher prevalence of drug related adverse effects as more drugs are prescribed. These latest findings, which have just been published in the journal BMJ Open, are drawn from Wave 1 of IDS-TILDA, a nationally representative longitudinal study of older adults with intellectual disability by researchers from Trinity College Dublin. As people with intellectual disability continue to move from institutional to community settings in Ireland, this research is significant as it highlights the need for education and interventions to ensure appropriate provision of medicines. Professor Mary McCarron, the Principal Investigator for IDSTILDA and Dean of the Faculty of Health Sciences noted, “This is the first time there has been a comprehensive review of medicines use in people with

Professor Mary McCarron

The longitudinal nature of our study will allow us to provide a comprehensive insight into changes in medication patterns as people with intellectual disability age and move into community settings and will enable us to examine the effect of multiple medicines on health outcomes and quality of life intellectual disabilities, and particularly older people with intellectual disabilities in Ireland. “The longitudinal nature of our study will allow us to provide a comprehensive insight into changes in medication patterns as people with intellectual disability age and move into community settings and will enable us to examine the effect of multiple medicines on health outcomes and quality of life.” Lead author and Assistant Professor in the School of Pharmacy and Pharmaceutical Sciences Dr Máire O’Dwyer commented, “Our findings highlight that polypharmacy is

commonplace for older adults with intellectual disabilities in Ireland, reflecting the high prevalence of multiple chronic conditions experienced by people with intellectual disabilities. Comprehensive, regular reviews of medicines use are essential, given that polypharmacy may place older adults with intellectual disabilities at risk of side effects.” Dr Martin Henman, co-author and Associate Professor in the School of Pharmacy and Pharmaceutical Sciences commented: “This study provides the first evidence that can be used as the basis for the development of guidelines and education to help health care professionals, especially general

practitioners and community pharmacists in primary care who are called upon to care for older people with ID, as more of them begin to live in the community. “It is also vital that information and education about polypharmacy is made available in an accessible format for people with intellectual disability, and their carers, and IDS-TILDA is looking to bring this work forward in the future.” Initiatives to address these polypharmacy concerns will also likely benefit all older people especially those with cognitive impairment.

Cross border service for heart attack patients Minister for Health Leo Varadkar has welcomed an important new cross-border cardiology service which will give Donegal patients suffering from a STEMI heart attack direct access to services in Altnagelvin Hospital in Derry. “This is the first cross-border service of its kind and represents a mile-stone in medical provision in the north west,” Minister Varadkar said. April 2016 • HPN

“Up to 60 patients suffering from a STEMI heart attack will be treated in Altnagelvin every year. Previously, patients from the region had to be transported to University Hospital Galway so this represents a big saving in terms of treatment time and also distance. It’s just the latest cross-border medical service to be provided and I look forward to future expansion of this service. A further step will be to give

access to Radiotherapy services at Altnagelvin for patients from the Republic.” Patients within 90 minutes’ travelling distance of Altnagelvin Hospital will now have access to 24/7 primary Percutaneous Coronary Invention (pPCI) at the Hospital. It means that STEMI heart attack patients will have rapid access to high quality services on their doorstep.

In a further development, the Saolta Group has appointed a Consultant Interventional Cardiologist at Letterkenny University Hospital, who will help to deliver the pPCI service from Altnagelvin.


BE THE

ONE WHO CAN CHANGE WHAT’S POSSIBLE FOR HCV GT1 ADULT PATIENTS1

HARVONI® – Make cure a reality for the majority of your GT1 patients1–4 In clinical trials of compensated hepatitis C (HCV) patients: • Upto 99% Cure 1-4 •

94–97% of treatment-naïve, non-cirrhotic patients with 8 wks*4

99% of treatment-naïve patients with 12 wks2

94–99% of treatment-experienced patients with 12–24 wks 3

• 8 weeks may be considered for treatment-naïve, non-cirrhotic patients1 •

One pill once a day1

• The 1st and ONLY HCV GT1 SINGLE TABLET REGIMEN Compensated cirrhosis, decompensated cirrhosis and post-transplant patients may require the addition of RBV

Albert Einstein used with permission of the HUJ/GreenLight.

*97% relates to the SVR for patients with a viral load of less than 6 million IU/ml

HARVONI is indicated for the treatment of chronic hepatitis C infection in adults1 ®

PRESCRIBING INFORMATION Consult the Summary of Product Characteristics before prescribing. HARVONI® 90mg ledipasvir/400mg sofosbuvir film coated tablets. Indications: For the treatment of chronic hepatitis C (CHC) in adults. Dosage & Administration: Adults: One tablet, taken orally, once daily with or without food. Genotype 1, 4, 5 or 6; without cirrhosis: 12 weeks of treatment with Harvoni is recommended. 8 weeks may be considered in previously untreated genotype 1-infected patients. Harvoni + ribavirin for 12 weeks or Harvoni (without ribavirin) for 24 weeks should be considered for previously treated patients with uncertain subsequent retreatment options. Genotype 1, 4, 5 or 6; with compensated cirrhosis: Harvoni + ribavirin for 12 weeks or Harvoni (without ribavirin) for 24 weeks of treatment with is recommended. Harvoni (without ribavirin) for 12 weeks may be considered for patients deemed at low risk for clinical disease progression and who have subsequent retreatment options. Genotype 1, 4, 5 or 6; post liver transplant without cirrhosis or with compensated cirrhosis: Harvoni + ribavirin for 12 weeks. Harvoni (without ribavirin) for 12 weeks (in patients without cirrhosis) or 24 weeks (in patients with cirrhosis) may be considered for patients who are ineligible for or intolerant to ribavirin. Genotype 1, 4, 5 or 6; with decompensated cirrhosis: Harvoni + ribavirin for 12 weeks. Harvoni (without ribavirin) for 24 weeks may be considered in patients who are ineligible for or intolerant to ribavirin. Genotype 3 with compensated cirrhosis and/or prior treatment failure: 24 weeks treatment with Harvoni in combination with ribavirin is recommended. Please refer to the SmPC for recommended dose & treatment duration for combination therapy. When used in combination with ribavirin, refer also to the SmPC of ribavirin. Refer to the individual SmPCs for additional information regarding dose modifications & discontinuations. Renal impairment: Mild or moderate renal impairment: no dose adjustment required. Severe renal impairment or end stage renal disease (ESRD) requiring haemodialysis: not recommended. Refer to the SmPC for ribavirin for patients with creatinine clearance (CrCl) < 50 mL/min. Hepatic impairment: Mild, moderate or severe hepatic impairment: no dose adjustment required. Safety and efficacy of Harvoni have been established in patients with decompensated cirrhosis. Children and adolescents: The safety and efficacy of Harvoni in children & adolescents aged <18 years have not yet been established. Elderly: No dose adjustment is warranted for elderly patients. Contraindications: Hypersensitivity to the active substance or to any of the excipients, and co-administration with rosuvastatin or St. John’s wort (Hypericum perforatum). When Harvoni is used in combination with ribavirin, the contraindications applicable to that agent is applicable to combination therapies. Refer to the ribavirin SmPC for a list of contraindications. Warnings and Precautions: Harvoni should not be administered concomitantly with other medicinal products containing sofosbuvir. The clinical data to support the use of Harvoni in HCV genotype 2, 3 and 6 patients are limited. A conservative 24 weeks of therapy is advised in all treatment-experienced genotype 3 patients and those treatmentnaïve genotype 3 patients with cirrhosis. Severe bradycardia and heart block: Cases of severe bradycardia and heart block have been observed when Harvoni is used with concomitant amiodarone with or without other drugs that lower heart rate. The mechanism is not established. Should concomitant use of amiodarone be considered necessary, it is recommended that patients are closely monitored when initiating Harvoni. All patients receiving Harvoni in combination with amiodarone with or without other drugs that lower heart rate should be warned of the symptoms of bradycardia and heart block and should be advised to seek medical advice urgently should they experience them. Patients who are identified as being high risk of bradyarrhythmia should be continuously

Cure defined as SVR12

1. HARVONI® SmPC available at https://www.medicines.org.uk/emc/medicine/29471 (Accessed March 2016) 2. Afdhal N et al. N Engl J Med 2014;370:1889–1898. 3. Afdhal N et al. N Engl J Med 2014;370:1483–1493. 4. Kowdley KV et al. N Engl J Med 2014;370:1879– 1888. 5. Gilead Data On File – SOFUK1601 (February 2016)

monitored for 48 hours in an appropriate clinical setting. Due to the long half-life of amiodarone, appropriate monitoring should also be carried out for patients who have discontinued amiodarone within the past few months and are to be initiated with Harvoni. Treatment of patients with prior exposure to HCV direct-acting antivirals: There are no data to support the effectiveness of retreatment of patients who have failed Harvoni with a subsequent regimen that contains an NS5A inhibitor. Consideration should be given to longer treatment for patients with uncertain subsequent retreatment options. Patients with decompensated cirrhosis and/or who are awaiting liver transplant or post-liver transplant: The efficacy of Harvoni in genotype 5 and 6 with decompensated cirrhosis and/or who are awaiting liver transplant or post-liver transplant has not been investigated. Treatment with Harvoni should be guided by an assessment of the potential benefits and risks for the individual patient. Use with potent P-gp inducers: Medicinal products that are potent P-glycoprotein (P-gp) inducers (e.g. rifampicin, carbamazepine and phenytoin) may significantly decrease ledipasvir and sofosbuvir plasma concentration which may lead to reduced therapeutic effect of Harvoni. Such medicinal products should not be used with Harvoni. Use with certain HIV antiretroviral regimens: Harvoni has been shown to increase tenofovir exposure, especially when used together with an HIV regimen containing tenofovir disoproxil fumarate and a pharmacokinetic enhancer (ritonavir or cobicistat). The safety of tenofovir disoproxil fumarate in this setting has not been established. The potential risks and benefits associated with co-administration of Harvoni with the fixed-dose combination tablet containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate or tenofovir disoproxil fumarate given in conjunction with a boosted HIV protease inhibitor (e.g. atazanavir or darunavir) should be considered, particularly in patients at increased risk of renal dysfunction. Patients receiving Harvoni concomitantly with elvitegravir/cobicistat/ emtricitabine/tenofovir disoproxil fumarate or with tenofovir disoproxil fumarate and a boosted HIV protease inhibitor should be monitored for tenofovir-associated adverse reactions. Refer to the SmPCs of the aforementioned agents for recommendations on renal monitoring. Use with HMG-CoA reductase inhibitors: Co-administration of Harvoni and HMG-CoA reductase inhibitors (statins) can significantly increase the concentration of the statin, which increases the risk of myopathy and rhabdomyolysis. HCV/HBV co-infection: There are no data available. Excipients: Harvoni contains sunset yellow FCF aluminium lake (E110), which may cause allergic reactions. It also contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take Harvoni. Interactions: Harvoni should not be administered concomitantly with other medicinal products containing sofosbuvir. Ledipasvir is an in vitro inhibitor of drug transporter P-gp and breast cancer resistance protein (BCRP) and may increase intestinal absorption of co-administered substrates for these transporters. Ledipasvir may be a weak inducer of metabolising enzymes such as CYP3A4, CYP2C and UGT1A1. Compounds that are substrates of these enzymes may have decreased plasma concentrations when co-administered with Harvoni. In vitro ledipasvir inhibits intestinal CYP3A4 and UGT1A1. Medicinal products that have a narrow therapeutic range and which are metabolised by these isoenzymes should be used with caution and carefully monitored. Ledipasvir and sofosbuvir are substrates of drug transporter P-gp and BCRP while GS-331007 is not. Medicinal products that are potent P-gp inducers (e.g. rifampicin, St. John’s wort, carbamazepine and phenytoin) may decrease ledipasvir and sofosbuvir plasma concentrations leading to reduced therapeutic effect of Harvoni and should not be used with Harvoni. Co-administration with medicinal products that inhibit

P-gp and/or BCRP may increase ledipasvir and sofosbuvir plasma concentrations without increasing GS-331007 plasma concentration; Harvoni may be co-administered with P-gp and/or BCRP inhibitors. Refer to SPC for full information regarding interactions. Use in pregnancy and lactation: When Harvoni is used in combination with ribavirin; extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Significant teratogenic and/or embryocidal effects have been demonstrated in all animal species exposed to ribavirin. Women of childbearing potential or their male partners must use an effective form of contraception during treatment and for a period of time after the treatment has concluded as recommended in the SmPC for ribavirin. Refer to the SmPC for ribavirin for additional information. There are no or limited amount of data (<300 pregnancy outcomes) from the use of ledipasvir, sofosbuvir or Harvoni in pregnant women. As a precautionary measure, it is preferable to avoid the use of Harvoni during pregnancy. Harvoni should not be used during breast-feeding. See also the SmPC for ribavirin for pregnancy and breast-feeding. Side effects: When Harvoni was studied with ribavirin, the most frequent adverse drug reactions to Harvoni in combination with ribavirin were consistent with the known safety profile of ribavirin, without increasing the frequency or severity of the expected adverse drug reactions. The following adverse drug reactions have been identified with Harvoni. Frequencies are defined as follows: Very commonly reported adverse events (≥1/10): headache and fatigue. Description of selected adverse reactions; Cardiac arrhythmias: Cases of severe bradycardia and heart block have been observed when Harvoni is used with concomitant amiodarone and/or other drugs that lower heart rate. Legal Category: POM. Package Quantities: Bottle of 28 film-coated tablets. Price: UK NHS Price - £12,993.33; Eire Price - €TBA Marketing Authorisation Number: EU/1/14/958/001 Further information is available from the local representative of the marketing authorisation holder: Gilead Sciences Ltd, 280 High Holborn, London, WC1V 7EE, UK. Telephone: +44 (0) 8000 113700, For Ireland: +353 214 825 999. E-mail: ukmedinfo@gilead.com. Harvoni is a trademark. Date of PI preparation: January 2016: HAR/UK/15-11/MM/1992(1) This medicinal product is currently subject to additional monitoring. Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse reactions to Harvoni should be reported to Gilead via email to safety_FC@gilead.com or by telephone +44 (0) 1223 897500. Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Suspected adverse reactions should be reported to the HPRA Pharmacovigilance using a Yellow Card obtained either from the HPRA, or electronically via the website at www.hpra.ie. Adverse reactions can also be reported to the HPRA by calling +353 1 6764971. © 2016 Gilead Sciences, Inc. All rights reserved. Date of preparation: March 2016 HAR/UK/14-11/MI/1033(5)


14 Report

Stroke deaths down, but patients still suffering, finds report Professor Joe Harbison, HSE National Stroke Programme Lead; Ms Joan McCormack, Stroke Audit Project Manager, Irish Heart Foundation; and Dr Paul McElwaine, Research Fellow, St James’s Hospital, Dublin

guidelines. And whilst half of stroke survivors suffer anxiety, depression, or severe psychological distress, access to services was limited to just two hospitals nationally.

The death rate from stroke in Ireland has been cut by more than a quarter and the rate of direct discharge to nursing homes has almost halved in the last seven years, a national audit of acute stroke services carried out by the Irish Heart Foundation and HSE has revealed. This study showed that in-hospital mortality has been reduced from 19% to 14%, whilst 8% of patients are now being discharged to nursing homes, compared to 15% in 2008 when the previous national audit was conducted. Around 7,000 are hospitalised due to stroke here each year. The death toll of just below 2,000 makes stroke Ireland’s third biggest killer disease after cancer and heart disease. The improvement in outcomes has been driven by the HSE’s National Stroke Programme, which has led a reorganisation of acute stroke services in Ireland, increasing the number of hospitals with stroke units from one to 21 and raising the rate of potentially lifesaving thrombolysis (clot-busting) treatment tenfold to 11% - one of the highest national rates in the world – in the wake of the Irish Heart Foundation’s FAST campaign. Despite the Programme’s success in developing services, many stroke deaths remain preventable, whilst a high proportion of stroke survivors continue to suffer undue disability in terms of both severity and length of time due to inadequate rehabilitation services. For example, despite their crucial importance in improving outcomes, only 29% of patients are admitted directly to a stroke unit and almost half do not receive treatment in a unit at any point during their hospital April 2016 • HPN

stay. Nearly a quarter of hospitals providing acute stroke care do not meet minimum requirements and three of these had none of the required infrastructure in place for a stroke unit. In addition, there are staffing deficits of 50% for physiotherapists, 61% for occupational therapists and 31% for speech and language therapists, whilst only 44% of hospitals had any access to medical social workers and 19% had access to a neuropsychologist. “The audit shows encouraging improvement in many areas of stroke care that has been achieved in the midst of the worst economic crisis in the history of the State, a rapidly contracting health service and just a small amount of dedicated financial resource,” said National Stroke Programme colead Professor Joe Harbison, who led the audit along with, Dr Paul McElwaine and project manager Joan McCormack of the Irish Heart Foundation. Professor Harbison continued, “But the progress made cannot take away from persistent substantial deficits in services. The study shows that only about half of patients are admitted to a stroke unit at any time during their hospital stay. Treatment in a stroke unit is the most basic standard in the care of stroke patients and substantially improves the chances of independent recovery after a stroke.” Professor Harbison said there is also a large deficit in the availability of rehabilitation services to stroke patients with few receiving the level of any therapy recommended in national and international

He concluded that there had been little additional investment in stroke care since the National Stroke Programme was established, “To maintain the improvements and to progress care of our fellow citizens suffering stroke to a level commensurate with a modern Western country, further investment in stroke services is undoubtedly necessary.” Irish Heart Foundation Head of Advocacy, Chris Macey said given that only around half of patients were receiving the benefit of the service improvements, it was reasonable to assume that many patient deaths from stroke in Ireland were entirely preventable. In addition, whilst more people than ever were surviving stroke, in-hospital rehabilitation service levels were grossly inadequate and community rehabilitation provision was even worse. This was exemplified by audit results showing just one hospital in Ireland has access to a specialist community stroke rehabilitation team and only three have a hospital/community stroke liaison worker. Mr Macey said, “More people are returning home after stroke than ever before due to reductions in death and discharge to nursing homes. But after they pass back through the hospital gates most are effectively being abandoned. We need extra investment to ensure that nobody who has a stroke in Ireland dies because services fail to meet minimum standards. And we need to develop rehabilitation services to ensure that the recovery of patients is not squandered after so much skill and commitment is deployed to save their lives.” Professor Harbison added that Early Supported Discharge teams are currently operating from just four hospitals nationwide, despite strong evidence of their

effectiveness in reducing length of hospital stay. This now stands at 22.4 days according to the audit, which although a week less than in 2008 is still around a week longer than in the UK. He also called for greater investment in the new clot retrieval therapy, thrombectomy, which Irish doctors have helped to pioneer and which trials show could reduce death and severe permanent disability from stroke by 50%. KEY FACTS • 27 hospitals in Ireland treat stroke patients during the acute phase of their care. • 21 hospitals have a stroke unit, up from 1 stroke unit in the whole country in the 2008 audit. • The 2015 audit found 150 stroke beds nationally. However, 61% of inpatients with a stroke at the time of the audit were being managed on a ward other than a stroke unit. • 29% of patients are admitted directly to a stroke unit, whilst almost half do not receive treatment in a stroke unit at any point during their stay. • The estimated national thrombolysis rate of 11% (clotbusting treatment) is comparable to international rates, with the 2014 UK rate being approximately 12% of all strokes. • Only 36% of patients have a swallow screening in the first 24 hours, compared to over 80% in the UK. • 23 hospitals (85%) have a consultant physician with specialist knowledge of stroke; up from one third of hospitals in the 2008 audit. 23 hospitals have a clinical nurse specialist (CNS) in stroke. • There are large gaps in staffing of multidisciplinary stroke teams across the country. There is a staffing deficit of: 69% for clinical nutrition; 61% for occupational therapy; 50% for physiotherapy; and 31% for speech and language therapy. • The length of time stroke patients spend in hospital has reduced from almost 30 days in the 2008 audit to just over 22 days in 2015. • Only 8% of patients were newly admitted to nursing homes in 2015, compared to 15% in 2008. • There are only three early supported discharge teams in Ireland, serving suitable patients in four hospitals.


