HPN April 2017
HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication
IN THIS ISSUE: NEWS: IHCA outlines priorities for Hospitals Page 5 REPORT: Falsified Medicines Directive Page 12
Our passion is in the detail There are occasions when your patients have to deal with difficult challenges and you may need to arrange for special medicines. PharmaSource can help you source these medicines in a timely, reliable and safe manner. With over 70% of Irish pharmacies ordering from us every day, we are Ireland’s leading supplier of unlicensed medicines, manufactured specials and once off procured items to the Irish market. Our service is tried and tested and valued by our loyal customers. PharmaSource can help reduce the valuable time our customers are spending searching for medicines that are currently in short supply or discontinued in the national market. We can source these products for you, simply give our team a call.
Our team is made up of qualified pharmacists and pharmacy technicians who understand the importance of delivering your order on time every time. When you call PharmaSource you will be speaking to your peers.
PharmaSource was the first to market with our website. Others have tried to mimic but none can compare. Our site allows you to check stock levels in real time, confirm pricing, reprint monthly invoices and keep a record of what unlicensed medicines you have ordered for audit purposes. Placing your order with PharmaSource has never been easier.
For more information please contact: • Free Phone 1800 440 440 • Free Fax 1800 441 441 • Email PharmaSource@uniphar.ie • Web www.uniphar.ie
We have an unparalleled range of over 3,000 products in stock, including cold chain and controlled drugs and have immediate access to a database of more than 4 million medicines worldwide.
We are one of the most competitively priced, with no minimum order charge.
We also offer a Saturday delivery.
CPD: Cycle of Diabetes Care Page 31 AWARDS: 2017 Hospital Professional Awards Page 36 FEATURE: Cardiovascular Disease Morality Page 49 RESEARCH: Links between MND and Schizophrenia Page 52
Now for the treatment of pretreated mCRC
Make time for more moments that matter
Available on High Tech Scheme (from 01-02-2017)
LonsurfÂŽ is licensed to Servier by Taiho, co-developed globally and marketed in their respective territories.
qLonsurfÂŽ (trifluridine/tipiracil) Abbreviated prescribing information: COMPOSITION*: Lonsurf 15 mg/6.14 mg: film-coated tablet containing 15 mg trifluridine and 6.14 mg tipiracil (as hydrochloride). Lonsurf 20 mg/8.19 mg: film-coated tablet containing 20 mg trifluridine and 8.19 mg tipiracil (as hydrochloride). INDICATION*: Treatment of adult patients with metastatic colorectal cancer who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatinand irinotecan-based chemotherapies, anti-VEGF agents, and anti EGFR agents. DOSAGE AND ADMINISTRATION*: Recommended starting dose: 35 mg/m2/dose taken orally twice daily on Days 1 to 5 and Days 8 to 12 of each 28-day cycle, within 1 hour after completion of the morning and evening meals. Dosage calculated according to body surface area, not exceeding 80 mg/dose. Possible dosing adjustments based on individual safety and tolerability: 3 permitted dose reductions to a minimum dose of 20 mg/m2 twice daily, dose escalation permitted after a dose reduction. CONTRAINDICATIONS*: Hypersensitivity to the active substances or to any of the excipients. WARNINGS*: Bone marrow suppression: Complete blood cell counts must be obtained prior to initiation of therapy, prior to each cycle and as needed. Treatment must not be started if absolute neutrophil count <1.5 x109/L, if platelet counts <75x109/L, or if unresolved Grade 3 or 4 non-haematological clinically relevant toxicity. Patient should be monitored closely for infections, appropriate measures should be administered as clinically indicated. Gastrointestinal toxicity: anti-emetic, anti-diarrhoeal and other measures should be administered as clinically indicated, dose modifications should be applied as necessary. Renal impairment: not recommended if severe renal impairment or end-stage renal disease. Patients with moderate renal impairment should be more frequently monitored for haematological toxicities. Hepatic impairment: not recommended if moderate or severe hepatic impairment. Proteinuria: monitoring by dipstick urinalysis recommended prior to starting and during therapy. Excipients: contain lactose. INTERACTIONS*: Precautions: medicinal products that interact with nucleoside transporters CNT1, ENT1 and ENT2, inhibitors of OCT2 or MATE1, human thymidine kinase substrates (e.g. zidovudine), hormonal contraceptives. FERTILITY*. PREGNANCY AND BREASTFEEDING*: Not recommended. CONTRACEPTION*: For women and men, highly effective contraceptive measures must be used during treatment and for 6 months after stopping treatment. DRIVE & USE MACHINES*: Fatigue, dizziness or malaise may occur. UNDESIRABLE EFFECTS*: Very common: Neutropenia, leukopenia, anaemia, thrombocytopenia, decreased appetite, diarrhoea, nausea, vomiting, fatigue. Common: Lower respiratory tract infection, upper respiratory tract infection, febrile neutropenia, lymphopenia, monocytosis, hypoalbuminaemia, insomnia, dysgeusia, neuropathy peripheral, dizziness, headache, flushing, dyspnoea, cough, abdominal pain, constipation, stomatitis, oral disorder, hyperbilirubinaemia, Palmar-plantar erythrodysaesthesia syndrome, rash, alopecia, pruritus, dry skin, proteinuria, pyrexia, oedema, mucosal inflammation, malaise, hepatic enzyme increased, blood alkaline phosphatase increased, weight decreased. Uncommon: Septic shock, enteritis infectious, lung infection, biliary tract infection, influenza, urinary tract infection, gingival infection, herpes zoster, tinea pedis, candidiasis, bacterial infection, infection, cancer pain, pancytopenia, granulocytopenia, monocytopenia, erythropenia, leukocytosis, dehydration, hyperglycaemia, hyperkalaemia, hypokalaemia, hypophosphataemia, hypernatraemia, hyponatraemia, hypocalcaemia, gout, anxiety, neurotoxicity, dysaesthesia, hyperaesthesia, hypoaesthesia, syncope, paraesthesia, burning sensation, lethargy, visual acuity reduced, vision blurred, diplopia, cataract, conjunctivitis, dry eye, vertigo, ear discomfort, angina pectoris, arrhythmia, palpitations, embolism, hypertension, hypotension, pulmonary embolism, pleural effusion, rhinorrhoea, dysphonia, oropharyngeal pain, epistaxis, enterocolitis haemorrhagic, gastrointestinal haemorrhage, pancreatitis acute, ascites, ileus, subileus, colitis, gastritis, reflux gastritis, oesophagitis, impaired gastric emptying, abdominal distension, anal inflammation, mouth ulceration, dyspepsia, gastrooesophageal reflux disease, proctalgia, buccal polyp, gingival bleeding, glossitis, periodontal disease, tooth disorder, retching, flatulence, breath odour, hepatotoxicity, biliary dilatation, skin exfoliation, urticaria, photosensitivity reaction, erythema, acne, hyperhidrosis, blister, nail disorder, joint swelling, arthralgia, bone pain, myalgia, musculoskeletal pain, muscular weakness, muscle spasms, pain in extremity, sensation of heaviness, renal failure, cystitis noninfective, micturition disorder, haematuria, leukocyturia, menstrual disorder, general physical health deterioration, pain, feeling of body temperature change, xerosis, blood creatinine increased, electrocardiogram QT prolonged, international normalised ratio increased, activated partial thromboplastin time prolonged, blood urea increased, blood lactate dehydrogenase increased, protein total decreased, C-reactive protein increased, haematocrit decreased. Post-marketing experience: interstitial lung disease reported in Japanese patients. OVERDOSE*. PROPERTIES*: Trifluridine is an antineoplastic thymidine-based nucleoside analogue and tipiracil hydrochloride is a thymidine phosphorylase (TPase) inhibitor. Following uptake into cancer cells, trifluridine, is phosphorylated by thymidine kinase, further metabolised in cells to a deoxyribonucleic acid DNA substrate, and incorporated directly into DNA, preventing cell proliferation. However, trifluridine is rapidly degraded by TPase and readily metabolised by a first-pass effect following oral administration, hence the inclusion of the TPase inhibitor, tipiracil hydrochloride. PRESENTATION*: Pack of 20 or 60 film-coated tablets. LES LABORATOIRES SERVIER, 50 rue Carnot, 92284 Suresnes cedex France. www.servier.com. Marketing Authorisation: EU/1/16/1096/001-006. Legal Category: POM. Date of Text: April 2016. Further information available from: Servier Laboratories Ireland Ltd, Block 2, West Pier Business Campus, Old Dunleary Road, Dun Laoghaire, Co. Dublin, Tel (01) 6638110, Fax (01) 6638120, www.servier.ie. * For complete information, please refer to the Summary of Product Characteristics on www.medicines.ie. mCRC=metastatic ColoRectal Cancer Date of preparation of this item: January 2017. 1617C1LNPress.
HPN March 2016 Issue 37
European Association of Hospital Pharmacists host annual Congress in Cannes P4
Kelly Jo Eastwood
HPRA report finds variations in medication safety P5 4
Ireland must lead the way in CF treatment P8 Lack of intestinal unit for Ireland flaws discussed P10 Prescribers and Pharmacists to draw up cannabis legislation P14
Falsified Medicines Directive Report P20
Clinical Synopsis: ECC17 P16 CPD: Cycle of Diabetes P31 Feature: Cardiovascular Disease P49 36
Hospital Professional 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 All rights reserved by Hospital Professional News. All material published in Hospital Professional News is copyright and no part of this magazine may be reproduced, stored in a retrieval system of transmitted in any form without written permission. 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.
MANAGING DIRECTOR Natalie Maginnis firstname.lastname@example.org EDITOR Kelly Jo Eastwood email@example.com 00447876548989 ACCOUNTS Rachel Wilson firstname.lastname@example.org
Those in attendance heard about the latest development, the first biosimilar of a monoclonal antibody (infliximab), which was approved in 2013 and is now used in many EU countries. The oncological monoclonal antibodies will soon have approved biosimilars. ‘The financial stakes are higher than ever, with the ever-growing cost of new medications increasing the need for every saving that can be achieved,’ the Congress heard. Next month’s issue will carry full coverage from the event alongside contributed articles by some of Ireland Hospital Pharmacists who attended.
Feature: Childhood Cancer P23
PUBLISHER IPN Communications Ireland Ltd Clifton House, Lower Fitzwilliam Street, Dublin 2 (01) 669 0562
This is an addition to the EAHP website that offers an overview of why the European Statements of Hospital Pharmacy are so important. The Statements website provides stakeholders – such as hospital pharmacists, patients, policy makers, healthcare practitioners, academics or our many partners in industry – with access to a variety of different resources which should help individual hospitals throughout Europe with the implementation of the Statements. These resources include an evidence base for each of the Statements and are complemented by general material aimed at assisting EAHP's member associations with implementation. The Congress scientific programme covered a wide range of current and pressing issues; one of which was the emergence of biosimilars.
Hospital Professional Awards 2017 P36
Event Gallery P59
The European Association of Hospital Pharmacists held their annual Congress in Cannes last month with a theme of ‘Hospital pharmacists – catalysts for change’. EAHP President, Tullamore Regional Hospital Pharmacist Joan Peppard took the opportunity to officially launch the Hospital Statements website.
COMMERCIAL MANAGER Sharon Kennedy Sharon@ipnirishpharmacynews.ie
Mobile: 0044 7765 236886 CONTRIBUTORS Peter Kidd Lutz Heinemann G. Alexander Fleming John R. Petrie Reinhard W. Holl Richard M. Bergenstal Anne L. Peters
DESIGN DIRECTOR Ian Stoddart Design www.pharmacynewsireland.com www.facebook.com/ HospitalProfessionalNews
In other news, we cover the IrSPEN (Irish Society for Clinical Nutrition & Metabolism) biennial conference and policy seminar held in Dublin. The Society has made a call to the HSE to ring-fence €4.2 million to establish an eight-bed national centre for intestinal failure in St James' Hospital to manage people with IF who require prolonged parenteral nutrition (PN) as no specialist service is currently available in the Republic of Ireland. Currently there is no specialist service available for Intestinal Failure (IF) patients. This means that there is no tertiary referral centre for the highly complex hospitalised patients who develop severe IF each year, nor is there a single specialist unit to manage the existing adult patients receiving PN at home. The absence of a specialist IF service in the Republic of Ireland has been shown to be associated with significantly higher complication rates and hospital admissions for IF patients compared to international data. Turn to page 10 for the full story. Elsewhere in this issue we carry some further details of the 2017 Hospital Professional Awards, taking place on Saturday, September 16th. This is the fifth year of the Awards and Award Categories include those previously seen such as the Idis Hospital Pharmacist of the Year and the Consultant-Led Team of the Year as well as exciting new Categories such as the Respiratory Initiative of the Year. Turn to page 36 for full details.
HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication HPN • April 2017
Catalysts for Change in Cannes Professor Torsten Hoppe-Tichy, Chief Pharmacist at University Hospital of Heidelberg and President of the German Association of Hospital Pharmacists
congress is the largest congress for hospital pharmacy in Europe and attracts pharmacists from all over the world.
The 22nd congress of the European Association of Hospital Pharmacists (EAHP) took place recently in Cannes. Joan Peppard, EAHP President officially launched the Hospital Statements website. This is an addition to the EAHP website that offers an overview of why the European Statements of Hospital Pharmacy are so important. The Statements website provides stakeholders – such as hospital pharmacists, patients, policy makers, healthcare practitioners, academics or our many partners in industry – with access to a variety of different resources which
should help individual hospitals throughout Europe with the implementation of the Statements. These resources include an evidence base for each of the Statements and are complemented by general material aimed at assisting EAHP's member associations with implementation.
Satellite Symposiums included a discussion on ’10 years of Biosimilars – What have we learned.’ This was facilitated by Torsten Hoppe-Tichy, Chief Pharmacist at University Hospital of Heidelberg and President of the German Association of Hospital Pharmacists.
The 23rd Congress of the EAHP carried the theme of "Hospital pharmacists – catalysts for change" with a scientific programme relevant for those dealing with the challenge of rapid change in healthcare.
Back in 2006, the approval by the European Medicines Agency of the first biosimilar didn’t hit many headlines. More than ten years have passed, and the implementation of small molecule biosimilars like epoetin and filgrastim is now a fact in many countries in the EU.
The hospital pharmacist's role in facilitating change will be addressed. EAHP's annual
Delegates to this address heard how a new development is around the corner, which is the
first biosimilar of a monoclonal antibody (infliximab), which was approved in 2013 and is now used in many EU countries. The oncological monoclonal antibodies will soon have approved biosimilars. The financial stakes are higher than ever, with the evergrowing cost of new medications increasing the need for every saving that can be achieved. The real challenge is can we use the knowledge obtained with the small molecules to ensure that the biosimilars of monoclonal antibodies will be used to their full potential? Speakers included Professor Paul Declerck, Dean at the Faculty of Pharmaceutical Sciences, University of Leuven, Belgium; Professor Irene Kramer, Director of Pharmacy, University Medical Centre, Johannes Gutenberg-University, Mainz and Dr Paul Cornes, Consultant Oncologist, Bristol. Anticoagulants were also on the agenda alongside case studies on antimicrobial resistance. Next month’s issue of Hospital Professional News will carry full coverage from the Congress including keynote addresses, satellite symposia and workshops.
Date for your Diary The Irish Medical Organisation Annual General Meeting will take place on April 20th-23rd in the Radisson Blu Hotel, Galway. The Programme includes talks covering the road to a new NCHD contract, the future for Doctors in Ireland, investing in healthcare and cybersecurity. During several educational sessions Professor Trevor Duffy, Clinical Director and Consultant Rheumatologist, Connolly Hospital, will provide a practical demonstration of joint injections for those interested in improving their skills in pain management whilst Dr Mary O’Mahony, Specialist in Public Health Medicine, A/ Director Department of Public Health, HSE South, discusses the recognition and prevention of Foetal Alcohol Spectrum Disorder. For further information and to register visit www.imo.ie
Medical Council strikes agreement with Ombudsman The Medical Council and the Office of the Ombudsman have this month signed a Memorandum of Understanding (MoU) that will allow for the exchange of information and complaints between both offices. The agreement will also establish procedures to assist members of the public in accessing the services of both organisations. Several specific actions will be
April 2017 • HPN
covered by the agreement. These include: • The Medical Council referring complainants directly to the Ombudsman where appropriate. • The Ombudsman referring relevant complaints to the Medical Council with the consent of the complainant. • Joint initiatives such as projects and research on improving the quality and safety of patient care.
Any exchange of information between both organisations will be done in accordance with the law. Bill Prasifka, Chief Executive Officer of the Medical Council added, “Under this agreement, we at the Medical Council will continue to have legal responsibility for the regulation of doctors, with the Ombudsman responsible for public service providers. We are both committed to working within our statutory
remit to best serve the public. It’s important that we co-operate with the Ombudsman - we each receive complaints, and going forward we can each manage those complaints best suited to our particular remit. With this MoU, we can now accurately direct people to the best organisation for the timely resolution of their complaint.”
Wide variations in medication safety, report finds The Health Information and Quality Authority (HIQA) has said it found a wide variation in the medication safety arrangements in hospitals during the first inspections of this kind. Under-reporting of mistakes, non-reporting of near misses with drugs and outdated reference materials were revealed during the series of inspections. Particular problems were identified in University Hospital Waterford, Bantry General and Nenagh Hospital. University Hospital Waterford did not have essential governance arrangements for medication safety. HIQA said it was informed that medication-related clinical incidents were likely underreported at Waterford. There was also "outdated and potentially conflicting" reference information for using intravenous medication in clinical areas. HIQA said that in response to the risks it identified, the hospital appointed a medication safety pharmacist. At Bantry General, an immediate high risk was identified with instructions for administering
intravenous medications that could be incorrect. HIQA noted the low number of medication errors and near misses reported during 2016, relative to other hospitals.
ultimately accountable for patient safety regarding medication.
Medication safety was not systematically monitored and there was no up-to-date local list of medications stocked. The health watchdog found that near misses were not being reported at Nenagh Hospital.
There was no up-to-date local list of medications stocked in the pharmacy. At Connolly Hospital Blanchardstown, inspectors found it did not have a defined, multidisciplinary medication safety programme in place at the time of the HIQA visit. Senior management said there was likely under-reporting of medication errors.
The hospital did not have essential governance arrangements in place and there was "ambiguity" over who was
Frontline staff told HIQA inspectors that they had not received feedback on medicationrelated incidents they had
reported. The health watchdog has published the first inspection reports on medication safety in seven hospitals. The inspections were carried out between November and December 2016 at Bantry General, Connolly Hospital, Naas General, Nenagh Hospital, the Mater Misericordiae University Hospital, Sligo University Hospital and University Hospital Waterford.
Patient care still being compromised to critical levels There still exists numerous stark realities of clinical practice in Ireland’s acute hospitals and the difficulties which consultants face in their attempts to provide care to an ever increasing number of critically ill patients without the necessary resources. Any realistic plan to relieve emergency department overcrowding and to address the growing waiting lists must include an increase in acute hospital bed and operating theatre capacities. Otherwise the health service will continue to fail the public. This is according to the Irish Hospital Consultants Association (IHCA) who recently met with Minister for Health Simon Harris to highlight the critical capacity and other constraints affecting Ireland's health service. Dr Tom Ryan, President of the IHCA, said that the unresolved problems in Irish hospitals are now at such a critical level
that patient care and safety is compromised on a daily basis. “The current practice of healthcare rationing is the root cause of the trolley crisis and the ever growing waiting lists,” he says. “Now this practice is resulting in the cancellation of essential surgery with increasing frequency. Our capacity to deliver care has deteriorated to the point where surgical appointments for cancer patients are now being cancelled in significant numbers. “Our acute health services are also failing patients as we have over 400 permanent consultant posts vacant or filled on a temporary or agency basis. The absence of the necessary infrastructure and support services, compounded by persistent breaches of contracts by employers and discrimination against new entrants, are driving consultants to resign from their posts in increasing numbers to
practise medicine elsewhere. These vacant posts will not be filled with the high calibre permanent consultants that are required to develop an effective, integrated health service unless there is investment in both our hospitals and doctors'.” Dr Ryan welcomed the Minister’s acknowledgement of the scale of the consultant recruitment and retention crisis. This must be addressed in the forthcoming pay review if we are to succeed in attracting hospital consultants in a highly competitive global market. At this meeting the urgent need to overhaul the governance of the health service was also highlighted to the Minister. Dr Ryan said that accountability and transparency must be improved at all levels of planning and execution in our health service. Ireland’s health system must become more responsive to patients’ needs. Current
bureaucratic structures and processes are failing to adapt to the needs of the growing number of our patients and are no longer fit for purpose. To prioritise the needs of patients, there must be a greater emphasis on clinical leadership in all aspects of health care. Dr Ryan concluded that there is a real opportunity in the proposed 10 Year Healthcare Strategy to address the critical shortage of hospital beds, support services and frontline staff, in order to provide care for the increased number of patients arising from a growing and ageing population. He said the Strategy must include a blueprint outlining increased capacity and a yearly commissioning timetable. Anything less than this means that the Strategy will be seen as a ‘fudge’ that could set healthcare back for decades.
HPN • April 2017
Ireland leading contender for EMA location Ireland is one of the two forefront runners as the new home for the European Medicines Agency (EMA), Hospital Professional News has learned. The Agency will have to relocate from London to another EU Member State following the UK’s decision to leave the EU. Speaking at the Pharmaceutical Managers’ Institute (PMI) annual Business Day, QuintilesIMS Market Development Director Angela McFarlane declared the EMA ‘hot property’ adding that Ireland and Paris are the two leading contenders. The decision date is currently unknown, but could be imminent following the triggering of Article 30 on March 29th. Meanwhile, Minister of State for Health Promotion Marcella Corcoran Kennedy, TD, has thrown her weight behind the bid during a visit to Brussels, at which she held a number of meetings with key stakeholders and MEPs, as well as with the EU’s Deputy Chief Negotiator on Brexit Sabine Weyand.
Minister Corcoran Kennedy said, “The EMA plays a vital role in the protection and promotion of public health for 500 million European citizens and so it is vital the impact of a relocation is minimised. I am absolutely convinced that a move to Dublin would mean a seamless transition, ensuring continued protection of EU citizens and providing reassurance to the industries which it regulates.” Ireland firmly believes that Dublin offers the best outcome for the Agency for a number of reasons: • Dublin would prove very attractive to EMA staff and their families and maximise retention of existing staff. • Dublin is an English-speaking location and English is the working language of the EMA and the pharmaceutical industry. • The Irish medicines regulator – the Health Products Regulatory Authority – is a highly regarded regulator internationally, which already provides significant support to the EMA. This could be scaled up in the event of a relocation to Dublin.
The Minister added, “What we need, for the good of all Europeans, is a quick decision to be taken on the relocation of this key agency, but it must be the right decision. The EMA needs a home which will ensure the future sustainability of the agency. It is my firm belief that Dublin is that home.” An interdepartmental/interagency group has been established to develop a detailed proposal to promote the selection of Dublin as the new location for the EMA. This group includes the Department of the Taoiseach,
Department of Health, Department of Foreign Affairs and Trade, Department of Jobs, Enterprise & Innovation, Department of Agriculture, Food and the Marine, Health Products Regulatory Authority, IDA Ireland, Science Foundation Ireland, and the Health Research Board. The group is currently finalising a detailed proposal and engaging in discussions with the EU Commission, key stakeholders and other Members states to work to promote the selection of Dublin as the new location for the EMA.
MSc in Healthcare Education University College Cork is currently developing a multidisciplinary MSc in Healthcare Education, which will be a two-year part-time taught Masters programme, designed to enhance teaching and assessment skills for all healthcare professions. The programme is designed with the multidisciplinary team in mind and will be suitable for all healthcare professionals, including doctors, nurses, pharmacists, physiotherapists, dentists, occupational therapists and speech and language therapists. The programme consists of: Year One: A postgraduate certificate in Health Professions Education (30 credits). The certificate will be fully online. Year Two: A Postgraduate Diploma (60 credits) and Masters (90 credits). The Diploma and the Masters will be a blended learning format. This is a proposed programme currently undergoing the process of academic approval. For further information and registrations of interest please contact email@example.com
Information - key to tackling medicines shortages The European associations representing manufacturers of medicinal products, parallel distributors, pharmaceutical wholesalers and pharmacists have announced a series of recommendations on the provision of information, designed to help tackle medicines shortages.
pharmacists in Ireland and further across Europe was the European Association of Hospital Pharmacists (EAHP).
Focusing on the transparency and the availability of medicine shortage data, the Associations’ statement is part of their wider commitment to tackling the issue. Representing hospital
The recommendations call for greater transparency and availability of medicines shortage data, early detection and assessment of potential shortages, consistency of
April 2017 • HPN
Evidence suggests it is an increasing problem across the European Union, having a significant impact on patients, on health professionals, on healthcare systems and suppliers.
reporting, increased access to the information available across all parts of the supply chain, improved data infrastructure, and collaborative governance processes. The recommendations aim to mitigate the impact of shortages on patients, provide patients and health professionals with upto-date, meaningful information and improve the ability of health systems to diagnose and solve supply issues as they arise. This statement builds on existing good practices and recommends
some specific features of ideal medicines shortages information systems. The European associations representing manufacturers of medicinal products, parallel distributors, pharmaceutical wholesalers and pharmacists hope that, taking into consideration the national specificities of each country, these recommendations can help enhance information systems at a national level, and potentially form the basis of future European level action.
can maximise your patients’ treatment outcomes for the journey ahead in ALK+ and ROS1+ advanced NSCLC 1-7
XALKORI® is the ONLY ALK inhibitor approved, and guideline-recommended, as 1st-line standard of care, offering your patients the opportunity to benefit from treatment with next-generation ALK inhibitors after progression1–5,8–10 XALKORI® followed by next-generation ALK inhibitors has demonstrated a median OS of >4 years from diagnosis3,4 XALKORI® provides clinically meaningful benefits in advanced ROS1+ NSCLC, and is the 1st and only treatment indicated for these patients6,7 XALKORI® (crizotinib) PRESCRIBING INFORMATION. Please refer to the Summary of Product Characteristics (SmPC) before prescribing Xalkori 200 mg or 250 mg hard capsules. Presentation: Hard capsules containing 200 mg or 250 mg crizotinib. Indications: First-line treatment of adults with anaplastic lymphoma kinase (ALK) positive advanced non-small cell lung cancer (NSCLC), treatment of adults with previously treated ALK-positive advanced NSCLC and the treatment of adults with ROS1-positive advanced NSCLC. Dosage: Therapy should be initiated and supervised by a physician experienced in the administration of anti-cancer medicinal products. An accurate and validated assay for either ALK or ROS1 is necessary for the selection of patients for treatment with XALKORI. Either ALK-positive or ROS1-positive NSCLC status should be established prior to initiation of crizotinib therapy. Assessment should be performed by laboratories with demonstrated proficiency in the specific technology being utilised. The recommended dose of Xalkori is 250 mg taken orally (twice daily) with or without food, continuously. Dosing interruption and/or dose reduction may be required based on individual safety and tolerability. If dose reduction is necessary, then the dose of XALKORI should be reduced to 200 mg taken twice daily. If further dose reduction is necessary, then the dose should be modified to 250 mg taken once daily based on individual safety and tolerability. For dose reduction guidelines for haematologic and non-haematologic toxicities, refer to SmPC section 4.2. Treatment should be used with caution in patients with mild and moderate hepatic impairment and should not be used in patients with severe hepatic impairment. No starting dose adjustment is recommended for patients with mild (60 ≤ creatinine clearance [CLcr] <90 mL/min) or moderate (30≤ CLcr < 60mL/min) renal impairment, since the population pharmacokinetic analysis indicated no clinically meaningful changes in steady-state crizotinib exposure in these patients. Crizotinib plasma concentrations may be increased in patients with severe renal impairment (CLcr <30mL/min). The crizotinib dose should be adjusted to 250 mg taken orally once daily in patients with severe renal impairment not requiring peritoneal dialysis or hemodialysis. The dose may be increased to 200 mg twice daily based on individual safety and tolerability after at least 4 weeks of treatment, refer to SmPC section 4.2. The safety and efficacy of crizotinib in paediatric patients has not been established. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Severe hepatic impairment. Special warnings and precautions for use: Drug induced hepatotoxicity (including cases with fatal outcome) has been reported. Monitor liver function tests including ALT, AST, and total bilirubin once a week during the first 2 months of treatment then once a month, as clinically indicated with more frequent testing for Grades 2, 3 or 4 elevations. Severe, life-threatening, and/or fatal interstitial lung disease (ILD)/pneumonitis has been reported. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis. Withhold crizotinib treatment if ILD/pneumonitis is suspected. Drug-induced ILD/pneumonitis should be considered in the differential diagnosis of patients with ILD-like conditions such as: pneumonitis, radiation pneumonitis, hypersensitivity pneumonitis, interstitial pneumonitis, pulmonary fibrosis, acute respiratory distress syndrome (ARDS), alveolitis, lung infiltration, pneumonia, pulmonary edema, chronic obstructive pulmonary disease, pleural effusion, aspiration pneumonia, bronchitis, obliterative bronchiolitis, and bronchiectasis. Crizotinib should be permanently discontinued in patients diagnosed with treatment-related ILD/pneumonitis. QTc prolongation has been observed in clinical studies in patients treated with XALKORI which may lead to an increased risk for ventricular tachyarrhythmias (e.g., Torsade de Pointes) or sudden death. The benefits and potential risks of crizotinib should be considered before beginning therapy in patients with pre-existing bradycardia, who have a history of or predisposition for QTc prolongation, who are taking antiarrhythmics or other medicinal products that are known to prolong QT interval and in patients with relevant preexisting cardiac disease and/or electrolyte disturbances. Crizotinib should be administered with caution in these patients and periodic monitoring of electrocardiograms (ECG), electrolytes and renal function is required. When using crizotinib, ECG and electrolytes (e.g., calcium, magnesium, potassium) should be obtained as close as possible prior to the first dose and periodic monitoring with ECGs and electrolytes is recommended, especially at the beginning of treatment in case of vomiting, diarrhoea, dehydration or impaired renal function. Correct electrolytes as necessary. If QTc increases by greater than or equal to 60 msec from baseline but QTc is <500 msec, crizotinib should be withheld and cardiologist advice should be sought. If QTc increases to greater than or equal to 500 msec, cardiologist advice must be immediately sought. For patients who develop QTc prolongation, see SmPC sections 4.2, 4.8 and 5.2. All-causality bradycardia was reported in clinical studies in 13% of patients treated with crizotinib. Symptomatic bradycardia (e.g., syncope, dizziness, hypotension) can occur in patients receiving crizotinib. The full effect of crizotinib on reduction of heart rate may not develop until several
weeks after start of treatment. Avoid using crizotinib in combination with other bradycardic agents (e.g., beta-blockers, non-dihydropyridine calcium channel blockers such as verapamil and diltiazem, clonidine, digoxin) to the extent possible, due to the increased risk of symptomatic bradycardia. Monitor heart rate and blood pressure regularly. Dose modification is not required in cases of asymptomatic bradycardia. For management of patients who develop symptomatic bradycardia, see SmPC sections 4.2 and 4.8. In clinical studies with crizotinib and during post marketing surveillance, severe, lifethreatening, or fatal adverse reactions of cardiac failure were reported (see section 4.8). Patients with or without pre-existing cardiac disorders, receiving crizotinib, should be monitored for signs and symptoms of heart failure (dyspnoea, oedema, rapid weight gain from fluid retention, fatigue, arrhythmias). Dosing interruption, dose reduction, or discontinuation should be considered as appropriate if such symptoms are observed. In clinical studies with crizotinib in patients with either ALK-positive or ROS1-positive NSCLC Grade 3 or 4 neutropenia has been very commonly (12%) reported. Grade 3 or 4 leukopenia has been commonly (3%) reported. Less than 0.5% of patients experienced febrile neutropenia in clinical studies with crizotinib. Complete blood counts including differential white blood cell counts should be monitored as clinically indicated, with more frequent repeat testing if Grade 3 or 4 abnormalities are observed, or if fever or infection occurs. In clinical studies with crizotinib, events of gastrointestinal perforations were reported. There were reports of fatal cases of gastrointestinal perforation during post-marketing use of crizotinib (see SmPC section 4.8). Crizotinib should be used with caution in patients at risk for gastrointestinal perforation (e.g., history of diverticulitis, metastases to the gastrointestinal tract, concomitant use of medications with a recognized risk of gastrointestinal perforation). Crizotinib should be discontinued in patients who develop gastrointestinal perforation. Patients should be informed of the first signs of gastrointestinal perforations and be advised to consult rapidly in case of occurrence. Blood creatinine increase and creatinine clearance decreased were observed in patients in clinical studies with crizotinib. Renal failure and acute renal failure were reported in patients treated with crizotinib in clinical trials and during post marketing. Cases with fatal outcome, cases requiring hemodialysis and cases of grade 4 hyperkalemia were also observed. Monitoring of patients for renal function at baseline and during therapy with crizotinib is recommended, with particular attention to those who have risk factors or previous history of renal impairment (see SmPC section 4.8). In clinical studies with crizotinib, Grade 4 visual field defect with vision loss has been reported. Optic atrophy and optic nerve disorder have been reported as potential causes of vision loss. Ophthalmological evaluation is recommmended if vision disorder persists or worsens in severity. Concomitant use of crizotinib with strong CYP3A4 inhibitors or with strong and moderate CYP3A4 inducers and CYP3A4 substrates with narrow therapeutic indices should be avoided. Avoid using crizotinib in combination with other bradycardic agents, medicinal products that are known to prolong QT interval and/or antiarrhythmics. Drug interactions: In vitro studies indicated that crizotinib is an inhibitor of CYP2B6. Therefore, crizotinib may have the potential to increase plasma concentrations of coadministered drugs that are metabolised by CYP2B6 (e.g., bupropion, efavirenz). In vitro studies indicated that crizotinib may induce pregnane X receptor (PXR)- and constitutive androstane receptor (CAR)-regulated enzymes (e.g. CYP3A4, CYP2B6, CYP2C8, CYP2C9, UGT1A1, However, there was no observed induction in vivo when crizotinib was coadministered with the CYP3A probe substrate midazolam. Caution should be exercised in administering crizotinib in combination with medicinal products that are predominantly metabolised by these enzymes. Of note, the effectiveness of concomitant administration of oral contraceptives may be reduced. In vitro studies indicated that crizotinib is a weak inhibitor of uridine diphosphate glucuronosyltransferase (UGT)1A1 and UGT2B7. Therefore, crizotinib may have the potential to increase plasma concentrations of coadministered drugs that are metabolised predominantly by UGT1A1(e.g. raltegravir, irinotecan) or UGT2B7 (e.g. morphine, naloxone). Based on an in vitro study, crizotinib is predicted to inhibit intestinal P-gp. Therefore, administration of crizotinib with medicinal products that are substrates of P-gp (e.g. digoxin, dabigatran, colchicines, pravastatin) may increase their therapeutic effect and adverse reactions. Crizotinib is an inhibitor of OCT1 and OCT2 in vitro. Therefore, crizotinib may have the potential to increase plasma concentrations of coadministered drugs that are substrates of OCT1 or OCT2 (metformin, procainamide). Prolonged QT interval has been observed with crizotinib. The concomitant use of crizotinib with medicinal products known to prolong QT interval or able to induce Torsades de pointes (e.g., class IA [quinidine, disopyramide] or class III [e.g., amiodarone, sotalol, dofetilide, ibutilide], methadone, cisapride, moxifloxacine, antipsychotics, etc.) should be carefully considered. A monitoring of the QT interval should be made in case of combinations of such medicinal products Use with caution due to the risk of excessive bradycardia when used in combination with other bradycardic agents (e.g. nondihydropyridine calcium channel blockers such as verapamil and diltiazem, betablockers, clonidine, guanfacine, digoxin, mefloquine, anticholinesterases, pilocarpine). Fertility, pregnancy and lactation: Not recommended in pregnancy or whilst breast-feeding. Adequate contraceptive methods should be used during therapy, and for at least 90 days after completing therapy.