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Proven efficacy comparable to well-controlled warfarin1,2 Superior reduction in clinically relevant bleeding vs. well-controlled warfarin1,2 Once-daily dosing across both NVAF and VTE indications3 Indicated for: 3 Prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation (NVAF) with one or more risk factors, such as congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischaemic attack (TIA) Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults LIXIANA▼ (edoxaban) 60 mg/30 mg/15 mg film coated tablets ▼ This medicine is subject to additional monitoring. This will allow quick identification of new safety information. See summary of product characteristics prior to prescribing for full list of adverse events. Presentation: 60 mg (yellow) / 30 mg (pink) / 15 mg (orange) edoxaban film coated tablets (as tosilate). Indications: Prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation (NVAF) with one or more risk factors, such as congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischaemic attack (TIA) and treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults. Posology and method of administration: NVAF - The recommended dose is 60 mg edoxaban once daily with or without food. Therapy with edoxaban in NVAF patients should be continued long term. VTE - The recommended dose is 60 mg edoxaban once daily following initial use of parenteral anticoagulant for at least 5 days with or without food. Duration of therapy (at least 3 months) should be based on risk profile of the patient. For NVAF and VTE the recommended dose is 30 mg edoxaban once daily in patients with one or more of the following clinical factors: moderate or severe renal impairment (creatinine clearance (CrCl) 15–50 ml/min), low body weight ≤60 kg and/or concomitant use of the following P-glycoprotein (P-gp) inhibitors: ciclosporin, dronedarone, erythromycin, or ketoconazole. The 15 mg dose of edoxaban is not indicated as monotherapy, and should only be used during a switch from edoxaban to VKA (see SmPC for full details). If a dose of edoxaban is missed, the dose should be taken immediately and then continued once daily on the following day. Contraindications: Hypersensitivity to the active substance or to any of the excipients; clinically significant active bleeding. Hepatic disease associated with coagulopathy and clinically relevant bleeding risk. Lesion or condition, if considered to be a significant risk for major bleeding. This may include current or recent gastrointestinal (GI) ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities. Uncontrolled severe hypertension. Concomitant treatment with any other anticoagulants e.g. UFH, low molecular weight heparins, heparin derivatives (fondaparinux, etc.), VKA or NOACs except under specific circumstances of switching oral anticoagulant therapy or when UFH is given at doses necessary to maintain an open central venous or arterial catheter. Pregnancy and breastfeeding. Special warnings and precautions for use: Haemorrhagic risk: Use with caution in patients with increased risk of bleeding such as elderly on ASA and should be discontinued if severe haemorrhage occurs. The anticoagulant effect of edoxaban cannot be reliably monitored with standard laboratory testing. A specific anticoagulant reversal agent for edoxaban is not available. Haemodialysis does not significantly clear edoxaban. Renal impairment: Renal function should be assessed prior to initiation of edoxaban and afterwards when clinically indicated. Not recommended in patients with end stage renal disease or on dialysis. Renal function and NVAF: A trend towards decreasing efficacy with increasing creatinine clearance was observed for edoxaban compared to well-managed warfarin. Edoxaban should only be used in patients with NVAF and high creatinine clearance after a careful benefit risk evaluation. Hepatic impairment: Not recommended in patients with severe hepatic impairment and should be used with caution in patients with mild or

www.lixiana.ie

moderate hepatic impairment. Edoxaban should be used with caution in patients with elevated liver enzymes (ALT/ AST > 2 x ULN) or total bilirubin ≥1.5 x ULN. Surgery or other interventions: discontinue edoxaban at least 24 hours before the procedure. If the procedure cannot be delayed, the increased risk of bleeding should be weighed against the urgency of the procedure. Edoxaban should be restarted as soon as haemostasis is achieved. Prosthetic heart valves and moderate to severe mitral stenosis: Not recommended. Haemodynamically unstable PE patients or patients who require thrombolysis or pulmonary embolectomy: Not recommended. Patients with active cancer: Not recommended. Drug interactions: The P-gp inhibitors ciclosporin, dronedarone, erythromycin, or ketoconazole result in increased concentration of edoxaban and a dose reduction of 30 mg is required. Edoxaban should be used with caution with concomitant P-gp inducers (e.g. phenytoin, carbamazepine, phenobarbitol or St John’s Wort). Concomitant high dose ASA (325 mg) or chronic NSAIDs is not recommended. There is very limited experience with dual antiplatelet therapy or fibrinolytic agents. Pregnancy: Not recommended. Breastfeeding: discontinue breastfeeding or edoxaban therapy. Undesirable effects: Common: anaemia, epistaxis, lower GI haemorrhage, upper GI haemorrhage, oral/pharyngeal haemorrhage, nausea, blood bilirubin increased, gamma GT increased, cutaneous soft tissue haemorrhage, rash, pruritus, macroscopic haematuria/urethral haemorrhage, vaginal haemorrhage, puncture site haemorrhage, liver function test abnormal. Uncommon: hypersensitivity, intracranial haemorrhage (ICH), intraocular haemorrhage, other haemorrhage, haemoptysis, surgical site haemorrhage. Rare: anaphylactic reaction, allergic oedema, subarachnoid haemorrhage, pericardial haemorrhage, retroperitoneal haemorrhage, intramuscular haemorrhage (no compartment syndrome), intra-articular haemorrhage, subdural haemorrhage, procedural haemorrhage. Legal category: POM. Package quantities: 60 mg/30 mg – 28 tablets. 15 mg – 10 tablets. Marketing Authorisation (MA) number: EU/1/15/993/001-16. MA holder: Daiichi Sankyo Europe GmbH, Zielstattstrasse 48, 81379 Munich, Germany. Additional Information: Available on request from Daiichi Sankyo Ireland Ltd. Telephone: (01) 489 3000. Fax: (01) 489 3033. Email: medinfo@daiichi-sankyo.ie. Date of preparation: July 2015. ▼ This medicine is subject to additional monitoring. Adverse events and product complaints should be reported. To report an adverse event or a product complaint about a Daiichi Sankyo medicine, please call Daiichi Sankyo Ireland Ltd. on (01) 489 3000. Healthcare professionals are also asked to report any suspected adverse reactions to Daiichi Sankyo medicines to HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: (01) 676 4971; Fax: (01) 676 2517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

References: 1. Giugliano RP et al. NEJM 2013;369(22):2093–2104. 2. The Hokusai-VTE Investigators. NEJM 2013;369(15):1406–1415. 3. LIXIANA®, Summary of Product Characteristics, www.medicines.ie, September 2015. Date of item: July 2015. EDX/15/0169


16 News

Anticoagulants reduce risk of death in atrial fibrillation patients by 38% Anticoagulants reduce the risk of death in patients with newly diagnosed atrial fibrillation by 38%, according to the 2-year outcomes from the GARFIELD-AF registry, a mixed population of anticoagulated and non-anticoagulated patients representing real-life practice across the globe. The same was found for stroke/systemic embolism (SE)—a reduction in the range of 38%. DEATH IS THE MOST FREQUENT ADVERSE EVENT An analysis of GARFIELD-AF cohorts 1 and 2 (17 162 patients) shows that the most frequent adverse event was all-cause mortality. Stroke/SE and major bleeding were far less frequent. During the 2-year follow-up, ∼45% of these patients died from congestive heart failure or sudden/ unwitnessed death. Slightly fewer patients suffered noncardiovascular deaths, of which >50% died from malignancy or respiratory failure. PATIENT CHARACTERISTICS Patients were 70 years old on average, and almost 40% were over 75. Anticoagulation treatment was given to roughly 60% of patients, but only 10% of them were taking non-vitamin K antagonist oral anticoagulants (NOACs). The vast majority of patients had a CHA2DS2-VASc score above 2, an indicator for anticoagulant

treatment. HAS-BLED scores were low in most patients. Only 11% of patients had a HAS-BLED score of 3, which is considered to be high risk for bleeding. Uptake of anticoagulants rose with increasing CHA2DS2-VASc scores and declined with increasing HAS-BLED scores. VARIABLES ASSOCIATED WITH RISK OF DEATH, STROKE/SE, AND MAJOR BLEEDING Further analyses examined which variables of the CHA2DS2-VASc score were associated with risk of death, stroke/SE, and major bleeding. The 2-year adjusted hazard ratios show that age had the strongest association with all three events. Female gender, diabetes, and hypertension did not appear to have a significant impact on any of the events. Previous stroke/transient ischaemic attack (TIA)/SE had a major impact on risk of death and stroke but no effect on major bleeding. Cardiac failure and vascular disease also had a major impact on death but little effect on stroke/SE or major bleeding. Several variables not included in the CHA2DS2-VASc score were strongly associated with the risk of adverse outcomes. Renal disease was by far, with age, the variable most strongly associated with risk of death, stroke/SE, and major bleeding. Analysis by ethnicity showed that Asians had a lower risk of death.

Smoking, particularly in current smokers but also ex-smokers, had a huge impact on the risk of death. While it did not increase the risk of stroke/SE, smoking did result in an excess of bleeding. This effect of smoking on bleeding has been described in the setting of acute coronary syndrome and coronary artery disease. However, to the best of our knowledge, this is the first time it has been shown in newly diagnosed atrial fibrillation. Analysis by type of atrial fibrillation showed that permanent, persistent, and newly diagnosed atrial fibrillation was associated with a significantly higher risk of death compared with paroxysmal atrial fibrillation. The risk of stroke/ SE or bleeding did not differ by type of atrial fibrillation.

LOW-RISK PATIENTS There are a couple of interesting points to note about patients at truly low risk, meaning those with a CHA2DS2-VASc score of 0. First is that 40% of these patients were anticoagulated, which is not recommended in the guidelines. Second is that while the risks of stroke/SE, major bleeding, and all-cause mortality all rose with increasing CHA2DS2-VASc score, patients with a score of 0 still had a nearly 2% risk of death. It means that low risk does not mean no risk. The latest research study results were published in the 2016 Spring issue of the European Heart Journal.

Expression of interest – NCCP Working Group The National Cancer Control Program (NCCP) is seeking expressions of interest from hospital pharmacists working in aseptic compounding units in joining a working group to develop a capacity planning tool. In 2014 the NCCP published the findings of an Oncology Medication and Safety review which was conducted across the 26 hospitals in Ireland involved in the administration of systemic anti-cancer therapy (SACT) in adults and children. A key recommendation from this review was to develop: “A capacity-planning model to support hospitals in their local service planning with regard to day ward activity and staffing requirements” Capacity planning is used to examine volume and complexity of workload, time available and the staff and facilities required. It can be used as a tool to plan chemotherapy services in order to measure the growing demand for SACT using finite resources. In line with this, the NCCP has established a working group to develop a National Capacity Planning Model for pharmacy aseptic compounding units providing SACT in the hospital setting. This would be an initial step towards an overall capacity-planning model as outlined in recommendation 17 of the NCCP Oncology Medication Safety Review. The appointment term will be approximately six months, with three to four meetings being held during this time. All meetings can be facilitated by teleconference. The working group may be reconvened from time to time to facilitate refreshing of the documentation. Queries relating to this EoI should be addressed in writing to: oncologydrugs@cancercontrol.ie. In addition, the NCCP is seeking feedback on draft dose banding documents which include:  Dose banding tables  Dose banding guidance document  Dose banding implementation & FAQ document These will be issued to hospital CEOs on April 11th for distribution to staff working in the provision of cancer care services. Additional copies of the documentation and the feedback form can be requested from oncologydrugs@cancercontrol.ie

April 2016 • HPN


18 Feature

Genetics play a role in IBD patients Genetic variation in patients with inflammatory bowel disease (IBD) appears to play a major role in determining how sick they will become and could provide a road map for more effective treatments. The findings of an international study of 35,000 patients with the two most common forms of the illness, Crohn's disease and ulcerative colitis, appears in The Lancet. Investigators compared the clinical records of IBD patients with data collected from analysing their DNA in what is considered the largest study of its kind. The genetic information provided new insights into the progression of IBD and the rate at which the disease develops. Researchers said the findings showed that IBD actually may be an array of bowel disorders. "This new research strongly suggests that we are dealing a number of different diseases hidden within Crohn's disease and ulcerative colitis, constituting a large spectrum of inflammatory bowel disease," said Dermot McGovern, MD, PhD, MRCP(UK), director of Translational Medicine in the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute at Cedars-Sinai. IBD is caused when the body's immune system attacks the gastrointestinal tract, causing chronic and damaging inflammation. Around 15,000 people are living with IBD in Ireland. Both diseases cause ulceration of the digestive tract. Crohn’s disease can affect anywhere from the mouth to rectum (but most commonly affects the small intestine). Ulcerative colitis is restricted to the large intestine (colon). There is currently no known cause or cure for IBD. Surgery and medications that can repair the immune system are considered the most effective treatments. Researchers found that genetic analysis could potentially identify which patients might benefit from earlier intervention with more aggressive therapy. "We have very effective therapies for IBD if we use them sooner April 2016 • HPN

in the disease, especially for those patients who are at risk for developing a serious form of illness," said McGovern, co-senior author of the study. "We want to understand what the important, singular, genetic signature is for each individual patient because they may respond to available therapies very differently, even with the same IBD diagnosis." The research provides an important pathway to improve patient care. "Genetic research of this magnitude of sample size provides critical information about IBD that takes us farther down the road to providing personalized diagnosis and care to our patients with complex disorders," said Shlomo Melmed, MD, executive vice president of Academic Affairs and dean of the medical faculty. "Individualising treatment approaches will help ensure we are getting the most appropriate treatment to the right patient at the correct time." McGovern pointed out that while the study is an important step, it also raises new questions. He said that genes associated with IBD also are connected to other autoimmune diseases, including spondylitis and psoriasis. As such, the research has implications for managing those conditions. "For many of our patients, these new genetic insights could be very beneficial," McGovern said. "But we also need to look more closely at some of the sickest IBD patients in hopes of providing more effective treatment and disease management." School of Medicine Researchers Provide New Hope for Children With IBD Inflammatory Bowel Disease (IBD) affects hundreds of children in Ireland and the numbers are rising, but new research led by the School of Medicine’s Dr Patrick Walsh offers hope to people with IBD by opening the door to a new drug therapy. This National Children’s Research Centre (NCRC) and Science Foundation Ireland-funded research into IBD took place at Our Lady’s Children’s Hospital Crumlin (OLCHC) in children diagnosed

with the condition. The research was a collaboration between Dr Walsh and Consultant Paediatric Gastroenterologist Dr Seamus Hussey. IBD is the name used for diseases which cause ulceration of the digestive tract. The most common forms are Crohn’s disease and Ulcerative colitis. IBD is a chronic, debilitating condition, which prevents the digestive system from working. Symptoms include persistent diarrhea, vomiting, abdominal pain, bleeding, severe weight loss and chronic fatigue. There are in the region of 20,000 children and adults in Ireland affected by IBD in one former or another. The key finding from this research, which has just been published in the scientific Journal Muscosal Immunology, is that a protein called IL-36 is found in higher levels at diagnosis in children attending the national paediatric IBD service at OLCHC. By taking a translational approach, and examining younger patients upon initial diagnosis at Our Lady’s Children’s Hospital, Dr Walsh, along with Dr Shane Russell and Dr Rachel Horan, identified a gene which was altered among a specific group of patients presenting with a form of IBD known as ulcerative colitis.

They then went on to establish in the laboratory that this gene plays an important role in driving inflammation in the gut and may represent a possible future novel drug target for this disease. Commenting on the research findings, Dr Walsh said, “This is good news for children and adults with IBD as it means it is now possible for someone to develop a drug to treat the condition. If such a drug can be found to reduce IBD levels in children, this might turn off the disease or reduce the symptoms.” Dr Hussey added, “Ireland has a growing rate of IBD for reasons that we do not year clearly understand. In the past decade the number of new cases of IBD in children attending OLCHC has increased by over 90% and numbers continue to rise.” Dr Walsh further added, “The only way to find out exactly what’s happening is to continue our scientific investigations into IBD in children here in Ireland. It is only through these investigations that we can hope to find a reason for the increase, and ultimately to find a better way to treat the condition.”


Introducing Entyvio: the rst and only gut-selective biologic for patients with moderately to severely active ulcerative 1 colitis (UC) or Crohn’s disease (CD)

TREAT WITH PRECISION The first and only gut-selective biologic 1 Achieved remission at Week 52 in: 42% of UC patients vs 16% for placebo in patients responding at Week 6 (P<0.001) 39% of CD patients vs 22% for placebo in patients responding at Week 6 (P<0.001) Targeted mechanism of action 1 different from anti-TNFα therapies

One dose for all patients1 : 300-mg IV infusion

References: 1. Entyvio Summary of Product Characteristics. Takeda Pharmaceuticals Ireland Ltd. www.medicines.ie ITEM CODE: IRE/VED/14/0008c(1) DATE OF PREPARATION: October 2015

© 2015 Takeda Pharmaceuticals International GmbH Entyvio® ▼ (vedolizumab) PRESCRIBING INFORMATION Refer to the Summary of Product Characteristics (SmPC) before prescribing. Presentation: 300 mg powder for concentrate for solution for infusion. Indication: Adult patients with moderately to severely active ulcerative colitis(UC)/Crohn’s disease (CD) who have had an inadequate response with, lost response to, or were intolerant to either conventional therapy or a tumour necrosis factor-alpha (TNFα) antagonist. Dosage & Administration: Treatment should be initiated and supervised by a specialist healthcare professional experienced in diagnosis and treatment of ulcerative colitis or Crohn’s disease. Patients should be monitored during and after infusion in a setting equipped to manage anaphylaxis. Ulcerative colitis: Recommended dose regimen 300mg administered by intravenous infusion over approximately 30 minutes at 0, 2, 6 weeks and 8 weeks thereafter. Reconsider treatment if no evidence of therapeutic benefit at week 10. If patients experience a decrease in response, they may benefit from increased dosage frequency to 300mg every 4 weeks. Corticosteroids may be reduced/discontinued in patients who respond to treatment with Entyvio. If therapy is interrupted and needs to be restarted, Entyvio dosing every 4 weeks may be considered. Crohn’s disease: Recommended dose regimen is 300mg administered by intravenous infusion over approximately 30 minutes at 0, 2, 6 weeks and 8 weeks thereafter. Patients who have not shown evidence of therapeutic benefit may benefit from a dose at week 10. Continue therapy every 8 weeks from week 14 in responding patients. Therapy should be discontinued if no evidence of therapeutic benefit is observed at week 14. If therapy is interrupted and needs to be restarted, Entyvio dosing every 4 weeks may be considered. Paediatric populations: No data available in children aged 0-17 years. Not recommended. Elderly patients: No dosage adjustment required. Renal or hepatic impairment: Entyvio has not been studied in these populations. No dose recommendation can be given. Contraindications: Hypersensitivity to Entyvio or any of the excipients. Active infections such as tuberculosis (TB), sepsis, cytomegalovirus, listeriosis and opportunistic infections such as Progressive Multifocal Leukoencephalopathy (PML). Warnings and Precautions: Patients should be observed continuously during infusions for signs/symptoms of hypersensitivity reactions. Patients should continue to be observed for two hours following infusion completion for the first two infusions and one hour for subsequent infusions. Infusion-related reactions (IRR): Hypersensitivity reactions have been reported, the majority were of mild to moderate severity. Discontinue treatment if anaphylaxis or other serious allergic reactions occur and institute appropriate treatment. In mild to moderate IRR, slow or interrupt infusion. Consideration for pre-treatment with antihistamine, hydrocortisone and/or paracetamol should be given prior to next infusion, for patients with history of mild/moderate IRR to Entyvio. Infections: Not recommended in patients with active, severe infections until infections are controlled. Consider withholding in patients who develop severe infection while on treatment with Entyvio. Before initiating treatment, patients must be screened for TB. If latent TB is diagnosed, anti-tuberculosis appropriate treatment must be initiated prior to Entyvio treatment.

Progressive Multifocal Leukocephalopathy (PML): No cases were observed in Entyvio clinical trials, but John Cunningham (JC) virus infection resulting in PML and death has occurred in patients treated with other integrin receptor antagonists and systemic immunosuppressive agents. A risk of PML cannot be ruled out. Monitor patients for any new or worsening neurological signs/symptoms. Malignancy: Underlying increased risk of malignancy in UC and CD. Immunomodulatory products may increase risk. Prior and concurrent use of biological products: No clinical data available for Entyvio use in patients previously treated with natalizumab or rituximab. Patients previously exposed to natalizumab should wait at least 12 weeks prior to initiating Entyvio therapy. Entyvio not recommended for concomitant use with biologic immunosuppressants as no clinical data available. Live and oral vaccines: Patients may continue to receive non-live vaccines. Patients recommended to be up-to-date with all appropriate immunisations prior to initiating Entyvio. Live vaccines may be administered concurrently only if benefit clearly outweighs risk. Interactions: No interaction studies performed. Concomitant administration of corticosteroids, immunomodulators (azathioprine, 6-mercaptopurine, and methotrexate) and aminosalicylates did not have a clinically meaningful effect on Entyvio pharmacokinetics. Fertility, pregnancy and lactation: Women of child-bearing potential should use adequate contraception and continue for at least 18 weeks after last Entyvio treatment. Since maternal antibodies are excreted in breast milk, decision whether to discontinue breast-feeding or discontinue/abstain from Entyvio should be made according to relative benefit to child of breast-feeding or to mother of Entyvio. Undesirable Effects: Very Common (≥ 1/10): nasopharyngitis, headache, arthralgia. Common (≥1/100, <1/10): bronchitis, gastroenteritis, URTI, influenza, sinusitis, pharyngitis, paraesthesia, hypertension, oropharyngeal pain, nasal congestion, cough, anal abscess, anal fissure, nausea, dyspepsia, constipation, abdominal distension, flatulence, haemorrhoids, rash, pruritis, eczema, erythema, night sweats, acne, muscle spasm, back pain, muscular weakness, fatigue, pain in extremities, pyrexia. Other serious undesirable effects (≥1/1000 to <1/100): respiratory tract infection, infusion site reaction, infusion-related reaction. Refer to the SmPC for details on full side effect profile and interactions. Legal Classification: POM. Marketing Authorisation Number: EU/1/14/923/001; 300mg powder for concentrate for solution for infusion. Further information is available from Takeda UK Ltd. Building 3, Glory Park, Glory Park Avenue, Wooburn Green, Buckinghamshire, HP10 0DF. Tel: 01628 537900 Fax: 01628 526617. PI Approval Code: IRE/VED/15/0014 Date of revision: September 2015. Adverse Events should be reported to the Pharmacovigilance Unit at the Health Products Regulatory Authority (medsafety@hpra.ie). Information about Adverse Event reporting can be found on the HPRA website (www.hpra.ie). Adverse Events should also be reported to Takeda UK Ltd on 1800 937 970.


20 News

Creating a new advanced pharmacist role in the hospital setting The 12th National Health Summit took place in the Crowne Plaza Hotel last month and it drew interest from a plethora of high profile health strategists, economists, medical professionals and healthcare companies across Ireland. The summit featured a vast array of speakers who advised on how to systematically improve the Irish healthcare sector in a variety of different and explorative new ways. The theme of the conference was ‘Building a system that works for everyone’ with speakers including Tony O’Brien, Director General at the HSE, Professor Michael Barry, Clinical Director at the National Centre for Pharmacoeconomics (NCPE), Consultant Clinical Pharmacologist and Head of the Department of Pharmacology & Therapeutics at the University of Dublin, Trinity College, Dr Catriona Bradley, Executive Director at the IIOP, and Liam Doran, General Secretary, Irish Nurses and Midwives Organisation. As part of an afternoon seminar entitled ‘Fixing A&E’, Matt Aiello, Urgent and Acute Workforce Transformation Specialist at Health Education West Midlands, UK, gave a talk about how he and his team had prepared and delivered a portfolio of pilot projects in the UK. The results of the pilot projects uncovered a need for a potential new advanced clinical pharmacist role in the primary care setting. In terms of how Pharmacy can ease the burden on A&E departments, Aiello and his team focused on two pilot programmes: 1) investigating the role of pharmacists in the emergency department (ED) and 2) a pilot programme investigating the creation of a clinically enhanced non-medical prescribing programme for pharmacists. Speaking at the conference, Aiello explained how he and his team built a workforce transformation programme for Pharmacy April 2016 • HPN

essentially from scratch and he provided insight into how they intended to take steps towards expanding the role of the pharmacist both in the hospital and community setting.

“We wanted to find out what extra training they might need to enable them to be truly confident and competent and to develop an advanced clinical pharmacist in the ED.

“Part of what we did was based around a Department of Health mandate in 2013 to set up an ED task force in the UK. We wanted to look at how the medical and non medical front line clinical workforce is currently deployed in the ED,” said Aiello.

“We also wanted to look at what unique skills pharmacists themselves could bring to this type of advanced practice role. In essence, we wanted to look at what makes a pharmacist a pharmacist and then develop that onto a pharmacist plus something more. However, we still wanted to retain that core skillset of a pharmacist, i.e. we did not want to turn the pharmacist into a nurse.”

To get a clearer picture of what was happening in EDs around the UK, Aiello looked at how the workforce was operating. In particular, he wanted to analyse how pharmacists in the ED could be used more effectively if additional skills training could be implemented. He also wanted to look at how advanced skills training could be implemented to enhance parts of that workforce. When it came to the Pharmacy workforce, however, he told of how he had no previous reference point. “In relation to Pharmacy, we had absolutely no basis for comparison when trying to figure out how pharmacists are deployed in EDs and in urgent and acute settings from a clinical perspective. “What we were curious about was the recent push towards advanced clinical practice and the creation of what is loosely termed as a ‘generalist specialist’ role. A ‘generalist specialist’ role is when we take what are traditionally and originally specialist roles in the non-medical side and enhance the workers skillset. This allows us to almost blur the boundaries clinically between what they and others can do in theory, to make a more integrated workforce model.” Aiello explained that previously in England, pharmacists never had the opportunity to take on advanced clinical skills training to enable them to handle patients in the clinical setting.

PILOTING THE PROGRAMME Aiello and his team set about piloting a programme that he termed a “high impact, low cost approach.” “In December 2013, we took three prescribing pharmacists and we placed these pharmacists into three different EDs in the West Midlands. These three EDs were chosen to represent a cultural and geographical cross section of the area i.e. one was in the middle of a large dense population with high levels of poverty, another was in a very rural area, and the last one was a children’s hospital.” Over the course of five weeks, the pharmacists were asked to survey patients who came into the ED. The patients were surveyed over a randomised cross section so the team were looking at gender, age, day of week, time of day etc. In total, 782 patients were surveyed across the five week window which occurred in the middle of a winter pressure period. “We asked our pharmacists to categorise the patients as they were coming in and we asked them to note whether the patient could be managed in the community setting by a pharmacist with no additional skillset. We wanted to establish

whether the patient needed to be in the ED in the first place and whether that patient could be managed by an independent prescribing pharmacist as they currently are with a normal nonmedical prescribing qualification.” Aiello explained that prior to the commencement of the pilot programme, he gave the three pharmacists a description of a 12 month post-graduate clinical practice course, which included a double module of clinical examination skills training and an assessment of diagnostics training, and asked them to look at this in terms of the study. The subsequent results of the pilot programme were surprising. “The results suggested that the pharmacists felt that up to 48.1 per cent of patients that came through the EDs could have been managed by a pharmacist. The results also showed that 39.9 per cent of patients could have been managed by a pharmacist with advanced clinical practice training. “There was a level of agreement there that suggested that this was something that we needed to be looking at further.” The most important part of the survey, however, was centred around whether a pharmacist with advanced clinical practice training of no more than 12 months in duration could manage the patient or whether intervention by a medical team was needed, be that primary or secondary care. Aiello was careful to point out that the pharmacist is always part of a larger multi-professional team. “What I want to be really clear about is, as with all of our work, we were looking at these people working together as part of a multi-professional team both in the ED and in the urgent and acute setting. The pharmacist would always be working as a complementary part of a multiprofessional team.”


22 News MOVING THE PILOT FORWARD Following on from this initial pilot programme, Aiello and his team proceeded to implement a national version of the pilot programme over a cross section of the entire country to find out how this idea would work on a national scale. “This pilot was on a scale that had never been attempted before but it brought back some interesting results. We had the same categorisations as we did in the West Midlands but we expanded on certain parts of it.

2014 West Midlands ED Pharmacy Pilot: Study Findings

3.2%

Based on the information gathered from both the regional and national studies, Aiello and his team decided to focus on developing an evidence base to support the idea of creating a new role for clinical pharmacists. Originally, Aiello and his team focused their work on the ED but as they developed an evidence base to support a new clinical pharmacist role they realised that the role’s remit was beyond just the ED. It began to filter into acute care across the primary, secondary and community care settings. “We very quickly realised that there was a cross transferability of pharmacy skills here that we could push wider. We began to focus on areas such as medicine April 2016 • HPN

5.1%

Community Pharmacy (3.2%) Independent Prescriber (5.1%) Advanced Clinical Pharmacist (39.9%) Medical Team Only (51.8%)

51.8%

“There was a level of agreement between the national data and the regional data. We found that 35.7 per cent of patients that attended EDs could have been managed by a pharmacist. We wanted to give an extra level of robustness to this data though so we conducted a secondary categorisation and we sent our data off to different hospital trusts and asked ED consultants, pharmacists and nurses from each of the hospital trusts to compare the data. “The comparison was fascinating. What was interesting with this was that doctors, when conducting the characterisation, actually felt that 37.4 per cent of those patients could have been managed by pharmacists. We expected push back by doctors around what they felt the pharmacist could do, just in case they felt the pharmacists were over stepping or perhaps being a bit ambitious in what they thought they could do. But it was actually the converse so that was a really interesting come back.”

Patients suitable for management by:

39.9%

Of the 782 patients surveyed over the three sites, 48.1% of patients could be managed by a pharmacist, where those attendees present with symptoms likely to be seen in the Minors Area of the ED and under the overall supervision of a doctor. Of these, 39.9% could be managed by a pharmacist with 12 months’ focussed Advanced Practice training, aligned to the National Advanced Practice framework…

focused queues, pre-discharge medicine optimisation and sign off in the ED.

occupational therapists, physiotherapists, paramedics, and pharmacists.

“We found in some cases that that sign off in the ED was often being conducted by a range of people including consultants, locum consultants, middle grades, junior doctors, and this was creating a bottle neck. We began looking at how to optimise medicines and we looked beyond that using this new clinical skills training to actually allow clinical pharmacists to provide clinical health assessments and diagnostics in those settings. This could potentially help previously ill patients and it would ultimately free up doctors to conduct the work that they should be conducting at the level that they should be conducting it.

“What we found from the outcome of the 12 month advanced practice training module was that the pharmacists came through their clinical skills portfolio ahead of the rest of the group. What we also found, was that rather than working in silence, the groups were working collaboratively almost from day one.

“It is about creating that enhanced skills mix within these types of roles to create a multi-professional approach that includes the pharmacist.” To prove that their findings were accurate, Aiello and his team placed the three original pharmacists that took part in the pilot programme into the 12 month advanced practice training module as part of a multiprofessional cohort. The cohort was made up of 15 people that included nurses,

“From there, we wanted to look at the entire pathway for the pharmacist. We wanted to start at the point from which the pharmacist is registered, right the way through to developing the role through a graded graduated career development pathway. We wanted to create a staged entry and exit point for the pharmacist which would align with the needs of the workforce.” FUTURE IMPLEMENTATION OF THE ROLE Aiello explained that the next stage for himself and his team is to take a more in-depth look at how they can develop the full pathway for an advanced practice role. “Up until this point, all the work that we had carried out was centred on what a pharmacist can

do, what they might be able to do, and what training could they undertake. The question of what next was always going to come up in terms of where this new role could take pharmacists and from our point of view we have to prove that pharmacists can actually fit into this workforce. “Looking to the future, the challenge for myself and my team is to provide evidence to show the potential for a multi-specialty clinical pharmacy practitioner. “Originally, one of our Chief Pharmacists coined the term ‘generalist specialist pharmacist’ and that was the first time we started thinking about a specialist role, an allied health professional role. “Nurses have been doing it for years but we hadn’t really taken anything from that. Healthcare professionals don’t just have to do one thing. When you have a specialty, you have your specialty practice area but there could be more you could do, you could be more effective. It is only through that realisation that we can work towards a more integrated workforce.”


CPD 20: Relapsed mantle cell lymphoma Continuing Professional Development

CPD

Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up Authors: M. Dreyling1, C. Geisler2, O. Hermine3, H. C. Kluin-Nelemans4, S. Le Gouill5, S. Rule6, O. Shpilberg7, J. Walewski8 and M. Ladetto9 on behalf of the ESMO Guidelines Working Group* Correspondence to: ESMO Guidelines Working Group, ESMO Head Office, Via L. Taddei 4, CH-6962 Viganello-Lugano, Switzerland. E-mail: clinicalguidelines@esmo.org

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

3. PLAN - If I have identified a knowledge gap - will this article satisfy those needs or will more reading be required?

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.

4. EVALUATE - Did this article meet my learning needs - and how has my practise changed as a result? Have I identified further learning needs?

60 Second Summary Mantle cell lymphoma (MCL) is a less frequent subtype of lymphoid malignancies and represents 6%–9% of malignant lymphoma in Western Europe. The annual incidence of this disease has increased during recent decades to 1–2/100 000 recently. MCL is more common in males than in women with a 3 : 1 ratio. Core biopsies should only be carried out in patients without easily accessible lymph nodes (e.g. retroperitoneal bulk), keeping in mind the heterogeneity of MCL. The histological report should give the diagnosis according to the World Health Organization (WHO) classification and Ki-67 as the most established histomorphological risk factor. Most tumours have a classic morphology of small-medium sized cells with irregular nuclei. However, the malignant lymphocytes may present with a spectrum of morphological variants, including small round (resembling chronic lymphocytic leukaemia), marginal zone-like, pleomorphic and blastoid cells. Since treatment may differ depending on the stage of the disease, initial staging should be thorough, particularly in the rare cases with non-bulky stages I and II. Initial work-up should include a computed tomography (CT) scan of the neck, thorax, abdomen and pelvis, and a bone marrow aspirate and biopsy. RIT consolidation also prolongs PFS after chemotherapy, but its benefit seems to be inferior in comparison to rituximab maintenance.

23

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, sponsored by MSD. Copies can be downloaded from www.irishpharmacytraining.ie Disclaimer: All material published is copyright, no part of this can be used in any other publication without permission of the publishers and author. MSD has no editorial oversight of the CPD programmes included in these modules.

Relapsed mantle cell lymphoma INCIDENCE AND EPIDEMIOLOGY Mantle cell lymphoma (MCL) is a less frequent subtype of lymphoid malignancies and represents 6%–9% of malignant lymphoma in Western Europe. The annual incidence of this disease has increased during recent decades to 1–2/100 000 recently. MCL is more common in males than in women with a 3 : 1 ratio. DIAGNOSIS AND PATHOLOGY/ MOLECULAR BIOLOGY Diagnosis should be based on a surgical specimen, preferably a lymph node biopsy. Core biopsies should only be carried out in patients without easily accessible lymph nodes (e.g. retroperitoneal bulk), keeping in mind the heterogeneity of MCL. In the rare cases with leukaemic manifestation only, a bone marrow biopsy may be sufficient if additional diagnostic measures are applied [immunohistochemistry, detection of t(11;14) (q13;q32)]. Fine-needle aspirations are inappropriate for a reliable evaluation of additional risk factors (cytology, cell proliferation). The histological report should give the diagnosis according to the World Health Organisation (WHO) classification and Ki-67 as the most established histomorphological risk factor[1] [I, A]. Most tumours have a classic morphology of small-medium sized cells with irregular nuclei. However, the malignant lymphocytes may present with a spectrum of morphological variants, including small round (resembling chronic lymphocytic leukaemia), marginal zone-like, pleomorphic and blastoid cells. As only the minority of these

cases are correctly diagnosed based on classical histology only, review by an expert haematopathologist is advised. Specifically, additional immunohistochemistry for detection of the pathognomonic cyclin D1 overexpression is mandatory. In the rare cyclin D1-negative cases, detection of Sox-11 may help to establish the diagnosis[2]. Extended gene expression profiling suggests a more favourable clinical course in cases with low cell proliferation; however, this technique is not yet applicable in clinical routine practice. If possible, additional biopsy material should be stored freshly frozen to allow additional molecular (currently still investigational) analyses. STAGING AND RISK ASSESSMENT Since treatment may differ depending on the stage of the disease, initial staging should be thorough, particularly in the rare cases with non-bulky stages I and II (Table 1). Initial work-up should include a computed tomography (CT) scan of the neck, thorax, abdomen and pelvis, and a bone marrow aspirate and biopsy (Table 2). Positron emission tomography-CT (PET-CT) scan is not mandatory, but may be recommended and is especially useful in the rare limited stages I/II, before localised radiotherapy [IV, C]. Gastrointestinal endoscopy is also recommended in these rare cases to detect asymptomatic involvement. Of note, when analysed, the majority of MCL patients will have gastrointestinal involvement.

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CPD 20: Relapsed mantle cell lymphoma

Table 1: Ann Arbor classification Stage

Area of involvement

I (IE)

One lymph node region or extralymphatic site (IE)

FIGURE 1 Molecular pathogenesis of mantle cell lymphoma.

II (IIE) Two or more lymph node regions or at least one lymph node region plus a single localised extralymphatic site(IIE) on the same side of the diaphragm III (IIIE, IIIS)

Lymph node regions or lymphoid structures (e.g. thymus, Waldeyer's ring) on both sides of the diaphragm with optional localised extranodal site (IIIE) or spleen (IIIS)

IV Diffuse or disseminated extralymphatic organ involvement

M. Dreyling et al. Ann Oncol 2014;25:iii83-iii92 © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

A, no symptoms; B, unexplained fever of >38°C, drenching night sweats; or loss of >10% body weight within 6 months. Table 2: Diagnostic work-up History

B symptoms

Physical examination Waldeyer's ring, peripheral lymph nodes, liver, spleen Laboratory work-up Blood and differential count in leukaemic cases: FACS (CD5/ CD20+, CD23/ CD200), FISH for t(11;14) recommended LDH, uric acid, liver and renal function electrophoresis (optional: immune fixation) Serology

Hepatitis B, C and HIV serology

Imaging

Chest X-ray Abdominal ultrasound CT neck, chest, abdomen, pelvis MRT only in selected locations (CNS Optional: PET

Bone marrow Histology (cyclin D1 immunohisto chemistry) Cytology Recommended: FACS, FISH for t(11;14) Optional: PCR for IgH rearrangement Toxicity Electrocardiogram, cardiac ultrasound (before anthracy clines, ASCT) Pulmonary function (before ASCT) Creatinine clearance Optional: reproductive counselling in young patients FACS, fluorescence-activated cell sorting; FISH, fluorescence in situ hybridisation; LDH, lactate dehydrogenase; HIV, human immunodeficiency virus; CT, computed tomography; MRT, magnetic resonance tomography; CNS, central nervous system; PET, positron emission tomography; PCR, polymerase chain reaction; ASCT, autologous stem-cell transplantation.

Central nervous system involvement is rare in asymptomatic patients at diagnosis, but a lumbar puncture may be considered in high-risk cases [at least two of the following risk factors: blastoid variant, elevated lactate dehydrogenase (LDH), impaired performance status] or neurological symptoms[3]. A full blood count, blood chemistry including LDH and uric acid as well as screening tests for human immunodeficiency virus (HIV) and hepatitis B and C are required. Staging is carried out according to the Ann Arbor classification system (Table 1), with mention of bulky disease >5 cm when appropriate. For prognostic purposes, a ‘Mantle cell lymphoma International Prognostic Index’ has been established[I, A] [4]. The evaluation of the Ki-67 proliferative antigen is the most applicable method to evaluate cell proliferation, and is considered the most established biological risk factor in MCL. As the reproducibility of quantitative scores among pathologists may vary, a standardised method has been suggested[5]. INDOLENT SUBTYPE OF MCL Most patients with MCL follow an aggressive clinical course. However, a subset of patients may exhibit a more indolent evolution. These cases are commonly characterised by a nonnodal leukaemic presentation with only bone marrow involvement, and splenomegaly[6]. In

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25 FIGURE 2 Therapeutic recommendations.

based schemes [R-FC (fludarabine and cyclophosphamide) or R-FM (fludarabine and mitoxantrone)] are also discouraged due to early failures and long-lasting myelosuppression[17] [I, D]. In frail patients, a less intense immunochemotherapy [chlorambucil, VADC (vincristine, doxorubicin, oral dexamethasone, chlorambucil) or PEP-C (prednisone, etoposide, procarbazine, cyclophosphamide)] may be considered, aiming primarily at palliation[II, B]. However, targeted therapy exhibiting a low toxicity profile may be used in this population. Antibody monotherapy [rituximab, radioimmunotherapy (RIT)] achieves only moderate response rates and is therefore not recommended[III, B] [20]. In patients with positive hepatitis B serology, prophylactic antiviral medication is strongly recommended[I, A] [21]. Consolidation/maintenance

M. Dreyling et al. Ann Oncol 2014;25:iii83-iii92 © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

addition, cases with low Ki-67 (≤10%) tend to have a more indolent course. SOX-11 negativity may also identify cases with more indolent clinical behaviour. However, its role is controversial and additional p53 mutations may cause an aggressive clinical evolution[7] (Figure 1). Unfortunately, there are no markers to definitely predict indolent behaviour, but a short watch-and-wait period under close observation seems to be appropriate in suspected indolent cases with low tumour burden[III, B] [9]. Treatment First line STAGE I–II In the small proportion of patients with limited non-bulky stages I–II, radiotherapy (involved field, 30–36 Gy) has been suggested to achieve long-term remissions[10]. In contrast, in a randomised study, all patients with early-stage MCL relapsed within 1 year[11]. Thus, a shortened conventional chemotherapy induction followed by consolidating radiation (similar to diffuse large-cell lymphoma) may be most appropriate in these cases[IV, B]. In stage I–II patients with large tumour burden or adverse prognostic features, systemic therapy as indicated for advanced stages would be appropriate in most

Rituximab maintenance significantly improves PFS and even OS after R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) (75% versus 58% after 3 years, P < 0.0001)[I, A] [17].

cases; a radiation consolidation may be considered, depending on tumour location and anticipated side-effects[IV, B].

RIT consolidation also prolongs PFS after chemotherapy, but its benefit seems to be inferior in comparison to rituximab maintenance[II, B] [22].

STAGE III–IV

Younger patients

Induction

Although no curative treatment is available for MCL so far, an intensive approach, e.g. by ASCT, has been demonstrated to induce higher response and survival rates in fit patients, independent of the addition of rituximab[I, B] [23, 24].

In all symptomatic patients and asymptomatic cases with high tumour burden, therapy should be initiated at diagnosis[I, A]. The current therapeutic approach is based on clinical risk factors, symptoms and patient characteristics (Figure 2). Elderly patients Based on a median age of 65 years at first diagnosis, the majority of patients do not qualify for dose-intensified regimens. Three prospective first-line trials, a salvage trial and a systematic meta-analysis support an improved overall response, progression-free survival (PFS) and overall survival (OS) if rituximab was added to chemotherapy[I, A] (12) Rituximab in combination with chemotherapy such as CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or bendamustine should be used[I, B] [13, 18]. R-CVP (cyclophosphamide, vincristine and prednisone) combination results in inferior response rates and PFS[19]. Purine analogue-

In addition, a randomised trial confirmed that a cytarabine-containing induction achieves a significantly improved median time to treatment failure (P = 0.038) and a trend for median OS (P = 0.045)[I, B] [25]. In contrast, an induction based on high-dose cytarabine alone achieves only insufficient response rates[III, D] [34]. Therefore, a rituximab containing induction of CHOP and high dose Ara-C followed by high dose consolidation and ASCT is recommended. In a retrospective study comparison of the Nordic, HOVON and MCL younger protocols, total body irradiation (TBI) before ASCT was confirmed to be beneficial only in partial response (PR) patients[II, B] [35]. In contrast, the benefit of RIT has not been demonstrated in inter-study comparisons. An upfront, dose-intensified approach (R-Hyper-CVAD, rituximab in combination with fractionated cyclophosphamide,

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CPD 20: Relapsed mantle cell lymphoma

vincristine, anthracycline and dexamethasone) with alternating highdose methotrexate/cytarabine cycles also achieved very high response and survival rates in phase II studies, but its feasibility is hampered by a significant therapyassociated toxicity[II, C] [31–33]. The role of rituximab and lenalidomide maintenance after autologous transplantation is currently being investigated by the randomised LyMa[36] and MCL 0208 trials, respectively. So far, there are no data to support the application of allogeneic transplantation as part of front-line treatment[II, D] [37]. RELAPSED DISEASE A repeated biopsy is strongly recommended to identify prognostically important features of MCL. Selection of salvage treatment depends on efficacy of prior regimens. In early relapses (<12–24 months), a non-cross-resistant scheme should be preferred (bendamustine or high-dose-Ara-C containing regimens, e.g. R-BAC after CHOP or vice versa)[38]. Rituximab should be added if the previous antibody-containing scheme achieved >6–12 months duration of remission[IV, B]. In cases of early relapses or in refractory cases, newer targeted approaches should be strongly considered (Figure 2). Currently, temsirolimus is the only compound registered for relapsed MCL in the EU based on a randomised trial[39]. Among the compounds registered in the United States (bortezomib, ibrutinib and lenalidomide), ibrutinib achieves the highest response rates but longer follow-up is warranted[40–42]. Targeted approaches in combination with immunochemotherapy have been suggested but are still investigational.

In younger patients, allogeneic stem-cell transplantation is potentially curative and has achieved long-term remissions, even in patients following early relapse and with refractory disease. Based on the advanced age of most patients, a dose-reduced conditioning is appropriate[IV, B] [61]. Haplo-identical bone marrow transplantation achieves high response rates but is still experimental in MCL.

• Optional CT scan (or chest X-ray/ ultrasound examinations to reduce radiation exposure) every 3–6 months for 2 years and every 6–12 months up to 5 years. However, there is no strong evidence to support a regular radiological follow-up. PET-CT should not be used for surveillance. These recommendations are driven by the concern to minimise radiation exposure.

RESPONSE EVALUATION

• Some studies suggest that pre-emptive treatment may be efficient. However, MRD screening may be carried out but should not guide therapeutic strategies outside clinical studies.