Crizotinib may impair fertility and both men and women should seek advice for fertility preservation before treatment. Driving and operating machinery: Caution should be exercised when driving or operating machines as patients may experience symptomatic bradycardia (e.g., syncope, dizziness, hypotension), vision disorder, or fatigue while taking XALKORI. Undesirable effects: The most serious adverse reactions in patients with either ALK-positive or ROS1-positive advanced NSCLC are hepatotoxicity, ILD/pneumonitis, neutropenia and QT interval prolongation. Very common adverse events are neutropenia, anaemia, leukopenia, decreased appetite, neuropathy, dysgeusia, vision disorder, dizziness, bradycardia, diarrhoea, vomiting, nausea, constipation, abdominal pain, elevated transaminases, rash, oedema, fatigue. Commonly reported adverse events are hypophosphataemia, cardiac failure, electrocardiogram QT prolonged, syncope, interstitial lung disease, dyspepsia, oesophagitis, blood alkaline phosphatase increased, renal cyst, blood creatinine increased, blood testosterone decreased. Refer to SmPC for further information on side effects Legal Category: S1A. Marketing Authorisation Number: EU/1/12/793/001 - 200mg, 60 capsules; EU/1/12/793/003 250mg, 60 capsules. The Marketing Authorisation Holder: Pfizer Limited, Sandwich, Kent, CT13 9NJ, United Kingdom. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at EUMEDINFO@pfizer.com. For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 4676500. Last revised: 08/2016. Ref: XI 13_1 References: 1. Shaw AT, et al. Alectinib in ALK-positive, crizotinib-resistant, non-small-cell lung cancer: a single-group, multicentre, phase 2 trial. Lancet Oncol. 2016;17(2):234–42. 2. Kim DW, et al. Activity and safety of ceritinib in patients with ALK-rearranged non-small-cell lung cancer (ASCEND-1): updated results from the multicentre, open-label, phase 1 trial. Lancet Oncol. 2016;17(4):452–63. 3. Gainor JF, et al. Progression-free and overall survival in ALKpositive NSCLC patients treated with sequential crizotinib and ceritinib. Clin Cancer Res. 2015;21(12):2745-52.4. Watanabe S, et al. Progression-free and overall survival of patients with ALK rearrangement-positive non-small cell lung cancer treated sequentially with crizotinib and alectinib. Clin Lung Cancer. 2016. 5. Chiari R, et al. Clinical impact of sequential treatment with ALK-TKIs in patients with advanced ALK-positive non-small cell lung cancer: results of a multicenter analysis. Lung Cancer. 2015;90(2):255-60. 6. Shaw AT, et al. Crizotinib treatment of ROS1-positive advanced non-small cell lung cancer: results from the updated PROFILE 1001 analysis. Oral presentation at the European Society for Medical Oncology Congress, 7–11 October 2016, Copenhagen, Denmark. 7. Xalkori (crizotinib) Summary of Product Characteristics. 8. Solomon BJ, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167–2177. 9. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: non-small lung cancer - Version 2, 2017. 2016. 10. Novello S, et al. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 2016: 27 (supplement 5):v1–v27. Date of preparation: March 2017. Job code: PP-XLK-IRL-0045. This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 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. Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 676 4971; Fax: +353 1 676 2517. Website: www.hpra.ie; e-mail: firstname.lastname@example.org
8 News Ireland's responsibility to lead world in CF treatment Prof essorStuart Elborn, Clinical Professor and Centre Director for Specialist Adult Cystic Fibrosis, Royal Brompton Hospital, London, Dr Charles Haworth, Consultant in Respiratory Medicine & Director, Cambridge Centre for Lung Infection, Philip Watt, Chief Executive, Cystic Fibrosis Ireland, Dr Abi Jackson, Research Fellow and Principal Investigator, Cystic Fibrosis Registry of Ireland, and Professor Barry Plant, Director, Adult Cystic Fibrosis Centre, Cork University Hospital
Time to Deliver on Orkambi & Kalydeco As the world's centre for cystic fibrosis (CF) – with more cases per head of population than anywhere else, and some of the most severe types – Ireland has a responsibility to set the standard for other countries to follow when it comes to the management and treatment of CF. This was the clear message conveyed at Cystic Fibrosis Ireland's annual patient conference which took place in Killarney on Saturday April 1, ahead of its 65 Roses Day flagship fundraising appeal on Thursday April 13. The conference came against a backdrop of growing frustration among the CF community in relation to the approval of the Orkambi and Kalydeco therapies, which remain to be given the green light by the Minister for Health. With latest figures from the Cystic Fibrosis Registry of Ireland showing that in 2015 there were 1,219 people registered with CF, with 19 years the median age, the conference heard from some of Europe's leading experts on the latest developments in CF treatment and care. There were contributions on a range of topics, from new therapies coming down the line, to the latest transplant developments, to updates on the progress of the National Clinical Care Programme for Cystic Fibrosis. Success Brings New Challenges Professor Barry Plant, Director of the Adult Cystic Fibrosis Centre at Cork University Hospital, and Chairperson of the Medical & Scientific Committee, Cystic Fibrosis Ireland, believes that given the level of CF in Ireland, we have a responsibility to lead the world in this area. "For all intents and purposes, cystic fibrosis is an Irish disease. We have the highest incidence worldwide,” he said. April 2017 • HPN
“We have some of the most severe CF genotypes. Therefore, we have a duty and responsibility to lead from the front when it comes to CF treatment and care. Over the past ten years we have seen great strides in treating this disease. Survival rates are increasing. We have designated CF centres with dedicated in-patient and outpatient facilities. We have had some really exciting therapeutic developments too with new personalised CF therapies that treat the disease rather than the symptoms. "But now we need to look at the next stage of optimising CF care. We know from European Registry projections that the number of adults with CF in Ireland will increase by 75% by 2025, and the number of children by 25%. These will present additional challenges which will need to be addressed. "In my view, with more people with CF than anywhere else worldwide, we shouldn't be looking to others for guidance. Other countries should be looking to us as leaders in CF care. “From research to new drugs to medical devices to social care supports, we have a responsibility to tackle this issue well. The HSE has recently established a National Clinical Care Programme for Cystic Fibrosis which is looking at all aspects of the treatment of patients with CF in Ireland including appropriate ratios of services/staffing to patients. In this way, every person with CF should be able to access the same level of service no matter what part of the country that they are in. Currently every CF centre has staffing and service challenges, but with the support of Government and the HSE, the future recommendations of the National Clinical Care Programme for Cystic Fibrosis could create CF services fit for the 21st century."
Philip Watt, Chief Executive of Cystic Fibrosis Ireland, is calling for clarity from the Minister for Health with regard to the approval of Orkambi and Kalydeco, following on a recent statement by Vertex Pharmaceuticals. He said, "On March 6 last, the Minister for Health stated on national radio that he was 'very close to a deal' in relation to Orkambi and Kalydeco and that he expected the 'process to conclude within a matter of weeks'. This positive development was greeted warmly, if cautiously, by the CF community. “Now into the fourth week following these comments we have learned from a recent statement by the pharmaceutical company that it has received no response to a proposal it submitted 11 weeks ago and that it is looking for clarity from the Minister. Cystic Fibrosis Ireland too would welcome clarity. These therapies have the potential to benefit up to 600 patients. People with cystic fibrosis accept the need for a fair deal for the taxpayer. They have been very patient - indeed nine months' patient - during which time their quality of life could have been measurably better and progression of the disease slowed. "With Cystic Fibrosis National Awareness Week taking place from April 10 to 16, it is important to acknowledge that we have made great strides in relation to CF treatment and care in this country. We have seen the population of people with cystic fibrosis continue to rise over the past five years, up from 1,025 in 2011 to 1,219 in 2015 - that's almost 20%. “Behind those figures is a real person trying to live their life to the full. Let's not lose that momentum and progress now. The Minister has previously acknowledged that this has been an 'extraordinarily stressful and worrying time for many CF patients'. The Minister
has the power to lift that stress and worry. It's time to deliver." CF is Ireland’s most common life-threatening inherited disease. CF is a genetic disorder. It is not contagious, rather people are born with it. Approximately 1 in 19 people are carriers of the CF gene and when two carriers have a child there is a one in four chance of a child being born with it. CF affects the regulation of absorption and secretion of salt and water in various parts of the body including the lungs, sweat glands, pancreas, and gastrointestinal tracts. This defect inhibits the flow of salt and water through the body’s cells, causing a build-up of thick, sticky mucus, which can clog airways and harbour harmful bacteria. Symptoms reported by people with CF vary significantly in severity from mild to debilitating. The most common symptom is recurrent chest infection, which results in lung damage, with the majority of deaths occurring through respiratory failure. There is a high prevalence of CF in Europe, with the highest prevalence in Ireland, which is almost three times the average rate in other EU countries and the United States. The Cystic Fibrosis Registry of Ireland (CFRI) is a medical research information technology system which records and analyses data about the health and treatment of people with CF in the Republic of Ireland. It was established in 2001 to keep medical records of each person with CF in a central database. By bringing together and analysing the information on all people with CF in Ireland, we can get a better understanding of, for example, treatments that affect people with CF. Information is held on a secure and confidential computer database. In 2015 there were 1,219 people registered with CF, with 19 years the median age. Nearly 30% of people with CF were hospitalised for a pulmonary exacerbation in 2015 - 23.1% of children and 34.6% of adults - of these, 47.2% were admitted two or more times over the 12-month period. The average cumulative length of stay was 27 days in the year. Over 6,500 outpatients visits to CF specialist centres and CF clinics were attended by people with CF in 2015. The number of people with CF receiving a bilateral lung transplant during 2015 was 10. For more, visit www.cfri.ie
Take a closer look at why you can
Uveitis (noninfectious intermediate, Posterior and Panuveitis)
The most of any self-administered biologic1
Active and progressive Psoriatic Arthritis
AS Severe active Ankylosing Spondylitis
Severe Paediatric chronic Plaque Psoriasis (from the age of 4 years)
Moderately to severely active Crohn’s Disease
Active Enthesitisrelated Arthritis (from the age of 6 years)
Moderate to severe chronic Plaque Psoriasis
one million patients currently treated worldwide2
References: 1. HUMIRA [summary of product characteristics]. AbbVie Ltd. 2. Data on File, AbbVie.
Moderately to severely active Paediatric Crohn’s Disease (from the age of 6 years)
Prescribing Information Humira (adalimumab) 40mg solution for injection in pre-filled pen or pre-filled syringe or Humira 40mg/0.8ml solution for injection for paediatric use. * Refer to Summary of Product Characteristics (SmPC) for full information. Presentation: Each 0.4ml single dose pre-filled pen or pre-filled syringe contains 40mg of adalimumab. Each 0.8ml single dose vial contains 40mg of adalimumab. Indications: Rheumatoid arthritis (RA), adults: In combination with methotrexate (MTX) for moderate to severe, active RA with inadequate response to disease-modifying anti-rheumatic drugs (DMARDs) including MTX. In combination with MTX for severe, active and progressive RA when not previously treated with MTX. Can be given as monotherapy if intolerance to or when continued treatment with MTX is inappropriate. Reduces rate of progression of joint damage on X-ray and improves physical function, in combination with MTX. Polyarticular juvenile idiopathic arthritis (pJIA), paediatrics 2 years and above: In combination with MTX, for active pJIA, with inadequate response to one or more DMARDs; or monotherapy if intolerance to or when continued treatment with MTX is inappropriate. Enthesitis-related arthritis (ERA), paediatrics 6 years and above: For active ERA with inadequate response to or intolerance to, conventional therapy. Psoriatic arthritis (PsA), adults: For active and progressive PsA with inadequate response to DMARDs. Reduces rate of progression of peripheral joint damage on X-ray in polyarticular symmetrical subtypes of the disease and improves physical function. Ankylosing spondylitis (AS), adults: For severe active AS with inadequate response to conventional therapy. Axial spondyloarthritis without radiographic evidence of AS (nr-axSpA), adults: For severe nr-axSpA with objective signs of inflammation (elevated CRP and/or MRI), and an inadequate response to, or intolerance to nonsteroidal anti-inflammatory drugs (NSAIDs). Crohn’s disease (CD), adults: For moderately to severely, active CD with inadequate response, contraindication or intolerance to corticosteroid and/or an immunosuppressant therapy. Crohn’s disease (CD), Paediatrics 6 years and above: For moderately to severely active CD with inadequate response, contraindication or intolerance to conventional therapy including primary nutrition therapy and a corticosteroid, and/or an immunomodulator. Psoriasis (Ps), adults: For moderate to severe chronic plaque psoriasis who are candidates for systemic therapy. Psoriasis, paediatrics 4 years and above: For severe chronic plaque psoriasis with inadequate response, or if topical therapy and phototherapies are inappropriate. Hidradenitis suppurativa (HS), adults: For active moderate to severe hidradenitis suppurativa (acne inversa) in patients with an inadequate response to conventional systemic HS therapy. Ulcerative colitis (UC), adults: For moderately to severely active UC with inadequate response, contraindication or intolerance to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA). Uveitis, adults: For non-infectious intermediate, posterior and panuveitis with inadequate response to corticosteroids, in need of corticosteroid-sparing, or in whom corticosteroid treatment is inappropriate. Dosage and administration: Specialist physicians experienced in the diagnosis and treatment of the condition, to initiate and supervise treatment. Ophthalmologists to consult with an appropriate specialist before initiation of treatment. Provide patients with special alert card. Patients may self-inject after proper injection training, with physician approval and appropriate medical follow-up. Optimise other concomitant therapies. RA,adults: 40mg dose every other week. Concomitant MTX should be continued. During monotherapy patients may require 40mg each week if they experience a decrease in clinical response. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. Consider need for dose interruption, e.g. before surgery or if serious infection occurs. Re-introduction after 70 days dose interruption gave same magnitudes of clinical response and similar safety profile as before dose interruption. pJIA, paediatrics 2 years and above: pJIA, paediatrics 2-<4 years: 24mg/m² body surface area up to 20mg maximum single dose every other week (see SmPC for height/weight dosing chart). pJIA, paediatrics 4-12 years: 24mg/m² body surface area up to 40mg maximum single dose every other week (see SmPC for height/weight dosing chart). pJIA, paediatrics 13 years and above: 40mg every other week regardless of body surface area. Treatment beyond 12 weeks reconsidered if no clinical response in that time. ERA, paediatrics 6 years and above: 24mg/m² body surface area up to a maximum single dose of 40mg every other week. (see SmPC for height/weight dosing chart). PsA, AS and nr-axSpA, adults: 40mg every other week. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. CD: Adults: Induction:80mg at Week 0 followed by 40mg at Week 2. For a more rapid response, 160mg at Week 0 (either as 4 injections in 1 day or 2 injections/ day for 2 consecutive days), 80mg at Week 2; risk of adverse events higher during induction. Maintenance: 40mg every other week. If decrease in clinical response, can increase dose to 40mg weekly. Corticosteroids may be tapered in maintenance phase in accordance with clinical guidelines. Patients with no response by Week 4 may benefit from continued therapy to Week 12. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. CD, paediatrics 6 years and above<40Kg: Induction: 40mg at Week 0, 20mg at Week 2. For a more rapid response: 80mg at Week 0 (2 injections in 1 day), 40mg at Week 2; risk of adverse events higher during induction. Maintenance: 20mg every other week. If insufficient response, consider 20mg every week. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. CD, paediatrics 6 years and above ≥40Kg: Induction: 80mg Week 0, 40mg at Week 2. For a more rapid response: 160mg at Week 0 (4 injections in 1 day or 2 injections/day for 2 consecutive days), 80mg at Week 2; risk of adverse events higher during induction. Maintenance: 40mg every other week. If insufficient response, consider 40mg every week. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. Psoriasis, adults: 80mg induction dose at week 0, 40mg every other week from week 1. Treatment beyond 16 weeks should be reconsidered if no clinical response in that time. Beyond 16 weeks, patients with inadequate response can increase dosing frequency to 40mg every week. If adequate response is achieved with an increased dosing frequency, dose may subsequently be reduced to 40mg every other week. If there is inadequate response to the increased frequency, carefully reconsider treatment. Psoriasis, Paediatrics 4 years and above: 0.8mg per kg body weight (maximum of 40mg/dose) weekly for the first 2 doses and then every other week (see SmPC for weight dosing chart). Treatment beyond 16 weeks should be reconsidered if no response in that time. HS: Adults: 160mg initially at Day 1 (four 40mg injections in one day or two 40mg injections per day for two consecutive days), followed by 80mg two weeks later at Day 15 (two 40mg injections in one day). Two weeks later (Day 29) continue with a dose of 40mg every week. Antibiotics may be continued if necessary. Concomitant topical antiseptic wash on HS lesions should be used on a daily basis. Treatment beyond 12 weeks should be reconsidered if no clinical response in that time. Reintroduction after interruption: 40mg every week. Evaluate periodically the benefit and risk of continued long-term treatment. UC: Adults: Induction: 160mg at week 0 (4 injections in 1 day or 2 injections/day for 2 consecutive days) and 80mg at week 2. Maintenance: 40mg every other week. During maintenance, corticosteroids may be tapered in accordance with clinical practice guidelines. If insufficient Date of Preparation: December 2016 IREHUR160874
Active Moderate to Severe Hidradenitis Suppurativa (from the age of 12 years)
Moderate to severe active Rheumatoid
Active Polyarticular juvenile idiopathic Arthritis (from the age of 2 years)
Severe Axial Spondyloarthritis (nonradiographic)
Moderately to severely active Ulcerative Colitis
response, consider 40mg every week. Treatment beyond 8 weeks should be reconsidered if no clinical response in that time. Uveitis: Adults: 80mg induction dose at week 0, 40mg every other week from week 1. Experience of initiating treatment with Humira alone is limited. Treatment can be initiated in combination with corticosteroids and/or other nonbiologic immunomodulatory agents. Two weeks after initiating treatment, concomitant corticosteroids may be tapered in accordance with clinical guidelines. Evaluate on a yearly basis, the benefit and risk of continued long term treatment. Contraindications: Active tuberculosis (TB), severe infections (e.g. sepsis), and opportunistic infections; moderate to severe heart failure (NYHA class III/IV);hypersensitivity to adalimumab or any of the excipients. Precautions and Warnings: Clearly record trade name and batch number of administered product to improve traceability of biological medicinal product. Infections: Patients are more susceptible to serious infections especially if impaired lung function. Monitor for infections, including TB, before, during and for 4 months after treatment. Do not initiate treatment with an active infection, until it is controlled. Consider risk/benefit prior to treatment in patients exposed to high risk of TB or endemic mycoses. Evaluate new infections during treatment and monitor closely. Stop treatment if new serious infection or sepsis, and treat appropriately. Exercise caution in patients with a history of recurring infections or who are predisposed to infections. Serious infections: Serious infections, including those with hospitalisation or death reported in patients receiving treatment. TB: Consult SmPC for details. Reactivation and new onset TB, both pulmonary and extrapulmonary (disseminated) reported. Screen all patients before therapy initiation for active or latent TB. If active TB is diagnosed Humira therapy must not be initiated. If latent TB is suspected, consult a physician with appropriate expertise and follow local treatment recommendations for prophylaxis prior to initiation of Humira. Despite prophylaxis TB reactivation has occurred on Humira. Other opportunistic infections: Opportunistic infections observed in patients receiving Humira. Stop treatment in patients with signs and symptoms of such infections. Consult with physician with appropriate expertise for diagnosis and administration of empiric antifungal therapy in these patients. Hepatitis B Reactivation: Reactivation has occurred in chronic carriers (i.e. surface antigen positive) tested for HBV infection before initiating treatment. HBV carriers should consult with a specialist physician and be closely monitored for reactivation of HBV infection throughout therapy and for several months following termination of Humira. If reactivation occurs stop treatment and initiate appropriate anti-viral and supportive treatment. Neurological events: Caution in patients with pre-existing or recent-onset central or peripheral nervous system demyelinating disorders and consider stopping treatment if these disorders develop. Rare association with new onset or exacerbation of symptoms and/or radiographic evidence of central and peripheral demyelinating disease. Known association between intermediate uveitis and central demyelinating disorders. Evaluate patients with non- infectious intermediate uveitis before therapy initiation and regularly during treatment to assess for pre-existing or developing central demyelinating disorders. Allergic reactions: Reports of serious allergic reactions including anaphylaxis received. For serious allergic or anaphylactic reaction stop Humira immediately and initiate appropriate therapy. Malignancies and lymphoproliferative disorders: A possible risk of malignancy, including lymphoma and leukaemia, in all patients including paediatric patients, treated with TNF antagonists. Monitor all patients, especially those with a medical history of extensive immunosuppressant or PUVA treatment for non-melanoma skin cancer prior to and during Humira therapy, caution in COPD patients, and in patients with increased risk of malignancy due to heavy smoking. Consider the potential risk with the combination of AZA or 6-MP and Humira (hepatosplenic T-cell lymphoma has occurred). Risk of hepatosplenic T-cell lymphoma cannot be excluded. Caution in patients with a history of malignancy. Risk for developing dysplasia or colon cancer is unknown. Patients with UC, prior history of dysplasia or colon carcinoma to be screened for dysplasia before therapy and during treatment. Haematologic reactions: Adverse events of the haematologic system reported with Humira. Patients should seek immediate medical attention if signs and symptoms of blood dyscrasias. Vaccinations: Patients may receive concurrent vaccinations, except for live vaccines. Bring paediatric patients up to date with all immunisations prior to Humira treatment Congestive heart failure: See contraindications. Caution is advised in mild heart failure (NYHA class I/II). Discontinue treatment for new or worsening symptoms of congestive heart failure. Autoimmune processes: Autoimmune antibodies may form. Stop treatment if development of a lupus-like syndrome with positive antibodies against double- stranded DNA. Surgery: Consider the long half-life of Humira for planned surgical procedures. Closely monitor for infections. Small bowel obstruction: Failure to respond to treatment for CD may indicate the presence of fixed fibrotic stricture requiring surgical treatment. Elderly: Serious infections were higher in patients over 65 years of age, some of whom had fatal outcomes. Consider risk of infection. Interactions: Combination of adalimumab with other biologic DMARDS (e.g. anakinra and abatacept) or other TNF-antagonists is not recommended. Fertility, pregnancy and lactation: Not recommended during pregnancy. Women of childbearing potential should use adequate contraception and continue its use for at least five months after the last Humira treatment. Women must not breast-feed for at least five months after the last treatment. Side Effects: Very common ≥ 1/10: Infections, leucopaenia, anaemia, lipids increased, headache, abdominal pain, nausea and vomiting, elevated liver enzymes, rash (including exfoliative rash), musculoskeletal pain, injection site reaction. Serious, including fatal, side effects have been reported including infections/sepsis, intestinal perforation, opportunistic infections, TB, endemic mycoses, demyelinating disease, malignancies including lymphoma (including hepatosplenic T-cell lymphoma), leukaemia and skin cancer (including melanoma and merkel cell carcinoma), cytopenias, worsening heart failure, myocardial infarction, pulmonary embolism, pleural effusion, pulmonary fibrosis, cerebrovascular accident, interstitial lung disease, lupus, StevensJohnson syndrome, angioedema, anaphylaxis, sarcoidosis, hepatitis, liver failure and worsening of symptoms of dermatomyositis. Prescribers should consult the SmPC for the complete list of reported side effects. Legal Category: POM. Marketing Authorisation Numbers/Presentations: Vial: EU/1/03/256/001; Pre-filled Syringe: EU/1/03/256/013; Pre-filled Pen: EU/1/03/256/017. Further information is available from AbbVie Limited, 14 Riverwalk, Citywest Business Campus, Dublin 24. HCPs are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: email@example.com. Date of revision of PI: June 2016 PI/256/017
Experts highlight major gaps in services for patients with complex nutritional problems According to available data more than 256 patients with intestinal failure were discharged on intravenous nutrition (HPN) between 2010 and 2016 from at least 21 hospitals in Ireland, none of which have the training, resources or specialist experience required to meet minimum guidelines or commissioning standards produced within the NHS system. To address this and bring Ireland in line with international best practice, IrSPEN (Irish Society for Clinical Nutrition & Metabolism) is calling on the HSE to ring-fence ¤4.2 million to establish an eightbed national centre for intestinal failure in St James' Hospital to manage people with IF who require prolonged parenteral nutrition (PN) as no specialist service is currently available in the Republic of Ireland. IrSPEN (Irish Society for Clinical Nutrition & Metabolism) recently hosted their biennial conference and policy seminar in Dublin with a variety of national and international experts examining malnutrition and the important role of nutrition in the development and management of patients with chronic diseases. "This relatively small group of patients with highly complex needs challenge even the most experienced clinicians. The current dispersal of patients to non-specialist hospitals poses unacceptable risks for them and puts significant pressures on resources and on nurses and clinicians to provide effective treatment and care management", says Dr David Kevans, Consultant Gastroenterologist and Clinical Lead Gastroenterology, St James's Hospital.
Professor John Reynolds, Chair IrSPEN (Irish Society for Clinical Nutrition & Metabolism) Photo: Jason Clarke
"If correctly managed within a specialist facility some of these patients may avoid a long-term requirement for parenteral nutrition or nutrition could be provided in the home through home parenteral nutrition. This would significantly improve their quality of life and avoiding serious complications including infections which result in frequent emergency hospital admissions and even death.” As there is no tertiary referral centre for the highly complex patients that develop severe acute IF each year in Ireland, there's also no specialist unit to manage the existing patients on HPN or those awaiting transition to adult services from the national paediatric unit at Our Lady's Children's Hospital Crumlin (OLCHC). "Abstracting data from the UK, we estimate that there is between 12 and 20 avoidable deaths per year in Ireland in patients with intestinal failure due to the lack of any
provision for adults within a tertiary centre", said Professor John Reynolds, Chairman of IrSPEN. "In relation to costs, the true cost of inadequate provision of care is undoubtedly considerably higher than the cost savings accrued from the provision of specialist care. International experience attests to specialist IF and HPN programmes being associated with reduced morbidity and mortality, reduced length of hospital stay, and improved outcomes and quality of life in patients on intravenous nutrition". The specialist unit in St James' Hospital would allow for the streamlining and integration of services for complicated IF and HPN patients. In addition to improving people with IF's quality of life, savings of between 50 and 60% have been demonstrated from when patients are given HPN as opposed to PN in hospital. A similar evaluation undertaken
Dr David Kevans, Consultant Gastroenterologist and Clinical Lead Gastroenterology, St James' Hospital, Professor John Reynolds, Chair of IrSPEN and Dr Graham Turner, Consultant Gastroenterologist, Belfast City Hospital. Photo: Jason Clarke
April 2017 • HPN
by OLCHC in 2005 estimated a ¤95,000 per patient per year saving when they are given HPN in their own home and managed through the specialist service in Crumlin. Malnutrition and disease go hand in hand, with many patients becoming undernourished due to the effects of diseases, such as cancer. The policy seminar highlighted the lack of specialist service available for people with intestinal failure – a condition where the intestines are unable to digest food or absorb fluids –and for patients who receive home parenteral nutrition (HPN) – nutrients infused into their veins. This lack of specialist service has contributed to far higher rates of emergency admissions than reported by specialist centres in the UK and elsewhere, with admissions rates here averaging 2.86 that last 13.4 days to 36 days per patient in total within the 12-month audit period. Experts also discussed the management of complex obesity including the under-utilisation of bariatric or gastric-band surgery as a treatment option in Irish healthcare policy. Malnutrition can develop relatively quickly, even in patients that are overweight or obese, due to reduced appetite, increased requirements due to altered metabolism or inability to eat normally. One of the most extreme examples is in patients that develop intestinal failure, which can occur due to surgical removal, obstruction or extensive disease affecting the small intestine.
24 HOUR EFFICACY
Relvar Ellipta (92/22 or 184/22 mcg) is an ICS/LABA for patients (≥12 years) uncontrolled on ICS alone and ‘as needed’ SABA1
• 24 hours of continuous efﬁcacy from just one daily dose2 • More symptom-free hours per week vs. an ICS alone2 • Meaningful improvements in patients’ quality of life vs. baseline3-6 • Delivered through an easy-to-use device7 • Relvar should not be used to treat acute asthma symptoms
Will you prescribe Relvar and help your asthma patients get back moments they’ve been missing?
Relvar® Ellipta® (ﬂuticasone furoate/ vilanterol [as trifenatate]) Prescribing information This medicinal product is subject to additional monitoring. This will allow quick identiﬁcation of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. (Please consult the full Summary of Product Characteristics (SmPC) before prescribing) Relvar® Ellipta® (ﬂuticasone furoate/vilanterol [as trifenatate]) inhalation powder. Each single inhalation of ﬂuticasone furoate (FF) 100 micrograms (mcg) and vilanterol (VI) 25mcg provides a delivered dose of 92mcg FF and 22mcg VI. Each single inhalation of FF 200mcg and VI 25mcg provides a delivered dose of 184mcg of FF and 22mcg of VI. Indications: Asthma: Regular treatment of asthma in patients ≥12 years and older not adequately controlled on inhaled corticosteroids and ‘’as needed” shortacting inhaled β2-agonists, where a long-acting β2-agonist and inhaled corticosteroid combination is appropriate. COPD (Relvar 92/22mcg only): Symptomatic treatment of adults with COPD with a FEV1<70% predicted normal (post-bronchodilator) and an exacerbation history despite regular bronchodilator therapy). Dosage and administration: Inhalation only. Asthma: Adults and adolescents ≥12 years: one inhalation once daily of: Relvar 92/22mcg for patients who require a low to mid dose of inhaled corticosteroid in combination with a long-acting beta2-agonist. If patients are inadequately controlled then the dose can be increased to one inhalation once daily Relvar 184/22mcg. Relvar 184/22mcg can also be considered for patients who require a higher dose of inhaled corticosteroid in combination with a long-acting beta2-agonist. Regularly review patients and reduce dose to lowest that maintains effective symptom control. COPD: one inhalation once daily of Relvar 92/22mcg. Contraindications: Hypersensitivity to the active substances or to any of the excipients (lactose monohydrate & magnesium stearate). Precautions: Pulmonary tuberculosis, severe cardiovascular disorders, heart rhythm abnormalities, thyrotoxicosis, uncorrected hypokalaemia or patients predisposed to low levels of serum potassium. chronic or untreated infections, diabetes mellitus.
Paradoxical bronchospasm – substitute alternative therapy if necessary. In patients with hepatic with moderate to severe impairment 92/22mcg dose should be used. Acute symptoms: Not for acute symptoms, use shortacting inhaled bronchodilator. Warn patients to seek medical advice if short-acting inhaled bronchodilator use increases. Therapy should not be abruptly stopped without physician supervision due to risk of symptom recurrence. Asthma-related adverse events and exacerbations may occur during treatment. Patients should continue treatment but seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of Relvar. Systemic effects: Systemic effects of inhaled corticosteroids may occur, particularly at high doses for long periods, but much less likely than with oral corticosteroids. Possible Systemic effects include: Cushing’s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, growth retardation in children and adolescents, cataract, glaucoma. More rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). Increased incidence of pneumonia, including pneumonia requiring hospitalisation, has been observed in patients with COPD receiving inhaled corticosteroids. Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of such infections overlap with the symptoms of COPD exacerbations.Risk factors for pneumonia include: current smoking, older age, low body mass indexand severe COPD. The incidence of pneumonia in patients with asthma was common at the higher dose of Relvar (184/22mcg). Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deﬁciency or glucose-galactose malabsorption should not take Relvar. Interactions with other medicinal products: Interaction studies have only been performed in adults. Avoid β-blockers. Caution is advised when co-administering with strong CYP 3A4 inhibitors (e.g. ketoconazole, ritonavir). Concomitant administration of other sympathomimetic medicinal products may potentiate the adverse reactions of FF/VI. Relvar should not be used in conjunction with other long-acting β2-adrenergic agonists or medicinal products containing long-acting β2adrenergic agonists. Pregnancy and breast-feeding: Experience limited.
Balance risks against beneﬁts. Side effects: Very Common (≥1/10): Headache, nasopharyngitis. Common (≥1/100 to <1/10): Candidiasis of the mouth and throat, pneumonia, bronchitis, upper respiratory tract infection, inﬂuenza, oropharyngeal pain, sinusitis, pharyngitis, rhinitis, cough, dysphonia, abdominal pain, arthralgia, back pain, muscle spasms, fractures, pyrexia. Uncommon (≥1/1,000 to <1/100): Extrasystoles. Rare (≥1/10,000 to <1/1,000): Hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria, palpitations, and tachycardia. Tremor, Anxiety. Marketing authorisation (MA) Holder: Glaxo Group Ltd, 980 Great West Road, Brentford, Middlesex TW8 9GS, UK. MA Nrs: 92/22mcg 1x30 doses [EU/1/13/886/002]; 184/22mcg 1x30 doses [EU/1/13/886/005]. Legal category: POM B. Last date of revision: November 2016. Job Ref: IE/FFT/0046/15 (3). Further information available on request from GlaxoSmithKline, 12 Riverwalk, Citywest Business Campus, Dublin 24. Tel: 01-4955000. References: 1. Relvar Ellipta Summary of Product Characteristics. GlaxoSmithKline; 2015. 2. Bleecker ER et al. Fluticasone furoate/ vilanterol 100/25mcg compared with fluticasone furoate 100mcg in asthma: a randomized trial. JACI In Practice 2014; 2(5): 563-561. 3. Woodcock A et al. Efficacy and safety of fluticasone furoate/vilanterol compared with fluticasone propionate/salmeterol combination in adult and adolescent patients with persistent asthma: a randomized trial. Chest. 2013; 144(4):1222-1229. 4. Woodcock A et al. Efficacy and safety of fluticasone furoate/vilanterol compared with fluticasone propionate/ salmeterol combination in adult and adolescent patients with persistent asthma: a randomized trial. Chest. 2013, Online supplement: 1-7. 5. Juniper EF et al. Determining a minimal important change in a diseasespecific quality of life questionnaire. J Clin Epidemiol. 1994; 47(1): 81-87. 6. GSK. Data on file 113091. 2014; RECE/FFT/0148/14. 7. Svedstater H et al. Ease of use of the ELLIPTA™ dry powder inhaler; data from three condomised controlled trials in patients with asthma. npj Prim Care Resp Med 2014; 24: 14019.
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. IE/FFT/0001/16a(1)a
Date of Preparation: January 2017
12 Conference John Devlin, Deputy Chief Medical Officer, Department of Health, Ursula O’ Dwyer, Department of Health and Professor John Reynolds, Chair of IrSPEN Photo: Jason Clarke
David Kevans, Consultant Gastroenterologist and Clinical Lead Gastroenterology, St James' Hospital, Professor John Reynolds, Chair of IrSPEN and Dr Graham Turner, Consultant Gastroenterologist, Belfast City Hospital. Photo: Jason Clarke
Audience pictured at the 2017 IrSPEN (Irish Society for Clinical Nutrition & Metabolism) Photo: Jason Clarke
treatment programmes for each individual that can include: diet, exercise, medical and surgical interventions. IrSPEN wants the right treatment for the right person at the right time to help reduce the effects of obesity-related diseases, reduce disease management costs and improve their quality of life. But unfortunately, specialist intensive intervention is often not available", says Professor Carel Le Roux, Diabetes Complications Research Centre, Conway Institute, UCD and IrSPEN board member. "Research shows that while Sweden has a population twice that of Ireland, it has half the obesity rate so both countries have the same number of people with complex obesity. Yet, 6,000 bariatric or gastric band operations are performed in Sweden annually versus about 60 in Ireland – again showing a severe under-utilisation of specialist treatment to reduce obesity-related disease in Ireland.” Intestinal failure occurs when a person's intestines can't digest food and absorb the fluids, electrolytes and nutrients essential to life and normal development. People with IF must receive total parenteral nutrition (TPN), which provides liquid nutrition through a catheter or needle inserted into a central vein in the chest – resulting in the need for highly specialised care. IF can happen as a result of the removal of the small intestine due to injury, surgery, blood clots or digestive disorders such as Crohn's Disease. The European Society for Clinical Nutrition and Metabolism defined intestinal failure (IF) as "the reduction of gut function below the minimum necessary for the absorption of macronutrients and/or water and electrolytes, such that intravenous supplementation is required to maintain health and/or growth.” Based on onset, metabolic and expected outcome criteria, IF is classified as type I, type II or type III.
Managing complex obesity International and national experts also examined best practise for the management of malnutrition caused by complex obesity. A recent interventional study of overweight or obese people with type 2 diabetes using an intensive lifestyle weight-loss programme revealed that only people who lost at least 10% of their bodyweight had a 20% lower risk of death
April 2017 • HPN
from cardiovascular causes, such as heart attacks and stroke. In addition, treatment of obesityrelated diseases including the use of bariatric surgery is clinically effective to improve health and the quality of life of Irish patients. New Irish research shows a substantial proportion of older Irish adults (7.9%) are potentially eligible for gastric band surgery. While many will not want, or be
suitable for the procedure, findings indicate that current public service provision of gastric band surgery in Ireland meets the needs of fewer than 1 in every 1000 people that would benefit. This shows a clear need for a strategy to develop and expand the provision of specialist care and interventional programmes for complex obesity in Ireland. "Obesity is a complex and chronic disease that requires personalised
The need for establishing the IF centre is outlined as part of the business case submitted to the Joint Oireachtas Committee on the Future of Healthcare in August, 2016, and is supported by findings from similar specialist units in other jurisdictions of significantly improved morbidity and mortality. The business case highlights several reasons why the national centre could be located at St James's Hospital, key being the need for collaboration between the national paediatric service and a service for adults.
The first biosimilar monoclonal antibody (mAb) for use in rheumatology, gastroenterology and dermatology
The first biosimilar monoclonal antibody (mAb) for use in rheumatology, gastroenterology and dermatology
Gain a fresh perspective
Gain a fresh perspective
INFLECTRA™ is the first biosimilar mAb. Designed with comparable efficacy and safety to reference infliximab to increase the treatment options for your rheumatology, gastroenterology and dermatology patients.1 Change your perspective. Choose INFLECTRA™.
INFLECTRA™ is the first biosimilar mAb. Designed with comparable efficacy and safety to reference infliximab to increase the treatment options for your rheumatology, gastroenterology and dermatology patients.1
Abbreviated Prescribing Information INFLECTRA (Infliximab) powder for concentrate for solution for infusion. Please refer to full Summary of Product Characteristics (SmPC) before prescribing. Presentation: Vial containing 100 mg of infliximab powder for concentrate for solution for infusion. Indications: 1) Rheumatoid arthritis (RA) in combination with methotrexate (MTX) in adult patients with active disease with inadequate response to disease-modifying antirheumatic drugs (DMARDs) or adult patients with severe, active and progressive disease not previously treated with MTX or other DMARDs. 2) Adult Crohn’s disease (CD) a) In patients with moderately to severely active CD who have not responded despite a full and adequate course of therapy with a corticosteroid and/or an immunosuppressant; or who are intolerant to or have medical contraindications for such therapies. b) In patients with fistulising, active CD who have not responded despite a full and adequate course of conventional treatment (including antibiotics, drainage and immunosuppressive therapy). 3) Paediatric CD Severe, active CD in patients aged 6 to 17 years, who have not responded to conventional therapy including corticosteroid, immunomodulator and primary nutrition therapy; or who are intolerant to or have contraindications for such therapies. 4) Ulcerative colitis (UC) In both adult patients with moderate to severely active UC, and children and adolescents aged 6 to 17 years with severely active UC and an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or those who are intolerant to, or have medical contraindications for such therapies. 5) Ankylosing spondylitis (AS) In adult patients with severe active AS who have responded inadequately to conventional therapy. 6) Psoriatic arthritis (PsA) In adult patients with active and progressive PsA when response to previous DMARD therapy has been inadequate. Inflectra should be administered in combination with MTX - or alone in patients who show intolerance to MTX, or for whom MTX is contraindicated. 7) Psoriasis (PsO) In adult patients with moderate to severe plaque PsO who failed to respond to, or who have a contraindication to, or are intolerant to systemic therapy including cyclosporine, MTX or Psoralen ultra-violet A (PUVA.) Dosage & Administration: All doses to be administered as an intravenous (IV) infusion over 2 hours initially and monitor post-infusion for at least 1-2 hours for infusion- related reactions. 1) RA 3 mg/kg repeated 2 and 6 weeks after initiation, then every 8 weeks. Inflectra must be given concomitantly with MTX. 2) Moderately to severely active CD 5 mg/kg repeated 2 weeks after initiation. If no response after 2 doses, no additional dose should be given. In responding patients: Maintenance dose of 5 mg/kg at 6 weeks after the initial dose, followed every 8 weeks, or: Readministration of 5 mg/kg if signs and symptoms recur. 3) Fistulising, active CD 5 mg/kg repeated 2 and 6 weeks after initiation. If no response after 3 doses, no additional dose should be given. In responding patients: Maintenance dose of 5 mg/kg every 8 weeks or: Re-administration of 5 mg/kg if signs and symptoms recur, followed by 5 mg/kg every 8 weeks. 4) UC 5 mg/kg repeated 2 and 6 weeks after initiation, then every 8 weeks. 5) AS 5 mg/kg repeated 2 and 6 weeks after initiation, then every 6 to 8 weeks. If no response by 6 weeks, no additional dose should be given. 6) PsA 5 mg/ kg repeated at 2 and 6 weeks after initiation, then every 8 weeks. 7) PsO 5 mg/kg repeated 2 and 6 weeks after initiation, then every 8 weeks. If no response after 14 weeks no additional dose should be given. 8) Paediatric CD (6 to 17 years): 5 mg/kg repeated 2 and 6 weeks later, then every 8 weeks. Data do not support further treatment in children and adolescents not responding within the first 10 weeks. 9) Paediatric UC (6 to 17 years): 5 mg/kg repeated at 2 and 6 weeks, then every 8 weeks. Available data do not support further treatment in in patients not responding within the first 8 weeks. Older people (≥ 65 years): Studies have not been conducted. No major age-related
differences in clearance or volume of distribution observed in clinical studies. No dose adjustment is required. Impaired renal and/or hepatic function: Not studied. No dose recommendations can be made. Contraindications: Hypersensitivity to infliximab, to other murine proteins, or to any excipients. Tuberculosis (TB) or other severe infections such as sepsis, abscesses, and opportunistic infections. Moderate or severe heart failure (NYHA class III/IV). Warnings and Precautions: Caution in patients with or at risk of infusion reactions and hypersensitivity. Do not administer in patients with bacterial infections, invasive fungal, viral or other opportunistic infections. Monitor for TB, and do not use in patients with TB. Test for latent/active TB prior to initiation of therapy. Do not use Inflectra in patients with active TB. In patients with latent TB, treatment with anti-TB therapy must be started before the initiation of Inflectra, and in accordance with local recommendations. Consult a physician with expertise in the treatment of TB. Monitor closely for infections, including TB before, during and for six months post-treatment. Patients with fistulising CD with acute suppurative fistulas must not initiate therapy until source of infection, specifically abscess, is excluded. Test for HBV infection before initiating treatment. For patients who test positive, consult a physician with expertise in the treatment of hepatitis B. Closely monitor carriers of HBV for signs and symptoms of active HBV infection during and after therapy. In patients with HBV reactivation, stop Inflectra and initiate effective antiviral therapy with supportive treatment. Symptoms or signs of liver dysfunction should be evaluated for evidence of liver injury. If jaundice and/or ALT elevations ≥5 times the upper limit of normal develop(s), stop Inflectra and initiate thorough investigation. Concurrent administration of Inflectra with anakinra, abatacept or other biologic therapeutics is not recommended due to possible increased risk of infection and/or other potential pharmacological interactions. Live vaccines or therapeutic infectious agents should not be used concurrently with Inflectra. Patients should continue to be monitored while switching from one biologic to another. If a patient develops symptoms suggestive of lupus-like syndrome following treatment with Inflectra and is positive for antibodies against double stranded DNA, discontinue Inflectra treatment. In patients with preexisting or recent onset of demyelinating disorders (including multiple sclerosis and Guillain Barré syndrome), the risk/benefit of anti-TNF treatment should be carefully considered before initiation of Inflectra. Discontinuation of Inflectra should be considered if these disorders develop. Caution should be exercised in considering treatment of patients with increased risk for malignancy or when considering treatment in patients that develop a dysplasia or a malignancy or with previous history of malignancy. Caution should also be exercised in patients with psoriasis and a medical history of extensive immunosuppressant therapy or prolonged PUVA treatment. Potential risk of development of hepatosplenic T-cell lymphoma (HSTCL) when used in combination with AZA or 6-MP, especially in adolescents and young adult males with CD or UC. Periodic skin examination is recommended, particularly for patients with risk factors for skin cancer. Patients with UC who are at increased risk or prior history of dysplasia for dysplasia or colon carcinoma should be screened for dysplasia (including colonoscopy and biopsies) at regular intervals before therapy and throughout their disease course. Use with caution and monitor closely in mild heart failure (NYHA class I/II). Discontinue Inflectra treatment in patients who develop new or worsening symptoms of heart failure. Patients should be advised to seek immediate medical attention if they develop signs and symptoms suggestive of blood dyscrasias. Discontinuation of Inflectra should be considered in patients with confirmed significant haematologic abnormalities. For patients that require surgery, Inflectra long half-life should be taken into account and should be monitored for infections. Special populations: Risk of infections should be considered when treating elderly and paediatric patients. If possible, comply
Change your perspective. Choose INFLECTRA™.
with vaccination program for paediatric patients prior initiating treatment with Inflectra. Women of childbearing potential: Use adequate contraception to prevent pregnancy and continue its use for at least 6 months after the last Inflectra treatment. Pregnancy: Administration of infliximab is not recommended during pregnancy. Breast feeding: Unknown whether infliximab is excreted in human milk or absorbed systemically after ingestion. As human immunoglobulins are excreted in milk, women must not breast feed for at least 6 months after Inflectra treatment. Undesirable effects: Viral infection (e.g. influenza, herpes virus infection), bacterial infection (e.g. sepsis, cellulitis, abscess), TB, fungal infection (e.g. candidiasis), meningitis, opportunistic infection, parasitic infection, hepatitis B reactivation, vaccine breakthrough infection, lymphoma, non-Hodgkin’s lymphoma, Hodgkin’s disease, leukaemia, melanoma, cervical cancer, hepatosplenic T-cell lymphoma, Merkel cell carcinoma, neutropenia, leucopenia, anaemia, lymphadenopathy, thrombocytopenia, lymphopenia, lymphocytosis, agranulocytosis, thrombotic thrombocytopenic purpura, pancytopenia, haemolytic anaemia, idiopathic thrombocytopenic purpura, allergic respiratory symptom, anaphylactic reaction/shock, lupus-like syndrome, serum sickness like reaction, vasculitis, sarcoid-like reaction, depression, insomnia, amnesia, agitation, confusion, somnolence, nervousness, apathy, headache, vertigo, dizziness, hypoaesthesia, paraesthesia, seizure, neuropathy. transverse myelitis, demyelinating disorders, conjunctivitis, keratitis, periorbital oedema, hordeolum, endophthalmitis, transient visual loss, tachycardia, palpitation, cardiac failure, arrhythmia, syncope, bradycardia, cyanosis, pericardial effusion, myocardial ischaemia/ infarction, hypotension, hypertension, ecchymosis, hot flush, flushing, peripheral ischaemia, thrombophlebitis, haematoma, circulatory failure, petechia, vasospasm, upper respiratory tract infection, sinusitis, lower respiratory tract infection, dyspnoea, epistaxis, pulmonary oedema, bronchospasm, pleurisy, pleural effusion, interstitial lung disease, abdominal pain, nausea, gastrointestinal haemorrhage, diarrhoea, dyspepsia, gastroesophageal reflux, constipation, intestinal perforation/stenosis, diverticulitis, pancreatitis, cheilitis, hepatic function abnormal, transaminases increased, hepatitis, hepatocellular damage, cholecystitis, jaundice, liver failure, psoriasis (new onset or worsening), urticaria, rash, pruritus, hyperhidrosis, dry skin, fungal dermatitis, eczema, alopecia, bullous eruption, onychomycosis, seborrhoea, rosacea, skin papilloma, hyperkeratosis, abnormal skin pigmentation, Toxic Epidermal Necrolysis, Stevens Johnson syndrome, erythema multiforme, furunculosis, worsening of symptoms of dermatomyositis, arthralgia, myalgia, back pain, urinary tract infection, pyelonephritis, vaginitis, infusion related reaction, pain, chest pain, fatigue, fever, injection site reaction, chills, oedema, impaired healing, granulomatous lesion, autoantibody positive, complement factor abnormal. Legal category: POM; S1A Marketing Authorisation Number: EU/1/13/854/001, EU/1/13/854/002, EU/1/13/854/003, EU/1/13/854/004, EU/1/13/854/005. Marketing Authorisation Holder: Hospira UK Limited, Queensway, Royal Leamington Spa, CV31 3RW, UK. Last Revised: August 2016. Ref: IF 1_0 IE. ▼ This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for how to report adverse reactions. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at EUMEDINFO@pfizer.com. For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 467650.
References: 1. INFLECTRA™. European Public Assessment Report (EPAR). June 2013. Available at: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Summary_for_the_public/human/002778/WC500151491.pdf. [Accessed June 2016] PP-IFA-IRL-0018 October 2016
14 News Prescribers and Pharmacists to draw up Cannabis guidance Dr Mairín Ryan, Director of Health Technology Assessment, HIQA
has now announced a pivotal step in the progress towards operationalising this initiative. The HPRA review concluded that a cannabis access programme could include access to cannabisbased therapies for the treatment of patients with: Following the Minister for Health’s publication of the Health Products Regulatory Authority’s (HPRA) report ‘Cannabis for Medical Use – A Scientific Review’ earlier this year, and his announcement that he will establish a Cannabis Access Programme for cannabisbased treatments for qualifying patients, Minister Simon Harris
• Spasticity associated with multiple sclerosis resistant to all standard therapies and interventions whilst under expert medical supervision; • Intractable nausea and vomiting associated with chemotherapy, despite the use of standard anti-emetic regimes whilst under expert medical supervision;
• Severe, refractory (treatmentresistant) epilepsy that has failed to respond to standard anticonvulsant medications whilst under expert medical supervision. As noted by the HPRA in their review, there is an absence of scientific data demonstrating the effectiveness of cannabis products and the safety of cannabis as a medical treatment is not well characterised. Given these concerns, it is particularly important that the planned Cannabis Access Programmes draws on the expertise of medical specialists who are responsible for the management of the patient groups listed above. Consequently, a critical focus of the Department’s work in setting-up the Cannabis Access Programme has been engagement with clinicians, patients and pharmacists who will be central to the drawing up of guidelines on the safe use of cannabis for those patients who
will be prescribed cannabis-based treatments through the Cannabis Access Programme. The Expert Reference Group will be chaired by Dr Mairín Ryan, Director of Health Technology Assessment at the Health Information and Quality Authority (HIQA). The group comprises representation from the areas of Oncology, Palliative care, Anaesthesiology, General Practice, Adult Neurology, Paediatric Neurology, Multiple Sclerosis, Psychiatry, Pharmacy, Patients, Ethics, Health Technology Assessment, Health Products Regulator. The Reference Group convened at the end of last month to commence work on drafting guidelines, in line with National Standards for Clinical Practice Guidance Development, to facilitate the prescription and supply of medicinal cannabis to qualifying patients.
HIV transmissions still occurring across Europe Figure 1
Among the main proposals for effective antenatal screening are: • Testing for HIV, syphilis and hepatitis B during the first trimester of pregnancy.
However, children are still being born with these infections in the EU/EEA. For example, 424 congenital syphilis infections and 274 HIV infections were reported in children born between 2010 and 2014. In its evidence-based guidance, ECDC aims to help Member States to strengthen antenatal screening in the general population and in particular among vulnerable groups for MTCT.
Transmission of infections with HIV, hepatitis B, syphilis or rubella from mother to child before and during birth as well as in infancy still occur across Europe - despite existing prevention methods. A new ECDC report outlines the cornerstones for effective antenatal screening programmes across the EU/EEA countries. April 2017 • HPN
Each year, more than five million live births are recorded in the European Union. Almost as many pregnant women are screened for infections - namely for HIV, syphilis, hepatitis B and rubella susceptibility - in order to prevent possible mother-to-child transmission (MTCT).
The guidance looks at which elements of a national antenatal screening programme for infections influence effectiveness, and which are the specific approaches to be used for reaching the vulnerable groups in order to increase the uptake of prenatal care and reduce mother-to-child transmission. The guidance is accompanied by two technical reports of literature reviews.
• Repeat testing offer during the third trimester for pregnant women at increased risk of infection and/or for those who previously refused testing. • Testing at delivery to women who had not previously been tested. • For HIV and syphilis in particular, a universal approach should be considered for the antenatal screening, which means voluntary testing for all pregnant women with an opt-out possibility. To improve the uptake of antenatal testing among vulnerable groups like migrant women or women at higher risk for infections due to injecting drug use or those engaging in high risk sexual practices, several options may be considered. This includes addressing communication barriers regarding language, literacy levels, or individual or cultural specifics, and improving access to antenatal care through outreach services and informal networks can help.
multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis. Basic NHS costs: Tivicay is a registered trademark of the ViiV Healthcare Group of Companies : August 2015 Zinc code: UK/DLG/0055/13(7) 30 tablets: £798.16 EU/1/14/940/001. MA holder: ViiV HealtBUILD hcare UK Ltd, A980 GrREGIMEN eat Date of approvalWITH West Road, Brentford, Middlesex TW8 DOLUTEGRAVIR 9GS. Further information is available from References: 1. Walmsley S et al. J Acquir Immune Defic Syndr. 2015;70(5):515-519. Customer Contact Centre, GlaxoSmithAT Kline UK Ltd, StockleyTHE Park West, Uxbridge, 2. MolCORE ina J-M et al. Lancet HIV. 2015;2(4):e127-e136. 3. Orrel C et al. Presented at: Annual Middlesex UB11 1BT. THE ONLY INI THAT International AIDOFFERS: S Conference; July 18-22, 2016; Durban, South Africa. Abstract THAB0205LB. 4. Raffi F et al. Lancet Infect Dis. 2013;13(11):927-935. 5. TIVICAY (dolutegravir) POM S1A Summary of Product Characteristics. Available from: www.medicines.ie, accessed: Triumeq is a registered trademark of the ViiV Healthcare Gro+up of Companies September 2016. 6. +Triumeq (dolutegravir/avacavir/lamivudine) Summary of Product Date of approval: July 2016 Zinc code: UK/TRIM/0037/14(5) Characteristics. Available from: www.medicines.ie, accessed: September 2016. STATISTICALLY SUPERIOR EFFICACY
HIGH BARRIER TO RESISTANCE
in treatment-naïve patients vs EFV/TDF/FTC, darunavir/r and atazanavir/r (in women) 1-3
0 resistance to dolutegravir-based regimens in treatment-naïve trials to date1-5
with few clinically signiﬁcant drug-drug interactions5
For your treatment-naïve patients and for patients who may benefit from a change in ART regimen, CHOOSE...
Adverse events should be reported. For the UK, reporting forms and information can be found at www.mhra.gov.uk/yel owcard. Adverse events should also be reported to GlaxoSmithKline on 0800 221 441. dolutegravir/abacavir/ lamivudine
TRIUMEQ is indicated for the treatment of HIV-infected adults and adolescents above 12 years of age weighing at least 40 kg. Before initiating treatment with abacavir-containing products, HLA-B*5701 status must always be documented. Abacavir should not be used in patients known to carry the HLA-B*5701 allele due to the risk of hypersensitivity reaction. TIVICAY is indicated in combination with other antiretroviral medicinal products for the treatment of HIV-infected adults and adolescents above 12 years of age. Triumeq and Tivicay are contraindicated: in patients with hypersensitivity to dolutegravir, abacavir or lamivudine or to any of the excipients, and with co-administration with dofetilide.5,6
Adverse events should be reported. For Ireland, adverse events should be reported directly to the HPRA; Fre post, Pharmacovigilance Section, Health Products Regulatory Authority, Earlsfort Ter ace, Dublin 2, Tel: +353 1 676 4971, firstname.lastname@example.org. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255.
These medicinal products are subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. Prescribing Information Triumeq® dolutegravir 50mg/abacavir 600mg/lamivudine 300mg tablets See Summary of Product Characteristics before prescribing. Indication: HIV in over 12 years and ≥ 40kg. Screen for HLA-B*5701 prior to use. Do not use if HLA-B*5701 positive. Dose: one tablet once daily with or without food. Elderly: Limited data in 65+ yrs. Creatinine clearance <50ml/min or moderate/severe hepatic impairment: Not recommended. Contraindications: Hypersensitivity to any ingredient. Co-administration with dofetilide. Warnings/precautions: Both abacavir and dolutegravir are associated with risk of hypersensitivity reactions (HSR). Do not initiate in HLA-B*5701+ or previous suspected abacavir HSR. Stop Triumeq without delay if HSR suspected. Never reintroduce any dolutegravir- or abacavir-containing product after suspected HSR. Risks of immune reactivation syndrome, osteonecrosis, increased weight, lipids, glucose. Monitor LFTs in Hepatitis B/C co-infection. Inconclusive data on relationship between abacavir and MI; minimise all modifiable CV risk factors (e.g. smoking, hypertension, hyperlipidaemia). Not recommended if dolutegravir required b.d. (with etravirine [without boosted PI], efavirenz, nevirapine, rifampicin, boosted tipranavir, carbamazepine, oxcarbazepine, phenytoin, phenobarbital and St John’s Wort). Use with cladribine not recommended. Use with Mg/Al-containing antacids, calcium, multivitamins or iron requires dosage separation. Caution with metformin: monitor renal function and consider metformin dose adjustment. Pregnancy/lactation: Not recommended. Avoid breast-feeding. Side effects: See SPC for details. Headache, insomnia, sleep/dream disorders, GI disturbance, fatigue, hypersensitivity, anorexia, depression, dizziness, somnolence, lethargy, malaise, cough, nasal symptoms, rash, pruritus, alopecia, arthralgia, muscle disorders, asthenia, fever, elevations of ALT, AST and CPK, blood dyscrasias, suicidal ideation or suicide attempt, rhabdomyolysis, lactic acidosis, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis. Basic NHS costs: 30 tablets: £798.16 EU/1/14/940/001. MA holder: ViiV Healthcare UK Ltd, 980 Great West Road, Brentford, Middlesex TW8 9GS. Further information is available from Customer Contact Centre, GlaxoSmithKline UK Ltd, Stockley Park West, Uxbridge, Middlesex UB11 1BT.
dolutegravir 50mg tablets Tivicay® See Summary of Product Characteristics before prescribing Indication: HIV in >12 years and ≥40kg as part of combination therapy. Dosing: 50mg once daily with or without food if no proven/suspected integrase resistance. 50mg twice daily with efavirenz, nevirapine, tipranavir/ritonavir, etravirine (without boosted PI), carbamazepine, oxcarbazepine, phenytoin, phenobarbital, St John’s Wort or rifampicin. Adults with proven/suspected integrase resistance: 50mg twice daily preferably with food. Elderly: Limited data in 65+ yrs. Caution in severe hepatic impairment. Contraindications: Hypersensitivity to any ingredient. Co-administration with dofetilide. Warnings/precautions: Risk of hypersensitivity reactions. Discontinue dolutegravir and other suspect agents immediately if suspected. Risks of osteonecrosis, immune reactivation syndrome. Monitor LFTs in Hepatitis B/C co-infection and ensure effective Hepatitis B therapy. Caution with metformin: monitor renal function and consider metformin dose adjustment. Use with etravirine requires boosted PI or increased dose of dolutegravir. Use with Mg/Al-containing antacids, calcium, multivitamins or iron requires dosage separation. Pregnancy/ lactation: Not recommended. Avoid breast-feeding. Side effects: See SPC for full details. Headache, GI disturbance, insomnia, abnormal dreams, depression, dizziness, rash, pruritus, fatigue, elevations of ALT, AST and CPK, hypersensitivity, suicidal ideation or suicide attempt. Basic NHS costs: 30 tablets £498.75 EU/1/13/892/001. MA holder: ViiV Healthcare UK Ltd, 980 Great West Road, Brentford, Middlesex TW8 9GS. Further information available from Customer Contact Centre, GlaxoSmithKline UK Ltd, Stockley Park West, Uxbridge, Middlesex UB11 1BT.
TRIUMEQ and TIVICAY are registered trademarks of the ViiV Healthcare group of companies. ©2016 ViiV Healthcare group of companies All rights reserved.
Triumeq is a registered trademark of the ViiV Healthcare Group of Companies Date of approval: July 2016 Zinc code: UK/TRIM/0037/14(5)
POM S1A Tivicay is a registered trademark of the ViiV Healthcare Group of Companies Date of approval: August 2015 Zinc code: UK/DLG/0055/13(7)
Date of preparation: September 2016 IE/DGR/0016/16
References: 1. Walmsley S et al. J Acquir Immune Defic Syndr. 2015;70(5):515-519. 2. Molina J-M et al. Lancet HIV. 2015;2(4):e127-e136. 3. Orrell C et al. Presented at: Annual International AIDS Conference; July 18-22, 2016; Durban, South Africa. Abstract THAB0205LB. 4. Raffi F et al. Lancet Infect Dis. 2013;13(11):927-935. 5. TIVICAY (dolutegravir) Summary of Product Characteristics. Available from: www.medicines.ie, accessed: September 2016. 6. Triumeq (dolutegravir/avacavir/lamivudine) Summary of Product Characteristics. Available from: www.medicines.ie, accessed: September 2016.
Adverse events should be reported. For the UK, reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to GlaxoSmithKline on 0800 221 441.
Adverse events should be reported. For Ireland, adverse events should be reported directly to the HPRA; Freepost, Pharmacovigilance Section, Health Products Regulatory Authority, Earlsfort Terrace, Dublin 2, Tel: +353 1 676 4971, email@example.com. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255. TRIUMEQ and TIVICAY are registered trademarks of the ViiV Healthcare group of companies. ©2016 ViiV Healthcare group of companies All rights reserved.
Date of preparation: September 2016 IE/DGR/0016/16
10/19/2016 1:42:14 PM
16 Clinical Synopsis
European Cancer Congress The 2017 European Cancer Congress took place at the start of this year in Amsterdam. ECCO2017 is the only truly multidisciplinary oncology Congress in Europe which gives delegates the most recent developments in monodisciplines from a multidisciplinary perspective with evidence of how these developments impact clinical practice . There were numerous educational programmes developed by a leading team of experts alongside hot discussions on the cost and organisation of cancer care in Europe. Below are some of the key research and clinical findings which arose from the event. Diabetes - early warning sign for pancreatic cancer Patients and their doctors should be aware that the onset of diabetes, or a rapid deterioration in existing diabetes that requires more aggressive treatment, could be a sign of early, hidden pancreatic cancer, according to research presented. Ms Alice Koechlin, from the International Prevention Research Institute in Lyon, France, told the meeting that an analysis linking nearly a million patients with type 2 diabetes in Lombardy (Italy) and Belgium with recorded cases of pancreatic cancer showed that 50% of all pancreatic cancers cases in the two regions were diagnosed within one year of patients being diagnosed with type 2 diabetes and being given their first prescription to control it. “In Belgium 25% of cases were diagnosed within 90 days and in Lombardy it was 18%. After the first year, the proportion of diagnosed pancreatic cancers dropped dramatically,” she said. The researchers found that compared with patients who were able to continue with oral anti-diabetic drugs, patients in Belgium and in Lombardy had a 3.5-fold greater risk of being diagnosed with pancreatic cancer in the first three months after their first prescription for incretins (metabolic hormones that stimulate the pancreas to produce more insulin to lower blood glucose levels); this fell to a 2.3-fold risk in the next three to six months, to a two-fold risk for the next six to 12 months and 1.7-fold risk after the first year. Among patients who already had type 2 diabetes and were managing it with oral anti-diabetic drugs, the switch to incretins or insulin happened faster among diabetic patients who were subsequently diagnosed with pancreatic cancer. In addition, a deterioration in their condition that necessitated them being switched to more aggressive anti-diabetic therapy with injections of insulin was associated with a seven-fold increased risk of being diagnosed with pancreatic cancer. Ms Alice Koechlin, Professor Philippe Autier (also from the International Prevention Research Institute) and colleagues in Belgium and Italy used prescription data to identify 368,377 patients with type 2 diabetes in Belgium between 2008 and 2013 and 456,311 patients in Lombardy between 2008 and 2012. The data were linked to pancreatic cancer cases in the Belgian Cancer Registry and the hospital discharge databases in Lombardy. There were 885 and 1,872 cases of pancreatic cancer diagnosed during this time in Belgium and Lombardy respectively. “There is currently no good, non-invasive method for detecting pancreatic cancer that is not yet showing any visible signs or symptoms. We hope that our results will encourage the search for blood markers indicating the presence of pancreatic cancer, which could guide decisions to perform a confirmation examination like endoscopy,” said Ms Koechlin. Pancreatic cancer is one of the most lethal cancers, partly because it is difficult to detect at an early stage and because there are few effective treatments for it. Less than one per cent of people live for ten or more years after a diagnosis. In Europe around 104,000 new cases were diagnosed in 2012 and approximately the same number of people died from it. Worldwide there were an estimated 338,000 cases of pancreatic cancer diagnosed in 2012 and 330,000 people died from it. Some early stage breast cancer patients may benefit more from breast conserving therapy than from mastectomy Breast conserving therapy (BCT, breast conserving surgery combined with radiation therapy) is superior to mastectomy in certain types of breast cancer patients, according to results from the largest study to date presented to the Congress. Professor Sabine Siesling, from the Netherlands Comprehensive Cancer Organisation (IKNL) and University of Twente and Mirelle Lagendijk, MD, from the Department of Surgical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands, and colleagues from other hospitals, studied survival nationwide in nearly 130,000 breast cancer patients, divided into two groups: those diagnosed between 1999-2005 and those diagnosed between 2006-2012. The patients selected from the Netherlands Cancer Registry had no metastases (spread of the cancer to organs other than the lymph nodes close to the tumour). To obtain information on cause of death, data were linked to the cause of death register. Although randomised trials initiated in the 1980s have shown equal survival outcomes for BCT and mastectomy, trials often exclude elderly patients or patients with existing disease other than breast cancer (comorbidity). Studies with large, population-based groups, including comorbidity and those who are elderly, can add to the knowledge based on these trials and provide outcome that is more widely applicable and reflect daily practice. Several recent population-based studies showed a survival advantage for BCT. However, these studies tended to lack long-term follow-up, evaluated limited patient numbers, had differences in April 2017 • HPN
Professor Sabine Siesling, Netherlands Comprehensive Cancer Organisation
MSc (Health Economics)
Choose NUI Galway for an MSc (Health Economics) and you will gain far more than just a qualification. Our program was developed in response to industry needs and is delivered by enthusiastic, research-active faculty. Applications from people with experience in the pharmaceutical industry or the health care system are especially welcome. Applicants without a background in economics will be offered an opportunity to take a course in economics before starting the programme. Working professionals can complete the program on a part-time basis over a two year period.
Find out more: firstname.lastname@example.org www.nuigalway.ie/health-economics
18 Clinical Synopsis medication after surgery between both groups and lacked the data on cause of death that are needed to evaluate breast cancer-specific survival. All this could have led to the introduction of confounding factors such as severity of disease or death due to other causes, the researchers say. In the current study, a number of prognostic factors such as age, stage, comorbidity, hormonal receptor and HER2 status , and differences in systemic treatments (medication after surgery) were included and considered as possible explanations for the previously reported survival differences between BCT and mastectomy. This enabled the identification of possible prognostic factors that might, in future, predict which patients could benefit most from BCT. To identify patients who could possibly benefit most from BCT, both time cohorts were divided into subgroups. Evaluation of T1-2N0-1M0 cancers, which are at a stage when metastasis to distant organs has not yet occurred, in both groups showed a considerable advantage for BCT in patients with increasing age, those with comorbidity, and those who did not receive chemotherapy. The immunotherapy, pembrolizumab, is active against mucosal melanoma tumours and prolongs survival for patients with bladder cancer Clinical trials of a new immunotherapy, pembrolizumab, have shown that it prolongs life significantly for patients with bladder cancer and is active against a rare sub-type of melanoma, called mucosal melanoma. The findings were presented in two presentations at the Congress. Reporting the results from three trials of pembrolizumab for patients with advanced melanoma, Dr Marcus Butler, a medical oncologist at the Princess Margaret Cancer Centre, Toronto, Canada, told ECCO2017 that 84 of the 1567 patients in the KEYNOTE-001, 002 and 006 studies had advanced mucosal melanoma. “Sixteen of these patients (19%) responded to treatment with pembrolizumab, of whom 12 are still alive without their disease progressing and, so far, the longest time some of these patients have continued to be successfully treated is more than 27 months,” he said. Of the 1483 patients in these KEYNOTE trials who had other forms of advanced melanoma and who received at least one dose of pembrolizumab, 33% responded to the treatment, 72% were still alive without their disease progressing and the median (average)  overall survival time was nearly two years. Median overall survival for patients with mucosal melanoma was 11.3 months.
Dr Marcus Butler, Medical Oncologist, Princess Margaret Cancer Centre, Toronto
“Immunotherapy for melanoma has revolutionised treatment of the disease. There are some patients with mucosal melanoma who have had complete responses to pembrolizumab and essentially return to a normal life. Some, of course, have less spectacular responses, but they still benefit from therapy. In earlier studies, mucosal melanoma was excluded since it is a rare subtype. These findings suggest that mucosal melanoma patients should be offered immunotherapy as standard of care and not excluded. Response rates may be a bit lower than for other types of melanoma, so further studies to improve benefit need to be conducted.” In the KEYNOTE trials, 70% of the mucosal melanoma patients with known PD-L1 status had PD-L1 positive tumours. Ninety per cent of the mucosal melanoma patients had already received at least one prior treatment and 39% of them had received ipilimumab, a type of monoclonal antibody that is already used in the treatment of melanoma. Patients in the KEYNOTE trials received pembrolizumab intravenously at doses of 2 mg/kg or 10 mg/kg every three weeks, or 10 mg/kg every two weeks. In a second, late-breaking presentation, Dr Andrea Necchi, attending physician in the Department of Medical Oncology at the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, said results from the phase III KEYNOTE-045 trial showed that treatment with pembrolizumab resulted in longer overall survival with fewer side-effects for patients with previously treated advanced bladder (urothelial) cancer compared with patients given chemotherapy. He said, “KEYNOTE-045 is a landmark study. It represents a real advance in the second-line treatment of advanced bladder cancer because pembrolizumab is the first therapy to show a significant survival advantage over chemotherapy for these patients.” He said survival and response benefits for pembrolizumab were seen regardless of the levels of PD-L1 expression. Delays in access to new cancer medicines and unjustifiable price rises for old ones disadvantage patients unnecessarily Cancer patients are living longer and in many cases the disease is becoming chronic rather than acute. Access to drugs that help extend life and improve quality of life, and fair prices for those drugs are therefore essential for more and more people. But patients are badly served in this respect, with delays in the availability of new treatments and incomprehensible price rises for well-established therapies, including generics, researchers told the Congress. There is no value for patients if new cancer drugs are developed and approved but they are unable to benefit from them, says Markus Hartmann PhD, Principal Consultant of European Consulting and Contracting in Oncology, a regulatory affairs consultancy based in Trier, Germany. Approval decisions for cancer drugs are currently granted centrally by the European Commission, in order to ensure that risk/benefit judgments are applied on the same basis across the European Union. But decisions
April 2017 • HPN
Markus Hartmann, PhD, Principle Consultant, European Consulting and Contracting
19 on reimbursement and pricing, and therefore on access to new medicines, are taken at individual EU Member State level, and this results in major differences in the overall availability as well as the time taken before patients are able to obtain new medicines, adds co-author Daniel Dröschel, Market Access Consultant at MArS Market Access & Pricing Strategy GmbH, Weil am Rhein (Germany). The researchers studied approval processes for the 48 new cancer drugs that were evaluated between 201115 by the European Medicines Agency for use in the European Union. In 17 cases, approvals were based on a principal trial using overall survival  as the primary endpoint; in 19 cases on trials using progression-free survival ; and in 12 cases on trials – most often single-arm trials – using overall response rate  as primary endpoints. “These new drugs all show clinical benefit,” says Dr Hartmann. “Our data indicate in the overall survival group a median survival gain of 3.0 months, while in the progression-free survival group the median gain was 3.8 months. However, the trial design, trial endpoint and magnitude of effect is evaluated quite differently by the health technology assessment (HTA) authorities in the UK, France and Germany, even though they reviewed the same, or very similar, clinical data.”
Dr Andrew Hill, Senior Research Fellow, Department of Pharmacology and Therapeutics, University of Liverpool
These disparities in national HTA outcomes depend on a number of factors. Additionally, HTAs use different methodologies in their assessments: France, as well as the UK’s National Institute for Clinical Excellence (NICE) and the Scottish Medical Council, apply health economics that have an impact on the final reimbursement decision, whereas Germany relies purely on a benefit assessment followed by price negotiations. “In our study, in France and Germany around 80% of decisions were positive, whereas for UK’s NICE, every third assessment ended with a negative outcome,” Dr Hartmann will say. Patients’ access to new cancer drugs in England and Wales is also hampered by laterdecision-making compared with Scotland, France and Germany, he adds. In a second presentation, Dr Andrew Hill, Senior Research Fellow in the Department of Pharmacology and Therapeutics, University of Liverpool, UK, will tell the congress that UK prices for cancer drugs, including generics, have recently shown a sharp rise. Between 2011 and 2016, prices for some common drugs increased by more than 1000%. At a time when the UK Cancer Drugs Fund is being re-examined because of the pressure caused by high prices, this is particularly worrying, says Dr Hill. “We were surprised to find several companies consistently raising the prices of cancer treatment. Twenty treatments have shown rises of over 100% in the last five years, and in two – busulfan (used to treat leukaemia) and tamoxifen (breast cancer) – prices have increased by over 1000%. We have found that some companies take over the supply of some generic cancer medicines and then raise the price progressively,” Dr Hill will say. In the UK, the Department of Health is aware of this issue and has introduced the Health Services Medical Supplies (Costs) Bill in order to be able to regulate prices in the future, he says. Companies found to be raising prices with no clear justification will be referred to the Competition and Markets Authority, and could face fines. Paying these high prices puts undue strain on health systems, and the long-term result could be negative consequences for disease progression and survival. The researchers say that they are finding similar cases in other European countries. In Spain and Italy, failure to accept the high prices demanded for some generic treatments has led to warnings from companies that they could stop their supply. “We hope that, by explaining what we have found in the UK, other European countries will take note and protect themselves against these kinds of price rises,” says Dr Hill. “At a time when cancer patients are living longer and better lives due to effective treatments, this situation is particularly worrying.” Ms Melissa Barber, from the London School of Hygiene and Tropical Medicine, London, UK, will describe to the congress the results of her analysis of the manufacturing costs of all the medicines used to treat cancer included in the World Health Organisation’s (WHO’s) Essential Medicines List. The results show that several key cancer treatments could be manufactured for less than one per cent of the prices charged in the US and UK. “For example, tamoxifen, used to treat breast cancer, can be manufactured for less than two US dollars per month of treatment, and imatinib, used in the treatment of chronic myeloid leukaemia, can be produced for $54 per month,” Ms Barber will say. Costs this low could form the initial step in setting up programmes in low and middle income countries for the mass treatment of certain cancers, following the successful precedent of mass treatment for HIV and AIDS. The researchers would like to see the expansion of pilot studies for such treatments; such pilots exist already for cancer treatment in Rwanda and Haiti. “Showing that certain cancers could be treated for very low prices could transform the future of people with these cancers in very low-income countries where there are usually few or no treatment options,” Ms Barber will conclude. Professor Ian Banks, ECCO Board Member and chair of the Patient Advisory Committee, who was not involved with the research, commented: “Research presented at the ECCO Congress covers the whole of the cancer field, including important policy issues like those raised in these abstracts. The availability and pricing of treatments are of great interest and concern to cancer patients, and we consider it important to encourage the widest possible debate on them, as well as on other issues that affect patients’ quality of life.”
We hope that, by explaining what we have found in the UK, other European countries will take note and protect themselves against these kinds of price rises HPN • April 2017
Falsified Medicines Directive - Supply chain interoperability in support of safer medication usage The Pharmacy Domain of Integrating the Health Enterprise (IHE) has published an educational article describing how interoperability can support the effort against falsified medicines. ‘Falsified Medicines Directive - Supply chain interoperability in support of safer medication usage’ explains how the standard interoperability architecture for the supply of healthcare products of IHE could help to monitor the supply chain and support the enforcement of the Falsified Medicines Directive. Falsified Medicines Falsified medicines are a growing economical and health problem, and it deserves the attention of organisations at highest level. Monitoring the supply chain of medicinal products can help ensure that these falsified products do not enter the circuit. IHE provides a standard interoperability architecture for the supply of healthcare products. This effort covers traceability, barcode scanning, message exchange, etc. All of these matters help monitor the supply chain and thus support the enforcement of the Falsified Medicines Directive. This article explains that the requirements of the Falsified Medicines Directive constitute in identifying the medicinal products along the supply chain, and reporting that to a central data hub. Using publicly available message structures helps software solution providers benefit of IHE’s testing opportunities and support a truly interoperable tracking mechanism. Scanning the products poses an operational challenge for users: even for easy barcode scanning, for normal volumes it becomes burdensome. In a medium hospital, the effort of identifying all the received primary packages upon reception would exceed one dedicated professional. For this, it is essential to use standardized AIDC (Automatic Identification and Data Capture) technologies: standard media (e.g. Datamatrix barcodes) and standardized content. Standardised interoperability mechanisms also play a role in this: By providing a standard
April 2017 • HPN
electronic shipment list, the supplier can inform about the content and unique identification numbers included in each shipped carton so that the users may scan the outside package, and the contents of the package are automatically filled into the necessary systems. This article explains how these mechanisms - reporting and shipment content - can enable proper tracing of medicinal products, and when standardised they enable the different actors to do so with reduced effort. Supply chain and traceability as applied to the FMD
• the information can be properly acquired (using standard barcodes that can be read by every party)
To facilitate the integration of the hospital with other systems, and to improve the implementation of the data submission between the hospital and the hub, this interoperability should be done in a standardised manner.
• the content of the barcode is standardized and can be correctly parsed and used.
Every institution should have one standard way of reporting FMD information to its local repository.
The data captured - usually by scanning the barcodes - should then be transmitted to the parties using it. This means that upon the scan of a barcode, the information about that product is then reported to a shared data pool - a hub.
The repositories are conceived to be able to share and cross information among them in a standard manner to ensure continuity of the information.
(Automatic Identification and Data Capture) technologies ensures that
The data must be captured from one Datamatrix. This is intensive This tracking of the items and work, as it could require scanning For the DirectiveThe to berepositories effective, providing the tracking each barcode each sales unit.among th are conceived to bedata able to share and crossofinformation the items must be tracked, and to a central hub is useful for But since the data captured standard manner to ensure continuity of the information. the tracking information must be detecting possible issues, etc., is also conveyed by standard accessible in order to cross-check as preconized in the Falsified interoperability mechanisms, this the tracked items to check the Medicines Directive. Each Member can be facilitated: integrity of the supply chain - track State will implement the local hub the flow of items, detect untraced The data must be captured Datamatrix. This aissupplier intensive work, When packs items as for it could r –connectedfrom to the one central hub, origins, duplicate serial numbers, shipment, this is captured at the and there are companies providing scanning each barcode of each sales unit. But since the data captured is also convey etc. supplier side, and each shipment integration services. standard interoperability mechanisms, this can beis facilitated: individually labelled with a This requires that a few The exchange of information is barcode that identifies that unique mechanisms to When be functioning: thus an essential a supplier packs items formechanism shipment, this isshipment captured at the The supplier container. contentside, and in preventing or detecting the of that container unit is tracked labelled with a barcode that identifies that unique shipment • The medicinalshipment products is individually introduction of illegitimate and can be made available by a packages must bear safety of that The content container unit is tracked and can be made available by a dispatc products in the healthcare dispatch advice - a detailed list of features and should be supplied supply chain. what is shipped. list of what is shipped. with tracking detailed data that enables better identification. • The tracking information must be captured at least at the time they are supplied to the public. o For most products, the FMD does not mandate the tracking information to be captured at each inventory movement; rather that it is captured at least once. o This means retailers, pharmacies, hospital pharmacies • Once captured, the tracking information must be exchanged to the repository. The first mechanism is handled by measures of serialization and standardization in the production process as well as by using overt and/or covert features. The second is made possible by the use of Datamatrix (one form of Automatic Identification and Data Capture (AIDC)). The use standardized AIDC
Figure 1 - Levels of Packaging (Source: GS1) Figure 1 - Levels of Packaging (Source: GS1)
The levels of packaging may vary - what is important is that several items with an id barcode can be packed in a container that is itself identified with a barcode.