Radiological tests should be carried out mid-treatment and following the completion of chemotherapy. Patients who achieve less than a PR should be considered for early salvage regimens. Patients achieving a PR may convert to a complete response after post-induction treatment. PET-CT for response evaluation is optional[62]. The independent prognostic role of minimal residual disease (MRD) applying patientspecific primers has been confirmed in numerous studies[63, 64]. However, because of limitations of applicability and the need for qualified and standardised laboratories, its use is advised in clinical trials but not recommended in clinical routine except the setting of donor lymphocyte infusion post allograft. PERSONALISED MEDICINE In this disease setting, more research is needed to identify molecular markers which could lead to advances in personalised medicine. The selection of optimal treatment is mainly based on clinical and biological risk factors, symptoms and tumour load (Figure 2). PETand MRD-based tailored treatments are currently evaluated in studies but are not yet routine clinical practice.

Rituximab maintenance has a favourable safety profile and prolongs PFS and OS in relapsed disease[I, A] [59]. However, such a second-line maintenance treatment has not been investigated in patients relapsing after front-line maintenance[IV, D].

New agents (especially inhibitors of Bruton's tyrosine kinase as well as PI3 kinases and BCL-2) are currently being investigated[42].

RIT consolidation seems to result in extended remission durations[55], especially in elderly patients with comorbidities not eligible for dose intensification[IV, B].

The following recommendations are based on consensus rather than on evidence :

High-dose chemotherapy with ASCT may be considered in patients relapsed after conventional first-line therapy. However, the benefit seems to be minor in this setting[60], and there is no role for a second autograft at relapse.

FOLLOW-UP AND LONG-TERM IMPLICATIONS

• History and physical examination, blood counts and routine chemistry every 3 months for 2 years, every 4–6 months for 3 additional years and subsequently once a year[V, D].

A summary of recommended treatment strategies outside clinical studies is provided in Figure 2, and a summary of recommendations is provided in Table 8. Statements without grading were considered justified standard clinical practice by the experts and the ESMO faculty. Table 8: Summary of recommendations  Diagnostic procedures include histomorphology by an expert haematopathologist and mandatory detection of cyclin D1 overexpression or t(11;14)(q13;q32)  Clinical (MIPI) and biological (Ki-67) prognosticators should be applied in clinical routine to estimate the clinical behaviour  In localised stages: discuss conventional chemotherapy followed by radiotherapy (30–36 Gy)  In advanced stages

Younger patients: high-dose cytarabinecontaining regimens plus rituximab with dose intensification (e.g. autologous stemcell transplantation)

  Elderly patients: conventional immunochemotherapy (R-CHOP, R-B) followed by rituximab maintenance  In relapse   (Combined) targeted approaches (bortezomib, ibrutinib, temsirolimus, lenalidomide) should be considered In younger patients, an allogeneic transplantation should be discussed among possible options. REFERENCES AVAILABLE ON REQUEST

• Annual evaluation of thyroid function in patients with irradiation of the neck.

Support by


Single Agent Once Daily Oral Therapy for R/R CLL and R/R MCL*

Discover how far therapy can go * Relapse/Refractory Chronic Lymphocytic Leukemia and Relapse/Refractory Mantle Cell Lymphoma.

IMBRUVICA® is indicated for the treatment of adult patients with: 1 • Relapsed or refractory mantle cell lymphoma • Chronic lymphocytic leukaemia who have received at least one prior therapy, or in first line in the presence of 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy • Waldenström’s macroglobulinaemia who have received at least one prior therapy, or in first-line treatment for patients unsuitable for chemo-immunotherapy IMBRUVICA® 140 mg Hard Capsules PRESCRIBING INFORMATION ACTIVE INGREDIENT: Ibrutinib. Please refer to Summary of Product Characteristics (SmPC) before prescribing. INDICATIONS: Treatment of adult patients with: relapsed or refractory mantle cell lymphoma (MCL); chronic lymphocytic leukaemia (CLL) who have received ≥ one prior therapy, or first line in presence of 17p deletion/TP53 mutation and are unsuitable for chemo-immunotherapy; Waldenström’s macroglobulinaemia (WM) who have received ≥ one prior therapy, or in first line in patients unsuitable for chemo immunotherapy. DOSAGE & ADMINISTRATION: Adults: Orally, once daily, swallowed whole with water. MCL - 4 capsules. CLL & WM - 3 capsules. Concomitant moderate/ strong CYP3A4 inhibitors – reduce to 1 capsule (or, with strong inhibitors, withhold IMBRUVICA for up to 7 days). Withhold IMBRUVICA therapy for any new onset/worsening grade ≥ 3 non-haematological toxicity, grade ≥ 3 neutropenia with infection/fever, or grade 4 haematological toxicities. Re-initiate when toxicities resolved to grade 1 or baseline. If toxicities recur, reduce dose by 1-2 capsules. Discontinue IMBRUVICA if toxicities persist/recur following two dose reductions. Children: Safety/efficacy not established ≤ 18 years old. Elderly: No dose adjustment required. Renal impairment: Mild/moderate - no dose adjustment. Severe – no data; consider benefit/risk and monitor closely. No data with dialysis. Hepatic impairment: Mild (Child-Pugh class A) – 2 capsules daily; moderate (Child-Pugh class B) – 1 capsule daily; severe (Child-Pugh class C) – not recommended. Monitor for toxicities. Severe cardiac disease: No clinical data. CONTRAINDICATIONS: Hypersensitivity to active substance/excipients. St. John’s Wort preparations. SPECIAL WARNINGS & PRECAUTIONS: Bleeding-related events: Minor and major haemorrhagic events reported; caution with anticoagulant therapy – do not use concomitantly with warfarin or other vitamin K antagonists, avoid fish oil and vitamin E preparations. Withhold IMBRUVICA ≥ 3 to 7 days pre-/post-surgery. Leukostasis: Cases reported; consider temporary withhold of IMBRUVICA; monitor closely, give supportive care. Infections: Infections seen, some resulting in hospitalisation and death; monitor for fever, neutropenia and infections and give anti-infective therapy. Cytopenias: Treatment-emergent grade 3/4 cytopenias reported; monitor complete blood counts monthly. Atrial fibrillation/flutter: reported particularly in patients with cardiac risk factors/acute infections/previous history of atrial fibrillation; periodic clinical monitoring; consider ECG if arrhythmic symptoms or new onset dyspnoea develop; consider alternative to IMBRUVICA when pre-

existing atrial fibrillation requiring anticoagulant therapy or high risk of thromboembolic disease; where no suitable alternatives to IMBRUVICA, consider tightly controlled treatment with anticoagulants. Tumour lysis syndrome: cases reported. Monitor at risk patients closely, take precautions. Effects on the QT interval: mild decrease in QTcF interval seen; use clinical judgment before prescribing for patients at risk from further shortening QTc duration. Drug-drug interactions: Strong/ moderate CYP3A4 inhibitors may increase ibrutinib exposure; CYP3A4 inducers may decrease ibrutinib exposure. Avoid where possible, if not monitor closely for toxicities/lack of efficacy. SIDE EFFECTS: Very common: Pneumonia, upper respiratory tract infection, urinary tract infection, sinusitis, skin infection, neutropenia, thrombocytopenia, anaemia, dizziness, headache, haemorrhage, epistaxis, bruising, petechiae, diarrhoea, vomiting, stomatitis, nausea, constipation, rash, arthralgia, musculoskeletal pain, pyrexia, oedema peripheral. Common: Sepsis, febrile neutropenia, leukocytosis, lymphocytosis, dehydration, hyperuricaemia, vision blurred, atrial fibrillation, subdural haematoma, dry mouth. Other side effects: Leukostasis, tumour lysis syndrome, hepatic failure, angioedema. Refer to SmPC for other side effects. PREGNANCY: Women of child-bearing potential must use highly effective contraceptive measures during and for 3 months after stopping treatment; if using hormonal contraceptives, add barrier method. Not to be used during pregnancy. LACTATION: Discontinue breast-feeding during treatment. INTERACTIONS: CYP3A4 inhibitors: Strong: Avoid where possible or reduce dose (or withhold IMBRUVICA for ≤ 7 days) and monitor closely; e.g. ketoconazole, indinavir, nelfinavir, ritonavir, saquinavir, clarithromycin, telithromycin, itraconazole, nefazadone, cobicistat. Moderate: Avoid where possible or reduce dose and monitor closely; e.g. diltiazem, voriconazole, erythromycin, amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ ritonavir, diltiazem, fluconazole, fosamprenavir, imatinib, verapamil, amiodarone, dronedarone. Avoid grapefruit and Seville oranges. Mild: No dose adjustment required; monitor closely. CYP3A inducers: Strong/moderate: Avoid or monitor closely for lack of efficacy; e.g. carbamazepine, rifampicin, phenytoin. Mild: may be used; monitor for lack of efficacy. Medicines that increase stomach pH (e.g. proton pump inhibitors) may decrease ibrutinib exposure. Potential interactions: Oral narrow therapeutic range P gp or breast cancer resistance protein (BCRP) substrates (e.g. digoxin, methotrexate) should be taken ≥ 6 h before/after IMBRUVICA. Ibrutinib may inhibit BCRP in the liver and

so increase exposure of drugs undergoing BCRP-mediated hepatic efflux (e.g. rosuvastatin). Ibrutinib may inhibit intestinal CYP3A4 and thus increase exposure of some CYP3A4 substrates sensitive to gut CYP3A metabolism; caution with narrow therapeutic range oral CYP3A4 substrates (e.g. dihydroergotamine, ergotamine, fentanyl, cyclosporine, sirolimus, tacrolimus). Ibrutinib is a weak CYP2B6 inducer and may affect expression of other enzymes and transporters regulated via the constitutive androstane receptor (CAR) (e.g. CYP2C9, CYP2C19, UGT1A1, MRP2). Exposure to substrates of CYP2B6 (e.g. efavirenz, bupropion) and co -regulated enzymes may be reduced with ibrutinib. Refer to SmPC for full details of interactions. LEGAL CATEGORY: Prescription only medicine. PRESENTATIONS PACK SIZES Bottles Bottles

90 capsules 120 capsules

MARKETING AUTHORISATION HOLDER: Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK. Prescribing information last revised: February 2016. Reference: 1. Imbruvica® Summary of Product Characteristics. Janssen Cilag International Feb. 2016. Date of preparation: March 2016 PHIR/IBR/0316/0010 Adverse events should be reported. This medicinal product is subject to additional monitoring and it is therefore important to report any suspected adverse events related to this medicinal product. Healthcare professionals are asked to report any suspected adverse events via: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, Website: www.hpra.ie, E-mail: medsafety@hpra.ie Adverse events should also be reported to Janssen-Cilag Limited on +44 1494 567447 or at dsafety@its.jnj.com

IMBRUVICA® is co-developed with Pharmacyclics. Janssen-Cilag Limited is the marketing authorisation holder and responsible editor of this document.

@JanssenIE © Pharmacyclics LLC 2016

MARKETING AUTHORISATION NUMBER(S) EU/1/14/945/001 EU/1/14/945/002

© Janssen Cilag Limited 2016


Awards 28 Awards

The Hospital Professional News Ireland

2016

Hospital Rising Star Award 2016

The Hospital Rising Star Award recognises rising talent – those individuals who despite being in the early stages of their hospital careers are already demonstrating that they can make a difference to the profession and the companies for whom they work and the patients they serve. This award is open to hospital professionals aged up to 30 - at the date of entry submission - who are working within any hospital department where their involvement has been greater than six months. It is the individual qualities that will be evaluated, rather than those of any of the projects worked on. JUDGES WILL BE LOOKING FOR:  Judges will want to see effective communication skills with both staff and customers  Demonstration of a commitment to mentoring or other leadership activities  Operation within their own pharmacy liaising with key staff members and management and developing key communication skills  A dedication and commitment to furthering the profession into the future HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

Deadline for Entries: Friday, June 24th, 2016 April 2016 • HPN


Awards The Hospital Professional News Ireland

Awards 29

2016

Medisource Hospital Pharmacy Technician of the Year 2016

It is evident that hospital pharmacy technicians are playing an increasingly important supporting role as pharmacists are increasingly spending more time with patient consultations and engaging local stakeholders. The shift in emphasis from dispensing to healthcare provision has meant that the wider pharmacy team has to pull together – pharmacy technicians capture the essence of this in everything that they do. This Award will recognise the winner’s important contribution to the hospital pharmacy technician profession. The judges will be looking for those who can demonstrate promotion of the role of the Pharmacy Technician and those who continue to champion excellence through forward thinking and innovation. The winners’ achievements will be an inspiration to those pursuing innovative practice; to those striving to raise standards; and to pharmacists who, through their professionalism, provide models for others within pharmacy. JUDGES WILL BE LOOKING FOR:  Evidence of long-term, consistent dedication and outstanding achievements that have led to the advancement of the profession of pharmacy and public health  Evidence of a large variety of skills, attributes and accomplishments  Evidence of an individual strong in character, cumulative professional accomplishments and the ability to properly represent and model what pharmacy technicians as a profession encompasses  Evidence of an understanding the goals of pharmacy, and significantly contributing to how these goals may be achieved HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

Deadline for Entries: Friday, June 24th, 2016 HPN • April 2016


Awards 30 Awards

The Hospital Professional News Ireland

2016

Excellence in Patient Safety Award 2016

This Award will seek applicants who have shown commitment and dedication to improving patient safety/medication safety amongst patients in the secondary care setting. This may be through team working with consultants, nurses, pharmacy colleagues but the endpoint result will be to improve this area for patients in terms of medication efficacy and adherence, as just two examples of many. This Award will encompass all aspects of patient safety within the hospital pharmacy sector in Ireland and invites applications from those who have recently undertaken patient safety initiatives to the betterment of the profession; those who are or who have offered patient safety expertise to the profession perhaps in the line of lecturing; or even those who have undertaken a recent patient safety innovation or initiative within a field pertinent to hospital pharmacy that will have a positive effect on the whole profession. JUDGES WILL BE LOOKING FOR:  Evidence of safety improvements and enhancements through collaborative working, introduction of new services, improved systems of work and/or new training standards  Innovative application of new standards, systems, protocols or services  Evidence of benefits to patients and colleagues  Examples of potential roll-out across Ireland HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

Deadline for Entries: Friday, June 24th, 2016 April 2016 • HPN


Awards The Hospital Professional News Ireland

Awards 31

2016

Roche Oncology Pharmacist of the Year 2016

Recognising those who provide quality patient care in relation to a patient’s oncologic diagnosis, prescribed treatment, age group and other identified needs and provides comprehensive pharmaceutical care to oncology patients to assure safe and effective drug therapy. The judging panel will be looking for a high calibre individual who can demonstrate organisation, management and quality of care and services that optimise outcomes in patients with malignant diseases. This person will be able to show how they coordinate the drug therapy process through drug selection, drug information, dosing, monitoring, outcomes management, and patient education/ counselling. JUDGES WILL BE LOOKING FOR:  Evidence of a clinical role or a project that combines with developing a clinical service  A new approach to managing a clinical team, delivering a service or producing outstanding clinical work within oncology  Development of a new service or technique that refines/ changes clinical oncology practice  Research involving a clinical oncology service/setting or a new method of teaching oncology skills  Examples of a multi-disciplinary approach to oncology services HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

Deadline for Entries: Friday, June 24th, 2016 HPN • April 2016


Awards 32 Awards

The Hospital Professional News Ireland

2016

Innovation and Service Development Award 2015

The Innovation and Service Development Award is defined as the successful introduction of an idea, method or device that makes a genuine difference or positive change for the hospital pharmacy or patients, or both. The Innovation and Service Development Award will be presented to an individual or team from any hospital pharmacy department who has demonstrated an innovative pharmacy practice programme, resulting in improved patient care or safety, advancement of the profession enhanced pharmacy systems or other professional development. This Award will go to those that can best demonstrate an innovation or innovative approach that has created competitive advantage, contributed to growth, transformed the organisation, improved overall financial advantage or achieved operational excellence. JUDGES WILL BE LOOKING FOR:  Activities that may involve pioneering new models or systems that improve pharmacists' impact as members of the health care team; patient safety and outcomes; patient care in general and other professional development  A system or tool for pharmacy professionals that will directly or immediately impact patient care or the profession and/ or serve as an example or template for other pharmacy professionals to follow  Cumulative achievements or a single outstanding programme/ project completed or carried out over the past twelve months HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

Deadline for Entries: Friday, June 24th, 2016 April 2016 • HPN


Awards The Hospital Professional News Ireland

Awards 33

2016

Multidisciplinary Award 2015 Treatment of patients is, in most cases, a combined effort of several individuals and it is recognised that the outcome of a procedure is optimal when the professionals do indeed work together as a team. Obviously, pharmacists are part of treatment teams in healthcare establishments. With expertise of product and processes, they improve the therapeutic outcome and the quality of work flow. Although it seems obvious that a pharmacist form part of a team, this Award will seek to recognise those who can demonstrate added value by their contribution. The judging panel will want to see actual multidisciplinary healthcare working and actual examples of it in practice as well as an outline of what lessons have been learnt from its implementation. JUDGES WILL BE LOOKING FOR:  Evidence of how the applicant/team has shown exemplary teamwork  A clear dissemination of why this project as initiated, market research conducted on identifying need  Details of the challenges/innovations they overcome/initiated. Judges will expect to see evidence of results  A demonstration of the impact this applicant/project has had on the wider hospital team  Demonstration of how this initiative might be rolled out in hospitals across Ireland HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

Deadline for Entries: Friday, June 24th, 2016 HPN • April 2016


Awards 34 Awards

The Hospital Professional News Ireland

2016

Idis Hospital Pharmacist of the Year Award 2016

Part of the Clinigen Group

The Hospital Pharmacist of the Award recognises a hospital pharmacist who demonstrates leadership and exemplifies the evolution of the pharmacy profession toward an expanded role in health care. The winner will demonstrate significant contributions to the pharmacy industry overall resulting in meaningful improvements in the quality of patient care and improved delivery models and pharmacy’s role on the health care team. JUDGES WILL BE LOOKING FOR:  Evidence of long-term, consistent dedication and outstanding achievements that have led to the advancement of the profession of pharmacy and public health  Evidence of a large variety of skills, attributes and accomplishments  Evidence of an individual strong in character, cumulative professional accomplishments and the ability to properly represent and model what pharmacy as a profession encompasses  Evidence of an understanding the goals of pharmacy, and significantly contributing to how these goals may be achieved HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

Deadline for Entries: Friday, June 24th, 2016 April 2016 • HPN


Awards The Hospital Professional News Ireland

Awards 35

2016

Hospital Team of the Year Award 2016 This Award will be given to the hospital team that demonstrates the best combination of team spirit and enhancement of patient care at all levels. The judges will be looking for those who encourage and support each other and those who have collectively demonstrated innovation and forward thinking. The key to any successful hospital department is team work and this award recognises the power and potential of a focused and unified approach to health care initiatives. Teams can be based within one organisation or spread over multiple organisations; but they must comprise individuals working towards the same objective or goal. JUDGES WILL BE LOOKING FOR:  How the team has demonstrated their ability to deliver clear benefits to patients; and/or staff members through working together efficiently and effectively  How the team has worked together to achieve its objectives over the past twelve months  Projects that the team has successfully managed which demonstrate excellence in quality, innovation, productivity and prevention  A clear display of the principles underpinning their success as a team HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

Deadline for Entries: Friday, June 24th, 2016 HPN • April 2016


Awards 36 Awards

The Hospital Professional News Ireland

2016

Professional Contribution Award 2016

This is a new Award for 2016 and will be presented to those who can demonstrate outstanding contribution to the field of secondary care through work outside of the hospital setting. This may include those working in industry, academia, research & development or for trade and regulatory bodies or within the HSE. JUDGES WILL BE LOOKING FOR:  Those who have shown dedication to their profession by contributing to the standards of practice for the profession as a whole  Examples of bringing attention and awareness to the pharmacy profession throughout Ireland and further afield  Evidence of significant collaboration between other allied healthcare professionals  Demonstration of efforts to enhance the future of the profession through innovations, initiatives, standards, training and research WHO CAN ENTER: All Hospital professionals working outside the Irish hospital setting Previous Professional Contribution Award entrants, including winners HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

Deadline for Entries: Friday, June 24th, 2016 April 2016 • HPN


Feature 37

Current management updates in Hay Fever

Allergies are becoming more commonplace, particularly in industrialised countries. In addition to hay fever, allergic asthma is currently considered to be one of the most widespread allergies. UFZ researchers and their colleagues from the University of Leipzig have recently been successful in finding a protein that plays a critical role in the development of allergic airway inflammation. The discovery could pave the way for new therapies, as it also influences the progression of the allergy. Worldwide, there are more than 300 million asthma patients. With the medications available today,

symptoms can be effectively relieved, but without tackling the root cause. The precise reasons as to why certain people suffer from allergic asthma are still not fully clear. Tobias Polte and his team from the Department of Environmental Immunology at the Helmholtz Centre for Environmental Research (UFZ) collaborated with Jan Simon and his colleagues from the Clinic for Dermatology, Venereology and Allergology at the University of Leipzig and have recently been successful in discovering a molecule that plays a significant role in the development of allergic airway inflammation. The protein syndecan-4 is

found in the cell membrane of antigen presenting cells (APCs). These are immune cells that detect exogenous substances (antigens). They internalise them and migrate to the nearest lymph node, where they present them to other immune cells, namely T-cells. In this way they initiate an immune reaction that leads to sensitization to a particular antigen, like for example to a pollen allergen. It is upon renewed contact with this pollen allergen that the typical symptoms of allergic asthma arise. “In our study we were able to demonstrate that syndecan-4 plays a critical role in APC migration,” says Polte. “When syndecan-4 is lacking, the APCs

cannot find their way to the T-cells and consequently cannot activate them. As a result, the immune reaction cannot take place and the sensitization to a particular antigen ceases.” Through investigations at the University of Leipzig, the researchers were also able to show that syndecan-4 in the APCs also plays a central role in the inflammatory process of allergic asthma: the allergic asthma symptoms of mice improved when they were given antibodies against syndecan-4. “In principle, syndecan-4 would be a good starting point for new therapies”, says Polte. “Since it exhibits various other

HPN • April 2016


38 Feature functions in cell metabolism, potential side effects are still difficult to assess.” To relieve the symptoms of patients with allergic asthma, the treatment of allergic airway inflammation with glucocorticoids and the use of a bronchodilator asthma spray will continue to be paramount in the near future. “There will only be an effective therapy that gets to the root cause when we have fully understood the relationships behind the development of allergic asthma”, says Polte. “Nevertheless, in our study we were able to discover an important component with syndecan-4 that should help us on the road to identifying new therapies.” There will be close to one million hay fever sufferers in Ireland this summer (24% of the population). That’s a significant demand on healthcare professional’s time and professionalism. All allergy conditions, but especially hay fever, are on the rise internationally. Experts believe 50% of the global population will have some type of allergy by 2026. Not every pollen allergic patient will have the same discomfort. Hay-fever is usually a seasonal (mid-summer) problem but can start earlier and even drag on until late autumn. Most sufferers are troubled with grass pollen only (10,000 pollen grains fit on the tip of a pin) but a significant number are troubled with a combination of tree and grass pollen allergy. Their season starts in early spring with mild nasal irritation but by the time the summer months arrive they are already compromised so that even small amounts of grass pollen can trigger quite aggressive hay-fever. If the summer is especially warm and sunny with high surges of pollen, then those three to four months can be a write-off. For those with the extra burden of mould spore allergy hay fever misery can drag on through the autumn/fall months. POLLEN SEASON In Ireland aggressive sneezes can be heard first along the warmer western coasts.