The dispatch advice is a declaration of the items that are contained within each ship
Besides presenting the lot number and expiry date in the package, as is common practice, t manufacturer has –according to the Falsified Medicines Directive - to include this informati 21 the product code and the serial component, into one single Datamatrix.: The levels of packaging may vary - what is important is that several items with an identifying barcode can be packed in a container that is itself identified with a barcode. The dispatch advice is a declaration of the items that are contained within each shipment. If this information is transmitted electronically, it can be used to inform the consumer, and the consumer can simply scan the container identifier label to know the content, and does not have to scan each individual package label. This is of course assuming that there is a level of confidence that gives assurance that the content of the container matches the declaration of the vendor.
The vendor assigns 100 boxes of Medication GoodRest Tabs from stock to prep to the hospital (Step 2 in Figure 4). All of these 100 boxes are of the same produ the lot number of all primary packages is 00ABC. The expiry date is also the sam
Each box has a serial number; since the serial numbers of the 100 boxes are no pseudo-randomized, it is impossible to anticipate which numbers will be includ shipment. These are the items reserved to be shipped to the hospital: (box #)
Figure 2 - Datamatrix with serialization (Source: GS1) 1 01234567890123 Figure 2 - Datamatrix with serialisation (Source: GS1)
In terms of interoperability, this means the following requirement:
During normal operation, the hospital issues an order for Medication GoodRest Tabs02.05.2017 - 100 100 … 00123 boxes (Step 1scanned in Figure 4). The hospitalmanufacturer specifieshasthe product byThe using theare manufacturer's co 100 boxes contained in a –according per working day, which A standardized dispatch advice bigger box (tertiary package) as to the Falsified Medicines corresponds to about 13 units The 100 boxes are contained in a bigger box (tertiary package) as illustrated he should be in placeGTIN so that01234567890123. the Directive - to include this illustrated here: to be scanned per minute. As is supplier and customers can simplify, automate and control the delivery of items and the tracking of the delivered items.
evident, only the scanning of the secondary packaging (boxes) is more than a full time job.
information, the product code and the serial component, into one single Datamatrix.:
__________________________________________________________________________ During normal operation, the In addition to this, there are other
This information will be used to:
operational issues like displacing the items for scanning, data entry in the software applications, Rev. 1.0 – 2017-02-08 etc. This makes such barcode scanning impractical. Especially • Scan the shipment container considering that the Directive label and electronically match establishes that such reporting is the shipment notice with its to be done within 10 days content, avoiding having to of reception. open and scan every retail pack upon reception. An interoperable supply chain can improve this: Example: Product reception • Scan the shipment labels to track the shipments;
hospital issues an order for 10 Medication GoodRest Tabs - 100 boxes (Step 1 in Figure 4). The hospital specifies the product Copyright by using the manufacturer's code GTIN 01234567890123.
© 2017: IHE International, Inc Figure 3 - Box with barcode
The vendor assigns 100 boxes of Figure 3 - Box with barcode Medication GoodRest Tabs from This information is submitted to the hub for enabling posterior verification and stock to prepareinaFigure shipment to the 4). information is submitted to hospital (Step 2At inthe Figure 4).this AlldocumentThis end of there is a simplified example of the dispatch advice the hub for enabling posterior of these 100 boxes are the of the contains data in the table above. verification and tracing (Step 3 in same production batch - the lot When the vendor ships items to4). theWhen hospital (Step 4 in Figure the vendor ships4), the receiv number of all primary packages is the Figure (usually theisPharmacy) beitems expected to acknowledge the reception of the the to the hospital (Step 4 in 00ABC. The expiry date also the could Figure 4), the receiving department same - 02/05/2017. (usually the Pharmacy) could be expected to acknowledge Each box has a ________________________________________________________________ serial number; the reception of the since the serial numbers of the 11 100 items. This is the burdensome situation 100 boxes are not Rev. sequential, 1.0 – 2017-02-08 Copyright © 2017: IHE Inte described before: For each of the but pseudo-randomized, it is primary packages received, the impossible to anticipate which hospital must scan and submit to numbers will be included in the hub (Step 7 in Figure 4). the shipment.
For sakeof of example, a vendor,GoodRest Tabs from stock to prepare a shipment The vendor assigns 100 boxes Medication GoodSource Pharmaceuticals, to the hospital (Step 2 in produces Figure Medication 4). All ofGoodRest these 100 boxes are of the same production batch Tabs. It packages it in boxes of the lot number of all primary packages is 00ABC. The expiry date is also the same - 02/05/2017. 20 tablets.
A pioneer hospital with 500 beds scans their items and is piloting of a program to detect and avoid falsified medicines. The hospital must be ready for submitting the data to a regional hub. This requires interoperability to be implemented.
The hospital has the an serial numbers of the 100 boxes are not sequential, but Each box has a serial number; since agreement with a GoodSource pseudo-randomized, it is Pharmaceuticals impossible for tothe anticipate which numbers will be included in the purchase If the hospital consumes about of Medication GoodRest. shipment. 1’400’000 boxes (secondary packaging) of medicinal products each year, this means that about 6’000 items would have to be
Besides presenting the lot number
are the items reserved to be and expiry date shipped in the package, These are the items reserved to be to the These hospital: shipped to the hospital: as is common practice, the
This operation contributes to drastically increasing protection
The 100 boxes are contained in a bigger box (tertiary package) as illustrated here:
HPN • April 2017
This operation contributes to drastically increasing protection against falsification: checking that the items that are dispensed have been correctly declared in a clear supply chain is a final step in a controlled chain of data and materials.
Figure 4 - Example process: ordering, shipment and verification
The shipment is itself identified against falsification: checking that identifier. Upon scanning the Figure 4 - Example process: with a unique identifier. The tertiary the items that are dispensed have shipment ID, the Warehouse ordering, shipment and verification package is also identified with been correctly declared in a clear Management System (WMS) a unique identifier, although this supply chain is a final step in a looks up the content of the is not mandated by the Falsified when controlled chain datainteroperable Withof an supply chain, however, the vendor sends shipment notice and since the items, they notify the Medicines Directive. Since the and materials. there is a match, the ERP gets to the discretion of the hospital that the items have been sentthe- content and indicate, via dispatch advice (StepItcustomer 5is left in Figure 4). , manufacturer declared to decide if individual updated with the received items, With an interoperable supply of the shipment and the content of secondary included packs should not when onlythe the quantity, batch / expiry date, but theincluding detailed listtraceability of the unique numbers their chain, however, vendor the carton in the dispatch advice, be scanned in addition for data (lot/batch number, expiry sends the items, they notify the in the shipment. then the warehouse management conformance testing. date and serial numbers). hospital that the items have been system at the pharmacy is capable This way, with one scan of the sent - and indicate, via dispatch Proper receiving thiswith information. The shipment is itselfof identified a unique identifier. The tertiary package is alsointeroperability identified should outside container, the WMS in advice (Step 5 in Figure 4) - not support continuous control of the the hospital can Falsified acknowledge with batch a unique although this is not mandated by the Medicines If such interoperability exists, only the quantity, / expiryidentifier, items,Directive. not only at the point the reception of the 100 items then the pharmacy simply needs date, but the detailed list of the of reception but anywhere in Since the manufacturer declared the content of the shipment and the contentthe ofcomplete the carton in shipped without scanning them to scan the shipment identifier, unique numbers included in supply and delivery chain. of thethe tertiary package management the shipment. individually. the dispatch advice, and then warehouse system at the pharmacy is capable
receiving this information.
News __________________________________________________________________________ 12
CEO for National Rev. 1.0 – 2017-02-08 Treatment Purchase Fund Copyright © 2017: IHE International, Inc. Mr Liam Sloyan has been appointed as the CEO of the National Treatment Purchase Fund (NTPF), following an open recruitment process administered by the Public Appointments Service. Mr Sloyan takes up this appointment from his current position as the first Regulator of the National Lottery where he established the Office and
April 2017 • HPN
regulated the National Lottery from the commencement of the new National Lottery Licence. Prior to leading this Office, he was Chief Executive of the Health Insurance Authority where he played a key role in the development of the regulatory infrastructure of the health insurance market. Mr Sloyan is a Fellow of the Society of Actuaries in Ireland and a member of its Healthcare
Committee. He holds a M.Sc. in Mathematics and Statistics from University College Dublin. Commenting on the appointment, the Minister added, “Mr Sloyan’s appointment comes at an important time for the NTPF, as the NTPF again takes on a role in the commissioning of patient treatment, in line with commitments in the Programme for a Partnership Government
to reduce waiting times for our longest waiting patients. I look forward to continuing to work with both the Board of the NTPF and with Mr Sloyan and his Executive Team.” The Minister also thanked Mr Jim O’Sullivan who served as acting CEO on a part-time basis for the last four years.
cases per million), and incide significantly) higher in boys than cancers (group II) were the seco group (40 cases per million), aga incidence rates in boys.
appendix have changed recently, but here we have provisionally counted all carcinoids as malignant, in diagnostic group XI.]
The ICCC subdivides childhood cancers into 12 main diagnostic groups, as listed in Table 1. Approximately 2 in every 3 cancers in young children (aged <15 years) were either haematological malignancies (i.e. leukaemia and lymphoma) or tumours of the brain and nervous system (ICCC groups I-III). Although these were also the main cancers in older teenagers, 27% of cancers at ages 15-19 were in the “other epithelial tumours and melanoma” category. The remainder of this report deals with cancer in children aged <15 only, the standard grouping used for most international analyses.
1 National Cancer Trends: Childhood Cancer The latest short report from the National Cancer Registry, notes increases in incidence of childhood cancer between 1994 and 2014, partly reflecting population increases and diagnostic improvements, but ongoing major reductions in mortality. Commenting on the findings, Professor Kerri Clough-Gorr, Director of the National Cancer Registry notes, “Although childhood cancers are thankfully rare, their impact on families is high, and the potential loss of years of life averages much higher than for adult cancers. Monitoring of trends in these cancers is therefore important. “While incidence appears to be increasing, the consensus internationally is that this may, to a large extent, reflect improvements in diagnosis. Treatment improvements have led to marked reductions in mortality from childhood cancer, but further work is needed to follow-up the growing numbers of survivors of childhood cancer, who may experience longterm health consequences related to their cancer treatment.” Between 1994 and 2014 an average of 137 cancers were diagnosed per year in children aged under 15 (Table 1). In older teenagers (15-19 years), an additional 74 cases were diagnosed per year, giving a total of 211 cases per year for ages 0-19 (Table 1).
These figures mostly involve malignant cancers but the International Classification of Childhood Cancer (ICCC), followed in this report, also includes nonmalignant tumours of the brain & nervous (c10% of RI has central published on system childhood cases tabulated here). 1
vering 1994-2011 . To facilitate subdivides childhood mplexity The of ICCC material included, cancers into 12 main diagnostic neral retained thatinreport. groups,from as listed Table 1.
Approximately 2 in every 3 cancers in young children (aged <15 years) were either haematological malignancies (i.e. leukaemia erage of 137 cancers were and lymphoma) or tumours of the d underbrain 15 and (Table 1). In older(ICCC nervous system Although these were nal 74 groups casesI-III). were diagnosed also the main cancers in older per year for ages 0-19 (Tableat ages teenagers, 27% of cancers 15-19 were in the but “otherthe epithelial malignant cancers tumours and melanoma” category. 2 hood Cancer (ICCC) , followed The remainder of this report deals
ignant tumours of the brain & of cases tabulated here).
ion of carcinoid tumours of the
Table 1. Annual average number of cancers diagnosed in children and teenagers in Ireland, 1994-2014
all cancers (ICCC definition) ICCC group# I leukaemias & related II lymphomas & related III brain & CNS* IV neuroblastomas & peripheral nervous system tumours V retinoblastoma VI renal tumours VII hepatic tumours VIII malignant bone tumours IX soft tissue sarcomas X gonadal & germ cell tumours XI other epithelial tumours & melanomas XII other & unspecified
<15 years N % of all 137
15-19 years N % of all 74
41 14 35
30% 10% 26%
8 17 12
11% 23% 16%
49 31 47
3 8 2 6 9 4
2% 5% 1% 4% 6% 3%
0 <1 1 4 4 7
0% <1% 1% 6% 6% 10%
3 8 2 10 13 11
counts are rounded to the nearest whole number; see Appendix (p. 9) for individual years # International Classification of Childhood Cancer, 3rd edition2 * central nervous system
Incidence rates and variation between boys and girls
total N 211
On average, 9 boys and 5 girls w (group III) each year. The incide million) was significantly highe million). The incidence rate of sof also significantly higher in boys (1 (8 cases per million). The inciden tumours & melanomas” (group X (8 cases per million) with (non-significantly) higher than in boy incidence rates in boys.did not differ signi other cancers
On average, 9 boys and 5 girls Figure 1. Incidence rates of each chil were diagnosed with lymphoma girls and boys aged under 15 years, 1 (group III) each year. The incidence & %s of cases are shown. rate in boys (19 cases per million) was significantly higher than in girls (11 cases per million). The incidence rate of soft-tissue sarcomas (group IX) was also significantly higher in boys (12 cases per million) than in girls (8 cases per million). The incidence rate for the “other epithelial tumours & melanomas” (group XI) was significantly higher in girls (8 cases per million) than in boys (5 cases per million). Rates of other cancers did not differ significantly by sex. Age at diagnosis
There was considerable variation between cancer types in the age at which children were diagnosed. Some cancers were more frequent in very young children and rarer in older boys and girls. Neuroblastomas and ganglioneuroblastomas were particularly rare in children aged over 6 years; while www.ncri.ie almost all retinoblastomas and © National hepatoblastomas were diagnosed in children aged 4 or under.
non-malignant tumours and nonwith cancer in children aged <15 melanoma cancers cancer (NMSC), in only, standard grouping used rate (WASR) The the world age-standardised ofskin childhood the WASR was 142 cases per for most international analyses. Ireland during 1994-2014 averaged 158 cases per million per million per year. Incidence rates variation year (Table 2), and a slight increase from the rate (150.5) for 1994Incidence rates for all cancers between boys and girls 20111. The European age-standardised rate (EASR)in boys was combined were 8% higher The world age-standardised rate than in girls, but the difference was (WASR) of childhood cancer in on cancer More information is available on our website February 2017 not statistically significant. Ireland during 1994-2014 averaged Leukaemias (ICCC group I) had the 158 cases per million per year marginally lower thanfrom the WASR, reflecting the (41 EASR’s highest incidence rate childrenlower (Table 2), a slight increase Most children diagnosed with annually or an agethe rate (150.5) for 1994-20111. weighting of the 0-4 age-group, under which15has the highest incidence. lymphoma were older, particularly standardised rate of 49 cases per The European age-standardised The WASRwasismarginally used inlower the restmillion), of this in the case of Hodgkin lymphoma and report. incidenceExcluding was slightly nonrate (EASR) which was more frequent in (though non-significantly) higher in the than the WASR, reflecting thenon-melanoma malignant tumours and skin cancers (NMSC), children over 10 years. Hodgkin boys than in girls (Figure 1). Brain/ EASR’s lower weighting of the 0-4 WASR waswhich 142has cases per million percancers year. (group II) were the lymphoma is most frequently CNS age-group, the highest second most commonly diagnosed diagnosed in children and incidence. The WASR is used in young adults aged over 153. Incidence rates forExcluding all cancers combined wereper8% higher in boys group (40 cases million), again the rest of this report. were also much than in girls, but the difference was not statistically significant. Osteosarcomas rarer in very young children and most patients were aged over Table 2. Number of cases diagnosed per year and incidence 10 when they were diagnosed. rates per million in girls and boys aged under 15, 1994-2014 Leukaemia and cancers of girls boys total the brain and central nervous all ICCC I-XII cancers system had a somewhat more cases/year 64 73 137 even distribution, although crude rate 148 160 154 acute myeloid leukaemia and WASR* 152 164 158 ependymomas of the brain were (95% CI) (143.5-159.8) (155.8-172.3) (152.0-163.6) most frequently registered in very EASR† 150 162 156 young children, aged 2 or younger. (95% CI) (141.9-158.0) (154.2-170.4) (150.4-161.8) Overall, there was relatively little malignant cancers only & excl NMSC# change in the distribution of cases/year 57 65 123 cancers by age at diagnosis since crude rate 132 143 138 the previous report. WASR* 136 148 142 (95% CI) (125.5-146.2) (137-158.1) (134.3-149.1) Incidence trends over time EASR† 134 146 140 In general there was little change (95% CI) (123.9-144.3) (135.3-156.1) (132.6-147.2) in the distribution of cancer types *WASR: world age-standardised rate (cases per million per year) diagnosed over time (Figure 3). †EASR: European age-standardised rate (cases per million per year) # NMSC: non-melanoma skin cancer Leukaemia accounted for 30%
Leukaemias (ICCC group I) had the highest incidence rate (41 children under 15 annually or an age-standardised rate of 49 cases per million), and incidence was slightly (though non-
HPN • April 2017
In general there was little change in the distribution of cancer types diagnosed over time (Figure 3). Leukaemia accounted for 30% of all childhood cancers in each time period since 1994, whereas brain & CNS varied between 24% and 27% over time. There was a slight decline in the proportion of lymphoma, from representing 12% of cancers in 1994-2000 to 9% in 2008-2014, and a slight increase in renal tumours from 4% to 6%. Cancer Trends No 32. Childhood cancer
Figure 3. Percentage breakdown of childhood cancers (ICCC I-XII, <15
years), 1994-2000, 2001-2007 & 2008-2014 Tumour-directed treatment
Chemotherapy was the principal treatment for all childhood cancers combined, either alone or in combination with surgery and/or radiotherapy. Between 2008 and 2013 over two-thirds of all patients received chemotherapy (Table 4). For all cancers combined, there has been little change over time in the percentage of patients in each treatment category. About 10% of patients apparently did not receive specifically tumourdirected treatment within 12 months of diagnosis. However it should be noted that some patients died before treatment could begin,Although and a small number of patients were treated theincidence 12 the distribution of cancer types was after stable, month cut-off shown here or had other therapies not directed rates of all cancers combined increased significantly, by 27%, between the periods 1994-2000 and 2008-2014. specifically at reducing/removing cancer. of all childhood cancers in each their cases falling from 39Annual patientsrates time period since 1994, whereas in 1994 to 21 patients in 1999. are shown below (Figure 4).
Tablebrain 4. Combinations of the main of treatment*increased for all & CNS varied between 24%categories Rates subsequently childhood cancers (ICCC and theaof3 all largest cancercancers groups diagnosed and 27% time. There was Figure 4.over Trends inI-XII) incidence childhood (ICCC I-XII, <15 significantly by 2.9% per year, with in 1994-2000, 2001-2007 & 2008-2013 slight decline in the proportion of 56 cases inchange 2014. (APC) is shown years), 1994-2014: average annual percentage lymphoma, from representing1994-2000 12% 2001-2007 2008-2013 Tumour-directed treatment of cancers in 1994-2000 to 9%N=816 in all cancers (ICCC-I-XII) N=927 N=954 2008-2014, and a slight increase in Chemotherapy was 18% the principal surgery only 19% 16% renal tumours from 4% to 6%. chemotherapy only# 38% treatment 42%for all childhood 38% cancers combined, either alone or in Although only the distribution of cancer radiotherapy 3% 3% 2% combination with surgery and/or types stable, incidence rates surgery & was chemotherapy 12% radiotherapy. 15% Between 15%2008 and of all cancers combined increased surgery & radiotherapy 3% 3% two-thirds2% 2013 over of all patients significantly, by 27%, between the radio& chemotherapy 5%chemotherapy. 7% received periods 1994-2000 and 2008- 7% all three 6% 9% 8% 2014.treatments For all cancers combined, there no treatment 12% 7% 9%
Annual incidence rates varied from
121 to 202 cases per million per I leukaemia N=245 yearonly in girls (46-98 patients per 0% surgery year) and from chemotherapy only#125 to 219 cases87% per million per year in boys (52-91 radiotherapy onlyyear). 0% patients per surgery & chemotherapy 0% The & previous childhood cancer 0% surgery radiotherapy trends report1 found that radio& chemotherapy 5% childhood cancers in girls all three treatments 0% increased non-significantly by no treatment 0.8% per year 1994-2011. The 7% incidence rate for girls appeared
II lymphoma N=94 to increase more steeply between surgery 3% 2011only and 2014, producing a chemotherapy only# significant average increase of 70% radiotherapy 1.6% per only year 1994-2014. No 5% significant trend was seen in surgery & chemotherapy 7% rates&among boys, but rates for 0% surgery radiotherapy both sexes combined increase 10% radio& chemotherapy significantly by 1.1% per year. all three treatments 0% Leukaemia incidence rates varied no treatment 4%
has been little change over time in the percentage of patients N=281 N=285 in each treatment category. About 10% of 0% 0% patients apparently did not receive 91% 94% specifically tumour-directed 0% within 12 months 0% treatment of 1% However it0% diagnosis. should be 0% some patients 0% died noted that before treatment could 2% 2%begin, and a small 0% number of 0%patients were treated after the 12 month 5% 3% cut-off shown here or had other therapies not directed specifically N=94 N=86 at reducing/removing their cancer. 2% 3%
74%varied considerably 51% Treatment 3%the three most 0% common between cancers diagnosed. Almost all 10% 6% leukaemia 0% patients received 0% chemotherapy. In over 90% of 2% 29% cases, patients had this treatment 0% 1% alone (or chemotherapy followed 9% cell by bone9% marrow or stem considerably between years and transplant (BMT/SCT)). Similarly III brain & CNS N=220 N=246 showed only weak evidence ofN=215 any lymphoma patients were treated longer-term trend, with an annual surgery only 36% mostly37% 32% with chemotherapy alone # percentageonly increase of 0.8%. 4% chemotherapy 8% by BMT/SCT), 10% (or followed Leukaemia case numbers ranged radiotherapy only 9% 9%there was a6% although notable from 25 patients in 1994 to 60 surgery & chemotherapy 5% 8%in the proportion 9% of increase in 2009. patients receiving chemotherapy surgery & radiotherapy 7% 10% 6% in combination with radiotherapy Lymphoma incidence rates were3% radio& chemotherapy 3% 6% also very variable over time, with all three treatments 10% in 2008-2013 13% compared 9% to Radiotherapy without an average increase of 0.5% per25% 1994-2000. no treatment 12% 22% chemotherapy was not used at all year. Cases ranged 7 in of2011 * only treatments received within from 12 months diagnosis are included # or chemotherapy during the period. to 22 in 2014. followed by bone marrow transplant (BMT) or stem celllatter transplant (SCT) There was an initial non-significant
per year in girls (46-98 patients per year) and from 125 to 219 cases per million per year in boys (52-91 patients per year). The previous childhood cancer trends report1 found that childhood cancers in girls increased non-significantly by 0.8% per year 1994-2011. The incidence rate for girls appeared to increase more steeply between 2011 and 2014, producing a significant average increase of 1.6% per year 1994-2014. No February 2017 significant trend was seen in Survival rates among boys, but rates for both tumours were treated surgically, either alone or together with sexes combined increase significantly by 1.1%survival per year. Five-year observed for chemotherapy and radiotherapy. Similarly lymphoma patients all were treated mostly with childhood cancers combined However approximately 1 in 5 Incidence trends are described for the three most common averaged 81% for cases chemotherapy followed by BMT/SCT), although there patients with brainalone & CNS(or tumours diagnosed the most cancer groups (girls and boysduring combined) inrecent Figure 5. had noindividual recorded tumour-directed was a notable in the proportion of patients receiving ten-year period (2004-2013), and treatment within a increase year of their wasmost similar (80%) for 1994-2013 Figure 5. Trends in incidence with of the frequent childhood cancer diagnosis. chemotherapy in combination radiotherapy in 2008-2013 groups (<15 years), 1994-2014 as a whole. Figure 6 illustrates the treatmentRadiotherapy without chemotherapy compared to 1994-2000. Five-year survival exceeded 80% combinations received by during 2004-2013 for 7 of the 12 was notdiagnosed used at all during the latter period. children with the ten major groups: leukaemias and main ICCC diagnostic groups related cancers (85%), lymphomas during 2008-2013. Along with In contrast to the haematological malignancies, 60% of and related (96%), about retinoblastoma brain & CNS patients, children (98%), renal tumours (89%), patients with & CNS tumours were treated surgically, either diagnosed with brain retinoblastoma hepatic tumours (95%), germ and gonadal/germ cell tumours alone or together with chemotherapy andgonadal radiotherapy. cell and tumoursHowever had the highest proportion of and other carcinomas / treatment involving surgery only with(92%), approximately 1 in 5 patients brain & CNS tumours had no melanomas (91%). (>30% of children). Surgery in recorded tumour-directed within a year of their combination with chemotherapy treatment Average survival was poorer for was the most common treatment patients with brain and other CNS diagnosis. for both neuroblastomas and tumours (71%), neuroblastoma retinoblastoma as well as for & related tumours (69%), bone Figure 6 illustrates the treatment combinations received by renal, hepatic and bone cancers. tumours (66%) and soft-tissue Approximately 20% of patients sarcomas (76%). children diagnosed with the ten main ICCC diagnostic groups received radiotherapy, mostly Overall, little change in combination with either during 2008-2013. Along with brain & there CNS was patients, children in survival between diagnosis chemotherapy (lymphoma, diagnosed with and gonadal/germ cell tumours periods, but for five major groups neuroblastoma andretinoblastoma soft tissue (leukaemia, lymphomas, hepatic sarcoma) or with chemotherapy had the highest proportion of treatment involving surgery only tumours, soft tissue sarcomas and surgery (neuroblastoma, and germ cell / gonadal tumours) retinoblastoma, renal cancers and (>30% of children). Surgery in combination with chemotherapy there was some indication of soft tissue carcinomas).
was the most common treatment for both neuroblastomas and retinoblastoma as well as for renal, hepatic and bone cancers.
Figure 6. Combinations of the main categories of treatment for individual cancer groups (ICCC I-XII), 2008-2013
Leukaemia incidence rates varied considerably between years and showed only weak evidence of any longer-term trend, with an annual percentage increase of 0.8%. Leukaemia case numbers ranged from 25 patients in 1994 to 60 in 2009. Lymphoma incidence rates were also very variable over time, with an average increase of 0.5% per year (Figure 5). Cases ranged from 7 in 2011 to 22 in 2014. There was an initial non-significant decline in incidence rates of brain & CNS tumours (Figure 5), with cases falling from 39 patients in 1994 to 21 patients in 1999. Rates subsequently increased significantly by 2.9% per year, with 56 cases in 2014.
In contrast to the haematological
Treatment considerably theisthree most common malignancies, about 60% declinevaried in incidence rates of between More information on cancer available on our of website www.ncri.ie with brain &patients CNS brain diagnosed & CNS tumours, with 4). Almostpatients cancers (Table all leukaemia
received chemotherapy. In over 90% of cases, patients had this treatment alone (or chemotherapy followed by bone marrow or April 2017 â€˘ HPN stem cell transplant (BMT/SCT)).
ÂŠ National Cancer Registry 2017
Approximately 20% of patients received radiotherapy, mostly in combination
neuroblastoma and soft tissue sarcoma) or with chemotherapy
Prescribing Information (Ireland) ▼Vargatef® (nintedanib) 100 mg and 150 mg soft capsules Prescribing Information (Ireland) Soft capsules containing 100100 mg mg or 150 (as esilate). Indication: Vargatef is ▼Vargatef® (nintedanib) andmg 150nintedanib mg soft capsules indicated in combination docetaxel for mg the nintedanib treatment of(asadult patientsIndication: with locallyVargatef advanced,is Prescribing Information (Ireland) Soft capsules containingwith 100 mg or 150 esilate). metastatic or locally recurrent non-small cell lung cancer (NSCLC) of adenocarcinoma tumour ▼Vargatef® (nintedanib) 100 mg and 150treatment mg soft capsules indicated in combination with docetaxel for the of adult patients with locally advanced, histology after first-line chemotherapy. andcancer Administration: Vargatef Soft capsules containing 100 mg or 150 Dose mg nintedanib (as(NSCLC) esilate).of Treatment Indication:withVargatef is metastatic or locally recurrent non-small cell lung adenocarcinoma tumour should be initiated and supervised by a physician experienced in the use of anticancer therapies. indicated inafter combination docetaxel forDose the treatment of adult patients with locally histology first-line with chemotherapy. and Administration: Treatment withadvanced, Vargatef The recommended dose of nintedanib 200cellmglung twice daily administered 12tumour hours metastatic or locally non-small cancer (NSCLC) of adenocarcinoma should be initiated andrecurrent supervised by aisphysician experienced in the use ofapproximately anticancer therapies. apart, on days to dose 21 of ofachemotherapy. standard docetaxel cycle. Vargatef mustwith not 12 be taken histology after2first-line Dose Administration: Treatment Vargatef The recommended nintedanib21isday200 mg and twicetreatment daily administered approximately hours on theonsame day docetaxel chemotherapy administration (=incycle. day If ofa dose of nintedanib is should bedays initiated and by21aday physician experienced the1).use anticancer apart, 2 toof21 ofsupervised a standard docetaxel treatment Vargatef must nottherapies. be taken missed, administration should resume at the next scheduled time at the recommended dose. Theis Thethe recommended of nintedanib is 200 mg twice daily administered 12 hours on same day ofdose docetaxel chemotherapy administration (= day 1). If aapproximately dose of nintedanib individual daily2doses not increased beyond therecommended recommended to apart, onadministration days to 21 ofofshould anintedanib standard 21should treatment cycle. Vargatef must notdose. bedose taken missed, resume atdaythedocetaxel nextbescheduled time at the The make for missed doses. The recommended maximum daily dose ofIf a400 mgofshould not be on theupsame of docetaxel chemotherapy administration (=beyond day 1).the dose nintedanib is individual dailyday doses of nintedanib should not be increased recommended dose to exceeded. Patients continue therapy nintedanib after discontinuation of docetaxel forThe as missed, should resume at with the next scheduled time at theofrecommended dose. make upadministration for missedmay doses. The recommended maximum daily dose 400 mg should not be long as clinical benefit is observed or until unacceptable toxicity occurs. For posology, methods of individual daily doses nintedanib should be increased the recommended to exceeded. Patients mayofcontinue therapy withnotnintedanib after beyond discontinuation of docetaxeldose for as administration, and dose modifications docetaxel, please refer to the corresponding product make for missed doses. The recommended maximum daily dose ofFor400 mg should not be long asupclinical benefit is observed or untilof unacceptable toxicity occurs. posology, methods of information for docetaxel. Dose adjustments should beplease considered intocase adverse reactions of exceeded. Patients therapyofwith nintedanib afterrefer discontinuation of docetaxel for as administration, andmay dosecontinue modifications docetaxel, the of corresponding product pre-specified vomiting, andbeother non haematological or haematological long as clinical benefitdiarrhoea, is observed or untilnausea unacceptable toxicity occurs. methods of information forseverity: docetaxel. Dose adjustments should considered in caseForofposology, adverse reactions adverse reactions, and aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) administration,severity: and dose modifications docetaxel, pleasenonrefer to the corresponding product pre-specified diarrhoea, vomiting,ofnausea and other haematological or haematological and bilirubin – Dose as initial measure should for the be management ofin adverse reactionsreactions treatment information forelevations docetaxel. adjustments considered case aminotransferase of adverse of adverse reactions, and aspartate aminotransferase (AST) and/or alanine (ALT) with nintedanib shoulddiarrhoea, interrupted. Please the Summary oftreatment Product pre-specified severity: vomiting, nausea andmanagement other nonrefer haematological or haematological and bilirubin elevations –beastemporarily initial measure for the oftoadverse reactions Characteristics (SPC) further information including when torefer discontinue treatment.ofPaediatric adverse reactions, andforaspartate aminotransferase (AST) and/or alanine (ALT) with nintedanib should be temporarily interrupted. Please to theaminotransferase Summary Product population: andforefficacy ininformation children yearstohave beentreatment. established. Elderly and bilirubinSafety elevations –further as initial measureaged for the0-18 management ofnotadverse reactions Paediatric treatment Characteristics (SPC) including when discontinue patients (≥ Safety 65 years): in 0-18 safetyPlease and have efficacy observed elderly with nintedanib should be overall temporarily interrupted. refer not to were the offorProduct population: and No efficacy in differences children aged years beenSummary established. Elderly patients. No adjustment of initial dosing required on the basis of a patient’s age. Race and body Characteristics discontinue Paediatric patients (≥ 65 (SPC) years):forNofurther overallinformation differencesincluding in safetywhen andtoefficacy were treatment. observed for elderly weight: Based on population pharmacokinetic analyses, no a have priori dosebeen adjustments population: and efficacy indosing children aged 0-18 established. patients. NoSafety adjustment of initial required on theyears basis of anot patient’s age. Racenecessary. andElderly body Safety data for Black and African American patients are limited. Renal impairment: Less than 1% patientsBased (≥ 65 onyears): No overall differences analyses, in safety no anda efficacy were observed for elderly weight: population pharmacokinetic priori dose adjustments necessary. of a single of nintedanib is excreted the kidney. the starting patients patients. initial dosingvia required onaretheAdjustment basis ofRenal aofpatient’s age.dose Race and body Safety dataNodose foradjustment Black andofAfrican American patients limited. impairment: Lessinthan 1% with mild to moderate renal impairment is not required. The safety, efficacy and pharmacokinetics weight: Based no a prioriofdose adjustments necessary. of a single doseonof population nintedanib ispharmacokinetic excreted via theanalyses, kidney. Adjustment the starting dose in patients have mild notdata been studied inrenal patients with severe renal impairment (<Renal 30efficacy ml/min creatinine Safety Black and African American patients are limited. impairment: Lessclearance). than 1 % with tofor moderate impairment is not required. The safety, and pharmacokinetics Hepatic Nintedanib iswith predominantly eliminated via biliary/faecal excretion 90%). of a single dosestudied of nintedanib is excreted via the kidney. Adjustment ofml/min the starting doseclearance). in(>patients have notimpairment: been in patients severe renal impairment (< 30 creatinine Exposure patients hepatic impairment (Child Pugh A,andChild Pugh(>B). No with mildimpairment: toincreased moderateinNintedanib renal impairment is not required. The safety, efficacy pharmacokinetics Hepatic iswith predominantly eliminated via biliary/faecal excretion 90%). adjustment of the starting dose is needed for patients with mild hepatic impairment (Child Pugh A) have not been studiedinin patients with impairment(Child (< 30 Pugh ml/minA,creatinine clearance). Exposure increased withsevere hepaticrenal impairment Child Pugh B). No based onimpairment: clinical data. Limited data available 9hepatic patients with excretion moderate hepatic Hepatic Nintedanib predominantly eliminated biliary/faecal 90%). adjustment of the starting dose isissafety needed for patients withfrom mildvia impairment (Child(>Pugh A) impairment (Child Pugh B) are insufficient to characterize this population. The safety, efficacy and Exposure in patients impairment Pugh with A, Child Pugh hepatic B). No based on increased clinical data. Limited with safetyhepatic data available from(Child 9 patients moderate pharmacokinetics of nintedanib have notfor investigated in patients severe hepatic adjustment of the starting is needed patients withthis mildpopulation. hepatic impairment (Child Pugh A) impairment (Child Pugh B)dose are insufficient tobeen characterize Thewith safety, efficacy and impairment (Child Pugh C). Treatment patients with moderate (Child Pugh B)moderate tosevere severehepatic (Child based on clinical data. Limited safety data available from 9 inpatients withwith pharmacokinetics of nintedanib have ofnot been investigated patients Pugh C) hepatic isinsufficient not recommended. The capsules must taken preferably (Childimpairment Pugh to characterize this population. The safety, efficacy and impairment Pugh B)C).are Treatment of patients with moderate (ChildbePugh B)orally, to severe (Child with food, swallowed with water, and be capsules chewed in ormust crushed. Contraindications: pharmacokinetics of whole nintedanib have notmust beennotinvestigated patients withorally, severepreferably hepatic Pugh C) hepatic impairment is not recommended. The be taken Hypersensitivity nintedanib, peanut orpatients soya, not orwith to any of the excipients. and impairment (ChildtoPugh C). with Treatment PughContraindications: B) Warnings to severe (Child with food, swallowed whole water, of and must be moderate chewed or(Child crushed. Precautions: Patients with gastrointestinal disorders including diarrhoea, nausea andpreferably vomiting Pugh C) hepatic to impairment is not recommended. be taken orally, Hypersensitivity nintedanib, peanut or soya, orThe to capsules any of themust excipients. Warnings and may require interruption, dose reduction or discontinuation of therapy. Diarrhoea should treated with food, swallowed whole with water, and must not beincluding chewed ordiarrhoea, crushed. Contraindications: Precautions: Patients with gastrointestinal disorders nausea andbevomiting at first signsinterruption, withto adequate anti-diarrhoeal products,should e.g. loperamide. Hypersensitivity nintedanib, peanut and soya, or to anyofmedicinal oftherapy. the excipients. Warnings and may require dosehydration reduction or discontinuation Diarrhoea be treated Supportive foradequate nausea and vomiting may include medicinal products with anti-emetic Precautions: Patients with gastrointestinal disorders including diarrhoea, nausea vomiting at first signscare with hydration and anti-diarrhoeal medicinal products, e.g.and loperamide. properties, e.g. glucocorticoids, anti histamines or 5 HT3 receptor antagonists and may require care interruption, dose and reduction or discontinuation therapy. Diarrhoea beadequate treated Supportive for nausea vomiting may include of medicinal products should with anti-emetic hydration. Ine.g. the event of dehydration, fluids is required. Plasma at first signs withglucocorticoids, adequate hydration and anti-diarrhoeal products, e.g.andloperamide. properties, anti administration histamines or of5 electrolytes HT3medicinal receptorandantagonists adequate levels of electrolytes should be monitored, if relevant gastrointestinal adverse events occur. Supportive for nausea and vomiting may include medicinalandproducts anti-emetic hydration. Incare the event of dehydration, administration of electrolytes fluids iswith required. Plasma Combination treatment with docetaxel is associated a receptor higher frequency of neutropenia of properties, e.g. glucocorticoids, histamines or 5with HT3 antagonists and adequate levels of electrolytes should be anti monitored, if relevant gastrointestinal adverse events occur. CTCAE grade ≥ 3 as compared to treatment with docetaxel alone. Subsequent complications such hydration. In the event ofwith dehydration, electrolytes fluids isofrequired. Plasma Combination treatment docetaxeladministration is associatedofwith a higherand frequency neutropenia of as sepsis or ≥febrile neutropenia have beenwith observed. Blood counts shouldadverse becomplications monitored levels of electrolytes should tobetreatment monitored, if docetaxel relevant gastrointestinal events during occur. CTCAE grade 3 as compared alone. Subsequent such therapy, referneutropenia to SPC. Based on increased risk for adverse Combination treatment with Hepatic docetaxel is associated with a counts higherexposure, frequency neutropenia of as sepsisplease or febrile havefunction: been observed. Blood should betheofmonitored during events grade may be≥ 3increased in patients with mild impairment (Child Pughthe A).risk Treatment with CTCAE as compared to treatment withhepatic docetaxel alone. Subsequent complications such therapy, please refer to SPC. Hepatic function: Based on increased exposure, for adverse Vargatef is not recommended in patients with moderate or severe hepatic impairment. Nintedanib as sepsis neutropenia havewith been Blood counts(Child should during events mayorbefebrile increased in patients mildobserved. hepatic impairment PughbeA).monitored Treatment with was associated with of liver enzymes (ALT,on AST, ALKP, gamma-glutamyltransferase) or therapy, please refer an to elevation SPC. Hepatic function: Based exposure, the risk for adverse Vargatef is not recommended in patients with moderate orincreased severe hepatic impairment. Nintedanib bilirubin, with potentially forenzymes female patients. increases wereA).reversible the events may beaincreased in higher patients with mild hepatic (Child Pugh Treatmentinwith was associated with an elevation ofrisk liver (ALT, impairment AST, These ALKP, gamma-glutamyltransferase) or majority of cases. Transaminase, ALKP and bilirubin levels be investigated beforeNintedanib initiation Vargatef iswith not in patients with moderate or should severe impairment. bilirubin, arecommended potentially higher risk for female patients. These hepatic increases were reversible in the of treatment and monitoring continued as required. relevant liver enzyme wascombination associated withTransaminase, an elevation of liverand enzymes (ALT, AST,should ALKP,If gamma-glutamyltransferase) or majority of cases. ALKP bilirubin levels be investigated beforeelevations initiation arecombination measured, dose reduction or discontinuation ofIfthe therapyliver withenzyme Vargatef may be bilirubin, with ainterruption, potentiallyand higher risk forcontinued female patients. These increases were reversible in the of treatment monitoring as required. relevant elevations required, please refer to the SPC. VEGFR inhibition might be associated with an increased risk be of majority of cases. Transaminase, ALKP and or bilirubin levels should betherapy investigated before initiation are measured, interruption, dose reduction discontinuation of the with Vargatef may bleeding. Vargatef is not patients with recent pulmonary bleeding (> 2.5elevations mlrisk of red of combination treatment andSPC. monitoring continued as required. If relevantwith liveranenzyme required, please refer to recommended the VEGFRin inhibition might be associated increased of blood) as well as patients with centrally located tumours with radiographic evidence of local are measured, interruption, dose reduction or discontinuation the therapy with Vargatef be bleeding. Vargatef is not recommended in patients with recent of pulmonary bleeding (> 2.5 mlmay of red invasionasofplease majorasrefer blood radiographic evidence ofbecavitary or necrotic required, tovessels the with SPC.orcentrally VEGFR inhibition might associated with antumours. increasedPatients of blood) well patients located tumours with radiographic evidence ofrisk local taking concomitant anticoagulation, such as warfarin orofphenprocoumon should bleeding. is not recommended in patients with recent pulmonary bleeding (>be2.5monitored ml of red invasion ofVargatef major blood vessels or radiographic evidence cavitary or necrotic tumours. Patients regularlyas for in prothrombin time, normalized ratioshould (INR), blood) wellchanges as patients with centrally located tumours with radiographic evidence ofclinical local taking concomitant anticoagulation, such as international warfarin or phenprocoumon beandmonitored bleeding Patients withorstable brain be closely monitored for and invasion ofepisodes. blood radiographic evidenceshould of cavitary or necrotic tumours. Patients regularly formajor changes invessels prothrombin time,metastasis international normalized ratio (INR), andsigns clinical symptoms of cerebral bleeding. Treatment not recommended patients withbefor active taking concomitant anticoagulation, such warfarin orshould phenprocoumon should monitored bleeding episodes. Patients with stable brainasmetastasis befor closely monitored signsbrain and metastasis. Patients should be closely monitored for thromboembolic events and Vargatef should regularly forof changes prothrombin time, not international normalized ratio (INR), and clinical symptoms cerebral inbleeding. Treatment recommended for patients with active brain be discontinued in patients life threatening venous thromboembolic reactions. Caution should bleeding episodes. Patients with stable brain metastasis should be closely monitored for signs and metastasis. Patients shouldwith be closely monitored for thromboembolic events and Vargatef should be used when patients a higher cardiovascular risk including known artery symptoms of treating cerebral bleeding. notvenous recommended for patients withcoronary activeshould brain be discontinued in patients with with lifeTreatment threatening thromboembolic reactions. Caution disease. Treatment interruption should be considered in patients develop signs or symptoms metastasis. Patients should be closely monitored for thromboembolic eventsknown and Vargatef should be used when treating patients with a higher cardiovascular risk who including coronary artery of myocardial ischaemia. on mechanism of action treated withsymptoms Vargatef be acute discontinued in patients with Based life threatening venousinthromboembolic reactions. should disease. Treatment interruption should bethe considered patients whopatients develop signsCaution or mayacute havewhen an increased risk of gastrointestinal perforations.ofParticular caution should be exercised be used treating patients with a on higher risk including known coronary artery of myocardial ischaemia. Based the cardiovascular mechanism action patients treated with Vargatef when treating patients with previous abdominal surgery or a recent history of a hollow organ disease. interruption should be considered in patients who caution developshould signs orbesymptoms may haveTreatment an increased risk of gastrointestinal perforations. Particular exercised perforation. Treatment should only be initiated at least 4 weeks major surgery. should of acute myocardial ischaemia. Based on the mechanism ofor action patients treated with Vargatef when treating patients with previous abdominal surgery aafter recent history of aTherapy hollow organ be permanently discontinued in patients who develop gastrointestinal perforation. Nintedanib may may have anTreatment increasedshould risk of only gastrointestinal perforations. Particular caution should be exercised perforation. be initiated at least 4 weeks after major surgery. Therapy should impair wound healing. Treatment should therefore only beorinitiated or,history in caseof ofNintedanib perioperative when treating patients with inprevious abdominal surgery a recentperforation. a hollow organ be permanently discontinued patients who develop gastrointestinal may interruption, resumed based on clinical judgement of adequate wound healing. Caution should be perforation. Treatment only be initiated at leastonly 4 weeks after major should impair wound healing.should Treatment should therefore be initiated or, insurgery. case ofTherapy perioperative exercised in patients who mayon prolongation. Dietary wound soya products known to cause be permanently discontinued indevelop patients who develop perforation. Nintedanib may interruption, resumed based clinicalQTc judgement of gastrointestinal adequate healing.are Caution should be allergic reactions including severe anaphylaxis in persons with soya allergy. Patients with known impair wound healing. should onlyDietary be initiated or, in case perioperative exercised in patients whoTreatment may develop QTc therefore prolongation. soya products are of known to cause allergy to peanut protein ananaphylaxis enhanced severe reactions toPatients soya preparations. interruption, resumed basedcarry on clinical judgement of for adequate healing. Caution should be allergic reactions including severe inrisk persons with wound soya allergy. with known Nintedanib exposure increased linearly withprolongation. patient was inversely correlated topreparations. weight, and exercisedtoinpeanut patientsprotein who may develop QTc soya products to cause allergy carry an enhanced risk age, for Dietary severe reactions to are soyaknown was generally higher in patients of anaphylaxis Asianwith racepatient which may insoya a higher risk of developing liver allergic reactions including severe in persons withinversely allergy. Patients with known Nintedanib exposure increased linearly age, result was correlated to weight, and enzyme elevations; close monitoring isenhanced recommended in patients severalrisk these risk factors. allergy to peanut carryofanAsian risk may for severeinwith reactions toofsoya preparations. was generally higherprotein in patients race which result a higher of developing liver Close monitoring is close recommended in ispatients weighingage, 50was kg.inversely Interactions: studies Nintedanib exposure increased linearly with patient correlated to risk weight, and enzyme elevations; monitoring recommended in<patients with several ofInteraction these factors. have only been performed in adults. P-glycoprotein (P-gp): Nintedanib is a substrate of P-gp. was generally higher in patients ofinAsian raceweighing which may< 50 result a higher risk Interaction of developing liverIf Close monitoring is recommended patients kg. inInteractions: studies co-administered, potent inhibitors e.g. ketoconazole orNintedanib erythromycin increase enzyme closeP-gp monitoring isP-glycoprotein recommended in patients with several of these risk factors.If have onlyelevations; been performed in adults. (P-gp): is may a substrate ofexposure P-gp. to nintedanib. should beinmonitored closely for of nintedanib. Potent P-gp Close monitoringPatients ispotent recommended patients weighing < 50tolerability Interactions: studies co-administered, P-gp inhibitors e.g. ketoconazole orkg.erythromycin mayInteraction increase exposure inducers carbamazepine, phenytoin and John’s Wortofmay exposure toIf have onlye.g. beenrifampicin, performed in adults. P-glycoprotein (P-gp): Nintedanib isnintedanib. a decrease substratePotent of P-gp. to nintedanib. Patients should be monitored closely forSt.tolerability P-gp nintedanib. Co-administration should be carefully considered. Cytochrome (CYP)enzymes: co-administered, potent P-gp inhibitors e.g. ketoconazole erythromycin increase exposure inducers e.g. rifampicin, carbamazepine, phenytoin and St.orJohn’s Wort maymay decrease exposure to Likelihood of drug-drug interactions withbenintedanib on CYP Cytochrome metabolism considered toP-gp be to nintedanib. Patients should beshould monitored closelybased for tolerability of nintedanib. Potent nintedanib. Co-administration carefully considered. (CYP)enzymes: low. Othere.g. medicinal products: The potential for interactions with hormonal wastonot inducers carbamazepine, andbased St. John’s Wort maycontraceptives decrease exposure to Likelihood of rifampicin, drug-drug interactions withphenytoin nintedanib on CYP metabolism considered be explored. Fertility, Pregnancy and Lactation: Nintedanib mayhormonal cause foetal harm humans; nintedanib. Co-administration be for carefully considered. Cytochrome (CYP)-in enzymes: low. Other medicinal products: Theshould potential interactions with contraceptives was not women should avoid becoming pregnant while receiving this treatment and use adequate Likelihood Fertility, of drug-drug interactions nintedanib based onmay CYPcause metabolism considered to be explored. Pregnancy andwith Lactation: Nintedanib foetal harm in humans; contraception during andbecoming for atThe least 3 months afterreceiving the lastwith dose of Vargatef. Sinceuse theadequate effect of low. Othershould medicinal potential for interactions contraceptives was not women avoidproducts: pregnant while thishormonal treatment and nintedanib on during the metabolism of contraceptives has cause been investigated, barrier explored. Fertility, Pregnancy andefficacy Nintedanib may foetal harmthe in humans; contraception and for at and least 3Lactation: months after the last dose ofnotVargatef. Since effect of methodsshould should bemetabolism applied as and a second form contraception, avoid pregnancy. is no women becoming pregnant while receiving this and useThere adequate nintedanib on theavoid efficacy of of contraceptives hastotreatment not been investigated, barrier information onduring the use pregnant women, pre-clinical studies have shown contraception and offorVargatef at least 3inmonths after the lastbutdose Vargatef. Since the effect of methods should be applied as a second form of contraception, toofavoid pregnancy. There is no reproductiveonon toxicity and oftherefore not bebutused during unless the nintedanib thethemetabolism and nintedanib efficacy of should contraceptives has not beenpregnancy investigated, barrier information use Vargatef in pregnant women, pre-clinical studies have shown clinical condition requires treatment. Pregnancy testing should be conducted at least prior to methods should be applied as a second form should of contraception, avoid pregnancy. no reproductive toxicity and therefore nintedanib not be usedto during pregnancy There unlessisthe treatment. Female patients should to notify their doctor pharmacist they information on therequires use oftreatment. Vargatefbeinadvised pregnant women, but pre-clinical studies havebecome shown clinical condition Pregnancy testing should beorconducted atifleast prior to pregnant during therapy. the patient becomestoshould pregnant while receiving Vargatef, should be reproductive toxicity and Iftherefore nintedanib bedoctor used during pregnancy unless the treatment. Female patients should be advised notifynot their or pharmacist ifshe they become apprisedcondition ofduring the potential to the foetus. Termination the treatment with Vargatef should clinical requireshazard treatment. Pregnancy testing ofshould be conducted at she leastshould prior be to pregnant therapy. If the patient becomes pregnant while receiving Vargatef, be considered. There ispatients no information the excretion nintedanib and itswith metabolites inbecome human treatment.ofFemale should beonfoetus. advised to notifyof their doctor or pharmacist if theyshould apprised the potential hazard to the Termination of the treatment Vargatef be milk. Pre-clinical studies that amounts nintedanib anditsitsVargatef, metabolites 0.5 be % pregnant during Ifshowed the patient becomes pregnant while receiving she should considered. Theretherapy. is no information onsmall the excretion ofofnintedanib and metabolites in(≤human of thePre-clinical administered dose)hazard were secreted into milk of lactating Aand riskits towith the newborns/infants apprised of the potential to that the foetus. Termination of therats. treatment Vargatef should milk. studies showed small amounts of nintedanib metabolites (≤ 0.5 be % cannot be excluded. Breast-feeding should discontinued during withnewborns/infants Vargatef. Based considered. There isdose) no information on the excretion of nintedanib in human of the administered were secreted intobe milk of lactating rats.treatment Aand riskitstometabolites the on preclinical investigations there is no evidence for impairment of male fertility. There(≤are milk. Pre-clinical studies showed that smallbeamounts of nintedanib and its metabolites 0.5 no % cannot be excluded. Breast-feeding should discontinued during treatment with Vargatef. Based human or animal datadose) on potential effects of nintedanib on female Undesirable of the administered werethere secreted milk offorlactating rats.fertility A risk to fertility. the newborns/infants on preclinical investigations is nointo evidence impairment of maleavailable. There are no effects: most frequently reported adverse reactions specific for nintedanib diarrhoea, cannot or beThe excluded. Breast-feeding should discontinued duringfertility treatment with were Vargatef. Based human animal data on potential effects ofbenintedanib on female available. Undesirable increased livermost enzymes (ALT and AST) vomiting. common Neutropenia (includes on preclinical investigations there is and noadverse evidence forVery impairment of1/10): male fertility. There are no effects: The frequently reported reactions specific (≥for nintedanib were diarrhoea, febrile electrolyte imbalance, neuropathy, bleeding, human neutropenia), or animal datadecreased on(ALT potential effects nintedanib oncommon femaleperipheral fertility Undesirable increased liver enzymes andappetite, AST) andof vomiting. Very (≥ 1/10):available. Neutropenia (includes diarrhoea, vomiting, nausea, reported abdominal pain, reactions alanine aminotransferase increased, aspartate effects: The most frequently specificperipheral for nintedanib were diarrhoea, febrile neutropenia), decreased appetite,adverse electrolyte imbalance, neuropathy, bleeding, aminotransferase increased, blood alkaline increased, mucositis increased liver enzymes (ALT andabdominal AST) and vomiting. Very common (≥ 1/10): Neutropenia (includes diarrhoea, vomiting, nausea, pain, phosphatase alanine aminotransferase increased, (including aspartate stomatitis), rash. increased, Common 1/100 < 1/10): Febrile neutropenia, abscesses,(including sepsis, febrile neutropenia), decreased(≥ appetite, electrolyte imbalance, peripheral mucositis neuropathy, bleeding, aminotransferase blood alkaline phosphatase increased, thrombocytopenia, dehydration, venous thromboembolism, hypertension, hyperbilirubinaemia, diarrhoea, vomiting, nausea, abdominal alanine aminotransferase stomatitis), rash. Common (≥ 1/100 pain, < 1/10): Febrile neutropenia, increased, abscesses,aspartate sepsis, gamma-glutamyltransferase increased. Uncommon (≥ 1/1,000hypertension, <increased, 1/100): Perforation, pancreatitis. aminotransferase increased, blood phosphatase mucositis (including thrombocytopenia, dehydration, venousalkaline thromboembolism, hyperbilirubinaemia, Prescribers theincreased. Summary of<Product for further information on side stomatitis), should rash. consult Common (≥ 1/100Uncommon 1/10):Characteristics abscesses, sepsis, gamma-glutamyltransferase (≥Febrile 1/1,000 neutropenia, < 1/100): Perforation, pancreatitis. effects and should recommended measures. sizes:Characteristics 100 mg 120 capsules; 60 capsules. thrombocytopenia, dehydration, venousPack hypertension, hyperbilirubinaemia, Prescribers consult the Summary ofthromboembolism, Product for further150mg information on side Legal category: POM. MA numbers: 100 mg: EU/1/14/954/002; 150 mg: EU/1/14/954/004. gamma-glutamyltransferase increased.Pack Uncommon 1/1,000 < 1/100): Perforation, pancreatitis. effects and recommended measures. sizes:(≥100 mg 120 capsules; 150mg 60 capsules. Marketing Authorisation Boehringer International GmbH, Binger Strasse Prescribers should consult Summary of Product Characteristics for150 further on side Legal category: POM. MAtheHolder: numbers: 100 mg: Ingelheim EU/1/14/954/002; mg:information EU/1/14/954/004. 173, 55216 am Rhein, Germany. theGmbH, Summary Product effects and Ingelheim recommended measures. PackPrescribers sizes: 100should mgInternational 120consult capsules; 150mgBinger 60ofcapsules. Marketing Authorisation Holder: Boehringer Ingelheim Strasse Characteristics forPOM. full prescribing information. Additional information on request from Legal category: MARhein, numbers: 100Prescribers mg: EU/1/14/954/002; EU/1/14/954/004. 173, 55216 Ingelheim am Germany. should consultis150available themg: Summary of Product Boehringer Ingelheim Ireland Ltd, The Crescent Building, Northwood, Santry, Dublin 9. Marketing Authorisation Holder: Boehringer Ingelheim International GmbH, Strasse Characteristics for full prescribing information. Additional information is available onBinger request from Prepared March 2017 173, 55216inIngelheim amIreland Rhein,Ltd, Germany. PrescribersBuilding, should consult the Summary Product Boehringer Ingelheim The Crescent Northwood, Santry, ofDublin 9. Characteristics for full prescribing information. Additional information is available on request from Prepared in March 2017 ▼This medicinal product is subject to additional monitoring. Boehringer Ingelheim Ireland Ltd, The Crescent Building, Northwood, Santry, Dublin 9. This medicinal ▼ Prepared in Marchproduct 2017 is subject to additional monitoring. Adverse events should be reported to the Health Products Regulatory ▼ThisAdverse medicinal product is subject to additional monitoring. Authority atshould www.hpra.ie or by to email to email@example.com. events be reported the Health Products Regulatory events should also be reported to AuthorityAdverse at www.hpra.ie or by email to firstname.lastname@example.org. Boehringer Ingelheim Pharmacovigilance on 291 3960 by email to Adverse events shouldevents be reported the Health Products Adverse shouldtoalso be01 reported to orRegulatory PV_local_uk_ireland@boehringer-ingelheim.com Authority at www.hpra.ie or by emailon to 01 email@example.com. Boehringer Ingelheim Pharmacovigilance 291 3960 or by email to Adverse events should also be reported to PV_local_uk_ireland@boehringer-ingelheim.com Boehringer Ingelheim Pharmacovigilance on 01 291 3960 or by email to PV_local_uk_ireland@boehringer-ingelheim.com
EXTENDING EXTENDING WHAT’S WHAT’S POSSIBLE POSSIBLE VARGATEF , the only triple angiokinase ® ® ®
VARGATEF , the only triple angiokinase VARGATEF the only triple angiokinaseof inhibitor for adenocarcinoma inhibitor for ,advanced advanced adenocarcinoma 1 of inhibitor for advanced adenocarcinoma the the lung lung after after first-line first-line chemotherapy chemotherapy11 of the lung after first-line chemotherapy VARGATEF® is indicated in combination with docetaxel ® VARGATEF is indicated combination with docetaxel for the treatment of adultin with locally advanced, ® VARGATEF is indicated inpatients combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent non-small cell lung for the treatment of adult patients with locally advanced, metastatic or locally recurrent non-small cellafter lung cancer of adenocarcinoma tumour histology metastatic or locally recurrent non-small cellafter lung cancer ofchemotherapy adenocarcinoma tumour histology 1 first-line 1 cancer of adenocarcinoma tumour histology after first-line chemotherapy first-line chemotherapy1
Reference: 1. VARGATEF® 100/150 mg Summary of Product Characteristics. Available at: http://www.medicines.ie/medicine/16211. Reference: Date accessed: Marchmg2017. ® 1. VARGATEF 100/150 Summary of Product Characteristics. Available at: http://www.medicines.ie/medicine/16211. Reference: Date accessed: March IRE/ONC-171014b | Date2017. of preparation: March 2017 1. VARGATEF® 100/150 mg Summary of Product Characteristics. Available at: http://www.medicines.ie/medicine/16211. IRE/ONC-171014b | Date2017. of preparation: March 2017 Date accessed: March IRE/ONC-171014b | Date of preparation: March 2017
26 Feature improvement. This was statistically significant only for leukaemias: five-year survival increased from 78% to 85%, equivalent to about a one-third reduction in mortality risk (age/sex/casemix-adjusted hazard ratio 0.67 [95% CI 0.490.93]. P=0.167). For lymphomas, improvements between the two periods were not significant, but in further analysis, five-year survival improved from 87% for 1994-1999 cases to 96% for 2000-2006, equivalent to a c70% reduction in mortality (hazard ratio 0.29 [0.090.90], P=0.032). Survival figures for specific subgroups include notably high survival for some subgroups (e.g. Hodgkin lymphoma) but poor survival for others (e.g. gliomas and embryonal tumours of the CNS). Again, there was only limited evidence of improvements in survival (most notably among leukaemia and lymphoma subgroups), including a statistically significant improvement for lymphoid leukaemias: five-year survival improved from 82% to 89%, equivalent to almost a 40% reduction in mortality risk (age/sexadjusted hazard ratio 0.61, 95% CI 0.40-0.91, P=0.016). Survival variation between boys and girls was relatively minor,
and not statistically significant overall or for any subgroup, having adjusted for age and case-mix. Prevalence: numbers of childhood cancer survivors The total number of survivors of childhood cancer in Ireland is not known, as national cancer registration has only covered the years 1994 onwards. However, of the 2873 patients aged 0-14 who were diagnosed with cancer (or with benign brain/CNS tumours) during 1994-2014 (2882 different cancers), 2289 (80%) were still alive at the end of 2014. Of the survivors, 1201 (52%) were male, 1088 (48%) female; 1050 (46%) had first been diagnosed at ages 0-4, 575 (25%) at ages 5-9 and 664 (29%) at ages 10-14. These percentages are similar to those of all patients diagnosed during 1994-2014, except for a slightly higher proportion of males (53%) among all cases. At the end of 2014, the ages of survivors ranged from 0 to almost 36 years, and the highest proportion (32%) had been diagnosed less than 5 years previously, with roughly equal proportions having survived 5-9, 10-14 and 15-20 full years since diagnosis.
These summary figures on years survived and current age would be very different if survivors of childhood cancer diagnosed before 1994 could be included. Even allowing for substantially lower survival from childhood cancer earlier in the 20th century, some patients are likely to have survived many decades. The majority had been diagnosed with leukaemias (31%) or brain / central nervous system tumours (23%). International variation in incidence and mortality Estimates of childhood cancer incidence and mortality rates for European countries over comparable periods were extracted from the EUREG database6, which provided data at individual population-based registry level for the period 19982006.7 More recent incidence figures (but covering a wider period of years, varying by country) were extracted from the IARC/IACR International Incidence of Childhood Cancer website. Irish incidence rates for childhood cancer as a whole (excluding non-malignant tumours and non-melanoma skin cancer)
ranked 13th of the 25 European countries examined for the period 1998-2006. [This is the same comparison as presented in the previous trends report on childhood cancer1.] Incidence rates in Ireland were equal to Swedish rates and similar to those in Germany, Norway and Switzerland, and to the overall European average. Highest incidence rates were observed in Italy, Portugal and Malta. Lowest incidence rates were in the Czech Republic and Poland. Based on the wider period covered by the IARC/IACR website (including Irish data for 1994-2012). This was similar to the ranking based on the EUREG database, although the IARC/IACR figures included all ‘eligible’ tumours covered by the International Classification of Childhood Tumours. For the period 1999-2005, Ireland had one of the lowest mortality rates for childhood cancers of the European countries examined, with only Switzerland and Austria having lower rates. Mortality rates in Ireland were similar to those in Northern Ireland and Wales and were 21% lower than the European average.
National Prevention Conference 2017 The 2017 National Prevention Conference will take place in the Croí Heart & Stroke Centre, Galway on Saturday, 18th November 2017. This will be the fourth year of this exciting event, bringing together national and global perspectives from leading experts in the field of prevention. You can register your interest by emailing firstname.lastname@example.org or why not join the NIPC Alliance to receive their monthly e-Bulletin with all the latest news as well as discounts to all of the short courses and conferences? The Alliance is free to join and members can also avail of the ePrevent Library and forum. Join today to help spread the word of prevention but visiting www.nipc.ie
News Innovative pen for Rheumatoid Arthritis and Psoriasis now available Nordimet® (methotrexate), a new, button-free, pre-filled autoinjector pen for the treatment of rheumatoid arthritis and psoriasis is now available in Ireland. It is the first auto-injector pen for methotrexate to enter the market. It has an innovative double-click mechanism, which audibly clicks at the start and at the end of the injection. Nordimet® is indicated for the treatment of active rheumatoid arthritis (RA) in adult patients, polyarthritic forms of severe, active juvenile idiopathic arthritis (JIA) after an inadequate response to April 2017 • HPN
nonsteroidal anti-inflammatory drugs (NSAIDs), severe recalcitrant disabling psoriasis (which is not adequately responsive to other forms of therapy such as phototherapy, psoralens and ultraviolet A (PUVA), and retinoids) and severe psoriatic arthritis in adults. RA is the second most common form of arthritis in the Ireland, affecting approximately 40,000 people and is about three times more common in women than in men. Although RA can occur at any age, it most commonly starts between the ages of 30 and 50.
JIA affects around 1,200 children (1 in 1000) under the age of 16, with 1 in 1,000 children being diagnosed each year. This new innovative pen will instil user confidence: it is pre-filled; it is for single use and is buttonfree. Nordimet® (methotrexate) is available in a range of 8 presentations, in 2.5mg increments from 7.5mg to 25mg. “By providing a button-free methotrexate pen option, Nordimet® addresses a patient’s possible lack of manual dexterity and will make it easier for patients to comply with their treatment. It
allows clinicians confidence that the methotrexate injection has been effectively administered”. “At Nordic Pharma we are passionate about developing medicines with patients in mind and want to provide treatments clinicians and nurses feel work well for their patient’s needs and lifestyles. We believe that our new, button-free, pre-filled, auto-injector pen offers a step forward for patients with RA,” they concluded. For Further information please refer to the SmPC on www.nordimet.ie or your local Key Account Manager.
For the treatment of rheumatoid arthritis in adults
NEW NORDIMET PEN ®
THE FIRST METHOTREXATE AUTO-INJECTOR FOR PATIENTS WITH RHEUMATOID ARTHRITIS Featuring a unique double click mechanism at the start and end of each injection, a compact design and no button to press – designed to give confidence to you and your patients.
Available in 8 dose presentations, in 2.5mg increments from 7.5mg to 25mg – giving you a wide dosage range and the flexibility you need when treating your patients.
NEW methotrexate auto-injector PEN Nordimet (methotrexate) Solution for Injection in Pre-Filled Pen Please refer to the Summary of Product Characteristics for full prescribing information. Further information is available on request Presentation: Nordimet: Pre-filled pen containing 7.5 mg (in 0.3 ml), 10 mg (in 0.4 ml), 12.5 mg (in 0.5 ml), 15 mg (in 0.6 ml), 17.5 mg (in 0.7 ml), 20 mg (in 0.8 ml), 22.5 mg (in 0.9 ml) and 25 mg (1.0 ml) methotrexate in solution for injection. Indications: Active rheumatoid arthritis in adult patients. Polyarthritic forms of severe, active juvenile idiopathic arthritis, when the response to nonsteroidal anti-inflammatory drugs (NSAIDs) has been inadequate. Severe recalcitrant disabling psoriasis, which is not adequately responsive to other forms of therapy such as phototherapy, PUVA, and retinoids, and severe psoriatic arthritis in adult patients. Dosage and administration: Nordimet should only be prescribed by physicians with experience in the various properties of the medicinal product and its mode of action. Nordimet is injected once weekly, administered subcutaneously. Rheumatoid arthritis: Recommended initial dose is 7.5 mg of methotrexate once weekly. Depending on the individual activity of the disease & patient tolerability, the initial dose may be increased. A weekly dose of 25 mg should in general not be exceeded. Once the desired therapeutic result has been achieved, the dose should be reduced gradually to the lowest possible effective maintenance dose. Polyarthritic forms of severe, active juvenile idiopathic arthritis: The recommended dose is 10-15 mg/m² BSA per week. In therapy-refractory cases the weekly dose may be increased up to 20mg/m² BSA per week. Use in children < 3 years of age is not recommended. Psoriasis vulgaris and psoriatic arthritis: A test dose of 5 - 10 mg subcutaneously administered one week prior to initiation of therapy is recommended. Recommended initial dose 7.5 mg Date of preparation: January 2017 NOR/16/043i
methotrexate once weekly. Dose increased gradually but should not, in general, exceed a weekly dose of 25 mg of methotrexate. Once the desired therapeutic result has been achieved, dose should be reduced gradually to the lowest possible effective maintenance dose.The dose should be increased as necessary but should in general not exceed the maximum recommended weekly dose of 25 mg. Renal impairment, hepatic impairment or eld erly patients: Please refer to SmPC. Note: When switching from oral to parenteral use, a reduction in the dose may be required, due to the variable bioavailability of methotrexate after oral administration. Contraindications: Hypersensitivity to methotrexate or to any of the excipients. Severe hepatic impairment, if serum bilirubin is > 5 mg/dl (85.5 µmol/l). Alcohol abuse. Severe renal impairment (creatinine clearance < 30 ml/min). Pre-existing blood dyscrasias (e.g. bone marrow hypoplasia, leukopenia, thrombocytopenia or significant anaemia). Immunodeficiency. Serious, acute or chronic infections such as tuberculosis & HIV. Stomatitis. Ulcers of the oral cavity and known active gastrointestinal ulcer disease. Pregnancy. Breast-feeding. Concurrent vaccination with live vaccines. Special warnings and precautions: Patients must be clearly advised that the therapy is to be administered once a week, and not every day. Patients receiving therapy should be appropriately monitored. Doses exceeding 20 mg/week can be associated with significant increase in toxicity, especially bone marrow suppression. The possible risks of effects on reproduction should be discussed with male and female patients of childbearing potential. Interactions: Consult SPC for detailed information on interactions. Undesirable effects: See SmPCs for full list of undesirable effects. Nordimet: Very common: Stomatitis. Dyspepsia. Appetite loss. Abdominal pain. Nausea. Raised liver enzymes. Common: Leukopenia. Anaemia.
Thrombopenia. Headache. Tiredness. Drowsiness. Pneumonia. Interstitial alveolitis/pneumonitis. Oral ulcers. Diarrhoea. Exanthema. Erythema. Pruritus. Uncommon: Pharyngitis. Pancytopenia. Precipitation of diabetes mellitus. Depression. Enteritis. Pancreatitis. Gastrointestinal ulceration and bleeding. Cirrhosis, Fibrosis and fatty degeneration of liver. Inflammation and ulceration of bladder. Renal impairment. Rare: Infection. Conjunctivitis. Sepsis. Allergic reactions. Anaphylactic shock. Hypogammaglobulinaemia. Visual disturbances. Pericarditis. Pericardial effusion. Pericardial tamponade. Thromboembolic events. Pulmonary fibrosis. Pneumocystis carinii pneumonia. Shortness of breath and bronchial asthma. Pleural effusion. Acute hepatitis. Renal failure. Anuria. Very rare: Lymphoma. Agranulocytosis. Severe courses of bone marrow depression. Acute aseptic meningitis. Convulsions. Paralysis. Impaired vision. Retinopathy. Haematemesis. Toxic megacolon. Hepatic failure. Stevens-Johnson syndrome. Toxic epidermal necrolysis. Not known: Eosinophilia. Encephalopathy/Leukoencephalopathy. Legal classification: POM. MA numbers: Nordimet: EU/1/16/1124/001 – 008. Further information available from: Nordic Pharma Ltd, Unit 3, Commerce Park, Brunel Road, Theale, Reading, United Kingdom. Date of prescribing information: January 2017. Code for PI: NOR/17/001i Adverse events should be reported. Adverse events should be reported. Reporting forms and information can be found at http://www.hpra.ie Adverse events should also be reported to Nordic Pharma Ireland: email@example.com Phone no. +353 (0)1 4004141
CVD in patients with Rheumatoid Arthritis In 2009, the European League Against Rheumatism (EULAR) task force was convened to critically appraise existing evidence on CVD risk in patients with IJD. This EULAR task force formulated 10 recommendations for the screening and identification of CVD risk factors and the implementation of CVD risk management in IJD (see online supplementary file 1).4 In view of substantial new evidence, an update of the CVD risk management recommendations was performed. For this update, a new EULAR task force reviewed all the previous recommendations from 2009 on CVD risk management in IJD. New areas were addressed, including the value of imaging in the routine assessment of CVD risk. Task force With the approval of the EULAR Executive Committee, the convenor (MTN) and methodologist (DPMS) who guided the task force in 2009 formed a new task force with the aim of reviewing and updating the 2009 EULAR recommendations for CVD risk management in RA and other IJD (see online supplementary file 1).4 The task force comprised 26 members from 13 European countries, including 2 patient representatives, 14 rheumatologists, 2 cardiologists, 3 internists, 1 healthcare professional and 4 fellows. The entire process was conducted in accordance with the 2014 EULAR standardised operating procedures.10 Overarching principles The task force defined three overarching principles of CVD risk management in RA and other IJD. 1. Clinicians should be aware of the higher risk for CVD in patients with RA compared with the general population. This may also apply to AS and PsA 2. The rheumatologist should ensure that CVD risk management is performed in patients with RA and other IJD. 3. The use of non-steroidal antiinflammatory drugs (NSAIDs)
April 2017 • HPN
and corticosteroids should be in accordance with treatmentspecific recommendations from EULAR and the Assessment of Spondyloarthritis International Society (ASAS).44, 45 Recommendations In line with the 2009 guidelines, we opted to give again 10 recommendations for CVD risk management. In total, three recommendations remained unchanged, six recommendations were altered and there is one new recommendation. One of the 2009 recommendations (#1) was moved to the overarching principles as described previously. A list of the updated recommendations, including the levels of evidence with the strength of recommendation and the LOA based on voting by the task force, is shown in table 1. The recommendations follow a logical sequence, and they are not listed in sequence of importance. All recommendations are discussed in detail below. Disease activity should be controlled optimally in order to lower CVD risk in all patients with RA, AS or PsA (unchanged, LOA 9.1 (1.3)). In the previous recommendations from 2009, the importance of control of disease activity to lower CVD risk was emphasised. New evidence still portrays an association between higher cumulative inflammatory burden and increased CVD risk in RA.49–54 Disease duration does not seem to affect CVD risk independently.50 However, disease activity as well as the number and duration of flares over time do contribute to the risk of CVD.49–52 There is now additional evidence showing a reduction of CVD risk in patients treated with disease-modifying antirheumatic drugs (DMARDs). Reducing inflammation is important in RA for CVD risk management, but the type of treatment may be less important. Conventional synthetic DMARDs (csDMARDs), in particular methotrexate (MTX), as well as biological DMARDs (bDMARDs), such as the TNF inhibitors (TNFi), are often associated with a significant reduction in CVD risk
Cardiovascular Disease (CVD) in RA Increased incidence of CVD and mortality in RA: 2-4 times Not only traditional CVD risk factors (smoking, lipids, hypertension, DM) increased Inflammation involved in pathogenesis of atherosclerosis High index of suspicion; atypical, silent chest pain, CHF, and sudden death common CVD accounts for much excess mortality in RA
in patients with RA.46, 49, 51, 53, 55–62 The CVD risk appears to decrease even further after long-term use.53, 56 Reduction of disease activity after treatment with tocilizumab or rituximab (RTX) shows a beneficial effect on cIMT, a surrogate marker for CVD, and CVD risk in a limited number of studies.54, 63–65 Beneficial effects of TNFi and MTX on arterial stiffness have also been described.43, 66–71 One study described a reduction in aortic inflammation and stiffness measured by 18F-FDG positron emission tomography-CT after TNFi treatment in patients with RA.72 For both AS and PsA, evidence for the association between inflammation and an enhanced CVD risk is less abundant compared with RA. In view of shared pathogenic mechanisms, it is plausible that decreasing the inflammatory burden in AS and PsA will also have favourable effects on the CVD risk in these patients. Therefore, control of disease activity, as is routinely recommended, is expected to lower CVD risk for both AS and PsA. • CVD risk assessment is recommended for all patients with RA, AS or PsA at least once every 5 years and should be reconsidered following major changes in antirheumatic therapy (changed, LOA 8.8 (1.1)).