April 2016 • HPN

By the end of May high pollen counts can be detected countrywide (the pollen count measures the amount of pollen in the air over 24 hours). Pollen allergy misery can change with weather -related production, dispersal and quantity of pollen grains in the air. Grass pollen surges about 2 – 3 weeks earlier at sea level compared to mountainous areas. High levels of pollen occur on warm, dry and sunny days with low levels occurring on wet, damp and cold days. Rain washes pollen out of the air. Pollen is released in the morning and carried higher into the air by midday. It descends again to ‘nose-level’ in the late afternoon. Cities and dense urban areas stay warmer longer and hold pollen. Combine this with atmospheric pollution from car fumes and you can understand why city dwellers suffer more aggressive hay-fever than their country cousins. HAY FEVER AND ASTHMA LINK Aggressive hay-fever causes both nose and sinus inflammation, however, the nose and sinuses link to the lungs by a number of pathways that include nerve ending and asthma triggering blood units (called Th2). These move from the nose and sinuses to the bone marrow to produce a number of other allergy chemicals which move into the blood circulation and ‘stick’ in the nose, sinuses and lungs, causing further allergic inflammation that triggers cough and wheeze. • Hay-fever may cause nose symptoms only. • Hay-fever often involves the sinuses as well as the nose. • Hay-fever may provoke chest symptoms. • Hay-fever may go hand-in-hand with asthma. • Hay-fever in children with asthma causes more asthma-related hospital admissions and greater total days spent in hospital

THUNDERSTORMS AND ASTHMA ATTACKS Thunderstorms during the pollen season can trigger asthma attacks ranging from mild to life threatening. Pollen grains are carried at ground level by the strong air currents in thunderstorms. Then the pollen grains burst, releasing their allergy provoking material (called allergens). The allergens are carried as aerosols in the wind currents and easily inhaled, penetrating deeply into the nose and sinuses and lungs triggering breathing crises. For some hay-fever sufferers this may be the first time they’ve ever experienced asthma. TREATMENTS There are five main medical compounds which, when used correctly, give relief from hay fever. (1) Anti-histamines ‘mop-up’ excess histamine circulating in the blood stream during allergy attacks. (2) Leukotrienes are released into the blood during hay fever and cause long term swelling within the nose and sinuses. Anti-leukotrienes reverse this. (3) Steroid or cortisone compounds (eye and nose drops, nasal sprays, and tablets) reverse allergic swelling and irritation that occur in the nose, sinuses, eyes and lungs. (4) Sodium cromoglycate drops for the eyes. This compound is totally safe for long or short term relief. (5) Fast acting nasal decongestants. Hay fever medicine reduces symptoms of irritable bowel syndrome IBS patients have extremely sensitive bowels associated with increased pain perception. This phenomenon is comparable to the increased sensitivity of our skin to hot water after sunburn. The exact cause of this hypersensitivity has long

been unknown. Researchers already knew that the bowels of patients with IBS contain larger quantities of the substance histamine, but the specific link with hypersensitivity had not yet been made. KU Leuven professor of gastroenterology Guy Boeckxstaens and his team have now shown that histamine has an impact on the pain receptor TRPV1. In IBS patients, histamine released in the gut makes TRPV1 hypersensitive. The researchers found that histamine interferes with the histamine 1 receptor, which is located on nerves that contain TRPV1. Importantly, they discovered that blocking the histamine 1 receptor prevented the sensitising effect of histamine on TRPV1. Taken together, these findings identify the mechanism behind IBS patients' increased pain perception. On the basis of these findings, the researchers set out to find a solution to the problem. They designed a pilot clinical study in IBS to evaluate the effect of a substance that blocks the histamine 1 receptor on the nerves, so that the sensitivity of TRPV1 no longer increases. This substance, ebastine, is already used in hay fever medication. Patients who were treated with ebastine for 12 weeks had significantly less abdominal pain than patients from the control group. A follow-up study will test the effect of ebastine on 200 IBS patients. Irritable bowel syndrome is a condition that affects 10-15% of the population. Treatment is currently limited to normalising the defecation pattern. It cannot reduce or end the abdominal pain experienced by IBS patients. The results of this study may help change that.


fluticasone furoate Allergic rhinitis relief

Relieving the symptoms of allergic rhinitis1

The incidence of epistaxis during long term treatment was higher than 10% but was generally mild to moderate in intensity1

Prescribing Information (Please refer to the full Summary of Product Characteristics before prescribing) Avamys® Nasal Spray Suspension (fluticasone furoate 27.5 micrograms/metered spray). Uses: Treatment of symptoms of allergic rhinitis in adults and children aged 6 years and over. Dosage and Administration: For intranasal use only. Adults and adolescents (12 years and older): Two sprays per nostril once daily (total daily dose, 110 micrograms). Once symptoms controlled, use maintenance dose of one spray per nostril once daily (total daily dose, 55 micrograms). Reduce to lowest dose at which effective control of symptoms is maintained. Children aged 6 to 11 years: One spray per nostril once daily (total daily dose, 55 micrograms). If patient is not adequately responding, increase daily dose to 110 micrograms (two sprays per nostril, once daily) and reduce back down to 55 micrograms daily dose once control is achieved. Contraindication: Hypersensitivity to active substance or excipients. Special warnings and precautions: Systemic effects of nasal corticosteroids may occur, particularly when prescribed at high doses for prolonged periods. These effects are much less likely to occur than with oral corticosteroids and may vary in individual patients and between different corticosteroid preparations. Potential systemic effects may include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, cataract, glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Treatment with higher than recommended doses of nasal corticosteroids may result in clinically significant adrenal suppression. Consider additional systemic corticosteroid cover during periods of stress or elective surgery. Caution when prescribing concurrently with other corticosteroids. A reduction in growth velocity has been observed in children treated with fluticasone

furoate 110 micrograms daily for one year. Therefore, children should be maintained on the lowest possible efficacious dose which delivers adequate symptom control. It is recommended that growth of children receiving prolonged treatment with nasal corticosteroids is regularly monitored. Consider referring to a paediatric specialist. May cause irritation of the nasal mucosa. Nasal and inhaled corticosteroids may result in the development of glaucoma and/or cataracts. Close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma and/or cataracts. Drug interactions: Caution is recommended when co-administering with potent CYP3A4 inhibitors e.g. ketoconazole and co-administration with ritonavir is not recommended because of the risk of increased systemic exposure of fluticasone furoate. Pregnancy and Lactation: No adequate data available. Recommended nasal doses result in minimal systemic exposure. It is unknown if fluticasone furoate nasal spray is excreted in breast milk. Only use if the expected benefits to the mother outweigh the possible risks to the foetus or child. Side effects: Very common (≥1/10): epistaxis. Epistaxis was generally mild to moderate, with incidences in adults and adolescents higher in longerterm use (more than 6 weeks). Common (≥1/100 and <1/10): headache, nasal ulceration. Uncommon (≥1/1000 and <1/100): rhinalgia, nasal discomfort (including nasal burning, nasal irritation, and nasal soreness), nasal dryness. Rare (≥1/10,000 and <1/1000): hypersensitivity reactions including anaphylaxis, angioedema, rash, and urticaria. Not known: transient ocular changes, growth retardation. Very rare (<1/10,000): Nasal septum perforation. Marketing Authorisation (MA) Holder: Glaxo Group Ltd, 980 Great West Road, Brentford, Middlesex, UK TW8 9GS. MA Number: EU/1/07/434/003. Legal category: POM S1B. Last date of revision: January 2016 Job Ref: IE/FF/0002/16. Further information available on request from GlaxoSmithKline, 12 Riverwalk, Citywest Business Camp, Dublin 24. Tel: 01-4955000.

Avamys® is a registered trademark of the GlaxoSmithKline group of companies. © GlaxoSmithKline group of companies 2015.

Adverse events should be reported to the Health Products Regulatory Authority (HPRA) using an Adverse Reaction Report Form obtained either from the HPRA or electronically via the website at www.hpra.ie. Adverse reactions can also be reported to the HPRA by calling (01) 6764971. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255. Reference: 1. Avamys Summary of Product Characteristics, available on www.medicines.ie, accessed 30 March 2016. IE/FF/0001/14a(1)a Date of preparation: March 2016

Not actual size


40 RA News

Gene regulating tissue damage discovery Professor Gerry Wilson, UCD School of Medicine and Medical Science

Although there is no cure for RA, new effective drugs are increasingly available to treat the disease and prevent deformed joints. Self-management of the condition by patients, including exercise, is also known to reduce pain and resulting disability.

Scientists have identified a new protein (C5orf30) which regulates the severity of tissue damage caused by rheumatoid arthritis (RA), an autoimmune disease that causes inflammation, pain, stiffness and damage to the joints of the feet, hips, knees, and hands. Following the discovery published in the scientific journal PNAS, rheumatoid arthritis patients most likely to suffer the severest effects of the condition can now be identified early and fast-tracked to the more aggressive treatments available.

To conduct the research, the international team of scientists from University College Dublin and the University of Sheffield, funded by Arthritis Ireland and the University of Sheffield, analysed DNA samples and biopsy samples from joints of over 1,000 Rheumatoid arthritis patients in the United Kingdom and Ireland. “Our findings provide a genetic marker that could be used to identify those RA patients who require more aggressive treatments or personalised medicine,” said Professor Gerry Wilson from the UCD School of Medicine and Medical Science, University College Dublin, who led the research. “They also point to the possibility that increasing the levels of

C5orf30 in the joints might be a novel method of reducing tissue damage caused by RA”. Dr Munitta Muthana from the Medical School at the University of Sheffield, who co-authored the study said: “These exciting findings will prompt us to further explore the role of this highly conserved protein that we know so little about, and its significance in human health and disease”. Rheumatoid arthritis is the most common inflammatory of the types of arthritis affecting around 1% of the population. It is estimated that 30% of patients with rheumatoid arthritis are unable to work within 10 years of onset of the condition. It affects more women than men, and often more severely. It is also most common between the ages of 40 and 70, but it can affect people of any age including children. One of the biggest difficulties with treating the condition is early diagnosis. With early diagnosis and aggressive treatment, it is possible to reduce the damage to the joints caused by RA. Deciding the most appropriate treatment for each patient at the earliest possible stage is central to effectively tackling the condition.

“Investing in research to find new treatments and ultimately a cure for arthritis is one of our key objectives at Arthritis Ireland,” said John Church, CEO, Arthritis Ireland. “Treatments for arthritis have improved enormously over the last number of years. Thirty years ago, rheumatologists’ waiting rooms were filled with people in wheelchairs. Today, that is no longer the case. The outlook for a person diagnosed with arthritis in 2015 is much brighter than it used to be. We are getting closer and closer to personalised medicine. This discovery is further proof that we are in the right space and investing our money wisely,” he added. In Ireland, it is estimated that some 40,000 people have the severe inflammatory auto-immune condition called rheumatoid arthritis (RA). 70% of these rheumatoid arthritis patients are women. In the UK, around 700,000 people are reported to have rheumatoid arthritis (RA). In the US, approximately 1.5 million US adults have rheumatoid arthritis (RA) and as with other countries these numbers are expected to rise in future years.

IANO President’s Prize The Irish Association of Nurses in Oncology (IANO), in association with Bayer are delighted to announce the launch of the 2016 IANO President’s Prize. Applicants are asked to submit a research project and one successful winner will be chosen to do a clinical placement in Memorial Sloan Kettering Cancer Centre (MSKCC) in New York for one week. This is the 4th IANO President’s Prize which is supported by an educational grant from Bayer. The prize in 2016 will be presented at the IANO session during the European Oncology Nursing Society (EONS) conference which is taking place in Ireland on the 17th and 18th of October 2016 in the Aviva Stadium. Memorial Sloan Kettering is the world’s oldest and largest private cancer centre which has devoted more than a century to patient care as well as innovative research, April 2016 • HPN

making significant contributions to new and better therapies for the treatment of cancer. MSKCC also recently announced that it has received Magnet recognition, the most prestigious distinction a healthcare organisation can receive for nursing excellence and quality patient outcomes. Ms Terry Hanan, 2014 IANO President’s Prize winner, recently spoke about her experience in MSKCC. “Winning the IANO President’s Prize was brilliant because it gave me such a unique opportunity to visit and learn from one of the biggest cancer centres in the world,” she said, “I gained so many insights from the range of clinical areas I visited in addition to learning a lot about their nurse education programme.” This award is an excellent opportunity for the successful candidate to work alongside a multi-disciplinary oncology team

Eilish Moran, Bayer and Pauline Kehoe, IANO within their chosen specialty area, in a world renowned centre of excellence. The deadline for submissions is Friday, 16th

September 2016. For further information please visit www.iano.ie/conference.html


IN DMARD-IR AND TNF-IR RA PATIENTS, WHEN COMBINATION WITH MTX IS NOT AN OPTION...

THINK RoACTEMRA

1

NOW AVAILABLE IN SUBCUTANEOUS (SC) ABRIDGED PRESCRIBING INFORMATION (For full prescribing information, refer to the Summary of Product Characteristics [SmPC]). RoActemra® (tocilizumab) 20mg/ml Concentrate for Solution for Infusion (RoActemra IV) and RoActemra® 162mg solution for injection in pre-filled syringe (RoActemra SC). Indications: ABRIDGED PRESCRIBING INFORMATION (For full prescribing information, refer to the Summary of Product Characteristics [SmPC]). RoActemra® (tocilizumab) 20mg/ml Concentrate for Solution for Infusion (RoActemra IV) and RoActemra® 162mg solution for injection in pre-filled syringe (RoActemra SC). Indications: RoActemra SC: In combination with methotrexate (MTX), for the treatment of adult patients with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response or intolerance to one or more disease-modifying anti-rheumatic drugs (DMARDs) or tumour necrosis factor (TNF) antagonists. RoActemra IV: In combination with MTX for the treatment of (i) severe, active and progressive RA in adults not previously treated with MTX, (ii) adult patients with moderate to severe active RA who have had an inadequate response or intolerance to one or more DMARDs or TNF antagonists, (ii) active systemic juvenile idiopathic arthritis (sJIA) in patients ≥ 2 years of age, who responded inadequately to previous therapy with NSAIDs and systemic corticosteroids, (iii) juvenile idiopathic polyarthritis (pJIA) (rheumatoid factor positive or negative and extended oligoarthritis) in patients ≥ 2 years of age, who responded inadequately to previous therapy with MTX, RoActemra IV/SC can be given as monotherapy in case of intolerance to MTX or where continued treatment with MTX is inappropriate for all indications. RoActemra IV/ SC has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function when given in combination with MTX for the treatment of adult RA patients. Dosage & Administration: Treatment should be initiated by HCPs experienced in the diagnosis and treatment of RA, sJIA or pJIA and all patients should be given the Patient Alert Card. RA: RoActemra IV: 8mg/kg diluted to a final volume of 100ml, given once every 4 weeks by IV infusion over 1 hour. For patients >100kg, doses >800mg per infusion are not recommended. No data on doses above 1.2g. RoActemra SC: 162mg once every week, irrespective of weight. Patients may self-inject after training. Rotate injection site frequently. sJIA (RoActemra IV only): Patients <2 years of age – no data. Patients >2 years, 8mg/kg diluted to final volume of 100ml for patients ≥ 30kg or 12mg/kg diluted to final volume of 50ml for patients < 30kg once every 2 weeks by IV infusion over 1 hour. Clinical improvement generally seen within 6 weeks of starting RoActemra; reconsider continued therapy if no improvement. pJIA (RoActemra IV only): Patients <2 years of age - no data. Patients >2 years of age, 8mg/kg diluted to final volume of 100ml for patients ≥ 30 kg or 10 mg/kg diluted to final volume of 50ml for patients <30kg once every 4 weeks by IV infusion over 1 hour. Clinical improvement generally seen within 12 weeks of starting RoActemra; reconsider continued therapy if no improvement. For pJIA/sJIA: check patient’s weight at each visit. Dose adjustments: For raised liver enzymes, modify concomitant DMARDs if appropriate, reduce or interrupt dose of RoActemra; for low absolute neutrophil count (ANC) or low platelet count reduce or interrupt RoActemra. In some instances discontinue RoActemra (see SmPC). Special Populations: No data available for RoActemra SC in patients <18 years of age. Closely monitor renal function in patients with moderate to severe renal impairment. No data in patients with hepatic impairment. No dose adjustments in patients >65 years. Contraindications: Hypersensitivity to any component of the product; active, severe infections. Warnings & Precautions: Cases of serious infections (sometimes fatal) have been reported; interrupt therapy until controlled. Caution in patients with recurring/chronic infections, or other underlying conditions (e.g. diverticulitis, diabetes and interstitial lung disease) which predisposes to infection. Patients and parents/guardians of sJIA and pJIA patients should contact their HCP when symptoms suggestive of infection appear. Screen for latent TB and treat if required prior to starting therapy. Patients to seek medical attention if sign/symptoms suggestive of TB occur during or after treatment. Viral reactivation (e.g. hepatitis B) reported with biologic therapies. Caution in patients with a history of intestinal ulceration or diverticulitis. Serious hypersensitivity reactions, including anaphylaxis, reported and may be more severe and potentially fatal in patients who have experienced hypersensitivity reactions during previous treatment even if they have received premedication with steroids and anti-histamines. If an anaphylactic reaction or other serious hypersensitivity/serious infusion related reaction occurs, permanently discontinue RoActemra. Use with caution in patients with active hepatic disease/impairment. Not recommended in patients with baseline ALT or AST > 5 x ULN; caution in patients with ALT or AST > 1.5 x ULN (see SmPC). Risk of neutropenia may increase in patients previously treated with TNF antagonist. Continued therapy not recommended in patients with ANC < 0.5 x 109/l or platelet count < 50 x 103/μl. Do not initiate RoActemra treatment were ANC is below 2 x 109/l. Caution in patients with low platelet count; monitor neutrophils and platelets in RA, sJIA and pJIA patients according to SmPC. Elevations in lipid parameters seen; if elevated, follow local guidelines. Be vigilant for symptoms of new-onset central demyelinating disorders. Immunomodulatory medicines may increase malignancy risk in RA patients. Live and live attenuated vaccines should not be given concurrently (see SmPC). Not recommended for use with other biological agents. Macrophage activation syndrome (MAS), a serious life-threatening disorder, may develop in sJIA patients – RoActemra not studied in patients during an active MAS episode. Trade name should be clearly recorded in patient file to improve traceability of biological medicines. Drug Interactions: Studies only performed in adults. Monitor patients taking medicines individually adjusted and metabolised via CYP450 3A4, 1A2 or 2C9 when starting/stopping RoActemra, as doses may need to be increased to maintain therapeutic effect. Effects of tocilizumab on CYP450 enzyme activity may persist for several weeks after stopping therapy (refer to SmPC for further details on cytochrome CYP450 and other drug interactions). Fertility, Pregnancy & Lactation: Women should use contraception during and up to 3 months after treatment. No adequate data from use in pregnant women. Animal study showed increased risk of spontaneous abortion/embryo-foetal death at high dose. RoActemra should not be used during pregnancy unless clearly necessary. No lactation data in humans. A decision on whether to continue/discontinue breastfeeding or RoActemra therapy should be made taking into account the relative benefits to the child and mother. Refer to SmPC. Effects on ability to drive and use machines: RoActemra has minor influence on the ability to drive and use machines (dizziness). Undesirable Effects: Prescribers should consult SmPC for full details of ADRs. RoActemra IV: RA: ADRs occurring in RoActemra trials: Very Common (> 1/10): upper respiratory tract infections, hypercholesterolaemia. Common (>1/100 - <1/10): cellulitis, pneumonia, oral herpes simplex, herpes zoster, abdominal pain, mouth ulceration, gastritis, rash, pruritus, urticaria, headache, dizziness, hepatic transaminases increased, weight increased, total bilirubin increased, hypertension, leucopenia, neutropenia, peripheral oedema, hypersensitivity reactions, conjunctivitis, cough and dyspnoea. sJIA: ADRs were similar to those seen in RA patients. Serious infections of varicella and otitis media reported (in addition to infections for RA). Hypersensitivity reactions requiring treatment discontinuation occurred in <1% of patients. Other events occurring within 24 hours of infusion (16% of patients) included rash, urticaria (considered serious), diarrhoea, epigastric discomfort, arthralgia and headache. Decreased IgG levels during therapy. pJIA: ADRs were similar to those seen in RA and sJIA patients. Nasopharyngitis, headache, nausea, and decreased neutrophil count more frequently reported in the pJIA population. The incidence of infections leading to dose interruptions was numerically higher in patients weighing <30 kg, the rate of serious infections was also higher in these patients. 20.2% experienced an infusion reaction within 24 hours of infusion. RoActemra SC: The safety and immunogenicity was consistent with the known safety profile of IV. Injection site reactions (including erythema, pruritus, pain and haematoma) were mild to moderate in severity. Serious or Potentially Serious: serious infections, active tuberculosis, invasive pulmonary infections, interstitial lung disease (including pneumonitis and pulmonary fibrosis), GI perforations (as complications of diverticulitis), serious hypersensitivity reactions, Stevens-Johnson syndrome. See SmPC section 4.8 for instructions on the reporting of Suspected Adverse Reactions. Legal Category: Subject to medical prescription which may not be renewed (A). Presentations & Marketing Authorisation Numbers: 80mg of tocilizumab in 4ml (20mg/ml) pack of 1 (EU/1/08/492/001); 200mg of tocilizumab in 10ml (20mg/ml) pack of 1 (EU/1/08/492/003); 400mg of tocilizumab in 20ml (20mg/ml) pack of 1 (EU/1/08/492/005); 162mg tocilizumab solution for injection (in 0.9ml) in pre-filled syringe (EU/1/08/492/007). Marketing Authorisation Holder: Roche Registration Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United Kingdom. RoActemra is a registered trade mark. Further information is available from Roche Products (Ireland) Limited, 3004 Lake Drive, Citywest, Naas Road, Dublin 24. Telephone: (01) 4690700. Fax: (01) 4690791. Date of Preparation: March 2015. Reference: 1. Nisar MK et al. The role of tocilizumab monotherapy in the management of rheumatoid arthritis: a review. Int. J. Clin. Rheumatol. (2012) 7(1): 9-19. Date of item: February 2016. IE/RACTE/0216/0001


42 Feature

Bridging the Data Gap feature Table 1: List of IPCOR participating hospitals Men in Ireland now have a onein-seven chance of developing prostate cancer, with 3,384 men diagnosed with prostate cancer in Ireland in 2012.1 Prostate cancer is a significant clinical problem in Ireland: incidence rates here are the third highest in Europe2 and over 500 Irish men die of advanced prostate cancer each year.1

Table1: List of IPCOR participating hospitals

Public hospitals St Vincent’s University Hospital

Area Dublin South

St James’s Hospital

Dublin South

Beaumont Hospital

Dublin North

Mater Misericordiae University Hospital

Dublin North

Tallaght (AMNCH) Hospital

Dublin South

University Hospital Waterford

South

Cork University Hospital

South

The 2006 Strategy for Cancer Control in Ireland specifically highlighted a deficit in epidemiological and health services research in cancer. A lack of information about prostate cancer patients and their care may negatively impact clinical outcomes for prostate cancer patients.