CVD risk assessment is recommended for all patients with RA, AS or PsA at least once every 5 years, so that lifestyle advice and CVD preventive treatment can be initiated when indicated. The advice to screen patients with IJD for CVD risk on a yearly basis has been changed to screening every 5 years, which is in line with the latest ESC guidelines.7 Currently, there is no evidence that annual CVD risk assessment compared with 5-year risk assessment leads to a more significant reduction in CVD mortality or morbidity in patients with IJD. Depending on the CVD risk algorithm that is used for screening, patients can be categorised as having low to moderate risk (eg, SCORE <5%), high risk (eg, SCORE ≥5% and <10%) and very high risk (eg, SCORE ≥10%).7 Once screened, patients with a low risk can be routinely screened again after 5 years. However, if the risk is intermediate rescreening may be done sooner, especially if disease progression is more rapid. Patients with a high risk or established CVD should be treated for all present CVD risk factors according to existing guidelines. A healthy lifestyle should be recommended to all persons, including patients with low and intermediate cardiovascular risk.7 CVD risk evaluation should be reconsidered after major changes in antirheumatic therapy, that is, the initiation of bDMARDs or other drugs that may cause pronounced
29 with RA by a 1.5 multiplication factor, if this is not already included in the risk algorithm (changed, LOA 7.5 (2.2)).
increases in low-density lipoprotein cholesterol (LDLc) or alter other CVD risk factors, so that doctors can act accordingly.73, 74 • CVD risk assessment for patients with RA, AS or PsA should be performed according to national guidelines and the SCORE CVD risk prediction model should be used if no national guideline is available (unchanged, LOA 8.7 (2.1)). Evidence is scarce with regard to the validity of disease-specific CVD risk prediction models to accurately predict risk in individual patients with RA, and it is therefore currently recommended to perform risk evaluation according to general population guidelines. Several novel and RA disease-specific factors have been associated with an increased risk of CVD, but at present it is uncertain if these factors will meaningfully and cost-effectively improve CVD risk prediction in patients with RA. • Total cholesterol (TC) and high-density lipoprotein cholesterol (HDLc) should be used in CVD risk assessment in RA, AS and PsA and lipids should ideally be measured when disease activity is stable or in remission. Non-fasting lipids are perfectly acceptable (changed, LOA 8.8 (1.2)). The relationship between serum lipid levels and CVD risk is non-linear and potentially paradoxical in RA. Patients with RA with highly active disease generally have lower serum TC and LDLc levels compared with the general population, while their CVD risk is elevated.73, 75–78 As described
in the 2009 recommendations, these patients also have reduced serum levels of HDLc and higher levels of triglycerides as compared with healthy controls.78–81 In general, controlling disease activity has widespread effects on the lipid profile. Treatment with TNFi and/ or csDMARDs (mainly MTX) results in an overall increase of lipid components, but mostly HDLc, which improves the TC/HDLc ratio.79–93 A limited number of studies have reported beneficial effects of RTX and tocilizumab on individual lipid components.64, 94, 95 However, the net effect of treatment with these agents is an overall increase of individual lipid components without changes in TC/HDLc ratio.54, 96–101 The same appears to be true for tofacitinib.100 Still, statins are effective at reducing lipid levels in tocilizumab or tofacitinib-treated patients with sustained elevations of TC and LDLc.99, 100 As described in the 2009 recommendations, the TC/ HDLc ratio is a better CVD risk predictor in RA than individual lipid components.78, 102 From a practical point of view, both TC and HDLc can be used when using online calculators. As lipid components appear to be modifiable by disease activity and anti-inflammatory therapy, assessment of the lipid profile should preferably be done when a patient has stable disease or is in remission. Finally, measurement of TC and HDLc are perfectly acceptable in non-fasting state, as noted in the recent 2016 European Guidelines on CVD prevention in clinical practice: prevention guidelines.7 • CVD risk prediction models should be adapted for patients
The SCORE risk calculator is recommended for CVD risk prediction in the general population by the ESC guidelines.103 However, CVD risk prediction models developed for the general population do not include non-traditional CVD risk factors and hence there is a possibility of underestimation of future CVD if these models are applied in patients with RA. It is indeed reported that several CVD prediction models inaccurately predict the risk of CVD in patients with RA.8, 104, 105 The 2009 EULAR recommendations for CVD risk management suggested a multiplication factor of 1.5 to the calculated total CVD risk if the patient fulfilled certain disease-specific criteria (ie, disease duration of >10 years, RF or ACPA positivity and the presence of certain extra-articular manifestations).4 It has been argued that the application of this multiplication factor does not reclassify as many patients as was expected into a more appropriate risk category.9, 106 In addition, QRESEARCH Cardiovascular Risk Algorithm (QRisk) 2, a CVD risk prediction model that includes RA as a risk factor with a multiplication factor of 1.4 for all patients with RA,107 tended to overestimate the CVD risk in patients with RA. QRISK 2 estimates the risk of fatal and non-fatal CVD combined.8 Currently, there are no alternative CVD risk prediction models with a proven accuracy and superiority for patients with IJD. Based on all recent epidemiology, this multiplication factor is still the most evidence-based way of estimating CVD risk in patients with RA. Therefore, the use of an RA-adapted risk prediction model is recommended over the use of an unadapted general population model, since there is a higher level of evidence on their predictive value. Based on this, the EULAR task force still recommends to adapt general population CVD risk algorithms (except for QRISK 2, in which the multiplication factor is intrinsic to the algorithm) with a 1.5 multiplication factor for all patients with RA. In contrast to the 2009 recommendations, the presence of certain RA-specific criteria is not mandatory anymore for the application of this multiplication factor, as evidence on the increased CVD risk in patients who are in the early stages of
RA, patients with a recent RA diagnosis and patients without extra-articular manifestations.108, 109 • Screening for asymptomatic atherosclerotic plaques by use of carotid ultrasound may be considered as part of the CVD risk evaluation in patients with RA (new, LOA 5.7 (3.9)). The presence of carotid plaques is associated with poor CVD-free survival and is strongly linked to future acute coronary syndrome (ACS) in patients with RA, with a rate of ACS of 1.1 (95% CI 0.6 to 1.7) per 100 person-years (pyrs) for patients with RA with no carotid plaques and 4.3 (95% CI 2.9 to 6.3) per 100 pyrs for those with bilateral plaques.66, 110 RA-specific factors contribute to the presence of carotid atherosclerosis in addition to traditional CVD risk factors.111 Disease duration and disease activity have been shown to be associated with plaque size and vulnerability in patients with RA.112, 113 The most recent ESC Guidelines on CVD prevention in clinical practice recommend considering screening for carotid artery atherosclerosis in patients with moderate CVD risk (class: IIa, level of evidence: B, GRADE: strong).7 Autoimmune diseases like RA, systemic lupus erythematosus and psoriasis were acknowledged as diseases with increased CVD risk.7 Due to the high pretest probability for detection of carotid artery plaques by use of ultrasound in patients with RA, and the clinical consequence of indication for statin treatment if a carotid plaque is present, this procedure could be of additional value for CVD risk evaluation. Ultrasound of the carotid arteries to identify atherosclerosis has been shown to reclassify a considerable proportion of patients with RA into a more appropriate CVD risk group in accordance with current guidelines.114 • Lifestyle recommendations should emphasise the benefits of a healthy diet, regular exercise and smoking cessation (changed, LOA 9.8 (0.3)). Since the 2009 recommendations, no new strong evidence has emerged on the role of smoking on CVD risk in IJD and hence this recommendation remains unchanged. Thus, patients should be advised to stop smoking and directed towards the locally defined evidence-based smoking cessation programmes, even if they have failed previously. The 2009 recommendations did not
HPN • April 2017
30 Feature discuss diet or exercise, but it was mentioned in the research agenda.4 Research on the role of exercise in RA management has advanced considerably since 2009. Physical inactivity is common in patients with RA, and has been associated with an adverse CVD risk profile.115–117 There is accumulating data that structured exercise therapy has beneficial CVD effects in patients with RA, at least in the short and medium term.118–120 Exercise has been shown to reduce long-term inflammation in epidemiological studies conducted in the general population and increased physical activity was associated with lower levels of C reactive protein (CRP).121 This has also been demonstrated in a study with patients with RA in which a 6-month exercise programme lowered CRP levels, probably related to a reduction in body fat.118 Moreover, improvements in both microvascular and macrovascular function were found after 3 months of exercise in RA.120 To date, no studies have shown any adverse effects as a result of exercise.119 Hence, in RA, high-intensity exercise is not contraindicated and should be encouraged in those already accustomed to activity. Physical activity that is enjoyable is more likely to be sustained. A Mediterranean diet is characterised by a high consumption of fruit, vegetables, legumes and cereals, and contains less red meat and more fish compared with common Western diets. Olive oil or vegetable oil is the primary source of fat intake. This diet has been shown to be associated with a reduced incidence of major CVD events in the general population.122 In RA, the positive effect of a Mediterranean diet may be mediated by the effect of this diet on disease activity.123 However, there is no specific evidence available on the effect of dietary modifications on CVD risk in patients with IJD. Therefore, we recommend national guidelines regarding a healthy diet as part of a healthy lifestyle as discussed below. An important issue remaining is how lifestyle interventions should be advocated to patients with IJD. Studies in this field demonstrate that if information is provided, this should be linked to behavioural education.124 A randomised controlled trial in patients with RA evaluated the effect of cognitive behavioural patient education
April 2017 • HPN
with regard to modifiable CVD risk factors in people with RA: patients receiving this intervention had more knowledge, and improved behavioural intentions, however, actual behaviour did not differ between groups.125 Obviously, this area is in need of more research. • CVD risk management should be carried out according to national guidelines in RA, AS or PsA, antihypertensives and statins may be used as in the general population (changed, LOA 9.2 (1.3)). Hypertension is a major modifiable risk factor contributing to increased CVD risk in IJD.126–128 Several mechanisms may lead to the development of hypertension, including the use of certain antirheumatic drugs such as corticosteroids, NSAIDs, ciclosporin and leflunomide.129–132 It is important to realise that hypertension seems to be both underdiagnosed and undertreated in patients with RA.127 For the management of hypertension and hyperlipidaemia, there is no evidence that treatment thresholds should differ in patients with IJD compared with the general population. In the past years, no new evidence has emerged that ACE inhibitors and angiotensin II (ATII) receptor blockers should be the preferred treatment choice for hypertension in patients with RA. Therefore, the previous treatment preferences for ACE inhibitors and ATII receptor blockers have been omitted. Since the 2009 recommendations, several studies have assessed the efficacy of statins in patients with RA. Statins appeared to be at least as effective in reducing cholesterol levels, atherosclerotic burden and CVD morbidity and mortality, and they do not have more adverse reactions in patients with RA when compared with non-RA controls.77, 133–139 In addition, statins have anti-inflammatory properties that may result in an even greater CVD risk reduction when combined with anti-inflammatory therapy in RA, but studies on this effect are scarce.140–142 A few preclinical studies found unfavourable effects of statins on RTX efficacy in patients with haematological malignancies.143, 144 However, several clinical studies showed no significant differences in outcome between statin users and non-users receiving RTX treatment for a haematological malignancy.145–148 Clinical trials investigating this issue in RA are scarce. Three clinical studies
in RA found no adverse effect of statins on RTX efficacy.149–151 Only one observational study reported a significant difference in disease activity 6 months after first RTX treatment in statin users as compared with non-users, but this finding was borderline significant (p=0.049) in a small sample size of statin-exposed patients (n=23 exposed vs n=164 non-exposed).152 Obviously, further research is necessary to address this issue properly. • Prescription of NSAIDs in RA and PsA should be given with caution, especially for patients with documented CVD or in the presence of CVD risk factors (changed, LOA 8.9 (2.1)). The 2009 recommendations advocate that NSAIDs should be used with caution in this population or may even be contraindicated.4, 153, 154 Since the publication of the former recommendations, new evidence has emerged on the role of cyclooxygenase-2 inhibitors (COXIBs) and non-selective NSAIDs in CVD risk. A recent meta-analysis concluded that, overall, both non-selective NSAIDs and COXIBs have adverse effects on CVD outcomes in patients with RA and PsA.46 However, the increased CVD risk was mainly observed for rofecoxib, which was withdrawn from the market in 2004. There is evidence that NSAIDs might increase CVD risk in RA to a lesser extent in comparison to the general population than was previously thought.48 Hence, there is no evidence to be stricter with NSAID treatment in patients with RA than what is recommended in the national guidelines for patients with no RA. Safety data regarding the use of NSAIDs in patients with IJD and prevalent CVD comorbidities are lacking. Naproxen seems to have the safest CVD risk profile.46, 48 In general, diclofenac is contraindicated in patients with established congestive heart failure (NYHA class II–IV), ischaemic heart disease, peripheral arterial disease or cerebrovascular disease, and new evidence supports similar restrictions for ibuprofen use.153, 154 For patients with AS, NSAIDs are recommended as first-line drug treatment by the ASAS/EULAR group in the recommendations for the management of pain and stiffness in patients with AS, and an individual clinical evaluation regarding NSAIDs use in patients with AS with established CVD is therefore needed.155
• Corticosteroids: for prolonged treatment, the glucocorticoid dosage should be kept to a minimum, and a glucocorticoid taper should be attempted in case of remission or low disease activity; the reasons to continue glucocorticoid therapy should be regularly checked (unchanged, LOA 9.5 (0.7)). Corticosteroids rapidly and effectively reduce inflammation in RA, but they have also been associated with an increased CVD risk, although the literature shows conflicting results. Since the 2009 recommendations, new studies have found a dose-dependent and durationdependent increase in CVD risk associated with corticosteroid use in RA.47,156,157 A relatively high daily dose (ie, already starting from 8 to 15 mg/day), a high cumulative dose and a longer exposure to corticosteroids (in years) appear to be associated with a higher CVD risk.47, 156–158 Some authors argued that this increased CVD risk was confounded by indication, as it was no longer significant after correction for disease activity.53, 159–161 On the contrary, other studies that had corrected for disease activity still found a (cumulative) dose-dependent and duration-dependent increase in CVD-related morbidity and mortality in patients with RA.47, 156 However, this does not mean that confounding by indication has been completely addressed and this is a major limitation of all safety studies on corticosteroids. There is no conclusive evidence about the long-term effects of corticosteroids, particularly in low daily dosage, on safety outcomes including CVD events in RA. In patients with active disease, the benefit of reducing high-grade inflammation may counteract the adverse CVD effects of corticosteroid use by reduction of inflammation and by improving mobility. In other words, steroids may help to abrogate the harmful effect of inflammation on the cardiovascular system, but they will still carry their own adverse effects on CVD risk. Altogether, from a CVD prevention point of view, the lowest effective dose of corticosteroids should be prescribed for the shortest possible duration in the treatment of active IJD. This recommendation is in line with the EULAR recommendations on management of glucocorticoid therapy.44 Refernces on request
CPD 31: Diabetes Continuing Professional Development
Sarah-Jo Sinnott,1,2 Sheena McHugh,1 Helen Whelton,3 Richard Layte,4,5 Steve Barron,5 and Patricia M Kearney1 Department of Epidemiology and Public Health, University College Cork, Cork, Ireland Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK 3 School of Dentistry, University of Leeds, Leeds, UK 4 Department of Sociology, School of Social Sciences and Philosophy, Trinity College Dublin, Dublin, Ireland 5 Economic and Social Research Institute, Dublin, Ireland 1 2
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 To estimate the prevalence and incidence of type 2 diabetes using a national pharmacy claims database. We used data from the Health Service Executive-Primary Care Reimbursement Service database in Ireland for this crosssectional study. Prevalent cases of type 2 diabetes were individuals using an oral hypoglycemic agent, irrespective of insulin use, in 2012. Incident cases were individuals using an oral hypoglycemic agent in 2012 who had not used one in the past. Population level estimates were calculated and stratified by age and sex. In 2012, there were 114 957 prevalent cases of type 2 diabetes giving a population prevalence of 2.51% (95% CI 2.49% to 2.52%). Among adults (â‰Ľ15yrs), this was 3.16% (95% CI 3.15% to 3.18%). The highest prevalence was in those aged 70+ years (12.1%). 21 574 people developed type 2 diabetes in 2012 giving an overall incidence of 0.48% (95% CI 0.48% to 0.49%). In adults, this was 0.60% (95% CI 0.60% to 0.61%). Incidence rose with age to a maximum of 2.08% (95% CI 2.02% to 2.15%) in people aged 65â€“69 years. Men had a higher prevalence (2.96% vs 2.04%) and incidence (0.54% vs 0.41%) of type 2 diabetes than women. Pharmacy claims data allow estimates of objectively defined type 2 diabetes at the population level using up-to-date data. These estimates can be generated quickly to inform health service planning or to evaluate the impact of population level interventions.
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.
Estimating the prevalence and incidence of type 2 diabetes using population level pharmacy claims data: a cross-sectional study Diabetes mellitus is a leading cause of death globally, causing almost 4 million deaths in 2010.1 Morbidity arising from the disease is also substantial; the Global Burden of Disease study estimated a 30% increase in disability-adjusted life years for diabetes between 1990 and 2010 due to increasing prevalence of the disease and increased longevity of those living with diabetes.2 To reduce diabetes-related mortality and morbidity, access to appropriate healthcare services for people with diabetes is a necessity. For this to be successful, up-to-date population level estimates of disease burden are required to rationally plan and deliver the required health services. The Institute of Public Health (IPH) estimates and forecasts for the prevalence of diabetes (combined type 1 and type 2) are often cited and are a valuable resource.3 However, the most recent estimates from the IPH are based on a cross-sectional survey of adults in the Survey of Lifestyle, Attitudes and Nutrition (SLAN) which dates back to 2007.3, 4 Other estimates of diabetes prevalence come from The Irish Longitudinal Study
of Ageing (TILDA), which is limited to those over 50 years,5, 6 the Mitchelstown cohort which was limited to adults aged 50â€“69 years in one rural area in the South of Ireland7 and the Central Statistics Office (CSO) Quarterly National Household Survey (QNHS) from 2010.8 These estimates are based on a variety of self-reported doctor diagnosis; selfreported diabetes medication usage; or a combination of self-report and HbA1c data; and all are limited to adult populations. Furthermore, there is a scarcity of data available on the incidence of diabetes in Ireland.9 In this study, we used national pharmacy claims data to estimate the prevalence and incidence of type 2 diabetes. These data provide an objective measure of treated diabetes in the total population to complement existing sample-based estimates. Health system In Ireland, access to and reimbursement for diabetes medicines occur via two publicly funded community drug schemes. The first is the General Medical Services (GMS) scheme; the main public health insurance program providing primary
Continuous Professional Development Modules are sponsored by MSD MSD has no editorial oversight of the CPD programmes included in these modules.
CPD 31: Diabetes
Table 1 Types of medicines used in 2012 Medicine group Biguanides
Sulfonylureas Thiazolidinediones DPP-4
A10BC, A10BF, A10BX
WHO ATC code n (%) Total
907 125 (51.9) 527, 886 (30.2) 25 658 (1.5)
126 345 (7.2) 60 069 (3.4)
1 747 755 (100.0)
12 537 (67.6)
18 554 (1.06)
48 558 (59.3)
17 542 (21.4)
81 960 (4.7)
125 732 (54.0) 57 833 (24.8)
14 760 (6.3)
14 168 (6.1)
232 955 (13.3)
236 515 (52.6) 122 554 (27.3) 7493 (1.7)
31 253 (6.9)
20 675 (4.6)
449 432 (25.7)
140 569 (52.0) 79 897 (29.6)
20 725 (7.7)
270 106 (15.5)
333 853 (49.3) 242 256 (35.8) 8435 (1.3)
53 435 (7.9)
10 600 (1.6)
677 401 (38.8)
368 707 (53.2) 204 465 (29.5) 9450 (1.4)
49 794 (7.2)
25 412 (3.7)
692 565 (39.6)
536 766 (51.0) 322 465 (30.7) 16 073 (1.5)
76 275 (7.3)
34 545 (3.3)
1 051 910 (60.2)
Numbers are numbers of prescriptions in 2012. Other includes sulfonamides, α glucosidase inhibitors and ‘other’ agents as defined by WHO ATC dictionary. DPP-4, dipeptidyl peptidase-4 inhibitors.
and secondary healthcare free at the point of access to ∼40% of the Irish population on a means-tested basis.10 Medicines are included under this scheme but are subject to a copayment (¤2.50 currently). The second drug scheme is the long-term illness (LTI) scheme. The LTI provides free access to condition-related medicines for individuals diagnosed with any of 16 chronic illnesses including diabetes. LTI coverage is independent of income. Data Pharmacists dispensing medicines to all patients (adults and children) on the GMS and the LTI scheme are reimbursed by the government via the Health Service Executive-Primary Care Reimbursement Service
(HSE-PCRS). We used dispensing data from the HSE-PCRS database from July 2011 to December 2012. Data were available for the drug dispensed (classified by WHO Anatomical Therapeutic Chemical (WHO ATC) code), date dispensed, quantity and strength, in addition to patient age and sex. Population denominator data for the year 2012 were population estimates derived by the CSO based on the 2011 census.11 Definitions Type 2 diabetes was classified as using any strength or quantity of an oral hypoglycemic agent (WHO ATC A10B), irrespective of age or insulin use. The different agents included in this study,
stratified by age and sex, are given in table 1. Calculation of incidence and prevalence To estimate the prevalence of type 2 diabetes, we used dispensing data for 2012. We counted the number of people in the database who met our definition of type 2 diabetes and used this as the numerator. The total population count published by the CSO was the denominator.11 To establish the annual incidence for type 2 diabetes in 2012, we used data from July 2011 to December 2012. An individual's first occurrence in 2012 meeting the definition of type 2 diabetes was referred to as the index date. A 6 month look-back period was used to rule out prior
use before the index date. If no prior use of an oral hypoglycemic agent occurred in the look-back period, then the individual was an incident user of oral hypoglycemic medicines and thus an incident case. This count was used as the numerator, while the denominator was the total population count published by the CSO minus the number of prevalent of cases.11 We carried out subgroup analyses by age group (<15 years, ≥15 years, 15–24 years, 25–34 years, 35–44 years, 45–54 years, 55–64 years, 65–69 years and >70+ years) and sex. Results In 2012, 1 655 013 people accessed a prescription on the GMS scheme and were
Continuous Professional Development Modules are sponsored by MSD MSD has no editorial oversight of the CPD programmes included in these modules.
33 Table 2 Prevalence and incidence of type 2 diabetes GMS
Population (CSO) Estimate (%)
4 585 000
2.49 to 2.52
Total population ≥15 years
3 590 600
3.15 to 3.18
0.18 to 0.20
0.12 to 0.14
0.32 to 0.35
1.03 to 1.08
2.87 to 2.95
6.43 to 6.57
10.61 to 10.90
11.99 to 12.20
2 315 800
2.02 to 2.06
2 269 600
2.94 to 2.98
4 470 043
0.48 to 0.49
Total population ≥15 years
3 476 995
0.60 to 0.61
0.04 to 0.05
0.08 to 0.09
0.16 to 0.18
0.33 to 0.36
0.68 to 0.72
1.23 to 1.29
2.02 to 2.15
1.81 to 1.9
2 268 601
0.40 to 0.41
2 202 383
0.53 to 0.55
available in our data set. The mean age was 42.9 years (SD 25.9), and the population was 54.4% women. On the LTI scheme, 68 996 people accessed at least one prescription in 2012. The mean age was 48.4 years (SD 25.2), and the population was 38% women. Type 2 diabetes mellitus In 2012, 114 957 people were classified as prevalent type 2 diabetes cases, leading to a prevalence of 2.51% (95% CI 2.49% to 2.52%) in the total population. After excluding
those aged <15 years, an adult population prevalence of 3.16% (95% CI 3.15% to 3.18%) was obtained (table 2). Figure 1 demonstrates how the prevalence increased with age; 55–64 years (6.50%), 65–69 years (10.75%) and 70+ years (12.10%). Men had a higher prevalence of type 2 diabetes than women at 2.96% (95% CI 2.94 to 2.98) vs 2.04% (95% CI 2.02% to 2.06%) (χ2 test for homogeneity p<0.0001).
0.49%). This was estimated at 0.60% (95% CI 0.60% to 0.61%) in the population aged ≥15 years. The incidence of type 2 diabetes increased with age, reaching its highest level of 2.08% (95% CI 2.02 to 2.15) in people aged 65–69 years. Men had a higher incidence of type 2 diabetes (0.54%) than women (0.41%) (table 2 and figure 1).
In the same year, 21 574 people developed type 2 diabetes giving an incidence of 0.48% (95% CI 0.48% to
This cross-sectional study estimated the prevalence and incidence of type 2 diabetes using population level data
from a national pharmacy claims database. The overall prevalence in the adult population was 3.16%. The incidence of type 2 diabetes was 6 cases per 1000 adult people in 2012. Existing prevalence estimates pertaining to the general adult population range from 3% in the Quarterly National Household survey to 3.5% in those aged ≥18 years using SLAN survey data.4, 8 Our estimate of 3.16% is thus comparable to previous figures. In addition, our age stratified estimates for people
Continuous Professional Development Modules are sponsored by MSD MSD has no editorial oversight of the CPD programmes included in these modules.
CPD 31: Diabetes
Figure 1: Prevalence and incidence of type 2 diabetes.
aged ≥50 years are similar to those based on TILDA using self-report of doctor diagnosis and HbA1c measures.5, 6 However, our estimates may underestimate the true burden of diabetes given that we have excluded type 1 diabetes and we also could not account for lifestyle-treated diabetes or undiagnosed diabetes. Despite this, the true prevalence rate of diabetes in Ireland is likely lower than that in the USA which was recently estimated at 8.3% in the adult population.12 In England, diagnosed diabetes in the population aged ≥16 years is estimated at 5.6% from Health Survey for England data.13 The only other estimate of incidence of type 2 diabetes in Ireland is 2 cases per 1000, in contrast to the 6 cases per 1000 we found in this study.9 An American study using the National Health Interview Survey found an incidence rate of 7.1/1,000 people aged ≥20 years in 2012, indicating that Irish incidence rates are below those in North America.12 A recent Danish study calculated incidence rates for every year of age.14 While it is difficult to compare single age estimates with
estimates for age categories, our estimates appear comparable to those in the Danish study, albeit somewhat higher in the older age groups.14 Making international comparisons is helpful to aid in understanding the plausibility of our estimates, however differences do exist between populations for demographic and methodological reasons.15 The study is limited by lack of information on undiagnosed diabetes and lifestyle-treated diabetes. Other data sources, for example the Mitchelstown Cohort and SLAN survey, provide information on undiagnosed diabetes, which can be used in tandem with our results.4, 7 Unpublished data from the Mitchelstown Cohort study of over 2000 adults aged 50–69 years reveal that ∼7% of those with self-reported diabetes are treated with diet only.16 Although these data are not nationally representative, they provide some context on the magnitude of underestimation. Furthermore, we relied on diagnosed individuals adhering to their treatment regimens, their dispensed medications thus appearing in the pharmacy claims database.
We did not anticipate nonadherence to be a major problem given that medicines are free on the LTI scheme and subject to a small copayment on the GMS scheme (¤0.50 per item in 2012).17 The study is strengthened by the objective and reliable nature of the data.18 Additionally, because diabetes medicines are generally provided only through the GMS and LTI drug schemes, data on those with diagnosed and treated diabetes should be nationally complete in this database offering population level data for all ages, including children, in contrast to previous surveys and cohort studies which are limited to adults. Unfortunately, the database does not have access to diagnosis codes, thus we made the assumption that all oral hypoglycemic agents were being used to treat diabetes. A notable exception is the use of metformin for polycystic ovarian syndrome (PCOS). However, as PCOS effects only a small proportion of women of reproductive age, ∼8%, and only some of these will be treated, any effect on our estimates is likely
to be small. Further, many women with PCOS will have diabetes, and we will have intended to include them in our estimates.19 Metformin is also used in pre-diabetes, which due to lack of diagnosis codes, we have not been able to separate from our estimates. We know from our prior research that the prevalence of pre-diabetes in those aged ≥45 years is 20%.20 From the most recent audit of diabetes management in General Practice, we know that ∼90% of those with pre-diabetes are treated with dietary intervention (unpublished).21 Thus, any bias contributed to our results from including those with metformin-treated pre-diabetes is likely to be inconsequential. Our study has demonstrated the utility of routinely collected administrative claims data in calculating measures of disease burden, including incidence. The method is straightforward, and while we used data from 2012 for this study, more current data would allow estimating disease burden for the most recently completed calendar year along with establishing longitudinal trends. This approach affords advantages in realtime monitoring of disease burden and thus presents a key resource for evaluating public health interventions to reduce the prevalence and incidence of type 2 diabetes, thus informing health policy and health service planning. To address acknowledged weaknesses in using these data, estimates for prevalence and incidence should be considered in combination with cross-sectional and cohort study results to account for undiagnosed and lifestyletreated cases. References available on request.
As an adjunct to diet and exercise for appropriate patients with type 2 diabetes
SUPPORT YOUR PATIENTS WITH
INCLUDING EVIDENCE FROM
TEC S TRIAL EVALUATING CARDIOVASCULAR
O U T C O M E S W I T H S I TA G L I P T I N
NOW EVEN MORE REASONS TO CHOOSE JANUVIA® FIRST AS A PARTNER TO METFORMIN1 Januvia or Janumet. For Januvia only– Renal Impairment: Lower dosages are recommended in patients with moderate and severe renal impairment, as well as in ESRD patients requiring haemodialysis or peritoneal dialysis- see Dosage. For Janumet only - Lactic acidosis and renal function: a very rare, but serious, metabolic complication can occur due to metformin accumulation. Cases in patients on metformin have occurred primarily in diabetic patients with significant renal failure. Reduce incidence by assessing other associated risk factors. If suspected, discontinue treatment and hospitalise patient immediately. Determine serum creatinine concentrations regularly, i.e. at least once a year in patients with normal renal function and at least two to four times a year in patients with serum creatinine levels at or above the upper limit of normal and in elderly patients. Decreased renal function in elderly patients is frequent and asymptomatic. Exercise special caution where renal function may become impaired, e.g. when initiating antihypertensive or diuretic therapy or when starting treatment with a non-steroidal anti-inflammatory drug (NSAID). Surgery: due to metformin hydrochloride content of Janumet, discontinue treatment 48 hours before elective surgery with general, spinal or epidural anaesthesia. Do not resume earlier than 48 hours afterwards and only after renal function is normal. INTERACTIONS For Janumet only - Alcohol: avoid alcohol and medicinal products containing alcohol due to risk of lactic acidosis. Cationic agents that are eliminated by renal tubular secretion (e.g., cimetidine): these may interact with metformin by competing for common renal tubular transport systems. Consider close monitoring of glycaemic control, dose adjustment within the recommended posology and changes in diabetic treatment when these agents are co-administered. Iodinated contrast agents in radiological studies: intravascular administration of these agents may lead to renal failure, resulting in metformin accumulation and a risk of lactic acidosis. Discontinue Janumet prior to, or at the time of the test and do not reinstitute until 48 hours afterwards, and only after renal function is found to be normal. Combination requiring precautions for use: glucocorticoids (given by systemic and local routes) beta-2-agonists, and diuretics have intrinsic hyperglycaemic activity. Inform the patient and perform more frequent blood glucose monitoring, especially at the beginning of treatment. If necessary, adjust dose of the anti-hyperglycaemic medicine during therapy with, or on discontinuation of the other medicine. ACE-inhibitors: as these may decrease the blood glucose levels, if necessary, adjust dose of the antihyperglycaemic during therapy with, or on discontinuation of the other medicine. PREGNANCY AND LACTATION: Do not use during pregnancy or breast-feeding. Animal data do not suggest an effect of treatment with sitagliptin on male and female fertility. Human data are lacking. SIDE EFFECTS Refer to SmPC for complete information on side effects There have been no therapeutic clinical trials conducted with Janumet tablets however Janumet is bioequivalent to co-administered sitagliptin and metformin. Sitagliptin: Serious adverse reactions including pancreatitis and hypersensitivity reactions have been reported. Hypoglycaemia has been reported in combination with sulphonylurea and insulin. The following adverse reactions were reported from both clinical trials and post-marketing experience: Sitagliptin only: Common: hypoglycaemia, headache, Uncommon: dizziness, constipation and pruritus. Sitagliptin with metformin: Common: hypoglycaemia, nausea, flatulence and vomiting; Uncommon: somnolence; upper abdominal pain, diarrhoea, constipation and pruritus. For Januvia and Janumet: Post-marketing experience additional side effects have been reported (frequency not known): hypersensitivity reactions, including anaphylaxis, angioedema, rash, urticaria, cutaneous vasculitis, exfoliative skin conditions including Stevens-Johnson syndrome (see precautions), and bullous pemphigoid; acute pancreatitis, including fatal and non-fatal haemorrhagic and necrotising pancreatitis (see precautions); impaired renal function, including acute renal failure (sometimes requiring dialysis); vomiting; pain in extremity, arthralgia, myalgia, back pain and arthropathy; interstitial lung disease. Januvia: Description of selected adverse reactions Adverse experiences reported regardless of causal relationship to medication and occurring more commonly in patients treated with sitagliptin included upper respiratory tract infection, nasopharyngitis, osteoarthritis and pain in extremity. In the Trial Evaluating Cardiovascular Outcomes with sitagliptin (TECOS), after a median follow up of 3 years, sitagliptin, when added to usual care, did not increase the risk of major adverse cardiovascular events, or the risk of hospitalisation for heart failure compared to usual care without sitagliptin in patients with type 2 diabetes and established cardiovascular disease. PACKAGE QUANTITIES Januvia 25 mg, 50 mg and 100 mg film-coated tablets 28 tablets Janumet 50mg/850mg and 50mg/1000mg film-coated tablets 56 tablets Legal Category: POM. Marketing Authorisation Numbers Januvia 25 mg: EU/1/07/383/002 Janumet 50 mg/850 mg: EU/1/08/455/003 Januvia 50 mg: EU/1/07/383/008 Janumet 50 mg/1000 mg: EU/1/08/455/010 Januvia 100mg: EU/1/07/383/014 Marketing Authorisation Holder Merck Sharp & Dohme Limited, Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, UK Date of revision: January 2016 © Merck Sharp & Dohme Ireland (Human Health) Limited, 2016. All rights reserved. Further information is available on request from: MSD, Red Oak North, South County Business Park, Leopardstown, Dublin 18 or from www.medicines.ie. Date of preparation: October 2016. Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie Adverse events should also be reported to MSD (Tel: 01-299 8700)
Reference: 1. Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373(3):232–242.
Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7 Ireland
JANUVIA® (Sitagliptin) JANUMET® (Sitagliptin/metformin hydrochloride) ABRIDGED PRESCRIBING INFORMATION Refer to Summary of Product Characteristics (SmPC) before prescribing. PRESENTATION Januvia® 25 mg, 50 mg and 100 mg film-coated tablet each containing 25 mg, 50 mg or 100 mg of sitagliptin respectively. Janumet® 50 mg/850 mg and 50 mg/1000 mg tablets each containing 50 mg sitagliptin and 850 mg or 1000 mg metformin hydrochloride. INDICATIONS For adult patients with type 2 diabetes mellitus Januvia is indicated to improve glycaemic control: as monotherapy • in patients inadequately controlled by diet and exercise alone and for whom metformin is inappropriate due to contraindications or intolerance as dual oral therapy in combination with • metformin when diet and exercise plus metformin alone do not provide adequate glycaemic control • a sulphonylurea when diet and exercise plus maximal tolerated dose of a sulphonylurea alone do not provide adequate glycaemic control and when metformin is inappropriate due to contra-indications or intolerance • a PPARγ agonist (i.e. a thiazolidinedione) when use of a PPARγ agonist is appropriate and when diet and exercise plus the PPARγ agonist alone do not provide adequate glycaemic control as triple oral therapy in combination with • a sulphonylurea and metformin when diet and exercise plus dual therapy with these medicinal products do not provide adequate glycaemic control. • a PPARγ agonist and metformin when use of a PPARγ agonist is appropriate and when diet and exercise plus dual therapy with these medicinal products do not provide adequate glycaemic control. Januvia is also indicated as add on to insulin (with or without metformin) when diet and exercise plus stable dosage of insulin do not provide adequate glycaemic control. Janumet: as an adjunct to diet and exercise to improve glycaemic control in patients inadequately controlled on their maximal tolerated dose of metformin alone or those already being treated with the combination of sitagliptin and metformin. • in combination with a sulphonylurea (i.e., triple combination therapy) as an adjunct to diet and exercise in patients inadequately controlled on their maximal tolerated dose of metformin and a sulphonylurea. • as triple combination therapy with a PPARγ agonist (i.e., a thiazolidinedione) as an adjunct to diet and exercise in patients inadequately controlled on their maximal tolerated dose of metformin and a PPARγ agonist. • as add on to insulin (i.e., triple combination therapy) as an adjunct to diet and exercise to improve glycaemic control in patients when stable dosage of insulin and metformin alone do not provide adequate glycaemic control. DOSAGE AND ADMINISTRATION Januvia - One 100 mg sitagliptin tablet once daily, with or without food. Janumet - The dose of antihyperglycaemic therapy with Janumet should be individualised on the basis of the patient’s current regimen, effectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100 mg sitagliptin. For patients not adequately controlled on metformin alone, the usual starting dose should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) plus the dose of metformin already being taken. For patients switching from co-administration of sitagliptin and metformin, Janumet should be initiated at the dose of sitagliptin and metformin already being taken. For patients inadequately controlled on dual combination therapy with the maximal tolerated dose of metformin and a sulphonylurea or with maximal tolerated dose of metformin and a PPARγ agonist or with maximal tolerated dose of metformin and insulin, the dose should provide sitagliptin dosed as 50 mg twice daily (100 mg total daily dose) and a dose of metformin similar to the dose already being taken. All patients should continue their recommended diet with an adequate distribution of carbohydrate intake during the day. Januvia and Janumet - In combination with a sulphonylurea or with insulin, consider a lower dose of sulphonylurea or insulin, to reduce risk of hypoglycaemia. Renal impairment: For Januvia only: When considering sitagliptin with another anti-diabetic product, its use in patients with renal impairment should be checked. Moderate impairment (CrCl ≥30 to <50 mL/min), the dose is 50 mg once daily. Severe impairment (CrCl <30 mL/min) or with end-stage renal disease (ESRD), the dose is 25 mg once daily. Mild impairment, no dose adjustment. Assessment of renal function is recommended prior to initiation of Januvia and periodically thereafter. For Janumet only: Should not be used in patients with moderate or severe renal impairment (creatinine clearance < 60 ml/min). Hepatic impairment: For Januvia only - no dosage adjustment necessary for patients with mild to moderate hepatic impairment. Januvia has not been studied in patients with severe hepatic impairment and care should be exercised. However, because sitagliptin is primarily renally eliminated, severe hepatic impairment is not expected to affect the dose of sitagliptin. For Janumet only – do not use. Elderly < 75 years: For Januvia only - no dosage adjustment necessary. For Janumet only - use with caution as age increases. Monitoring of renal function is necessary to aid prevention of metformin-associated lactic acidosis. Children: no data available. CONTRAINDICATIONS For Januvia - Hypersensitivity to active substance or excipients. For Janumet - Hypersensitivity. Diabetic ketoacidosis and diabetic pre-coma. Moderate and severe renal impairment (creatinine clearance < 60 ml/min). Acute conditions with the potential to alter renal function such as dehydration, severe infection, shock. Intravascular administration of iodinated contrast agents. Acute or chronic disease which may cause tissue hypoxia such as cardiac or respiratory failure, recent myocardial infarction, shock. Hepatic impairment. Acute alcohol intoxication, alcoholism. Lactation. PRECAUTIONS AND WARNINGS For Januvia and Janumet - General: do not use in patients with type 1 diabetes or for diabetic ketoacidosis. Acute pancreatitis: Use of DPP 4 inhibitors has been associated with a risk of developing acute pancreatitis Inform patients of the symptom of acute pancreatitis: persistent, severe abdominal pain. Resolution of pancreatitis has been observed after discontinuation of sitagliptin, but very rare cases of necrotising or haemorrhagic pancreatitis and/or death have been reported. If pancreatitis is suspected, Januvia or Janumet and other potentially suspect medicinal products should be discontinued; if acute pancreatitis is confirmed, Januvia or Janumet should not be restarted. Caution should be exercised in patients with a history of pancreatitis. Hypoglycaemia when used with other anti-hyperglycaemic medicinal products: Rates of hypoglycaemia reported with sitagliptin were generally similar to rates in patients taking placebo. Hypoglcaemia has been observed when sitagliptin was used in combination with insulin or a sulphonylurea (see side effects). Therefore consider a lower dose of sulphonylurea or insulin to reduce the risk of hypoglycaemia when administering Janumet or Januvia. Hypersensitivity reactions: Serious hypersensitivity reactions have been reported, including anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Onset occurred within the first 3 months after initiation of treatment with some reports occurring after the first dose. If suspected, discontinue
Awards 36 Awards
Hospital Professional Awards 2017 – Benchmarking Success The Hospital Professional Awards benchmark success and innovation within Ireland’s hospital industry, recognising the Consultants, Specialists, Hospital Pharmacists and clinical teams that are actively driving the medical and pharmaceutical agenda. The Hospital Professional Awards offer a unique programme to bring these leading professionals together to showcase the ongoing projects currently being undertaken
throughout Ireland's hospitals to disseminate results, promote learning and best practice so that the excellence in specialist work is shared in every hospital setting in Ireland. Winners of a Hospital Professional Award will be chosen by an esteemed judging panel for their evidence-based research and/ or work in the enhancement of a field and/or therapeutic area for the ultimate benefit of Ireland's
hospital patients or the growth of the profession as a whole. Investing in the further development of secondary care within Ireland, the education and clinical learning derived from entries to the Hospital Professional Awards will highlight the quantifiable projects that have been driving benefits to both clinical peers and patients with the objective of greater shared outcomes.