Galway University Hospital

West

Mercy University Hospital

South

University Hospital Limerick

West

Clinicians are unable to inform patients of their expected clinical outcomes with any accuracy as no data currently exists beyond overall and cancer-specific survival. Information is lacking on key intermediate clinical outcomes such as risk of recurrence or rates of treatment failure.

Beacon Hospital

Dublin South

Bon Secours Hospital Dublin

Dublin North

Bon Secours Hospital Galway

West

Recent population-based studies have investigated men’s functional wellbeing and health-related quality of life as well as treatment side-effects3,4,5 but there is little robust longitudinal data evaluating men’s experiences from diagnosis and throughout their treatments. Novel agents have been developed for the treatment of advanced prostatecancer,6 however, the challenge remains to collect data that will inform clinicians on the most effective treatment regimes to improve progressionfree survival and overall survival for metastatic prostate cancer patients. In order to address these issues, the Irish Prostate Cancer Outcomes Research study (IPCORS) is establishing a national registry to capture highquality information about newly diagnosed collect clinical data as well as patient reported outcome measurements (PROMs) from the time of diagnosis and throughout their treatments. The registry will generate robust data on a range of important clinical outcomes of men with prostate cancer and assess processes, consistency and quality of prostate cancer care. By providing evidence-based

April 2016 • HPN

Private hospitals

Area

Galway Clinic

West

Bon Secours Hospital Cork

data and recommendations to clinicians, hospitals, decisionmakers and the National Cancer Control Programme (NCCP), the registry will promote equity in access to services and improvements in care nationally. By bringing together, for the first time, data on clinical and patientreported outcomes that have been collected over time and fostering research on such data, the registry will ultimately lead to the improvement of treatment regimes, patient care and maximise quality of life for men diagnosed with prostate cancer in the Republic of Ireland. PARTICIPATING HOSPITALS The IPCOR study will identify patients in and collect clinical data from 17 hospitals that diagnose over 88% of prostate cancer cases in the Republic of Ireland. The study will follow these men over time as they undergo treatment for prostate cancer. The study has received ethical approval from the relevant ethics committees. (See Table 1 for list of participating hospitals) CLINICIAN RECRUITMENT For the IPCOR study to succeed, it is essential to have the support and commitment of prostate 12 cancer treating clinicians. IPCOR has recruited urologists, medical oncologists and radiation oncologists who have agreed to IPCOR collecting clinical data on

South

Mater Private Hospital

Dublin North

St Vincent’s Private Hospital

Dublin South

of treatment to obtain a baseline of men’s their prostate cancer patients and quality of life. contacting their patients to seek Due to this tight timeframe for data colconsent from them to take part in lection, IPCOR will establish mechanisms the PROMs components of the to ensureClinicians rapid routeswho for identification study. participateof men eligible to take part in thean study. For in the study will receive annual example, approximately one-third report ofcurrently their patients’ outcomes. of men with prostate cancer are diagnosed PATIENT through the IDENTIFICATION NCCP designated cancer cenIPCOR anAccess extension tres eitherrepresents via their Rapid Prostateof the present registration andsymptodata Clinics (RAPC) or directly through collection system at the National matic services and/or urology clinics. Cancer Registry (NCR). IPCOR IPCOR research officers will set-up proresearch officers will be employed cedures to access lists from the RAPC and by the NCR to identify patients from weekly multidisciplinary team (MDT) and to collect the data required meetings. Following current NCR processes, for IPCOR. the research officers will access other data sources, hospital patient All meneg.who have beenadministranewly tion systems, radiotherapy cliniccancer records, diagnosed with prostate in the 17 participating chemotherapy clinic records,hospitals and local HIPE will be eligible inclusion (hospital inpatientfor episode) recordsinto identheand IPCOR study and will be tify capture any missed cases. identified a rapid case Following through their diagnosis, men will be ascertainment system which sent written information about the will study be implemented hospital. and asked to consentintoeach the sharing of The first outcome patient andpatient-reported hospital-level data within data will project be collected in the the IPCOR team, participating in interval between diagnosis and the patient-reported outcomes compocommencement treatment nents of the study byof filling in qualityto obtain a baseline of men’s quality of life questionnaires annually, linking of life. their clinical and PROMs data to their biological specimens and for the use Due to this tight timeframe for of data their biological specimens, collection, IPCOR will including establish

mechanisms to ensure rapid routes for identification of men eligible to take part in the study. For cancerprofessional Spring 2016 example, currently approximately one-third of men with prostate cancer are diagnosed through the NCCP designated cancer centres

those taken for diagnostic tests, in future

either via their Rapid Access ethically approved research studies. Each Prostate Clinics (RAPC) or directly patient will be assigned a unique IPCOR through symptomatic services registration number at the time of initial and/or urology clinics. identification which will link their data

IPCOR officers will and theirresearch biological specimens. set-up procedures to access lists Data collection from the RAPC and from weekly Clinical data multidisciplinary team The NCR will extend their(MDT) current datameetings. Following current NCR base to incorporate the additional data processes, research officers items and thethe clinical follow-up of patients will other data sources, thataccess IPCOR will collect. Utilising the NCR eg. hospital model of data patient collectionadministration ensures that systems, radiotherapy clinic dataIPCOR will create a population-based records, clinic base with chemotherapy a high degree of completeness. records, and local HIPEcases (hospital When potentially eligible are inpatient episode) records ascertained, the research officers will to identify andand capture register the case collectany basic demomissed cases. graphic and clinical information (including name, address, date of birth, grade, Following their diagnosis, menPSA result). research officers will subsewill be The sent written information quentlythe collect dataand on disease about study askedstage, to morphology, consent to and the treatments sharing ofreceived patientin the first year post-diagnosis (surgicalthe proand hospital-level data within cedures, project radiotherapy, chemotherapy and IPCOR team, participating hormonal treatment), hospitals attended in the patient-reported outcomes and treating clinicians theby medical components of the from study filling record and other such as radioin quality of lifesources questionnaires therapy and oncology clinic records.and The annually, linking their clinical patient’s IPCOR number will PROMs data registration to their biological be used to track patients over time. specimens and for the use of their A unique aspect of the IPCOR study is biological specimens, including the active follow-up of patients on a yearly those taken for diagnostic tests, in future ethically approved research studies. Each patient will be assigned a unique IPCOR registration number at the time of initial identification which will link their data and their biological specimens.

basis offic tiona failu will i and l links prov this p infor (Tabl be co Patie (PRO IPC stand throu colle base ques gene The I Outc Canc that Com asses qual IPC and E healt will b naire syste coho plete of re decis Risk Th men strat meta overa will t Th poin at di clinic cores score appr radia nal-b thera Repo Th conta patie repo


feature

43

Table 2: Examples of clinical data items to be collected by the IPCOR study Table 2: Examples of clinical data items to be collected by the IPCOR study

VARIABLES

TREATMENT VARIABLES

ANNUAL FOLLOW-UP

Patient attributes Names Address DOB Occupation First-degree family members with prostate cancer

Surgery Hospital name Consultant code Surgical Approach Acute surgical complications Acute medical complications

Disease relapse Biochemical recurrence Clinical recurrence Local and systemic progression Castrate resistance Treatment of recurrence Complications of chemotherapy Patient’s status

Diagnosis Diagnosis date Symptoms at diagnosis Prebiopsy PSA level Imaging investigations Tumour characteristics Method of Diagnosis Method of Presentation Clinical TNM stage

DATA COLLECTION CLINICAL DATA The NCR will extend their current database to incorporate the additional data items and the clinical follow-up of patients that IPCOR will collect. Utilising the NCR model of data collection ensures that IPCOR will create a population-based database with a high degree of completeness. When potentially eligible cases are ascertained, the research officers will register the case and collect basic demographic and clinical information (including name, address, date of birth, grade, PSA result). The research officers will subsequently collect data on disease stage, morphology, and treatments received in the first year post-diagnosis (surgical procedures, radiotherapy, chemotherapy and hormonal treatment), hospitals attended and treating clinicians from the medical record and other sources such as radiotherapy and oncology clinic records. The patient’s IPCOR registration number will be used to track patients over time. A unique aspect of the IPCOR study is the active follow-up of

Surgical pathology Gleason grade Extra prostatic extension Seminal vesicle involvement Margin involvement Pathological TNM stage

Initial pathology Date of biopsy % of all biopsy cores involved with cancer Gleason grade and sum Total number of nodes sampled Number of nodes with cancer Complications for biopsy

Radiotherapy External beam Start date Completion date Dose (Gy) Brachytherapy Start date Completion date Dose (Gy) Dose rate Acute complications

Management First treatment Intent of First Treatment Radical Prostatectomy Radiotherapy ADT (chemical) ADT (Surgical) Chemotherapy Other systemic therapy Other therapy Watchful waiting Active surveillance

Chemotherapy Agent/protocol used Start and stop dates Clinical trial status Bone directed therapies Chemotherapy complications

decision-makers, such as the NCCP, with detailed reporting on quality indicators patients a yearly basis by the which can on facilitate decision-making and research The research drive serviceofficers. improvements. (Table 3. officers collect information on Examples will of quality indicators and rationadditional treatments received, ale for inclusion). treatment Data access failure, recurrence, metastases etc. Thiswithin will involve Information contained the accessing data be sources IPCOR registryvarious will routinely used by and with GPs. quality The NCR IPCORliaising personnel to assess of care routinely registrations withand provided tolinks men with prostate cancer death certificates by foster research leadingprovided to improvements the Central Statistics this in care and survival. CancerOffice; researchers process will be used to provide may request access to de-identified IPCOR robust information andby data. Data requests willon be date reviewed cause of death. the IPCOR Steering Committee and must be accompanied by relevant ethics com(Table 2. Examples of clinical mitteeitems certification. data to be collected by the Discussion IPCOR study) The IPCOR study is developing the first PATIENT-REPORTED national health outcomes prostate cancer

OUTCOMES MEASUREMENT (PROMS) DATA IPCOR is committed to better understanding the patient experience throughout the disease course and will collect patient-reported outcomes at baseline and annually thereafter. Validated questionnaires will be used to collect general and disease-specific quality of life. The International Consortium of Health Outcome Measurement (ICHOM) Prostate Cancer Working Group has determined that the Expanded

Androgen deprivation therapy Treatment phase First treatment used Second treatment used Surgical castration ADT complications

registry that will follow patients over time and provide a comprehensive overview of Prostate Cancer Index Composite men’s prostate cancer journey through the (EPIC-26) should be usedofto health system in the Republic Ireland. assess prostate cancer-specific The registry will be used to monitor qualeffects on quality of life. ity, benchmark outcomes and aid clinical research. It is hoped that high quality IPCOR will also utilisethis EORTC disease registry enable the identiQLQ-C30 andwill EuroQol EQ-5D-5L fication of best practices and improve to assess general health-related outcomes the use data of ‘real-life’ quality ofthrough life. PROMs data.be collected using postal will The registry dataand will be utilised to idenquestionnaires a web-based tify treatment patterns and the optimal data collection system. In the sequences or combinations treatmentof future, particular clinicalofcohorts regimens patients with and men mayforbe invited to local complete advanced prostaterelating cancer into order to maxquestionnaires areas of research as patients. imise positive interest outcomessuch for these treatment andall Randomiseddecision-making prospective trials to test service potentialsatisfaction. combinations or sequences of treatment are not feasible, thus the IPCOR RISK STRATIFICATION registry provides a valuable resource for

The Cancer of the Prostate Risk Assessment (CAPRA) model will be used to stratify patients according to their risk of metastasis, cancerspecific mortality, and overall mortality7 and patient outcomes will then be analysed. The CAPRA score is calculated using points assigned to: age at diagnosis, PSA at diagnosis, Gleason score of the biopsy, clinical stage and per cent of biopsy cores involved with cancer.8 A CAPRA score is valid across multiple treatment approaches

comparative effectiveness research using ‘real-life’ data to determine optimal treatsuch radicaland prostatectomy, ment as sequences their outcomes. radiation therapy (brachytherapy The registry will provide a better or external-beam), primaryin care understanding of the variation androgen deprivation or and treatment of prostatetherapy cancer across 7 active surveillance. the country and between the public and private healthcare sectors. Registry data REPORTING OUTCOMES will help in the identification of relevant The public IPCOR annual report population cohorts for future clinical trials will contain outcomes for prostate and diagnostic testing. availability of cancer patients at aThe national this information couldreports positivelywill influence level while clinical be the pharmaceutical industry’s selection aimed at clinicians and decisiondecisions and lead increased makers, such astothe NCCP,inclusion with of Irish patients in clinical trials. detailed reporting on quality The clinicalwhich and PROMs data in the indicators can facilitate registry will be linkedand to men’s decision-making drivediagnostic service biological samples(Table which have been conimprovements. 3. Examples sented for use in future ethically approved of quality indicators and rationale research. The registry will promote the for inclusion). use of the data and biological samples

DATA ACCESS Information contained within the IPCOR Spring registry routinely be 2016will cancerprofessional used by IPCOR personnel to assess quality of care provided to men with prostate cancer and foster research leading to improvements in care and survival. Cancer researchers may request access to de-identified IPCOR data. Data requests will be reviewed by the IPCOR Steering Committee and must be accompanied by relevant ethics committee certification.

HPN • April 2016

13


44 Feature

feature Table 3: Examples of quality indicators and rationale for inclusion

Table 3: Examples of quality indicators and rationale for inclusion

Safe and patient-directed care • Percentage of men failing primary treatment: Important to identify those failing curative therapy • Patient assessment of their physical health at baseline, 12, 24, 36 and 48 months: To identify men with limitations in overall healthrelated quality of life • Urinary, sexual and bowel function assessment performed at 12, 24, 36 and 48 months post primary treatment: To assess complications of treatment • Percentage of men with Intra-prostatic disease (pT2) or extra-prostatic disease (pT3) with positive surgical margins after surgery: To quantify adequacy of surgical resection Appropriate care • Percentage of men treated by radical prostatectomy with a detectable PSA at three-months post prostatectomy: Surgery is considered a curative therapy • Percentage of men with high risk disease receiving brachytherapy: Brachytherapy is not recommended for high risk disease • Percentage of men with high risk disease treated by active surveillance: Active surveillance not recommended for high risk disease • All complications recorded using the Clavien-Dindo classification for surgical morbidity: Reflects surgical best practice and relates to improved outcomes Access and equity of care • Time from initial referral to date of diagnosis: Delays may cause worse outcomes and increase patient anxiety • Time from diagnosis to date of treatment commencement: Reflects good organisational management • Distance travelled from residence to hospital of diagnosis and hospital of main treatment: Reflects access to healthcare • Percentage of cases diagnosed and/or treated at one of the eight designated cancer centres, and how this varies by socio-demographic group: Reflects equity of access to healthcare Data quality to be measured by IPCOR • Percentage of all prostate cancers in Ireland included in IPCOR: Indicator of completeness of case ascertainment by IPCOR • Percentage of patients with missing/unknown data for each clinical data field: Indicator of quality of clinical data • Percentage of patients from whom PROMs data was collected at baseline and each follow-up time point (ie. response rates): Indicator of how representative the PROMs data is of the whole population

DISCUSSION The IPCOR study is developing the first national health outcomes prostate cancer registry that will follow patients over time and provide a comprehensive overview of men’s prostate cancer journey through the health system in the Republic of Ireland. The registry will be used to monitor quality, benchmark outcomes and aid clinical research. It is hoped that this high quality disease registry will enable the identification of best practices and improve outcomes through the use of ‘real-life’ data. The registry data will be utilised to identify treatment patterns and the optimal sequences or combinations of treatment regimens for patients with local and advanced prostate cancer in order to maximise positive outcomes for these patients. Randomised prospective trials to test all potential combinations or sequences of treatment are not feasible, thus the IPCOR registry provides a valuable resource for comparative effectiveness research using ‘real-life’ data to determine optimal treatment sequences and their outcomes.14 The registry will provide a better understanding of the variation in care and treatment of prostate cancer across the country and between the public and private healthcare sectors. Registry data will help in the identification of relevant population cohorts for future clinical trials and diagnostic testing. The availability of this information could positively

April 2016 • HPN

by researchers to maximise the registry’s potential and facilitate studies which influence the pharmaceutical investigate of oncology, particularly industry’sareas selection decisions and lead to increased inclusionthat of Irish the identification of biomarkers are patients for in clinical predictive response trials. and resistance to treatments. The clinical and PROMs data in The IPCOR study will be a significant the registry will be linked to men’s contributor to international prostate diagnostic biological samples cancer research. IPCOR is collecting both which have been consented for clinical and PROMs data as recommended use in future ethically approved by the ICHOM Prostate Cancer Working research. The registry will promote Group andof has aligned data collection the use the dataits and biological with that currently being carried samples by researchers to out by the Prostate the Cancer Outcomes Registry maximise registry’s potential in Australia and New Zealand and and facilitate studies which the National Prostate Cancer Audit in the investigate areas of oncology, UK (England and These studies particularly theWales). identification of represent a unique to benchbiomarkers thatopportunity are predictive for mark prostate cancer care internationally response and resistance and promote improvements in care for to treatments. patients with prostate cancer. The IPCOR study will be a The IPCOR registry represents a novel significant contributor to model of translational research for both international prostate cancer local and advanced prostate cancer care research. IPCOR is collecting by improving our knowledge of patterns both clinical and PROMs data and quality of care; monitoring equity of as recommended by the ICHOM access to treatments and care; discovery Prostate Cancer Working Group of optimal therapeutic sequences and and has aligned its data collection improving compliance with best practice with that currently being carried guidelines for prostate cancer treatment.

out by the Prostate Cancer Outcomes Registry in Australia and New Zealand and the cancerprofessional Spring 2016 National Prostate Cancer Audit in the UK (England and Wales). These studies represent a unique opportunity to benchmark prostate cancer care internationally and promote improvements in care for patients with prostate cancer. The IPCOR registry represents a novel model of translational research for both local and advanced prostate cancer care by improving our knowledge

The analysis of PROMs data will inform

Society or Movember Foundation. The

thepatterns development implementation of andand quality of care; of strategies andequity supports help men monitoring oftoaccess tolive treatments and care; discovery better after prostate cancer. The IPCORof optimal therapeutic and infrastructure provides asequences template for the improving compliance establishment of enhanced with cancerbest regispractice guidelines for prostate tries in Ireland. cancer treatment. The analysis Áine Murphy is Irish prostate cancer of PROMs data project will inform theat outcomes research manager development andIreland, implementation Molecular Medicine Dublin; Linda of strategies andofsupports to Sharpe is professor cancer epidemiology help liveofbetter prostate at themen Institute Healthafter & Society, Newcancer. The IPCOR infrastructure castle University, UK; Ray McDermott is a provides a template for the consultant medical oncologist at Tallaght establishment of enhanced cancer Hospital and St Vincent’s University Hosregistries in Ireland.

authors would like thank the IPCOR like to thank thetoIPCOR Steering Steering Committee for reviewing Committee for reviewing andand approving this manuscript. approving this manuscript.

pital, Dublin; Frank Sullivan is director of

the Prostate Cancer Institute, NUI Galway, Áine Murphy is Irish Prostate and consultant radiation oncologist at the Cancer Outcomes Research Project Manager at Molecular Galway Clinic; and David Galvin is a conMedicine Ireland, sultant urologist at StDublin; Vincent’sLinda University Sharpe is Professor of Cancer Hospital and the Mater Hospital, Dublin Epidemiology at the Institute of Health & Society, Acknowledgements: ThisNewcastle work is University, McDermott funded by theUK; IrishRay Cancer Society Irishis a Consultant Medical Oncologist Prostate Cancer Outcomes Research at Tallaght Hospital and St Vincent’s Project, IPCOR14GAL, supported by the University Hospital, Any Dublin; Frank Movember Foundation. opinions, Sullivan is Director of the Prostate findings, conclusions or recommendations Cancer Institute, NUI Galway, and expressed are those of the authors and Consultant Radiation Oncologist not necessarily those of the Irish Cancer at the Galway Clinic; and David Galvin is a Consultant Urologist at St Vincent’s University Hospital and the Mater Hospital, Dublin

Acknowledgements: This work is funded by the Irish Cancer Society Irish Prostate Cancer Outcomes Research Project, IPCOR14GAL, supported by the Movember Foundation. Any opinions, findings, conclusions or recommendations expressed are those of the authors and not necessarily those of the Irish Cancer Society or Movember Foundation. The authors would

REFERENCES ON REQUEST References

1. Cancer Factsheet – Prostate. Cancer Registry 1. Cancer Factsheet – National Prostate. Ireland. Cork: 2015 National Cancer Registry Ireland. Cork: 2. Prostate Cancer Factsheet: Estimated incidence, mor2015

tality and prevalence. International Agency for Research

on Prostate Cancer, World Health Organisation. France: 2012 2. Cancer Factsheet: 3. Sharp L, O’Leary E, Kinnear H, et al. Cancer-related Estimated incidence, mortality and symptoms predict psychological wellbeing among prosprevalence. International Agency for tate cancer survivors: results from the PiCTure study. Research on 2015; Cancer, World Health Psycho-oncology DOI: 10.1002/pon.3909 Organisation. France: 2012E, et al. Long4. Drummond FJ, Kinnear H, O’Leary term health-related quality of life of prostate cancer

3. Sharp L, O’Leary E, Kinnear H, from et the survivors varies by primary treatment. Results al. Cancer-related symptoms PiCTure (Prostate Cancer Treatment, yourpredict experience) psychological wellbeing among study. J Cancer Surviv 2015; 9(2): 361-72 5. Gavin AT, cancer Drummond FJ, Donnelly results C, et al. Patientprostate survivors: from reported ‘ever had’ and ‘current’ long-term physical the PiCTure study. Psycho-oncology symptoms after prostate cancer treatments. BJU Int 2015; DOI: 10.1002/pon.3909 2015; 116(3): 397-406

6. Osanto S, Van Poppel Emerging H, novel therapies E, 4. Drummond FJ,H.Kinnear O’Leary foral. advanced prostate cancer. Ther Adv Urolquality 2012; of et Long-term health-related 4(1): 3-12 life of prostate cancer survivors varies 7. Cooperberg MR, Broering JM, Carroll PR. Risk assessby primary treatment. Results from the ment for prostate cancer metastasis and mortality PiCTure Treatment, at the time (Prostate of diagnosis. JCancer Natl Cancer Inst 2009; your experience) study. J Cancer Surviv 101(12): 878-87 2015; 9(2): MR, 361-72 8. Cooperberg Pasta DJ, Elkin EP, et al. The UCSF Cancer of the Prostate Risk Assessment (CAPRA) Score:

5. Gavin AT, Drummond FJ, Donnelly C, a straightforward and reliable pre-operative predictor et al. Patient-reported ‘ever had’ andJ Urol of disease recurrence after radical prostatectomy. 2005; 173(6): 1938-1942 ‘current’ long-term physical symptoms after prostate cancer treatments. BJU Int 2015; 116(3): 397-406 6. Osanto S, Van Poppel H. Emerging novel therapies for advanced prostate cancer. Ther Adv Urol 2012; 4(1): 3-12 7. Cooperberg MR, Broering JM, Carroll PR. Risk assessment for prostate cancer metastasis and mortality at the time of diagnosis. J Natl Cancer Inst 2009; 101(12): 878-87 8. Cooperberg MR, Pasta DJ, Elkin EP, et al. The UCSF Cancer of the Prostate Risk Assessment (CAPRA) Score: a straightforward and reliable pre-operative predictor of disease recurrence after radical prostatectomy. J Urol 2005; 173(6): 1938-1942


Feature 45

Maynooth scientists make Type 2 diabetes discovery Dr John Stevens Maynooth University Ireland's unparalleled economic success over the past decade has contributed to more sedentary lifestyles, fuelling the level of obesity. As a result, we are seeing a big increase in the level of diabetes.

A team of scientists in Ireland has developed a series of new compounds which in time could be used to help treat Type 2 diabetes. The chemicals mimic the effects of exercise on the body, by making it more difficult for cells to convert glucose into energy, and causing the sugar to be stored instead. Caused by higher than normal levels of glucose or blood sugars, diabetes can have serious health consequences for those with the chronic illness. It is a growing problem here and around the world, with 200,000 people in Ireland with the illness, while globally over 370 million people have Type 2 diabetes. According to the Healthy Ireland survey, 854,165 adults over 40 in the Republic of Ireland are at increased risk of developing (or have) Type 2 diabetes. More alarmingly, there are a further 304,382 in the 30 – 39 year age group that are overweight and not taking the weekly 150 minutes recommended physical activity, leaving them at an increased risk of chronic ill-health. This means that there are 1,158,547 adults in Ireland that need to consider making changes to their daily behaviours in terms of eating healthily and being more active. It is estimated that there are over 15,600 people over 80 years of age living with Type 2 diabetes based on the TILDA study which showed a prevalence of 11.9% in the over 75 age group. The International Diabetes Federation’s (2012) estimates that by 2030 there will be 278,850 people with the condition (prevalence of 7.5% in the population). Ireland is not dissimilar to other European countries in terms of diabetes levels. If anything,

According to local research, people with type 2 diabetes are relying heavily on oral medication to treat the condition, while avoiding a healthy diet and exercise - two components that are essential in managing the condition. After five years of work, a team at the Department of Chemistry at NUI Maynooth, led by Dr John Stephens, has developed a series of new compounds which could help treat the condition. When physical activity and exercise takes place, cells have to change more glucose into energy than when the body is at rest. The chemical mixtures developed by the Maynooth team make it more difficult for that process to take place, causing the cells to subsume more glucose than normal. By doing this, the high levels of glucose that Type 2 diabetes sufferers experience should be kept to a minimum, and weight gain kept down. The doses required should be lower than normal treatments for the condition, and the side effects reduced. At present the research has only been carried out on mice in the lab, and has not yet been tested on humans. "We are now looking forward to our next phase of research, which will see us undertake further lab studies and early clinical trials," said Dr Stephens in a statement.

published recently, that combined large scale clinical observations and innovative computer modelling. The study, led by researchers at the University of Michigan and the MRC Epidemiology Unit, University of Cambridge, used data from the ADDITION-Europe study of diabetes screening and treatment, which it combined with a computer simulation model of diabetes progression. This revealed that screening followed by treatment led to a reduced risk of cardiovascular disease or death within a 5-year follow-up period when compared to patients having no screening. The ADDITION-Europe study enrolled people 40 to 69 years of age without known diabetes from 343 general practices in the United Kingdom, Denmark, and the Netherlands. The study had two objectives: firstly, to determine if routine screening for type 2 diabetes was feasible; secondly, to determine if early, intensive, treatment of high blood sugar and cardiovascular risk factors such as blood pressure, cholesterol status and smoking in those diagnosed with type 2 diabetes reduced the risk of events such as stroke, heart attack, angioplasty, heart bypass surgery, amputation and death. The researchers found that screening was feasible, but that intensive treatment did not yield statistically significant benefits over routine care, most likely because of the overall high quality of routine diabetes care delivered in general practice. Professor William Herman of the University of Michigan, first author on the paper, said, “Comparing the results of our simulations with the real-world data gave

us confidence that our model successfully predicts the impact of delaying diagnosis of type 2 diabetes on future cardiovascular health outcomes. “Diabetes can be debilitating for patients and costly for healthcare. This research shows that the early identification of diabetes has major health benefits, and supports the introduction of measures such as screening to reduce the time between development of type 2 diabetes and its treatment.” Professor Nick Wareham, senior author on the paper and Director of the MRC Epidemiology Unit, University of Cambridge, added: “This work shows the value of public health modelling to assess impacts and interventions for diseases such as type 2 diabetes that pose an increasing public health challenge. “ADDITIONEurope is a large, high quality study, but even so there are limitations in how much direct clinical observation can tell us about the costs and benefits of screening. Computer simulations add an extra dimension which we hope will guide future research as well as the development of public health policy.” The authors caution that, even without a diabetes diagnosis, individuals might in the interim receive treatment for conditions such as blood pressure or cease smoking, so that the outcomes might be somewhat less pronounced than their model predicts. However, they note that the model assumes that, as in ADDITION-Europe, all participants were recruited from primary care, and were thus already receiving medical care, so this distortion is not expected to be large. Reference Herman, WH et al. Early detection and treatment of type 2 diabetes reduces cardiovascular morbidity and mortality: A simulation of the results of the Anglo-DanishDutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITIONEurope). Diabetes Care (2015)

"We are still a long way from seeing this reflected on the shelves in pharmacies; however, these compounds have the potential to become an important tool for the treatment of Type 2 diabetes for future generations." Screening to identify type 2 diabetes followed by early treatment could result in substantial health benefits, according to new research

HPN • April 2016


46 Clinical Profiles ALLERGAN COMPLETES TRANSFER OF EUROPEAN MA FOR IRONWOOD’S CONSTELLA® FROM ALMIRALL S.A Allergan, a leading global pharmaceutical company, announced that the European Commission has completed the transfer of the Marketing Authorisation for CONSTELLA® (linaclotide), a treatment for irritable bowel syndrome with constipation (IBS-C), from Almirall S.A. to Allergan Pharmaceuticals International Ltd. Allergan Pharmaceuticals International Ltd is now the legal license holder for CONSTELLA® within the 28 countries of the European Union, assuming responsibilities for the development, pharmacovigilance and commercialisation of the product. CONSTELLA® has a European Marketing Authorisation for the symptomatic treatment of moderate-tosevere IBS-C in adults and is the only pharmaceutical product specifically licensed to treat the multiple symptoms of IBS-C across the EU.1 It is also the first targeted therapy for IBS-C that is included in the UK National Institute of Clinical Excellence’s guidelines on diagnosis and management of IBS.2 “The transfer of license for CONSTELLA® in the European Union heralds a major step on our journey to becoming a leading partner for gastroenterology physicians by bringing innovative gastrointestinal therapies to patient communities with significant unmet needs,” said Paul Navarre, President of International Brands at Allergan. “CONSTELLA® adds an important flagship product for our International GI team, and positions us strongly to leverage mid-to-late stage GI pipeline programmes.” Estimates indicate that between 10–15% of the European population suffers from irritable bowel syndrome (IBS).3 One-third of patients with IBS are thought to have IBS-C and suffer from abdominal pain, bloating and constipation.4 In 2015, Allergan Pharmaceuticals International Ltd acquired rights to CONSTELLA® in over 40 countries around the world including the European Union, Switzerland, Turkey and the Commonwealth of Independent States from Almirall S.A. The transfer of Marketing Authorisation for CONSTELLA® April 2016 • HPN

to Allergan Pharmaceuticals International Ltd in Switzerland has not yet been granted. The company will begin to transition product packaging and promotional materials from Almirall S.A. to Allergan Pharmaceuticals International Ltd, which will be phased over the next few months.

NEW DATA DEMONSTRATES MSD’S KEYTRUDA (PEMBROLIZUMAB) SIGNIFICANTLY IMPROVES SURVIVAL COMPARED TO CHEMOTHERAPY IN PREVIOUSLY-TREATED PATIENTS WITH NON-SMALL CELL LUNG CANCER MSD recently announced results from the pivotal KEYNOTE-010 study, the first study of its kind to evaluate the potential of an immunotherapy compared to chemotherapy based on prospective measurement of PD-L1 expression in patients with advanced non-small cell lung cancer (NSCLC). In the Phase 2/3 study, KEYTRUDA (pembrolizumab), MSD’s antiPD-1 (programmed death receptor-1) therapy, significantly improved overall survival (OS) compared to chemotherapy in patients with any level of PD-L1 expression, as defined by a tumour proportion score (TPS) of 1 percent or more. The study, which was also published in The Lancet, included 1,034 patients with advanced NSCLC with PD-L1 expression. Among the patients who received the FDA-approved dose of KEYTRUDA (2 mg/ kg every three weeks) (n=345) and an investigational dose of KEYTRUDA (10 mg/kg every three weeks) (n=346), a similar response was found. Both groups of patients who received KEYTRUDA were compared to patients who received docetaxel (n=343). Based on findings from KEYNOTE-010, MSD has submitted a Marketing Authorisation Application to the European Medicines Agency for KEYTRUDA, following the submission of a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration. Commenting on the announcement, Louise Houson, Managing Director Human Health, MSD in Ireland, said “Lung cancer remains one of the most common and challenging cancers to treat, therefore understanding the

role that KEYTRUDA can play in helping to improve survival and quality of life for people suffering from a wide range of cancers, including NSCLC, is essential. This data clearly demonstrates KEYTRUDA’s efficacy, and is another exciting milestone in our continued efforts to improve patient outcomes, and help a larger proportion of cancer sufferers to live well and for longer.” KEYTRUDA is a humanised monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. By binding to the PD-1 receptor and blocking the interaction with the receptor ligands, KEYTRUDA releases the PD-1 pathway-mediated inhibition of the immune response, including the anti-tumour immune response. KEYTRUDA was the first anti-PD-1 therapy approved in the United States, and was approved by the U.S. Food and Drug Administration (FDA) in October 2015 for the treatment of patients with metastatic NSCLC. KEYTRUDA also received approval from the European Commission for the treatment of advanced (unresectable or metastatic) melanoma in adults in July 2015.

MATER HOSPITAL LAUNCHES ITS FIRST LUNG CANCER ANNUAL REPORT Patients are afraid to be assessed for lung cancer in case they turn out to have the disease, despite the improving and more effective treatments available. This is according to the inaugural Lung Cancer Annual Report from the Mater Misericordiae University Hospital, part of the Ireland East Hospital Group, launched recently. The report contains a comprehensive review of the hospital’s key lung cancer services and provides a framework for its performance against international expert centres. Minister Paschal Donohoe, TD, who is a local TD in the area, launched the annual report with Mr Gordon Dunne, CEO of the Mater at an event attended by many of the hospital’s senior consultants and staff. The report covers the hospital’s 2014 activities and highlights some important additional activity which is not captured by national studies. The report’s findings also include;

 Two thirds of assessed patients receiving an all-clear after initial assessment.  New, standard, surgical advances mean patients have shorter recovery times. “Significant strides have been made at the Mater recently in terms of advanced diagnostics and provision of state-of-the-art treatments for our patients with this devastating disease,” said Dr Dermot O’Callaghan, Consultant Respiratory, General Physician and Chair of the Hospital’s Lung Cancer Working Group. “This first annual report is an important milestone in detailing the activity of our National Cancer Control Programme and highlights the high level of complex care delivered for our lung cancer patients.” With over 2,000 cases of lung cancer diagnosed each year, the Mater Hospital is at the forefront of complex care services in Ireland. Although recent figures have shown that the risk of lung cancer is falling for men, due to a long-term drop in the number of men who are smokers that same risk is still increasing for women. In fact, although lung cancer is the second-commonest cancer in women, it is the number one cancer killer – more than breast cancer. Minister for Transport, Tourism & Sport, Paschal Donohoe, TD said, “I would like to acknowledge the dedication and hard work carried out by Dr O’Callaghan and his team in the Rapid Access Lung Clinic and to thank them for the difference they are making to the lives of those who are in need of cancer treatment. While we are working towards a Tobacco Free Ireland, it’s very concerning to learn about the number of women who continue to smoke and the fact that lung cancer is the number one cancer killer among our female population.” The Mater hospital is one of only four centres that cater for the disease in the country. As a result of recent efforts, lung cancer is trending downwards in men but is still trending upwards in women. For example, in the Mater Hospital catchment area, more young women smoke than do not.


47 GREATER SURVIVAL BENEFIT SHOWN IN MEN WITH EARLY AND LESS AGGRESSIVE METASTATIC CASTRATIONRESISTANT PROSTATE CANCER TREATED WITH ZYTIGA®Q (ABIRATERONE ACETATE) PLUS PREDNISONE Janssen Ireland have announced that data from a post-hoc analysis of the Phase 3 COU-AA-302 trial showed that ZYTIGA® (abiraterone acetate) plus prednisone provided an 11.8 months overall survival (OS) benefit (53.6 months vs 41.8 months; HR = 0.61 [95% CI, 0.43-0.87]; p = 0.0055), compared to an active control of placebo plus prednisone, in men with early and less aggressive chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC).[i] Data from the post-hoc analysis was presented recently at the European Association of Urology (EAU) 2016 Congress in Munich, Germany. The post-hoc analysis divided patients into two groups to identify which group experienced a greater treatment benefit. The patients in Group 1 were in an earlier, less advanced and less symptomatic stage of the disease (which was defined as having a Brief Pain Inventory [BPI] Short Form score of 0-1, prostatespecific antigen [PSA] below 80 ng/ml and a Gleason score [GS] of below 8). Those in Group 2 were in a later, more advanced and more symptomatic stage of the disease (defined as a having a BPI of 2 or over and/or PSA of 80 ng/ml or above, and/or a GS of 8 or more). The analysis revealed that patients in both groups experienced an OS benefit when treated with abiraterone acetate plus prednisone, compared to placebo plus prednisone (Group 1: 11.8 months; HR = 0.61 [95% CI, 0.43-0.87]; p = 0.0055) (Group 2: 2.8 months; HR = 0.84 [95% CI, 0.72-0.99]; p = 0.0321).1 “Post-hoc analyses such as this are very important in helping us to identify the patients who could benefit most from therapies such as novel hormone agents, and at what stage of a patient’s disease they could be most effective.” said Dr John Mc Caffrey, Consultant Medical Oncologist at Dublin's Mater Hospital. “As men with prostate cancer are living longer, quality of life is an increasingly important factor for them and their families. It is therefore encouraging to see that when used earlier, patients can stay on abiraterone acetate for longer and delay the need for additional, more invasive treatments,” he continued.

SOBI AND BIOGEN RECEIVE POSITIVE OPINION FROM CHMP FOR ALPROLIX® FOR THE TREATMENT OF HAEMOPHILIA B Swedish Orphan Biovitrum AB (publ) (SobiTM) and Biogen received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recommending that marketing authorisation be granted for Alprolix® (rFIXFc), a recombinant factor IX Fc fusion protein therapy for the treatment of haemophilia B. If approved, Alprolix would be among the first therapies in the European Union (EU) to offer people living with haemophilia B prolonged protection against bleeding episodes with prophylactic dosing intervals. "This positive opinion marks an important step in our efforts to bring treatment innovation to people with haemophilia in Europe and around the world," said Krassimir Mitchev, MD, PhD, vice president and medical therapeutic area head of Haemophilia at Sobi. "We are already seeing the benefits that Fc fusion technology can offer through our recent EU launch of Elocta® for people with haemophilia A. We are excited at the prospect of also offering the possibility for prolonged protection and reduced treatment burden to the haemophilia B community with Alprolix." The positive opinion was based on results from two global, Phase III clinical trials that demonstrated the efficacy, safety and pharmacokinetics of Alprolix for haemophilia B: the pivotal B-LONG study for previously treated adults and adolescents, and the Kids B-LONG study for previously treated children under age 12. The CHMP's recommendation is now referred to the European Commission (EC), which is responsible for granting marketing authorisation for medicines in the EU. "Therapies that offer prolonged protection from bleeds are changing the way many approach treatment of haemophilia," said Gilmore O'Neill, MD, senior vice president, Drug Innovation Units at Biogen. "We are proud to work with Sobi to continue bringing to Europe these innovative Fc fusion therapies, which are grounded in the most robust real-world experience of any prolonged circulation factor therapies to date." Sobi and Biogen are collaboration partners in the development and commercialisation of Alprolix for haemophilia B. Sobi has final development and commercialisation rights in the Sobi territory (essentially

Europe, North Africa, Russia and most Middle Eastern markets). Biogen leads development and manufacturing for Alprolix and has commercialisation rights in North America and all other regions in the world excluding the Sobi territory.