The fourth annual Hospital Professional Awards will be held in the Clayton Hotel, Dublin (formerly the Burlington) on Saturday, September 16th, 2017. On the following pages we detail the Award Categories now open for 2017 including entry criteria and details of how to enter. Deadline for all submissions is Wednesday, June 7th, 2017
Hospital Professional News - Charity of the Year - Hugh’s House Families are under severe pressure with a very ill child being separated at a time when they needed each other the most. When a child is in hospital, no one can cheer them up or excite them as much as their brothers and sisters. They wanted a place for children who face long journeys for outpatient appointments to have a place to go before they face the long journey home.
Ade Stack and Marty Curley Hugh’s House provides accommodation 365 days a year to the family of children who are long term inpatients of Temple Street and the Rotunda Hospitals. We opened in May 2015 and are located less than 5 minutes walk from both hospitals. Temple Street and the Rotunda hospital manage the referrals to the house. When their baby son Hugh was ill in hospital, Ade Stack and
Marty Curley were thankful they lived in Dublin. They witnessed the struggles of other families travelling from all over the country to visit their sick children, some of whom were unable to cope financially with the expense of accommodation and meals. They were devastated when they saw children, especially babies who rarely had visitors because their families lived too far away.
Hugh’s House provide them a space to spend time as a family, to play, to live and eat together. Everyone involved helps on a voluntary basis. The house is run by a dedicated team of caring and compassionate volunteers and supporters, without whom we would not be able to offer our families the support and care they need. HPN will be participating directly at Hugh’s House by
Part of the Clinigen Group
April 2017 • HPN
volunteering our time and urging our readers to do the same. Everyone can make a difference through by donating your time, even three hours would be amazing. Gifting unwanted household items and children’s toys. Gift of time from Skilled Trades such as Painters, Decorators, Electricians, Plumbers, Tilers, Carpenters, Cooks, Gardeners If you would like to get involved with your work colleagues to organize a picnic, a BBQ, or come as a team for the day, send us a message on Facebook, Email or use the Contact Page. Every hour helps.
Awards Hospital Professional
Musculoskeletal Disorders Project of the Year 2017
Movement dysfunction in musculoskeletal disorders can restrict everyday activities and reduce quality of life. This is a new Award for 2017 and will see to look for the hospital professionals/teams using innovative research approaches and health technologies across this field within the secondary care setting. Judges will be looking for entries which involve developmental studies, education initiatives, clinical trials or hospital-implemented programmes designed to increase understanding of normal musculoskeletal function and to find effective ways of managing joint and soft tissue conditions and other musculoskeletal disorders. Projects can be focused on areas including, but not limited to, back pain, hand conditions such as osteoarthritis and rheumatoid arthritis, shoulder pain, knee conditions such as osteoarthritis and joint replacement, foot conditions and healthy ageing.
Excellence in Psychiatry Initiative 2017 This is a new Award for 2017. The Excellence in Psychiatry Initiative seeks to recognise the pivotal role that psychiatric healthcare professionals and teams play in improving or innovating psychiatric services and care for Ireland’s patient population. This Award will be looking for those individuals and/or teams that can demonstrate quality improvement, effective leadership, good teamwork and effective use of resources. Judges will be looking for submissions that address prevention, diagnosis, or treatment in the field of psychiatry throughout Ireland. Judges will be looking for:
Judges will be looking for:
Excellence and leadership across the field of psychiatry and its development
Demonstration of developing objective assessment tools for research and clinical practice to guide patient management
Evidence of working effectively across organisational and departmental boundaries to deliver excellence in psychiatry
Developing effective treatment techniques and patient centred approaches Examples of excellence in delivery of care – communication and clinical decision making Projects showing evidence of impact on clinical outcomes, cost and patient experience Examples of ways in which musculoskeletal disorder services can be improved across Ireland Who Can Enter: This category is open to all hospital professionals working in the field of musculoskeletal disorders in any Irish hospital. Applications can be through nominating an individual or yourself. Each submission will be judged by an independent judging panel.
Evidence to show that innovative practice has markedly enhanced the field and its development An innovative project/development/service or new approach in the field or a research project involving psychiatry A multidisciplinary approach to clinically using medicines Who Can Enter: This category is open to all hospital professionals working in the field of Psychiatry in any Irish hospital. Applications can be through nominating an individual or yourself. Each submission will be judged by an independent judging panel.
Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the awards. If your entry is shortlisted, the Awards organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the awards including all press materials.
Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the awards. If your entry is shortlisted, the Awards organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the awards including all press materials.
The completed form must be returned by email to IPN Communications or via email to: firstname.lastname@example.org or posted to IPN Communications Ltd, 36 Clifton House, Lower Fitzwilliam Street, Dublin 2 marked with the reference: HPNAwards2017.
The completed form must be returned by email to IPN Communications or via email to: email@example.com or posted to IPN Communications Ltd, 36 Clifton House, Lower Fitzwilliam Street, Dublin 2 marked with the reference: HPNAwards2017.
Deadline: Wednesday 7th June, 2017
Deadline: Wednesday 7th June, 2017
HPN • April 2017
Awards 38 Awards
Accord Innovation in Aseptic Compounding Award 2017
Consultant-Led Hospital Team of the Year Award
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. This Award category is open to qualified, trained pharmacists and technicians engaged in the preparation of injectable and other sterile products for individual patient use. The judges will be looking for an individual within a pharmacy department or a pharmacy team that can best demonstrate innovation in safety and quality within their department while incorporating innovative initiatives. This could be through SOPs, cost saving projects, submitted posters, clinical trials medication, interaction with other departments, identification and fulfilment of training needs or other. The project/ process should show measurable results of having improved the service that they provide to the pharmacy department or their patients. This award does not differentiate between large and small hospitals. It also does not differentiate between a public or private hospital. The entry needs to demonstrate measurable results attributable to the innovations. Each submission will be judged by an independent judging panel.
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 and Consultant-led. 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 Each submission will be judged by an independent judging panel.
Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the awards. If your entry is shortlisted, the Awards organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the awards including all press materials.
The completed form must be returned by email to IPN Communications or via email to: firstname.lastname@example.org or posted to IPN Communications Ltd, 36 Clifton House, Lower Fitzwilliam Street, Dublin 2 marked with the reference: HPNAwards2017.
Deadline: Wednesday 7th June, 2017
April 2017 • HPN
Deadline: Wednesday 7th June, 2017
Awards Hospital Professional
Excellence in Patient Safety Award 2017
Medisource Hospital Pharmacy Technician of the Year 2017
This Award will seek applicants who have shown commitment and dedication to improving patient safety/medication safety amongst patients in the secondary care setting.
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 – Hospital Pharmacy Technicians capture the essence of this in everything that they do.
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 working across any discipline within secondary care.
This Award will recognise the winner’s important contribution to the Hospital Pharmacy Technician profession.
Judges will be looking for:
The judges will be looking for those who can demonstrate promotion of the role of the Hospital Pharmacy Technician and those who continue to champion excellence through forward thinking and innovation.
Entries clearly demonstrating recent patient safety initiatives to the betterment of a specific therapeutic area
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 hospital 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 Who Can Enter: This category is open to all Hospital Pharmacy Technicians working within the hospital sector in Ireland. Applications can be through nominating an individual or yourself. Previous Medisource Hospital Pharmacy Technician of the Year entrants, including winners, are also welcome to submit entries this year. Each submission will be judged by an independent judging panel. Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the awards. If your entry is shortlisted, the Awards organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the awards including all press materials. The completed form must be returned by email to IPN Communications or via email to: email@example.com or posted to IPN Communications Ltd, 36 Clifton House, Lower Fitzwilliam Street, Dublin 2 marked with the reference: HPNAwards2017.
Deadline: Wednesday 7th June, 2017
Evidence of those who have offered patient safety expertise to the profession, perhaps through lecturing
Entries showcasing a patient safety initiatives or innovation within a field pertinent to any discipline or therapeutic area that will have a positive impact on both the profession and patients
Examples of cross-disciplinary learning and support Evidence of impact on patient care and professional development arising from this patient safety initiative Who Can Enter: This category is open to all hospital professionals working across any disicpline. Applications can be through nominating an individual or yourself. Previous Excellence in Patient Safety Award entrants, including winners, are also welcome to submit entries this year. Each submission will be judged by an independent judging panel. Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the awards. If your entry is shortlisted, the Awards organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the awards including all press materials. The completed form must be returned by email to IPN Communications or via email to: firstname.lastname@example.org or posted to IPN Communications Ltd, 36 Clifton House, Lower Fitzwilliam Street, Dublin 2 marked with the reference: HPNAwards2017.
Deadline: Wednesday 7th June, 2017
HPN • April 2017
Awards 40 Awards
Idis Hospital Pharmacist of the Year Award
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.
Innovation and Service Development Award This Award will be presented to a practising hospital consultant, pharmacist, specialist and/or team working within any hospital department, in recognition of a project which could easily be accomplished regardless of hospital size or staff, which need not be sophisticated, and which serves a useful purpose or has recently been published. Judges will be looking for: Significant innovation in practice, method or service directly or indirectly resulting in improved patient care
Judges will be looking for:
Examples of the immediate and longer term impact the innovation has on the hospital sector
Evidence of long-term, consistent dedication and outstanding achievements that have led to the advancement of the profession of pharmacy and public health
Examples of how the innovation may establish a vision or be the basis of a larger system or platform of innovations
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 Who Can Enter: This category is open to all hospital pharmacists working within the hospital sector in Ireland. Applications can be through nominating an individual or yourself. Previous Hospital Pharmacy Awards Hospital Pharmacist of the Year entrants, including winners, are also welcome to submit entries this year. Each submission will be judged by an independent judging panel. Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the awards. If your entry is shortlisted, the Awards organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the awards including all press materials. The completed form must be returned by email to IPN Communications or via email to: email@example.com or posted to IPN Communications Ltd, 36 Clifton House, Lower Fitzwilliam Street, Dublin 2 marked with the reference: HPNAwards2017.
Deadline: Wednesday 7th June, 2017
April 2017 • HPN
Demonstration of how the innovation might be an inspiration to future hospital professionals and departments Who Can Enter: This category is open to all hospital professionals/teams working within any hospital department in Ireland. Applications can be through nominating an individual or yourself. Previous Innovation & Service Development Award entrants, including winners, are also welcome to submit entries this year. Each submission will be judged by an independent judging panel. Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the awards. If your entry is shortlisted, the Awards organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the awards including all press materials. The completed form must be returned by email to IPN Communications or via email to: firstname.lastname@example.org or posted to IPN Communications Ltd, 36 Clifton House, Lower Fitzwilliam Street, Dublin 2 marked with the reference: HPNAwards2017.
Deadline: Wednesday 7th June, 2017
Awards Hospital Professional
Hospital Multidisciplinary Award
Roche Oncology Hospital Pharmacist of the Year Award
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. 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 long-term, consistent dedication and outstanding achievements that have led to the advancement of the profession of oncology pharmacy Evidence of a large variety of skills, attributes and accomplishments within this specific field Examples of projects and/or innovations undertaken to enhance the field of oncology in Ireland and further afield Evidence of an understanding the goals of pharmacy, and significantly contributing to how these goals may be achieved Who Can Enter: This category is open to all hospital pharmacists working within the hospital sector in Ireland. Applications can be through nominating an individual or yourself. Previous Roche Oncology Pharmacist of the Year entrants, including winners, are also welcome to submit entries this year. Each submission will be judged by an independent judging panel. Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the awards. If your entry is shortlisted, the Awards organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the awards including all press materials. The completed form must be returned by email to IPN Communications or via email to: email@example.com or posted to IPN Communications Ltd, 36 Clifton House, Lower Fitzwilliam Street, Dublin 2 marked with the reference: HPNAwards2017.
Deadline: Wednesday 7th June, 2017
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:
Entries clearly demonstrating how groups of hospital professionals are working together to enhance care, for example by describing the difficult process of developing an effective team and barriers
Examples of systems that have facilitated the communication of information needed for different professions to bring together their skills to help patients Examples of cross-disciplinary learning and support Evidence of impact on patient care and professional development arising from multidisciplinary work Who Can Enter: This category is open to all hospital professionals working within the hospital sector in Ireland. Applications can be through nominating an individual or yourself. Previous Hospital Multidisciplinary Award entrants, including winners, are also welcome to submit entries this year. Each submission will be judged by an independent judging panel. Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the awards. If your entry is shortlisted, the Awards organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the awards including all press materials. The completed form must be returned by email to IPN Communications or via email to: firstname.lastname@example.org or posted to IPN Communications Ltd, 36 Clifton House, Lower Fitzwilliam Street, Dublin 2 marked with the reference: HPNAwards2017.
Deadline: Wednesday 7th June, 2017
HPN • April 2017
Awards 42 Awards
Cardiology Project of the Year Award
Excellence in Respiratory Initiative of the Year
The Cardiology Project of the Year Award will seek to recognise the specialist work being carried out by Irish cardiology specialists and their teams.
This new Award category for 2017 has been established to recognise a respiratory clinician or team who is providing compassion care, over and beyond that usually undertaken in a respiratory career.
This Award is to honour those who have established themselves as investigators and researchers who have made an outstanding contribution to cardiovascular science. The award is open for applications from clinicians and their teams who have an affiliation with an Irish hospital. The winner of the Award will be making an outstanding contribution to the development of services, someone who “makes real” the commitment to outstanding patient care through their own daily work, will have demonstrated a sustained contribution over a period of time and overcome challenges in order to achieve goals. Judges will be looking for: Service improvement which has benefited clinicians, healthcare organisations, and patients alike
The project can come from any background but must be involve those working predominately in the respiratory field. The judges will be looking for a project that demonstrates deliverable outcomes within respiratory care over that has really supported and evidenced the difference made to the patient experience in respiratory care. Entries can be self-nominated from but must be Consultant-led. Judges will be looking for: Entries that can clearly demonstrate defined objectives for quality improvement within a project
Innovative methods of delivering care
Clearly described respiratory interventions
A patient-focused approach, with service users engaged in any redesign
Clear evidence of innovation and new ways of working
Strong connections between specialist services and other providers and professionals Demonstrable improvements in value and patient satisfaction Who Can Enter:
Clarity of leadership and how the qualities have affected the team Quantifiable improvements in patient care, including clinical outcomes Who Can Enter:
This category is open to all hospital professionals working within any hospital in Ireland. Applications can be through nominating an individual or yourself.
This category is open to all hospital professionals working within any hospital in Ireland. Applications can be through nominating an individual or yourself.
Each submission will be judged by an independent judging panel.
Each submission will be judged by an independent judging panel.
Deadline: Wednesday 7th June, 2017
April 2017 • HPN
Deadline: Wednesday 7th June, 2017
Awards Hospital Professional
MSD Infectious Diseases Project of the Year
Young Hospital Professional of the Year Award Hospital professionals are vital elements of medicines and care management within the secondary care setting and those in their infancy years of the profession can hint at leadership excellence that inspires and develops the potential of others.
The MSD Infectious Diseases Project of the Year Award will seek to recognise those hospital professionals that have displayed levels of excellence and dedication within any category of infectious diseases and antimicrobials in Ireland. Key roles for the infectious diseases professionals include educating pharmacy, medical and nursing staff, auditing prescribing patterns and trends, monitoring antibiotic use, ensuring compliance with good practices and managing infection control issues, all of which contribute to reducing hospital associated infections. Judges will be seeking to see examples of excellence in practice, multidisciplinary team working across departments and those who have excelled in the fields of education and/or communication about infectious diseases. Judges will be looking for: Evidence of long-term, consistent dedication and outstanding achievements that have led to the advancement of this field, professionals within it and public health Evidence to show that innovative practice has markedly enhanced the field and its development An innovative project/development/service or new approach in the field or a research project within the field of infectious diseases Evidence of the initiation or development of interdisciplinary research projects and networks Evidence of a large variety of skills, attributes and accomplishments Who Can Enter: This category is open to all hospital professionals working within the hospital sector in Ireland. Applications can be through nominating an individual or yourself. Each submission will be judged by an independent judging panel.
The Young Hospital Professional of the Year Award recognises rising talent and potential amongst those at the beginning of their careers – those individuals who are already demonstrating that they can make a difference to their profession and the patients they serve. This Award focuses specially on the talent we will all rely on to deliver services for the next 20 years and more: the young professionals, currently delivering and planning services at the sharp end - but whose skills will be vitally important over the coming years. This Award is open to professionals up to age 30 who are working within any hospital department where their involvement has been greater than six months. 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 department liaising with key staff members and management and developing key communication skills A dedication and commitment to furthering the profession into the future Who Can Enter: This category is open to all hospital professionals under the age of 30 working within any hospital department in Ireland. Applications can be through nominating an individual or yourself. Previous Young Hospital Professional Awards entrants, including winners, are also welcome to submit entries this year. Each submission will be judged by an independent judging panel.
Deadline: Wednesday 7th June, 2017
Deadline: Wednesday 7th June, 2017
HPN • April 2017
Awards 44 Awards
Daiichi Sankyo Hospital Pharmacy Team of the Year Award
Hospital Specialist of the Year Award Speciality clinicians are essential components of service provision, providing a major share of the medical input in many teams. This award is to recognise Specialty Clinician who has demonstrated advanced clinical skills as well as excelling in service development, teaching, research and leadership.
There are many key elements to building a productive team, including communication and cooperation. Good communication means everyone is aware of their own responsibilities and what the team's goals are whilst cooperation leads to increased productivity.
Their contribution may be at local, regional or national level in the past three years. This Award will seek to recognise exemplary leadership within a speciality that demonstrates a positive and sustained impact on patients, service users, carers and staff.
A team that excels is the one who, together, endlessly work to improve their efforts. They comprehend the importance of on-going improvements and how this helps support the overall objectives of the department.
Judges will want to see evidence of speciality skills and leadership which are focused on improvement, and enhancing the quality of experience.
The Award is open to any hospital pharmacy team with a minimum of three team members.
Judges will be looking for:
Judges will be looking for:
Evidence of key competencies across areas such as team working, innovation, research and education
Judges will want to see effective communication skills with both staff and customers
Excellence in clinical work and/or medical education
Demonstration of a commitment to mentoring or other leadership activities
Parity of esteem
Operation within their own pharmacy liaising with key staff members and management and developing key communication skills
Commitment to improving services for service users and/ or staff alongside evidence of measurable improvement as a result of the entrants/nominees work
A dedication and commitment to furthering the profession into the future
Who Can Enter:
Who Can Enter:
This category is open to all hospital professionals working within any specialty, within any Irish hospital. Applications can be through nominating an individual or yourself. Previous Hospital Pharmacy Awards Hospital Pharmacist of the Year entrants, including winners, are also welcome to submit entries this year.
This category is open to all Pharmacy teams working within any hospital in Ireland. Applications can be through nominating an individual or yourself. Previous Daiichi Sankyo Hospital Pharmacy Team of the Year entrants, including winners, are also welcome to submit entries this year. Each submission will be judged by an independent judging panel. Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the awards. If your entry is shortlisted, the Awards organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the awards including all press materials. The completed form must be returned by email to IPN Communications or via email to: email@example.com or posted to IPN Communications Ltd, 36 Clifton House, Lower Fitzwilliam Street, Dublin 2 marked with the reference: HPNAwards2017.
Deadline: Wednesday 7th June, 2017
April 2017 • HPN
Each submission will be judged by an independent judging panel. Entries can be submitted by post or email. All entries will be handled in the strictest confidence and will not be made available to any party not involved with judging the awards. If your entry is shortlisted, the Awards organisers may wish to reproduce a summary of your entry, photographs and any other supporting materials in the finalists’ booklet or within other materials they produce to promote the awards including all press materials. The completed form must be returned by email to IPN Communications or via email to: firstname.lastname@example.org or posted to IPN Communications Ltd, 36 Clifton House, Lower Fitzwilliam Street, Dublin 2 marked with the reference: HPNAwards2017.
Deadline: Wednesday 7th June, 2017
Envarsus ® 0.75mg, 1mg, 4mg prolonged-release tablet Tacrolimus (as monohydrate) Please refer to Summary of Product Characteristics (SmPC) before prescribing Prescribing information Presentation Envarsus prolonged-release tablets containing 0.75mg, 1mg and 4mg of tacrolimus (as monohydrate) Indications Prophylaxis of transplant rejection in adult kidney or liver allograft recipients and treatment of allograft rejection resistant to treatment with other immunosuppressive medicinal products in adult patients Dosage and administration Envarsus is a once-a-day oral formulation of tacrolimus. Envarsus therapy requires careful monitoring by adequately qualified and equipped personnel. This medicinal product should only be prescribed, and changes in immunosuppressive therapy be initiated, by physicians experienced in immunosuppressive therapy and the management of transplant patients. Patients should be maintained on a single formulation of tacrolimus with the corresponding daily dosing regimen; alterations in formulation or regimen should only take place under the close supervision of a transplant specialist. The recommended initial doses presented below are intended to act solely as a guideline. Envarsus is routinely administered in conjunction with other immunosuppressive agents in the initial post-operative period. The dose may vary depending upon the immunosuppressive regimen chosen. Envarsus dosing should primarily be based on clinical assessments of rejection and tolerability in each patient individually aided by blood level monitoring. If clinical signs of rejection are apparent, alteration of the immunosuppressive regimen should be considered. As tacrolimus is a substance with low clearance, adjustments to the Envarsus dose regimen may take several days before steady state is achieved. Envarsus doses are usually reduced in the post-transplant period. Post-transplant changes in the condition of the patient may alter the pharmacokinetics of tacrolimus and may necessitate further dose adjustments. Prophylaxis of kidney transplant rejection: Envarsus therapy should commence at a dose of 0.17 mg/kg/day administered once daily in the morning. Administration should commence within 24 hours after the completion of surgery. Prophylaxis of liver transplant rejection: Envarsus therapy should commence at a dose of 0.11 – 0.13 mg/kg/day administered once daily in the morning. Administration should commence within 24 hours after the completion of surgery. Conversion of Prograf- or Advagraf-treated patients to Envarsus allograft transplant patients: Allograft transplant patients maintained on twice daily Prograf (immediate-release) or Advagraf (once daily) dosing requiring conversion to once daily Envarsus should be converted on a 1:0.7 (mg:mg) total daily dose basis and the Envarsus maintenance dose should, therefore, be 30% less than the Prograf or Advagraf dose. Envarsus should be administered in the morning. When converting from tacrolimus immediate-release products (e.g. Prograf capsules) or from Advagraf prolonged-release capsules to Envarsus, trough levels should be measured prior to conversion and within two weeks after conversion. Dose adjustments should be made to ensure that similar systemic exposure is maintained after the switch. In comparison to Caucasians, black patients may require higher tacrolimus doses to achieve similar trough levels. In clinical studies patients converted from twice daily Prograf were converted to Envarsus using a 1:0.85 (mg:mg) conversion. Conversion from ciclosporin to tacrolimus: Care should be taken when converting patients from ciclosporin-based to tacrolimus-based therapy. The combined administration of ciclosporin and tacrolimus is not recommended. Envarsus therapy should be initiated after considering ciclosporin blood concentrations and the clinical condition of the patient. Dosing should be delayed in the presence of elevated ciclosporin blood levels. In practice, tacrolimus-based therapy has been initiated 12 to 24 hours after discontinuation of ciclosporin. Monitoring of ciclosporin blood levels should be continued following conversion as the clearance of ciclosporin might be affected. Treatment of allograft rejection: Increased doses of tacrolimus, supplemental corticosteroid therapy, and introduction of short courses of mono-/polyclonal antibodies have all been used to manage rejection episodes. If signs of toxicity such as severe adverse reactions are noted, the dose of Envarsus may need to be reduced. Treatment of allograft rejection after kidney or liver transplantation: For conversion from other immunosuppressants to once daily Envarsus, treatment should begin with the initial oral dose recommended in kidney and liver transplantation respectively for prophylaxis of transplant rejection. Therapeutic drug monitoring: Dosing should primarily be based on clinical assessments of rejection and tolerability in each individual patient aided by whole blood tacrolimus trough level monitoring. As an aid to optimise dosing, several immunoassays are available for determining tacrolimus concentrations in whole blood. Comparisons of concentrations from the published literature to individual values in clinical practice should be assessed with care and knowledge of the assay methods employed. In current clinical practice, whole blood levels are monitored using immunoassay methods. The relationship between tacrolimus trough levels and systemic exposure (AUC 0-24) is well correlated and is similar between the immediate-release formulation and Envarsus. Blood trough levels of tacrolimus should be monitored during the post-transplantation period. Tacrolimus blood trough levels should be determined approximately 24 hours post-dosing of Envarsus, just prior to the next dose. Blood trough levels of tacrolimus should also be closely monitored following conversion from tacrolimus products, dose adjustments, changes in the immunosuppressive regimen, or
co-administration of substances which may alter tacrolimus whole blood concentrations. The frequency of blood level monitoring should be based on clinical needs. As tacrolimus is a substance with low clearance, following adjustments to the Envarsus dose regimen it may take several days before the targeted steady state is achieved. Data from clinical studies suggest that the majority of patients can be successfully managed if tacrolimus blood trough levels are maintained below 20ng/ml. It is necessary to consider the clinical condition of the patient when interpreting whole blood levels. In clinical practice, whole blood trough levels have generally been in the range of 5-20 ng/ml in kidney transplant patients in the early post-transplant period, and 5-15 ng/ml during subsequent maintenance therapy. See SmPC for dosage adjustments in special populations. Method of administration: Envarsus should be taken once daily in the morning, swallowed whole with fluid (preferably water) immediately following removal from the blister. Envarsus should generally be taken on an empty stomach to achieve maximal absorption. Contraindications Hypersensitivity to active substance or excipients. Hypersensitivity to macrolides. Warnings and precautions Medication errors, including inadvertent, unintentional or unsupervised substitution of immediate- or prolongedrelease tacrolimus formulations, have been observed with tacrolimus. This has led to serious adverse reactions, including graft rejection, or other adverse reactions which could be a consequence of either underor over-exposure to tacrolimus. Patients should be maintained on a single formulation of tacrolimus with the corresponding daily dosing regimen; alterations in formulation or regimen should only take place under the close supervision of a transplant specialist. Envarsus is not recommended for use in children below 18 years of age due to the limited data on safety and/or efficacy. During the initial post-transplant period, monitoring of the following parameters should be undertaken on a routine basis: blood pressure, ECG, neurological and visual status, fasting blood glucose levels, electrolytes (particularly potassium), liver and renal function tests, haematology parameters, coagulation values, and plasma protein determinations. If clinically relevant changes are seen, adjustments of the immunosuppressive regimen should be considered. Gastrointestinal perforation has been reported in patients treated with tacrolimus, adequate treatments should be considered immediately after suspected symptoms or signs occur. Extra monitoring of tacrolimus concentrations is recommended during episodes of diarrhoea. Cardiomyopathies have been observed in tacrolimus treated patients on rare occasions. Most cases have been reversible, occurring with tacrolimus blood trough concentrations much higher than the recommended maximum levels. Other factors observed to increase the risk of these clinical conditions included pre-existing heart disease, corticosteroid usage, hypertension, renal or hepatic dysfunction, infections, fluid overload, and oedema. Accordingly, high-risk patients receiving substantial immunosuppression should be monitored, using such procedures as echocardiography or ECG pre- and post-transplant (e.g. initially at 3 months and then at 9-12 months). If abnormalities develop, dose reduction of Envarsus or change of treatment to another immunosuppressive agent should be considered. Tacrolimus may prolong the QT interval, caution should be exercised in patients with diagnosed or suspected Congenital Long QT Syndrome. Patients treated with tacrolimus have been reported to develop EBV-associated lymphoproliferative disorders. Risk factors include using a combination of immunosuppressives, such as antilymphocytic antibodies (e.g. basiliximab, daclizumab) concomitantly, or EBV-Viral Capsid Antigen (VCA)-negative patients. Therefore, in this patient group, EBV-VCA serology should be ascertained before starting treatment with Envarsus. Careful monitoring with EBV-PCR is recommended. Positive EBV-PCR may persist for months and is per se not indicative of lymphoproliferative disease or lymphoma. As with other potent immunosuppressive compounds, the risk of secondary cancer is unknown. Exposure to sunlight and UV light should be limited. Patients treated with immunosuppressants, including Envarsus are at increased risk for opportunistic infections (bacterial, fungal, viral, and protozoal). Among these conditions are BK virus associated nephropathy and JC virus associated progressive multifocal leukoencephalopathy (PML).These infections are often related to a high total immunosuppressive burden and may lead to serious or fatal conditions that physicians should consider in the differential diagnosis in immunosuppressed patients with deteriorating renal function or neurological symptoms. Patients treated with tacrolimus have been reported to develop posterior reversible encephalopathy syndrome (PRES). If symptoms indicating PRES such as headache, altered mental status, seizures, and visual disturbances, a radiological procedure (e.g. MRI) should be performed. If PRES is diagnosed, adequate blood pressure and seizure control, and immediate discontinuation of systemic tacrolimus is advised. Cases of pure red cell aplasia (PRCA) have been reported in patients treated with tacrolimus. All patients reported risk factors for PRCA such as parvovirus B19 infection, underlying disease or concomitant medicinal product associated with PRCA. Dose reduction may be necessary in patients with severe liver impairment. Envarsus contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product. (Refer to SmPC for full list of interactions). Side effects Very common: tremor, renal impairment, hyperglycaemic conditions, diabetes mellitus, hyperkalaemia, infections, hypertension,
insomnia, headache, diarrhoea, nausea, abnormal liver function tests Common: anaemia, thrombocytopenia, leukopenia, abnormal red blood cell analyses, leukocytosis, anorexia, metabolic acidoses, other electrolyte abnormalities, hyponatraemia, fluid overload, hyperuricaemia, hypomagnesaemia, hypokalaemia, hypocalcaemia, decreased appetite, hypercholesterolaemia, hyperlipidaemia, hypertriglyceridaemia, hypophosphataemia, confusion and disorientation, depression, anxiety symptoms, hallucination, mental disorders, depressed mood, mood disorders and disturbances, nightmare, nervous system disorders, seizures, disturbances in consciousness, peripheral neuropathies, dizziness, paraesthesias and dyaesthesias, writing impaired, eye disorders, blurred vision, photophobia, tinnitus, ischaemic coronary artery disorders, tachycardia, thromboembolic and ischaemic events, vascular hypotensive disorders, haemorrhage, peripheral vascular disorders, parenchymal lung disorders, dyspnoea, pleural effusion, cough, pharyngitis, nasal congestion and inflammations, gastro-intestinal (GI) signs and symptoms, vomiting, GI and abdominal pains, GI inflammatory conditions, GI haemorrhages, GI ulceration and perforation, ascites, stomatitis and ulceration, constipation, dyspeptic signs and symptoms, flatulence, bloating and distension, loose stools, bile duct disorders, hepatocellular damage and hepatitis, cholestasis and jaundice, rash, pruritus, alopecias, acne, increased sweating, arthralgia, back pain, muscle cramps, pain in limb, renal failure, acute renal failure, toxic nephropathy, renal tubular necrosis, urinary abnormalities, oliguria, bladder and urethral symptoms, febrile disorders, pain and discomfort, asthenic conditions, oedema, disturbed body temperature perception, increased blood alkaline phosphatase, increased weight, primary graft dysfunction. In clinical studies in kidney transplant patients receiving Envarsus, the most frequent adverse reactions (at least in 2% of patients) were tremor, diabetes mellitus, blood creatinine increased, urinary tract infection, hypertension, BK virus infection, renal impairment, diarrhoea, toxicity to various agents, and toxic nephropathy. Among the most frequent adverse reactions (at least in 2% of patients) in clinical studies in liver transplant patients receiving Envarsus were tremor, headache, fatigue, hyperkalaemia, hypertension, renal failure, blood creatinine increased, dizziness, hepatitis C, muscle spasms, tinea infection, leukopenia, sinusitis, and URTI. Uncommon: coagulopathies, pancytopenia, neutropenia, abnormal coagulation and bleeding analyses, dehydration, hypoglycaemia, hypoproteinaemia, hyperphosphataemia, psychotic disorder, encephalopathy, central nervous system haemorrhages and cerebrovascular accidents, coma, speech and language abnormalities, paralysis and paresis, amnesia, cataract, hypoacusis, heart failures, ventricular arrhythmias and cardiac arrest, supraventricular arrhythmias, cardiomyopathies, abnormal ECG investigations, ventricular hypertrophy, palpitations, abnormal heart rate and pulse investigations, deep limb venous thrombosis, shock, infarction, respiratory failures, respiratory tract disorders, asthma, acute and chronic pancreatitis, peritonitis, increased blood amylase, paralytic ileus, gastrooesophageal reflux disease, impaired gastric emptying, dermatitis, photosensitivity, joint disorders, haemolytic uraemic syndrome, anuria, dysmenorrhoea and uterine bleeding, decreased weight, influenza like illness, increased blood lactate dehydrogenase, feeling jittery, feeling abnormal, multi-organ failure, chest pressure sensation, temperature intolerance. Rare: thrombotic thrombocytopenic purpura, hypoprothrombinaemia, hirsutism, hypertonia, blindness, neurosensory deafness, pericardial effusion, acute respiratory distress syndrome, pancreatic pseudocyst, subileus, veno-occlusive liver disease, hepatic artery thrombosis, toxic epidermal necrolysis (Lyell’s syndrome), fall, ulcer, chest tightness, decreased mobility, thirst. Very rare: myasthenia, impaired hearing, abnormal echocardiogram, hepatic failure, Stevens Johnson Syndrome, nephropathy, haemorrhagic cystitis, increased fat tissue. Not Known: pure red cell aplasia, agranulocytosis, haemolytic anaemia, allergic and anaphylactoid reactions (Refer to SmPC for full list of adverse reactions) Legal category POM Packs and prices 0.75mg £44.33 1x30 tablets, 1mg £59.10 1x30 tablets, 4mg £236.40 1x30 tablets Marketing authorisation numbers EU/1/14/935/001, EU/1/14/935/004, EU/1/14/935/007. Full prescribing information is available on request from the UK Distributor Chiesi Limited, 333 Styal Road, Manchester, M22 5LG Date of preparation July 2015
For the UK: Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Chiesi Limited, (address as above) Tel: +44(0)161 488 5555. For Ireland: Adverse events should be reported to HPRA Pharmacovigilance, Earlsfort Terrace, IRL, Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, Website: www.hpra.ie, e-mail: email@example.com. Adverse events should also be reported to Chiesi Limited, (address as above) Tel: +44(0)161 488 5555.
References: 1. Bunnapradist S, Ciechanowski K, West-Thielke P, et al. Conversion From Twice-Daily Tacrolimus to Once-Daily Extended Release Tacrolimus (LCPT): The Phase III Randomized MELT Trial. Am J Transplant 2013;13:760-9. 2. Budde K, Bunnapradist S, Grinyo JM, et al. Novel Once-Daily Extended-Release Tacrolimus (LCPT) Versus Twice-Daily Tacrolimus in De Novo Kidney Transplants: One-Year Results of Phase III, Double-Blind, Randomized Trial. American Journal of Transplantation 2014;14:2796-2806. 3. Bunnapradist S et al. LCPT once-daily extendedrelease tacrolimus tablets versus twice-daily capsules: a pooled analysis of two phase 3 trials in important de novo and stable kidney transplant recipient subgroups. Transplant International. 2016;29:603-11. Envarsus® is a registered trademark of Veloxis Pharmaceuticals A/S Ltd. Prograf® is a registered trademark of Astellas Pharma Europe Ltd. Date of preparation: March 2017 CHENV20170355
Prolonged-release tacrolimus tablets
TACROLIMUS REDEFINED For those patients who need a different tacrolimus...
In a post-hoc pooled analysis from two Phase 3 trials 1,2, elderly (≥65 years) kidney transplant recipients treated with Envarsus® were associated with fewer treatment failures vs. Prograf®.3 • The sub-populations did not reach statistical significance in the individual Phase 3 studies • The analyses were not adjusted for multiple comparisons • Caution should be exercised when interpreting p-values due to potential multiplicity Prolonged-release tacrolimus tablets
Prescribing information and references can be found on reverse. Date of Prep: March 2017 CHENV20170355
Pharmacy in a Hospital Setting systems will improve the entire medication administration process from the way medications can be prescribed, dispensed, to how medicine is given to patients. For example in: • ePrescribing to allow medical personnel to generate an electronic prescription anywhere within the hospital. • Core to pharmacy work is a modern and effective pharmacy system tracking medicines from time stock arrives in pharmacy right through until it is dispensed to a patient
Pharmacy is central to all care areas within a hospital setting and where significant investment in technology will be required over the coming years to assist Pharmacy and hospitals continue to deliver their service safely and efficiently. An informative presentation ‘Current State and Future Possibilities - Perspective of Hospital Pharmacist & Technology Manager’ from Peter Kidd, Deputy Chief Pharmacist with University Hospital Galway at the ePharmacy ecosystem meeting outlined a patient’s care pathway and where there are currently 20-30 steps required from prescribing to delivery.
pharmaceutical technicians to wards to ensure medicines are managed effectively including ordering and storage of medicines on the ward, is yielding very impressive results.
• Saved nursing time
There has been a reduction of orders to Pharmacy by about 10%, Monday to Friday and 25% at weekends. In addition a non-stock order requiring 20 items would typically take 2 hours to complete (Pharmacist and Technician time) can now be turned around in about 15 minutes.
Modern technologies are key
The resource gained is being redistributed to direct patient care. Audit of the pilot has demonstrated:
Tracking a prescription quickly highlights some of the challenges faced by pharmacy with their current technologies and manual processes.
• A 45% reduction in missed doses for patients
Electronic ordering and changing business processes
• A 20% reduction in time taken to complete drug rounds
A pilot running in the Adelaide & Meath National Hospital utilising mobile technology and redeploying
• A high degree of nurse satisfaction - 100% agreed that the WBT service has
• A 25% reduction in interruptions during drug rounds
• Improved time taken for ordered medications to reach the ward • Made locating medications on the ward easier
Some hospitals, such as the Mater Misericordiae University Hospital in Dublin, have over the years invested in technology to assist Pharmacy. The Mater is currently the only state hospital utilising robotic dispensing technology, with ordering available from anywhere in the hospital, good processes in place, almost paperless in the Pharmacy and an example of how technology is assisting Pharmacy within an Irish hospital. Chief pharmacists around the country have identified technologies that would revolutionise Pharmacy within Irish hospitals and are keen to be part of any National initiative that would progress this agenda.