MSD WELCOMES THE APPROVAL OF NEW INDICATIONS MSD has welcomed the approval by the European Medicines Agency (EMA) of new indications for EZETROL (ezetimibe), INEGY (ezetimibe and simvastatin) and ATOZET (ezetimibe and atorvastatin). The updated Prescribing Information for these medicines now includes outcomes from the landmark IMPROVEIT trial, which demonstrated that ezetimibe was the first non-statin cholesterol-lowering medication to show additional benefit in decreasing the risk of cardiovascular (CV) events when added to a statin. EZETROL, administered in combination with an HMG CoA reductase inhibitor (statin), is indicated to reduce the risk of cardiovascular events in patients with coronary heart disease (CHD) and a history of acute coronary syndrome (ACS) when added to ongoing statin therapy or initiated concomitantly with a statin. INEGY, which contains ezetimibe, a cholesterol absorption inhibitor, and simvastatin, an HMG-CoA reductase inhibitor (statin), is indicated to reduce the risk of cardiovascular events in patients with CHD and a history of ACS, either previously treated with a statin or not. ATOZET, which contains ezetimibe, a cholesterol absorption inhibitor, and atorvastatin, an HMG-CoA reductase inhibitor (statin), is indicated to reduce the risk of cardiovascular events in patients with CHD and a history of ACS, either previously treated with a statin or not. Commenting on these new indications for EZETROL, INEGY and ATOZET, Dr Niall Colwell, Consultant Cardiologist, South Tipperary General Hospital said “Ezetimibe is the first non-statin agent with an evidence base in the IMPROVE IT trial. Ezetimibe use alone in Statin-intolerant patients and more especially in combination with a statin in high CVD risk patients may assist clinicians in getting these subjects to their LDL goal which currently is as low as 1.3 mmol/L.” Louise Houson Managing Director Human Health, MSD in Ireland added, “These new indications for EZETROL, INEGY, and ATOZET demonstrate the value of MSD’s continuing efforts in progressing cardiovascular care. Because many patients with coronary heart

disease continue to have CV events, even when treated with statins, there is still a significant medical need. The results of IMPROVE-IT demonstrate our commitment to improving the treatment of cardiovascular disease, and establish the benefits of ezetimibe in improving cardiovascular outcomes in appropriate patients.” Because high-risk patients treated with statins, including those on treatment with low levels of LDLcholesterol (LDL-C), continue to be at increased cardiovascular risk, IMPROVE-IT was designed to address whether lowering LDL-C to under 1.8mmol/L by adding ezetimibe (EZETROL) to a statin further reduced cardiovascular events. Among patients participating in IMPROVE-IT who had blood samples obtained at one year, the mean LDL-C levels achieved were 1.8 mmol/L, in the simvastatin alone group and 1.4 mmol/L in the ezetimibe and simvastatin group. This 0.4 mmol/L difference (P<0.001) represents a 24 percent further lowering of LDL-C by ezetimibe relative to the LDL-C on simvastatin alone. Over a median follow-up of 6 years, IMPROVE-IT demonstrated a 6.4 percent relative risk reduction in the primary composite endpoint of major cardiovascular events. The primary endpoint occurred in 32.7 percent in the ezetimibe and simvastatin group and 34.7 percent in the simvastatin group alone at 7 years (Hazard Ratio 0.936, 95% CI, 0.887-0.988; p=0.016). These efficacy results were driven by a 13 percent reduction in non-fatal myocardial infarction and a 20 percent reduction in non-fatal stroke. Entitled IMProved Reduction of Outcomes: VYTORIN Efficacy International Trial, IMPROVE-IT was led by the Thrombolysis In Myocardial Infarction (TIMI) Study Group of Brigham and Women’s Hospital and the Duke Clinical Research Institute (DCRI), and was sponsored by MSD. It was an international, multi-centre, randomised, double-blind active comparator trial of 18,144 patients presenting with high-risk acute coronary syndromes (ACS), including unstable angina (UA), non-ST-segment elevation acute myocardial infarction (NSTEMI), and ST-segment elevation acute myocardial infarction (STEMI). The study assessed the incidence of major CV events, as measured by a composite of CV death, non-fatal MI, non-fatal stroke, rehospitalisation for unstable angina, or coronary revascularisation (occurring 30 days or more after the initial event), in patients treated with ezetimibe and simvastatin (INEGY) compared with patients treated with simvastatin alone. HPN • April 2016


The only licensed antidote to The only licensed antidote to1 anthracycline extravasation The only licensed antidote to1 The only licensed antidote to1 anthracycline extravasation anthracycline extravasation1 anthracycline extravasation • Highly effective in reducing tissue damage 2 • • • • •• • • • • •

2 Eliminated the need for surgery in 98% of patients Highly effective in reducing tissue damage 2 Allows for the majority of patients to continue their2 2 Eliminated the need for surgery indamage 98% of patients Highly effective in reducing tissue next scheduled dose of cancer therapy on time 2,3 2 Allows for the majority patients to continue their2 Eliminated the need forofsurgery indamage 98% of patients Highly effective in reducing tissue Easy-to-use anthracycline extravasation emergency kit 2,3 next scheduled dose ofofcancer therapy on timetheir 2 Allows for the majority patients to continue Eliminated the need for surgery in 98% of patients 2,3 kit Easy-to-use anthracycline extravasation emergency next scheduled dose ofofcancer therapy on timetheir Allows for the majority patients to continue 2 anthracycline 3 Easy-to-use extravasation emergency next scheduled dose of cancer therapy on time 2,3 kit

To learn about extravasation and 1 Tothe learn TREAT useabout of IDENTIFY RESUME • Easy-to-use anthracycline extravasation emergency kit ® ® extravasation and visit SAVENE can 1 Know how to recognise 2 Administer SAVENE 3 Treatment To learn about as indicated and respond to continue once TREATwithin the use of IDENTIFY RESUME www.savene.com extravasation and 1 an anthracycline 2 3 6 hours of the ® extravasation ® To learn about SAVENE visit Administer SAVENE Know how to recognise Treatment can TREAT the use of IDENTIFY RESUME extravasation³ extravasation symptoms are relieved² as indicated within and respond to continue once extravasation and 1 2 3 www.savene.com ® ® SAVENE visit Administer SAVENE Know to recognise Treatment can 6 hours of the an how anthracycline extravasation TREAT the use of IDENTIFY RESUME asextravasation³ indicated within and respond to continue once www.savene.com extravasation symptoms are relieved² REFERENCES 1. Savene Available at www.medicines.ie SAVENE® visitSummary of Product Characteristics Administer Know to recognise Treatment can 6 hours SAVENE of the ® an how anthracycline extravasation 2. Mouridsen HT et al. Ann Oncol 2007;18(3):546-50 3. Fontaine C et al. Support Care Cancer 2012;20(5):1109-12 asextravasation³ indicated within and respond to continue www.savene.com extravasation symptoms areonce relieved² ®

® for concentrate and diluent for solution for infusion Savene 20 mg/ml powder reactions. The most common adverse reactions are postoperative infection, infection, 6 hours of the anAvailable anthracycline extravasation REFERENCES 1. Savene Summary of Product Characteristics at www.medicines.ie Please refer to Summary of Product Characteristics (SmPC) before prescribing. infection, decreased appetite, dizziness, sensory loss, syncope, tremor, phlebitis, 2. Mouridsen HT et al. Ann Oncol 2007;18(3):546-50 3. Fontaine C et al. Support Care neutropenic Cancer 2012;20(5):1109-12 extravasation³ extravasation symptoms are relieved²

Active Ingredient: vial contains 500 mg dexrazoxane, each ml contains 20 mg of dexrazoxane superficial thrombophlebitis, limb venous thrombosis, dyspnea, pneumonia, nausea, vomiting, ® REFERENCES 1. with Savene Product Characteristics Available at of www.medicines.ie after reconstitution 25 mlSummary of diluent. ofPresentation: Each kit contains 10 vials Savene diarrhoea, stomatitis, dry mouth, alopecia, pruritus, myalgia, vaginal haemorrhage, injection site Savene 20 mg/ml powder for concentrate and diluent for solution for infusion reactions. Theinjection most site common adverse reactions are postoperative infection, infection, Powder and 3 bottles Diluent (500 ml each). Indication: Treatment anthracycline pyrexia, phlebitis, injection site erythema, fatigue, injection site induration, 2. Mouridsen HT etof al.Savene Ann Oncol 2007;18(3):546-50 3. Fontaine C etofal. Support Care pain, Cancer 2012;20(5):1109-12 Please refer to Summary of Product Characteristics (SmPC) before prescribing. neutropenic decreasedoedema, appetite,somnolence, dizziness, sensory loss,weight, syncope, tremor, phlebitis, extravasation in adults. Posology and Method of Administration: Administration should injection site infection, swelling, peripheral decreased would complication. ® REFERENCES Savene of Product Available atgiven www.medicines.ie Active Ingredient: vial contains 500 mg dexrazoxane, each ml contains 20 mg ofbedexrazoxane superficial thrombophlebitis, limbhyponatraemia, venous thrombosis, dyspnea, pneumonia, nausea, vomiting, begin as soon as 1. possible and Summary within 6 hours after and theCharacteristics accident. Savene should as an Neutropenia, thrombocytopenia, hypocalcaemia and increased concentrations Savene 20 mg/ml powder for concentrate diluent for solution for infusion reactions. The most common adverse reactions are postoperative infection, infection, after reconstitution with ml of diluent. Presentation: Each kit contains vials of surface SaveneCare of diarrhoea, stomatitis, dry mouth, alopecia, pruritus, myalgia, vaginal haemorrhage, injection site 2. Mouridsen HT et al.25 Ann Oncol 2007;18(3):546-50 3.days Fontaine C10etto al. Support Cancer 2012;20(5):1109-12 intravenous infusion over 1-2 hours once daily for 3(SmPC) consecutive according body liver enzymes (ALT/AST) have been reported as common findings. Interactions: Please refer to Summary Product Characteristics before prescribing. neutropenic infection, decreased appetite, dizziness, sensorylaboratory loss, syncope, tremor, phlebitis, Powder and 3 bottles of of Savene Diluent (500mg/m ml each). Indication: anthracycline pain, pyrexia, injection site phlebitis, injection erythema, fatigue, injection site induration, 2 2 area: day one, 1000vial mg/m2; day500 two,mg 1000 ; day three, 500 Treatment mg/m . mg Forof patients with a Patients treated with anticoagulants should be site monitored more frequently asnausea, cytotoxic agents Active Ingredient: contains dexrazoxane, each ml contains 20 of dexrazoxane superficial thrombophlebitis, limb venous thrombosis, dyspnea, pneumonia, vomiting, extravasation in adults. Posology and Method of Administration: Administration should injection site swelling, peripheral oedema, somnolence, decreased weight, would complication. 2 body surface area of more than 2 m the single dose should not exceed 2000 mg. Treatment may interact with oral anticoagulants. Concomitant use of immunosuppressives such site as reactions. The most common adverse reactions are postoperative infection, infection, Savene 20 mg/ml powder for concentrate and diluent for solution for infusion after reconstitution with 25and ml within of diluent. Presentation: Each kit contains 10 vials of Savene diarrhoea, stomatitis, dry mouth, alopecia, pruritus, myalgia, vaginal haemorrhage, injection begin as soon as possible 6 hours after the accident. Savene should be given as an Neutropenia, thrombocytopenia, hyponatraemia, hypocalcaemia and increased concentrations Day 2 and Day 3 should at the same(500 hourml± each). 3 (SmPC) hours as Day 1. Cooling procedures should ciclosporin and tacrolimus receive extra consideration due tofatigue, excessive immunosuppression. neutropenic infection, decreased appetite, dizziness, sensory loss, syncope, tremor, phlebitis, Please refer to Summary of Product Characteristics before prescribing. Powder and 3 bottles of start Savene Diluent Indication: Treatment of anthracycline pain, pyrexia, injection site have phlebitis, injection site erythema, injection site induration, intravenous infusion over 1-2 hours once daily for 3 consecutive days according to body surface of liver enzymes (ALT/AST) been reported as common laboratory findings. Interactions: have been removed the affected area at least 15 min before administration. Before Savene issite not recommended in combination with live attenuated vaccines with phenytoin and superficial thrombophlebitis, limb venous thrombosis, dyspnea, pneumonia, nausea, vomiting, Active Ingredient: vialfrom contains 500and mg dexrazoxane, each ml contains 20 mg of dexrazoxane extravasation adults. Posology Method should injection swelling, peripheral oedema, somnolence, decreased weight,orwould complication. 2of Administration: Administration 2 area: reconstitution day Savene one, in 1000 mg/m2; day 1000 mg/mand ; daydiluted three, 500 mg/m with a Patients treated with anticoagulants shouldpruritus, be monitored more frequently as cytotoxic agents infusion, must betwo, reconstituted Savene. For Diluent. is contraindicated with yellow fever vaccine. Dimethyl sulfoxide (DMSO) should not be used in diarrhoea, stomatitis, dry mouth, alopecia, myalgia, vaginal haemorrhage, injection site after with 25 ml of diluent. Presentation: Eachwith kit contains 10 patients vials Warnings of Savene begin surface as soonarea as Powder possible and within Neutropenia, thrombocytopenia, hyponatraemia, hypocalcaemia and increased concentrations 26 hours after the accident. Savene should be given as an body of more than 2 m the single dose should not exceed 2000 mg. Treatment may interact with oral anticoagulants. Concomitant use of immunosuppressives such as and Precautions: Local should be on adays regular basis of after treatment patients who are administered Savene. Savene may to the laboratory toxicity the chemotherapy cycle pain, pyrexia, injection site have phlebitis, injection site erythema, fatigue,ofinjection site induration, Powder and infusion 3 bottles of examination Savene Diluent (500 ml performed each). Indication: Treatment anthracycline intravenous over 1-2 hours daily 3 hours consecutive according to body surface of liver enzymes (ALT/AST) been reported as add common findings. Interactions: Day 2resolution and Day 3and should start at the once same hourfor ±should 3 asundertaken Day 1. Cooling procedures should ciclosporin and tacrolimus receive extra consideration due to excessive immunosuppression. until haematological monitoring be regularly. Routine liver therefore haematological monitoring is necessary. Pregnancy and Lactation: Savene should not injection site swelling, peripheral oedema, somnolence, decreased weight, would complication. extravasation in adults. Posology and Method of Administration: Administration should 2 2 area: day one, 1000 mg/m2; dayaffected two, 1000 mg/m ; day15 three, 500 mg/m . For patients Before with a Patients with anticoagulants should with be monitored more vaccines frequently as cytotoxic agents have been removed fromand the area at least min before administration. Savene istreated not recommended in combination live attenuated with phenytoin and function are recommended administration of Savene in patients known be administered to pregnant women unless clearly necessary. of or childbearing potential Neutropenia, hyponatraemia, hypocalcaemia and increased concentrations begin surface as tests soon as possible within after theshould accident. Savene should be with given as an 26 hours body area of moremust than 2before m theeach single dose not exceed 2000 mg. Treatment may interact thrombocytopenia, with oralyellow anticoagulants. Concomitant use ofWomen immunosuppressives as infusion, Savene Powder be reconstituted and diluted with Savene Diluent. Warnings is contraindicated with fever vaccine. Dimethyl sulfoxide (DMSO)isfindings. should not besuch used in liver function disorders. Patients with renal dysfunction should be monitored for signs of should use contraceptive measures during treatment. Breast-feeding contraindicated. Men of liver enzymes (ALT/AST) have been reported as common laboratory Interactions: intravenous infusion over 1-2 hours once daily for 3 consecutive days according to body surface Day 2Precautions: and Day 3 should start at the same hour ±performed 3 hours ason Daya 1. Cooling procedures should ciclosporin and tacrolimus receive extra consideration due to excessive immunosuppression. and Local examination should be regular basis after treatment patients who are administered Savene. Savene may add to the toxicity of the chemotherapy cycle 2 2 haematological toxicity. Previous history of allergy to dexrazoxane should be carefully considered are advised not to father a child during and up to 3 months after treatment. Distributed by: ; day three, 500 mg/m . For patients with a Patients treated with anticoagulants should be monitored more frequently as cytotoxic agents area: day one, 1000 mg/m2; day two, 1000 mg/m have been removed from the affected area atshould least 15 min before regularly. administration. Before Savene is not recommended in combination with live attenuated vaccines or with phenytoin and until andofhaematological monitoring be undertaken Routine liver therefore haematological monitoring is necessary. Pregnancy and Lactation: Savene should not 2 prior to administration. Asmust the Diluent contains potassium (98 mg/500 ml) the plasma Clinigen Healthcare Ltd, Pitcairn House, Crown Square, First Avenue, Burton-on-Trent, body resolution surface area more thanSavene 2m the single dose not exceed 2000 mg. Treatment may interact withwith oral anticoagulants. Concomitant use of immunosuppressives such infusion, Savene Powder be reconstituted and should diluted Savene Diluent. Warnings is contraindicated yellow fever vaccine. Dimethyl sulfoxide (DMSO) not bepotential used as in function tests are recommended before each administration ofwith Savene patients with known be administered to pregnant women unless clearly necessary. Women ofshould childbearing potassium level the patient be closely monitored inon patients at inrisk of after hyperkalaemia. Staffordshire, DE14 2WW, United Kingdom Day 2Precautions: and Day 3of should start atmust the same hour ±performed 3 hours as Day 1. Cooling procedures should ciclosporin and tacrolimus receive extra consideration due to excessive immunosuppression. and Local examination should be a regular basis treatment patients who are administered Savene. Savene may add to the toxicity of the chemotherapy cycle liver function disorders. Patients with renal dysfunction should be monitored for signs of should contraceptive measures during with treatment. Breast-feeding is or contraindicated. Men It alsoresolution contains sodium (1.16 g/500 ml) which be harmful to before patients on a low Routine sodium diet. have been removed from the affected areamay atshould least 15 min administration. Before Savene use is not recommended in combination live attenuated vaccines with phenytoin and until and haematological monitoring be undertaken regularly. liver therefore haematological monitoring is necessary. Pregnancy and Lactation: Savene should not haematological toxicity. Previous history of allergy to dexrazoxane should carefully considered are advised not to£6,750. father a child during and Dimethyl up to 3 months after treatment. Distributed Contraindications: Hypersensitivity to the active ingredient orofwith toSavene any of be thepatients excipients, women infusion, tests Savene must be reconstituted and diluted Savene Diluent. Warnings is contraindicated yellow fever vaccine. sulfoxide (DMSO) not bepotential usedby: in Basic NHS Price: Euro Price: €9,746 Legal Category: POM. Marketing Authorisation function arePowder recommended before each administration in with known be administered towith pregnant women unless clearly necessary. Women ofshould childbearing prior to administration. the using Savene Diluent contains potassium (98 mg/500 ml)concomitant the plasma Clinigen Healthcare Ltd, Pitcairn House, Crown First Avenue, Burton-on-Trent, of childbearing potential not contraceptive measures, and Precautions: LocalAs examination should be performed on breast-feeding a regular basis or after treatment patients who are administered Savene. Savene may add to the toxicity of is the chemotherapy cycle Number: EU/1/06/350/001. Additional information is Square, available on request from the Marketing liver function disorders. Patients with renal dysfunction should be monitored for signs of should use contraceptive measures during treatment. Breast-feeding contraindicated. Men potassium level ofyellow the patient must be closely monitored inundertaken patients at regularly. risk SmPC of hyperkalaemia. Staffordshire, DE14 2WW,Clinigen United Kingdom vaccination with fever vaccine. Undesirable Effects: (Consult the for further until resolution and haematological monitoring should be Routine liver therefore haematological monitoring is necessary. Pregnancy and Lactation: Savene should not Authorisation Holder: Healthcare Ltd, Pitcairn House, Crown Square, First Avenue, haematological toxicity. Previous history of allergy tobe dexrazoxane should be carefully considered are advised not to father a child during and up to 3 months after treatment. Distributed by: It also contains sodium (1.16 g/500 ml) which harmful toreactions patients a low sodium diet. details adverse reactions). Potentially serious adverse include function tests are recommended before eachmay administration of Savene inon patients with known be administered to pregnant women unlessUnited clearly necessary. Women of childbearing potential Burton-on-Trent, Staffordshire, DE14 House, 2WW, Kingdom Date of Preparation: 20 April 2015 prior toabout administration. As the Savene Diluent contains potassium (98ofmg/500 ml)anaphylactic the women plasma Clinigen Healthcare Ltd, Euro Pitcairn Crown Square, First Avenue, Burton-on-Trent, Contraindications: Hypersensitivity to the active ingredient or to any the excipients, Basic £6,750. Price:during €9,746treatment. Legal Category: POM. Marketing Authorisation liver function disorders. Patients with renal dysfunction should be monitored for signs of shouldNHS usePrice: contraceptive measures Breast-feeding is contraindicated. Men potassium level of the patient must be closely monitored in patients at risk ofor hyperkalaemia. Staffordshire, DE14 2WW, United Kingdom of childbearing potential not using contraceptive measures, breast-feeding concomitant Number: EU/1/06/350/001. Additional information is available on request from the Marketing haematological toxicity. Previous history of allergy dexrazoxane should be considered are advised not to father a child during and up to 3 months after treatment. Distributed by: It also contains sodium (1.16 g/500 ml) which maytobe harmful to(Consult patients oncarefully aSmPC low sodium diet. vaccination with yellow fever vaccine. Undesirable Effects: the for further Authorisation Holder: Clinigen Healthcare Ltd, Pitcairn House, Crown Square, First Avenue, priorAdverse to administration. Asshould the Savene Diluent contains potassium (98ofmg/500 ml) the women plasma Clinigen Healthcare Ltd, Euro Pitcairn Crown Square,(medsafety@hpra.ie). First Avenue, Burton-on-Trent, events bethe reported to the Pharmacovigilance Unit atBasic theNHS Health Products Regulatory Authority Contraindications: Hypersensitivity to active ingredient or to any the excipients, Price: Staffordshire, £6,750. Price:House, €9,746 Legal Category: POM. Marketing Authorisation details about reactions). Potentially adverse reactions include anaphylactic Burton-on-Trent, DE14 2WW, United Kingdom Date of Preparation: 20 April 2015 potassium leveladverse of the patient must closelyserious monitored in patients at risk ofor hyperkalaemia. Staffordshire, DE14 2WW, United Kingdom of childbearing potential not Information using be contraceptive measures, breast-feeding concomitant Number: EU/1/06/350/001. Additional information is available on request from the Marketing about adverse event reporting can be found on the HPRA website (www.hpra.ie). It also contains ml) which may be harmful patientsthe on aSmPC low sodium diet. vaccination withsodium yellow(1.16 feverg/500 vaccine. Undesirable Effects: to(Consult for further Authorisation Holder: Clinigen Healthcare Ltd, Pitcairn House, Crown Square, First Avenue, Adverse events shouldtoalso beserious reported Clinigen Healthcare patientsafety@clinigengroup.com or fax + 44 (0)Marketing 1283 495 034 Contraindications: Hypersensitivity the active ingredient orto to any of the excipients, womenLtd:Basic NHS Price: Staffordshire, £6,750. Euro DE14 Price:2WW, €9,746 Legal Category: POM. Authorisation details about adverse reactions). Potentially adverse reactions include anaphylactic United Kingdom Date of Preparation: 20 April 2015 Adverse events reported to the Pharmacovigilance Unit atBurton-on-Trent, the Health ProductsAdditional Regulatory Authority (medsafety@hpra.ie). of childbearing potential should not using be contraceptive measures, breast-feeding or concomitant Number: EU/1/06/350/001. information is available on request from the Marketing vaccination with yellow fever Information vaccine. Undesirable Effects: (Consult the SmPC for further Authorisation Clinigenwebsite Healthcare(www.hpra.ie). Ltd, Pitcairn House, Crown Square, First Avenue, about adverse event reporting can be found onHolder: the HPRA details about adverse reactions). Potentially serious adverse reactions include anaphylactic DE14 2WW, United Kingdom Date of Preparation: 20 April 2015 Adverse events should be reported to the Pharmacovigilance Unit atBurton-on-Trent, the Health Staffordshire, Products Regulatory Authority (medsafety@hpra.ie).

Adverse events should also be reported to Clinigen Healthcare Ltd: patientsafety@clinigengroup.com or fax + 44 (0) 1283 495 034

www.clinigengroup.com

Information about adverse event reporting can be found on the HPRA website (www.hpra.ie). Date of preparation: September 2015 SAV-032

Adverse reported to thetoPharmacovigilance Unit atpatientsafety@clinigengroup.com the Health Products Regulatory Authority Adverseevents eventsshould shouldbe also be reported Clinigen Healthcare Ltd: or fax +(medsafety@hpra.ie). 44 (0) 1283 495 034 Information about adverse event reporting can be found on the HPRA website (www.hpra.ie). DateAdverse of preparation: September SAV-032 events should2015 also be reported to Clinigen Healthcare Ltd: patientsafety@clinigengroup.com or fax + 44 (0) 1283 495 034 Date of preparation: September 2015

SAV-032

Date of preparation: September 2015

SAV-032

www.clinigengroup.com www.clinigengroup.com www.clinigengroup.com

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