• The introduction of robotic dispensing technology into the pharmacy to assist medicine preparation. Use of Robotics In the Public Sector here in Ireland there has been relatively low investment in robotic dispensing technology to date . The exception is in the Mater Misericordiae University Hospital, whose investment in a robotic dispensing system has been a huge success, central to their workflow and a working example in a public hospital within Irish Healthcare. Robotic dispensing technology in Pharmacy is well tested and utilised in hospitals and community pharmacies around the world and the technology has been adopted by a number of pharmacies across Ireland. For example in: • Weedle Pharmacy, Mallow in 2008 • Scottish hospital in 2010 • Broderick’s Pharmacy, Cork in 2013 • Waterford Health Park Pharmacy • Galway Clinic
Utilising automation and intelligent
Maternity EHR goes live in University Hospital Kerry University Hospital Kerry (UHK) went live with the Maternity EHR (Electronic Health Record) at the start of this month. UHK is the second hospital to go live with the Maternal & Newborn Clinical Management System (MNCMS) and the first general hospital to be making use of this solution. The learning from December’s go live in Cork University Maternity Hospital (CUMH) has been applied well to UHK, All technology solutions were in place well ahead of cut over, in excess of 3,700 April 2017 • HPN
hours of formal training was delivered to staff and engagement throughout the hospital best described as ‘calm excitement’ by the UHK project manager Fiona Lawlor. The concepts of the shared record and the identified benefits of a national EHR can be seen in Kerry already. A baby born into the Neonatal Intensive Care Unit (NICU) in CUMH six weeks ago has been transferred to the Kerry NICU in the last week. Previously this would have required a great deal of paperwork to be sent and
in some cases testing and re-testing of the patients in the new location. Mary Godley a Staff Nurse and trainer in Kerry Special Care Baby Unit (SCBU) says, “Before the introduction of the Maternity and Newborn system, significant time was spent writing and rewriting baby details. Now details are entered once and populate where required, thereby eliminating the need for duplication of data entry.” The first baby born following the go-live on the Saturday lunch time
was a very proud moment for the hospital and all the associated staff. Prior to the go-live, the administrative team in the hospital issued the last ever paper record in its usual efficient manner, this would be the final paper record ever to be issued like this in UHK for Maternity/ Neonatal services; a somewhat ceremonial destruction of the record and an audit of the first digital record took place and from that moment on maternity/ neonatal services in Kerry would be paperless.
Cardiovascular Disease – Leading cause of mortality The European Heart Network has this month published the fifth edition of European Cardiovascular Disease Statistics. The data presented show that cardiovascular diseases (CVD) remain the leading cause of mortality and a major cause of morbidity in Europe. Considerable inequalities in the burden of these diseases still exist across the region. CVD mortality, prevalence, and disability-adjusted life year (DALY) rates are, on average, lower in the European Union (EU) than outside of the EU. Furthermore, among both EU and non-EU member states, rates of CVD mortality and morbidity, as well as the prevalence of several key risk factors, tend to be higher in Central and Eastern European countries than in their Northern, Western and Southern European counterparts. Approximately 10,000 people die each year from cardiovascular disease (CVD) - including coronary heart disease (CHD), stroke and other circulatory diseases. CVD is the most common cause of death in Ireland, accounting for 36% of all deaths. The largest number of these deaths relate to CHD mainly heart attack - at 5,000. 22% of premature deaths (under age 65) are from CVD. Encouragingly, statistics indicate that CVD mortality is now decreasing in nearly all European countries, including those of Central and Eastern Europe, which saw substantial increases until the beginning of the 21st century. This is consistent with downward trends in several key CVD risk factors such as smoking, alcohol consumption and levels of mean blood cholesterol, and with the observed increases in rates of CVD treatment. That said, levels of other CVD risk factors, particularly the prevalence of overweight/ obesity and diabetes, have increased considerably in recent decades, raising concerns about the sustainability of the observed reduction in CVD mortality. However, incidence and prevalence are significant. Currently, there are more than 6 million new cases of CVD in the EU and more than 11 million in Europe
as a whole, every year. With almost 49 million people living with the disease in the EU, the cost to the EU economies is high at ¤210 billion a year. Mortality Diseases of the heart and circulatory system (CVD) are the leading cause of mortality in Europe as a whole, responsible for over 3.9 million deaths a year, or 45% of all deaths1. In men, CVD accounts for 1.8 million deaths (40% of all deaths), while in women it is responsible for 2.1 million deaths (49% of all deaths). By comparison, cancer – the next most common cause of death – accounts for just under 1.1 million deaths (24%) in men and just under 900,000 deaths (20%) in women respectively. The main forms of CVD are ischaemic heart disease (IHD) and stroke2. IHD is the leading single cause of mortality in Europe, responsible for 862,000 deaths a year (19% of all deaths) among men and 877,000 deaths (20%) among women each year. Stroke is the second most common single cause of death in Europe, accounting for 405,000 deaths (9%) in men and 583,000 (13%) deaths in women each year. CVD is also the leading cause of mortality in the EU, where it causes just over 1.8 million deaths each year – around 800,000 deaths in men and 1 million deaths in women (Table 1.1). Interestingly, the share of all deaths attributable to CVD in the EU is slightly lower than that in the continent as a whole, with CVD responsible for 37% of all EU deaths – 34% among men and 40% among women. Cancer, the next most common cause of death in the EU, accounts for 748,000 deaths (30%) in men and more than 590,000 deaths (24%) in women. As in Europe, IHD and stroke are, respectively, the first and second most common single causes of death in the EU. IHD is responsible for over 335,000 deaths (14%) among men and for over 297,000 deaths (12%) among women in the EU, while stroke accounts for over 176,000 (7%) male deaths and just under 250,000 (10%) female deaths Again, these proportions are lower
than the comparable figures for Europe as a whole. Premature deaths are of interest since many are deemed to be preventable through reduced exposure to behavioural risk factors plus timely and effective treatment. There is no standard definition of premature mortality; rather, what counts as ‘premature’ varies for different countries according to their average life expectancy at birth. CVD is the leading cause of mortality under 75 years in Europe as a whole, accounting for more than 1.3 million deaths (35% of all deaths under 75 years) each year. By comparison, cancer – the second most common cause of mortality – is responsible for around 1.1 million deaths (29%) under 75 years each year. Morbidity Incidence The incidence data reported here come from the Global Burden of Disease (GBD) project and are modelled on surveillance data, survey data, and records of inpatient and outpatient hospital visits.
in Andorra and Azerbaijan among males. The only countries to show a decrease in incidence over this period were the UK and Latvia for both sexes, as well as Hungary for males and Denmark, Georgia and Germany for females. Importantly, however, these crude incidence numbers do not take into account differences between populations in terms of size, age composition, or the efficiency of CVD surveillance. Therefore, comparisons over time, and also between countries, should be treated with caution. Prevalence In 2015, more than 85 million people across Europe were living with CVD; 48% of cases (41.2 million) had occurred in males and 52% (44.1 million) in females. The most prevalent cardiovascular conditions were peripheral vascular disease and IHD. Peripheral vascular disease accounted for 15.3 million cases (37% of all CVD) amongst males and for just over 21 million cases (48% of all CVD) amongst females, while IHD was responsible for almost 17 million cases (41% of all CVD) in males and just over 13 million cases (30% of all CVD) in females.
In 2015, there were just under 11.3 million new cases of CVD in Europe as a whole: 5.4 million among males and 5.8 million among females. Just over half of all new CVD cases in Europe were due to IHD, with slightly more new IHD cases among males (2.97 million) than females (2.78 million). By contrast, the incidence of stroke, which accounted for around 14% of all new CVD cases in Europe, was slightly higher in females (880,000) than males (680,000), with nearly 1.6 million new stroke cases in total.
Within the EU, almost 49 million people (24.3 million males and 24.6 million females) were living with CVD in 2015.
In the EU, there were 6.1 million new cases of CVD in 2015. Half of these new CVD cases were due to IHD (1.63 million new cases in males, 1.4 million new cases in females), while around 10% of new CVD cases were due to stroke (286,000 among males and 340,000 in females).
Age-standardised1 prevalence rates for CVD were higher in males than females in all European countries for which data were available. On average, CVD prevalence rates were lower in the EU (6,308 per 100,000 in males, 4,921 per 100,000 in females) than in Europe as a whole (7,147 per 100,000 in males, 5,612 per 100,000 in females). Among both EU and non-EU member states, CVD prevalence rates tended to be relatively high in Eastern and Central
Between 1990 and 2015, most European countries reported an increase in the number of new CVD cases, with the largest increases of nearly 100% reported
Again, peripheral vascular disease and IHD were responsible for the greatest share of CVD cases in the EU, with the former accounting for just under 10 million cases (41% of all CVD) in males and 12.5 million cases (51% of all CVD) in females, and the latter for 7.7 million (32% of all CVD) and 5.5 million (23% of all CVD) of CVD in males and females respectively.
HPN • April 2017
50 Feature Summary • Each year cardiovascular disease (CVD) causes 3.9 million deaths in Europe and over 1.8 million deaths in the European Union (EU). • CVD accounts for 45% of all deaths in Europe and 37% of all deaths in the EU. • CVD is the main cause of death in men in all but 12 countries of Europe and is the main cause of death in women in all but two countries. • Death rates from both ischaemic heart disease (IHD) and stroke are generally higher in Central and Eastern Europe than in Northern, Southern and Western Europe. • CVD mortality is now falling in most European countries, including Central and Eastern European countries which saw considerable increases until the beginning of the 21st century. • In 2015, there were just under 11.3 million new cases of CVD in Europe and 6.1 million new cases of CVD in the EU. • In 2015, more than 85 million people in Europe were living with CVD and almost 49 million people were living with CVD in the EU. • Over the past 25 years, the absolute number of CVD cases has increased in Europe and in the EU, with increases in the number of new CVD cases found in most countries. • However, the age-standardised prevalence rate of CVD has fallen in most European countries, with greater decreases in Northern, Western and Southern European countries compared to those in Central and Eastern Europe. • Although disability-adjusted life years (DALYs) due to CVD have been falling in most European countries over the last decade, CVD is responsible for the loss of more than 64 million DALYs in Europe (23% of all DALYs lost) and 26 million DALYs in the EU (19%). • Hospital discharge rates for CVD as a whole have increased steadily in Europe over the past 25 years. In the EU on average hospital discharge rates for CVD have plateaued since the early 2000s, following increases since 1990.
European countries and lower in Western, Northern and Southern European countries. Indeed, the age-standardised CVD prevalence rate in the EU ranged from 5,099/100,000 in Italy to 9,403/100,000 in Slovakia among men and from 3,975/100,000 in Italy to 7,135/100,000 in the Czech Republic among females. Over the past 25 years, there has been an increase in the absolute number of CVD cases in Europe. Among males, the number of cases increased by 34% between 1990 and 2015 and in females by 29%. Similarly, in the EU, the absolute number of CVD cases rose by 32% among males and 26% among females from 1990 to 2015. In fact, with the exception of Georgia, the absolute number of people living with CVD increased in all countries for which data were available. Importantly, the increase in the absolute number of CVD cases has corresponded with an increase in the size of the total population and older ages in particular. Analysing the age-standardised CVD prevalence rate per 100,000 population, which controls for these changes in population size and composition, reveals a slight decrease in Europe as a whole. Between 1990 and 2015, the rate fell by 9% and 5% in males and females respectively. The prevalence rate of CVD also decreased in the EU on average, by 12% among males and 9% among females – slightly greater than the percentage decrease in Europe as a whole. Focusing on individual countries, the sharpest decreases between 1990 and 2015 occurred in Israel (-15.2%), Finland (-15.3%) and Germany (-16.6%) among males, while in females, the sharpest decrease was found in Italy (-14.1%). Meanwhile, the highest percentage increase in the prevalence of CVD was observed amongst men in Belarus (+4.0%), with little change or slight increases also found in a number of other Central and Eastern European countries. Whilst these age standardised prevalence rates control for differences in population size and age structure, it should be noted that variation in the efficiency of CVD detection and diagnosis between countries and over time (i.e. differences in the size of the ‘hidden’ CVD burden) could account for some of the country-level and trend differences observed. Treatment Treatment of CVD in European countries can be measured along several dimensions.
April 2017 • HPN
For CVD as a whole, in the latest available year, inpatient admission rates in countries were 30% higher for males than females on average. Admission rates for acute myocardial infarction (AMI) were more than two times higher in males than females, while those for heart failure and cerebrovascular diseases were 10% higher in males than females on average. Significant variation in admission rates was also apparent between countries, reflecting a combination of differences in the severity of CVD burden, as well as differences in access to and the efficiency of health care systems. This variation did not follow a clear geographic pattern. Within the EU, admission rates for all CVD, were lowest in Cyprus for both sexes (6.1/1,000 in males, 2.9/1,000 in females) and highest in Lithuania (45.4/1,000 in males, 50.1/1,000 in females). Of the seven non-EU countries for which data were available, inpatient admission rates for all CVD were lowest in Israel (15.8/1,000 in males, 10.4/1,000 in females) and highest in Norway (28.5/1,000 in males, 19.1/1,000 in females). Comparing between countries, within the EU the average length of hospital stay for CVD as a whole varied two-fold in males from 5.5 days in Denmark to 11.0 days in Hungary, and almost three-fold among females from 5.8 days in Denmark to 15.9 days in Finland. Amongst non-EU countries, the average length of hospital stay was lowest in Turkey (4.2 days in males and 4.1 days in females) and highest in TFYR Macedonia (11.5 days in males, 11.6 days in females), although, as with inpatient admission rates, data were available for only seven of 25 non-EU countries. For specific cardiovascular conditions, the duration of stay was consistently low in Turkey for both sexes, whereas the longest periods of stay were reported in Germany and Luxembourg for AMI, in Hungary, Belgium and the UK for heart failure, and in Finland and the UK for cerebrovascular disease. Medications for treatment and prevention of CVD Prescription data on antihypertensive and cholesterollowering drugs in 2000 and 2013 are provided for the 23 European OECD countries, 19 of which are in the EU. For most countries, these data relate to prescriptions of the defined daily dose (DDD)2 among outpatients, with the exceptions
of the Czech Republic, Estonia, Italy and Sweden, where the data also include hospital inpatient prescriptions. Between 2000 and 2013, the use of antihypertensives increased in all European OECD countries for which data are available. The largest increases were observed in Estonia, where prescriptions of antihypertensives nearly tripled and in Luxembourg where prescriptions quadrupled. In 2013, prescriptions of antihypertensive drugs were highest in Germany (575 DDD prescriptions/1,000 people/day) and Hungary (543 DDD prescriptions/1,000 people/ day), around three times greater than those in Austria (184 DDD prescriptions/1,000 people/day) and more than four times greater than those in Turkey (124 DDD prescriptions/1,000 people/day). Prescriptions of cholesterollowering drugs also increased between 2000 and 2013 in all European OECD countries for which data are available. The smallest increase was observed in France, where the prescription rate rose by 1.5 times, while the largest increases were seen in Denmark and Estonia with increases of 14 times and 29 times respectively. In 2013, the highest levels of per capita cholesterol-lowering drug consumption were found in Slovakia (153 DDD prescriptions/1,000 people/ day) and the UK (135 DDD prescriptions/1,000 people/ day), while the lowest rates were found in Austria (44 DDD prescriptions/1,000 people/ day) and Turkey (26 DDD prescriptions/1,000 people/day). According to the OECD, these cross-national differences in drug use are a product of differences in the prevalence of elevated blood pressure and high cholesterol respectively, as well as variation in clinical practice. While the OECD data refer mainly to outpatient drug use, the European Society of Cardiology EUROASPIRE project collects self-reported data on drug prescriptions for hospital patients with diagnosed CVD conditions. These data are not necessarily representative of national prescribing patterns, although they do provide some indication of the scale of medication use in the 24 countries for which data are available. In 2013/14, antiplatelet drugs were the most commonly used form of medication. Within EU countries, their reported use ranged from 85.1% of hospital patients in Lithuania to 98.9% of hospital patients in Cyprus. The
51 economic costs, will decrease” says Mairead McGuinness cochair of the MEP Heart Group. “Our focus must be on prevention of heart health problems and identifying those at risk from heart disease early on.
Karin Kadenbach, co-chair of the MEP Heart Group
use of statins was also high, and varied from 73.5% in Lithuania to 96.1% in Greece, while the use of beta-blockers ranged from 67.8% in the UK to 89.5% in Spain. The greatest variation between EU countries was found for use of ACE inhibitors/ angiotensin receptor blockers (ARBs), with 49.0% of hospital patients in Belgium reporting use of such drugs compared to 82.2% of hospital patients in the Czech Republic. Among hospital patients in the five non-EU countries for which data were available, antiplatelet use ranged from 93.4% in Russia and Ukraine to 98.2% in Serbia; beta-blocker use varied from 77.7% in Ukraine to 96.7% in Bosnia Herzegovina; use of ACE inhibitors/ARBs ranged from 64.0% in Russia to 86.7% in Serbia; while use of statins ranged
“This requires a firm focus in member states on health promotion rather than treating problems as they arise. If we could achieve this focus on prevention then there would be reduced suffering for patients and reduced costs for member states. This report should reinforce our efforts in this direction”, she added.
from 74.6% in Russia to 92.3% in Serbia. It is important to note, however, that EUROASPIRE data were available for only one-fifth of all non-EU countries. The publication formed the basis of a debate recently in the European Parliament in Brussels. The debate was organised by the Members of the European Parliament (MEP) Heart Group, with the support of the European Society of Cardiology (ESC) and of the European Heart Network (EHN).
In a first presentation, the European Cardiovascular Disease Statistics 2017 report was presented. Cardiovascular disease (CVD) is still the number one cause of death in Europe but the fall in death rates from heart disease and stroke over recent decades shows a sustainable trend. “However, with obesity levels rising and diabetes increasing in Europe (in some countries by more than 50%) it is unlikely that the burden of cardiovascular disease, both in terms of human suffering and
A second presentation showed the increasing cost of cardiovascular diseases on societies. Whereas less people die from cardiovascular disease, more and more people live with the disease. “The total cost of ¤210 billion puts a heavy burden on the economy of the EU; if we want to be able to keep up the high living standard, the European Union has to put policies in place which reduce social and economic inequalities between different regions and countries in the EU and help people with chronic diseases to best manage their conditions” states Karin Kadenbach, co-chair of the MEP Heart Group.
News Irish collaboration targets new cancer therapies
Fujitsu, the Insight Centre for Data Analytics and Systems Biology Ireland at University College Dublin have joined forces to develop an automated system for predicting biochemical reactions that are involved in causing diseases such as cancer. The new automated engine will provide scientists with a powerful tool for discovering the next generation of drugs to target these reactions by enabling them to conduct more precise, computation-guided experiments. Recent biomedical research shows that many serious diseases, in particular cancer, are caused by
Professor Walter Kolch, Systems Biology Ireland, University College Dublin
increased rates of discoveries in cellular computing which can, in turn, deliver the targets for more efficient cancer drugs.
The team has applied the automated discovery technology to the use case of phosphorylation prediction.
persistent disruptions of cellular communication processes.
Fujitsu Laboratories Ltd, Fujitsu Ireland and Insight Centre for Data Analytics at NUI Galway have worked since 2015 on TOMOE, a novel discovery informatics platform based on knowledge graphs and statistical relational learning.
“This work with Fujitsu is an exciting glimpse into the future of drug target discovery in which computational modelling will shortcut a laborious experimental process,” said Professor Walter Kolch, Director, Systems Biology Ireland, University College Dublin.
Statistical relational learning is a subdiscipline of artificial intelligence and machine learning that is concerned with domain models that exhibit both uncertainty and complex, relational structure.
As of las month (March), the team has finished working on the first functioning prototype of the prediction engine.
The processes use a biochemical reaction called phosphorylation to control the information flow. These biochemical reactions are faulty in cancer, and drugs that block rogue phosphorylation reactions have proven to be effective cancer treatments. Despite half a century of intense research, the discovery of these critical phosphorylation reactions is still slow due to the extensive manual effort required. Scientists are now hoping that they will be able to make much more accurate predictions of previously unknown phosphorylation by using this new automated engine. They are also confident that this will lead to substantially
The Irish part of the TOMOE team, led by Dr Pierre-Yves Vandenbussche and Dr Vit Novacek, has recently initiated a proof-of-concept collaboration with Systems Biology Ireland at University College Dublin, led by Professor Walter Kolch.
The prototype is currently being tested on a comprehensive knowledge graph covering known phosphorylation reactions and related protein interactions in humans that are available in machine-readable format. Further implementation details and preliminary results will be released later this year.
HPN • April 2017
Shared genetic origin for MND and schizophrenia For the first time, it has been shown that Motor Neurone Disease (MND) - also known as Amyotrophic Lateral Sclerosis (ALS) - and schizophrenia have a shared genetic origin, indicating that the causes of these diverse conditions are biologically linked. By analysing the genetic profiles of almost 13,000 MND cases and over 30,000 schizophrenia cases, the Irish researchers have confirmed that many of the genes that are associated with these two very different conditions are the same. In fact, the research has shown an overlap of 14% in genetic susceptibility to the adult onset neuro-degeneration condition ALS/MND and the developmental neuropsychiatric disorder schizophrenia. While overlaps between schizophrenia and other neuropsychiatric conditions including bipolar affective disorder and autism have been shown in the past, this is the first time that an overlap in genetic susceptibility between MND and psychiatric conditions has been shown. Dr Russell McLaughlin, Ussher Assistant Professor in Genome Analysis at Trinity College Dublin, and lead author of the paper says, “This study demonstrates the power of genetics in understanding the causes of diseases. "While neurological and psychiatric conditions may have very different characteristics and clinical presentations, our work has shown that the biological pathways that lead to these diverse conditions have much in common.” Professor of Neurology in Trinity and Consultant Neurologist at the
Professor of Neurology in Trinity and Consultant Neurologist at the National Neuroscience Centre at Beaumont Hospital Dublin, Orla Hardiman
National Neuroscience Centre at Beaumont Hospital Dublin, Orla Hardiman, is the senior author and lead investigator on the project. She adds, “Our work over the years has shown us that MND is a much more complex disease than we originally thought. Our recent observations of links with psychiatric conditions in some families have made us think differently about how we should study MND. When combined with our clinical work and our studies using MRI and EEG, it becomes clear that MND is not just a disorder of individual nerve cells, but a disorder of the way these nerve cells talk to one another as part of a larger network.” She continues, “So instead of thinking of MND as a degeneration of one cell at a time, and looking for a ‘magic bullet’ treatment that works, we should think about MND in the same way that we think about schizophrenia, which is a problem of disruptions in connectivity between different regions of the brain, and we should look for drugs that help to stabilise the failing brain networks. “The other significant issue that this research brings up is that the divide between psychiatry and neurology is a false one. We need to recognise that brain disease has many different manifestations, and the best way to develop new
treatments is to understand the biology of what is happening. This will have major implications for how we classify diseases going forward, and in turn how we train our future doctors in both psychiatry and neurology. That in itself will have knock-on consequences for how society understands, approaches and treats people with psychiatric and neurological conditions." The new research was prompted by earlier epidemiological studies by researchers at Trinity, led by Professor Hardiman. These studies showed that people with MND were more likely than expected to have other family members with schizophrenia, and to have had another family member who had committed suicide. This was first noted as family histories were ascertained from people with MND in the National ALS Clinic and was subsequently investigated as part of case control studies in Ireland in which over 192 families with MND and 200 controls participated. Details
of over 12,000 relatives were analysed and the rates of various neurological and psychiatric conditions calculated in family member of those with MND and controls. This work was subsequently published in the prestigious American journal the Annals of Neurology in 2013. This led the Trinity group to team up with European collaborators in MND including the University of Utrecht, Kings College London and members of the Project MinE and Psychiatric Genome Consortia to see if these epidemiological observations could be due to a genetic overlap between MND and schizophrenia. The Trinity group, along with their partners in the University of Utrecht, will continue to study the links between MND and psychiatric conditions using modern genetics, epidemiology and neuroimaging, and in this way will develop new and more effective treatments that are based on stabilizing disrupted brain networks.
Businesses must support Wellness at Work Research has shown that half of Irish businesses consider stress and mental health a priority in their workplace, yet 84% do not have a wellness policy or wellness programme in place. Aware, the national organisation which provides support, education and information on depression and related conditions has said that with approximately 1.9 million people in employment in Ireland companies must prioritise mental health and wellness in the workplace. Aware runs a series of Wellness@ April 2017 • HPN
Work education and training programmes for employees and managers which are available nationwide.
workplace. These programmes have been developed under the guidance of Aware’s clinical team and there aims are four-fold:
Aware have been running the Wellness@ Work programme since 2014, proudly supported by Lundbeck Ireland Ltd and is delivered across a spectrum of business sectors including pharmaceutical, hospitality, banking and financial institutions.
1. Help employees understand the importance and value of looking after their mental health, and to use relevant coping skills to limit the impact of any challenges or concerns;
Aware offers a suite of workplace wellness programmes to respond to the increased need for mental health awareness within the
2. Help managers learn skills and identify strategies for assisting employees who are dealing with challenges, with a view to minimising the impact of these issues on the individual,
colleagues and the workplace generally. Educate managers on current employment legislation and best practice for effectively managing mental health issues in the workplace; 3. Gain awareness of the early warning signs of mental health problems and increase the opportunity to refer people to early support and intervention as required; You can find out further information by visiting https://www.aware. ie/help/education/educationprogrammes/wellness-at-work/
The ultimate treatment goal of depression is functional recovery1,2
es s are sentiall m y to
on al s tatus
r etu Patient r
t sen ab
The goals of depression therapy have evolved over time, from response, to remission, with functional recovery now being seen as the goal of treatment2
ns to cti n pre-m bid fu or
.....and so it’s time to rethink our approach References 1. McIntyre RS et al. Depress Anxiety. 2013;30(6):515–527. 2. Greer TL et al. CNS Drugs. 2010;24(4):167–284. Date of preparation: October 2016 UK/VOR/1610/0392a
Lundbeck Ireland Ltd, 4045 Kingswood Road, Citywest Business Park, Co. Dublin. Tel: 01 4689800.
9789 - Brintellix - Disease Awareness Press Ad 3 - October 2016_10x4_02.indd 1
30 years of cancer research in Ireland Dr Robert O'Connor, Head of Research, Irish Cancer Society
From novel treatments to new ways to prevent and detect cancers, the impact of cancer research has seen more Irish people survive the disease than ever before. In 1997 4 in 10 Irish cancer patients were alive 5 years after their diagnosis. Today, that figure is 6 in 10, thanks in large part to huge strides in cancer research that have improved our knowledge of how cancer is prevented, how we can detect it earlier (when it is often readily cured), how we can treat it better, and how we can make sure people live longer, better quality lives after their cancer diagnosis. Since Daffodil Day began 30 years ago, cancer research in Ireland has benefitted hugely from public support which has meant that the Irish Cancer Society has been able to invest in vital research being carried out by some of the country’s best scientists and doctors. As a result, the Irish Cancer Society is the leading non-state funder of cancer research in Ireland. Since 2010 they’ve invested ¤20 million in cancer research, all coming from public donations. Head of Research at the Irish Cancer Society, Dr Robert O’Connor, says, “A survival rate of 6 in 10 is a huge improvement, but cancer research won’t stop until that statistic is 10 in 10. The work of dedicated Irish cancer researchers over the past 30 years and more has given the present generation better, longer lives.
April 2017 • HPN
The work of today’s researchers and Irish patients who partake in clinical research will potentially mean that future generations can live free from the fear of cancer. By donating to Daffodil Day, the public is supporting the life-saving work of these researchers.” To mark 30 years of Daffodil Day, here are some of the ways in which cancer research has had a major impact on people’s lives. Prevention Thanks to research, we know how we can substantially reduce our risk of cancer. 4 in 10 cancer cases are preventable by adopting small lifestyle changes, many of which were discovered over the past 30 years. For example, we now know the role of the Human Papilloma Virus as the cause of cervical cancer, as well as some head and neck cancers, and, as a result, the HPV vaccination has been developed. In Ireland this safe and effective vaccine is administered free to first-year secondary school girls to protect against the strains of HPV which cause 7 in 10 of all cervical cancers and one in 40 of all cancers seen in men and women in Ireland. Reducing the risk of cancer by not smoking, having a healthy mixed balanced diet, keeping active, and avoiding excess sun and alcohol, are all discoveries made through cancer research over the years. As a result, these findings are saving lives.
early today is screening. Currently Ireland has three national screening services to detect breast, cervical and bowel cancers. The National Breast Screening Board was established in 1998 before becoming part of the National Screening Service in 2007. The following year BreastCheck became the first national screening service provider worldwide to offer a fully digital mammography service. BreastCheck has screened over 371,200 women and detected over 5,400 cancers. Cervical cancer is unfortunately common among women but can usually be cured if detected early through an examination (screen) of cells from the cervix. To make this life-saving test available to Irish women from all walks of life, in 2008 Ireland’s National Screening Service launched a free and accessible cervical screening programme, CervicalCheck. The National Screening Service also runs the free and simple home BowelScreen test. The bowel cancer screening test looks for tiny amounts of blood which are not visible to the eye, but which can be an early symptom of this malignancy. Breast, cervical and bowel cancer survival rates are improving in Ireland as a combined result of screening, early detection and more effective treatment options.
One of the major ways in which some cancers can be detected
An accurate prediction and understanding of a patient’s
cancer diagnosis and prognosis are essential to ensure the patient can receive the best treatment. Cancer imaging is a vital component in the cancer diagnosis process. The development of CT (computerised tomography) and MRI (magnetic resonance imaging) scanning in the early 1970s paved the way for continued advances in scanning for cancer. In 1974 the first human positron emission tomography (PET) scanner, an instrument which allows for the scanning of active tumour throughout the body, was built. PET imaging is based on the detection of traces of radiation that are released from mildly radioactive chemicals injected into the blood and taken up by many kinds of cancer and gives even more detail on the extent that a tumour may have spread than CT and MRI. Since then imaging has continued to improve in quality and is used not only for screening but for the assessment of treatment response, tumour size, and/or recurrence of cancer. Biomarkers are cancer-specific substances that can be found in blood, urine, or other body fluids, the level of which can indicate the presence of cancer. In recent years tests to detect the presence or absence of biomarkers have become a routine element of diagnosis. The advent of whole genome sequencing followed by molecular profiling in the early 2000’s provided a platform to allow the identification of the role and relevance of specific changes in genes (mutations) to cancer. As a result, we discovered that when we look at a group of genes or proteins we can not only diagnose cancer, but, in some cases, now predict which cancer medicine will likely work best, and the likelihood of recurrence, thus allowing doctors and patients decide on the best course of treatment, sometimes eliminating the need for chemotherapy treatment altogether. Treatment Many cancer medicines in use today were first discovered in the 1950s and 60s. By 1970
XOFIGO® prolongs the overall survival of patients with castration-resistant prostate cancer (CRPC) by intensive treatment at sites of bone metastases. Introduce Xofigo® for patient progressing on second-generation hormonal therapy1,2
v This medicinal product is subject to additional monitoring. Adverse events and product complaints should be reported. To report an adverse event or a product complaint about a Bayer product, please call Bayer on 01 2999 313. Adverse events and product complaints may also be reported to HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; e-mail: firstname.lastname@example.org. Xofigo 1100 kBq/mL solution for injection (radium Ra 223 dichloride) Please refer to full Summary of Product Characteristics (SmPC) before prescribing. Composition: Active ingredient: radium Ra 223 dichloride (radium-223 dichloride, 1100 kBq/ml, corresponding to 0.58 ng radium-223 at the reference date). Each vial contains 6 mL of solution (6.6 MBq radium-223 dichloride at the reference date). Contains sodium. Indication: Treatment of adults with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastases. Dosage and Administration: Xofigo should be administered only by persons authorised to handle radiopharmaceuticals in designated clinical settings and after evaluation of the patient by a qualified physician. Recommended dose is an activity of 55 kBq per kg body weight, given at 4 week intervals for 6 injections. Safety and efficacy beyond 6 injections with Xofigo have not been studied. Xofigo is administered by slow intravenous injection (generally up to 1 minute). The intravenous access line or cannula must be flushed with isotonic sodium chloride 9mg/ml (0.9%) solution for injection before and after injection of Xofigo. No dosage adjustment is considered necessary in elderly patients, patients with hepatic impairment or in patients with renal impairment. Safety and efficacy of Xofigo in children and adolescents below 18 years of age have not been studied. Contraindications: No known contraindications. Warnings and Precautions: Bone marrow suppression, notably thrombocytopenia, neutropenia, leukopenia and pancytopenia, has been reported. Haematological evaluation of patients must be performed at baseline and prior to every dose. In case there is no recovery in values for absolute neutrophil count (ANC) and haemoglobin within 6 weeks after the last administration of Xofigo despite receiving standard of care, further treatment with Xofigo should only be continued after careful benefit/risk evaluation.
Patients with evidence of compromised bone marrow reserve e.g. following prior cytotoxic chemotherapy and/or radiation treatment (EBRT) or patients with advanced diffuse infiltration of the bone (EOD4; “superscan”), should be treated with caution as an increased incidence of haematological adverse reactions such as neutropenia and thrombocytopenia has been observed. Limited available data indicates that patients receiving chemotherapy after Xofigo had a similar haematological profile compared to patients receiving chemotherapy after placebo. Crohn’s disease and ulcerative colitis: due to the faecal excretion of Xofigo, radiation may lead to aggravation of acute inflammatory bowel disease, therefore Xofigo should only be administered to these patients after a careful benefit-risk assessment. In patients with untreated imminent or established spinal cord compression, treatment with standard of care, as clinically indicated, should be completed before starting or resuming treatment with Xofigo. In patients with bone fractures, orthopaedic stabilisation of fractures should be performed before starting or resuming treatment with Xofigo. In patients treated with bisphosphonates and Xofigo, an increased risk of development of osteonecrosis of the jaw (ONJ) cannot be excluded. In the phase III study, cases of ONJ have been reported in 0.67% patients (4/600) in the Xofigo arm compared to 0.33% patients (1/301) in the placebo arm. However, all patients with ONJ were also exposed to prior or concomitant bisphosphonates and prior chemotherapy. Xofigo contributes to a patient’s overall long-term cumulative radiation exposure and therefore may be associated with an increased risk of cancer and hereditary defects. No cases of Xofigo-induced cancer have been reported in clinical trials in followup of up to three years. Depending on the volume administered, Xofigo can contain up to 2.35 mmol (54 mg) sodium per dose. Undesirable effects: Very common: thrombocytopenia, diarrhoea, vomiting, nausea; Common: neutropenia, pancytopenia, leukopenia, injection site reactions; Uncommon: lymphopenia. Classification for supply: Medicinal product subject to restricted medical prescription. Marketing Authorisation Holder: Bayer Pharma AG. 13342 Berlin. Germany. MA number(s): EU/1/13/873/001. Further information available from: Bayer Ltd., The Atrium, Blackthorn Road, Dublin 18. Tel: 01 2999313. Date of Preparation: October 2015
References: 1. Mohler JL, Armstrong AJ, Bahnson RR, et al. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Prostate Cancer. Version 2.2016. National Comprehensive Cancer Network; 2016:1-108. 2. Mottet N, Bellmunt J, Briers E, et al. Guidelines on Prostate Cancer. European Association of Urology; 2015 :1-156. 3. Xofigo® (radium Ra 223 dichloride) solution for injection Summary of Product Characteristics (SmPC), Bayer Pharma AG, 13342 Berlin, Germany, 2016.
© 2016 Bayer Pharma AG. September 2016. L.IE.MKT.09.2016.0632
One of the major ways in which some cancers can be detected early today is screening advanced Hodgkin's disease was the first cancer of a major organ system that could be cured by chemotherapy, thanks to a combination of therapies being used. In the same decade chemotherapy also began to be used side by side with surgery or radiotherapy. In the 1980s multiple new drugs were screened for effectiveness as anti-cancer agents. In more recent years, as our knowledge of molecular changes that occur in cancer cells continues to grow, so too has drug development moved towards more targeted, specific treatments, which have less side effects. In 2001 the first such targeted therapy, imatinib (Gleevec) for a blood cancer, chronic myelogenous leukemia (CML) was approved. Today, significant research has resulted in a huge growth in the number of new, targeted therapies. With this we are also moving towards companion diagnostics which allow patients be tested in advance to ensure the safe and effective use of a drug most likely to work for their individual form of cancer. Stem cell transplants (also known as bone marrow transplants) are
April 2017 • HPN
now used to treat, manage and sometimes cure many types of blood-related cancers such as leukaemia, lymphoma or multiple myeloma. These transplants involve patients receiving intensive chemo and/or radiotherapy to wipe out their own cancerous immune system followed by the transplant of healthy immune stem cells from a healthy donor in the hope that these will regenerate a new immune system free from cancer. The first bone marrow transplants were mostly unsuccessful until we realised that patients and donors must be matched in a specific aspect of genetics (HLA-typed) for a successful transplant. Since the 1980’s it has become possible to perform a transplant using donor marrow from individuals outside the family. In 1989 the Irish Unrelated Bone Marrow Registry was established to provide a panel of volunteer donors for Irish and International patients. Today there are over 21 million individuals worldwide who have been HLA-typed to serve as an unrelated donor. Advances mean it is now also possible to perform a mini stem cell transplant in people who are not fit or well enough for a traditional transplant, bringing hope to an even wider group of patients.
In the last 30 years researchers have also focussed on therapies which involve encouraging and reengineering the immune system to attack cancer cells, generally known as immunotherapy. The number of immunotherapies being approved for the treatment of cancer has steadily been increasing over the past 5 years. Encouragingly, research shows that many of these immunotherapies appear to have some positive effects for some patients in a wide variety of cancer types. In 2016, 9 immunotherapy drugs were approved across the US and Europe for more than 25 cancer indications. In 2017 this new area of cancer treatment is one of the largest areas of research as it holds the hope for a genuine cure for many previously poorly-responding forms of cancer, such as melanoma.
with government, industry, and academia, we are making progress in putting patients at the heart of cancer research, as well as policy, treatment innovation and care.
Proposals have been made to embed psychological care for cancer patients in The Department of Health’s upcoming Cancer Strategy, which is due to be presented to the Minister of Health shortly. This strategy will act as the blueprint for our cancer services over the next decade.
As more people survive cancer, researchers are focussing more on how their quality of life can be improved after their diagnosis and treatment. A key aspect to a better quality of life is emotional and physical wellbeing. 30 years ago the training and availability of psychologists to specialize in issues specific to people with cancer was rare. A 1983 study showed that rates of depression in patients with cancer ranged widely from 1% to 53%, depending on the population of patients and the diagnostic criteria used. The formation of the International Society of Psychosocial Oncology (IPOS) later established an increasingly cohesive body of knowledge in Psycho-Oncology and facilitated the development of best practice guidelines in the UK, Australia, Israel, Canada, and the USA to help support the difficult psychological challenges that a cancer diagnosis can meet on a patient and their loved ones. In the last 15 years three dedicated Psycho-Oncology Departments have been established in St. Vincent’s University Hospital, St. Luke’s Hospital and St. James’s Hospital, Dublin. The Future Cancer research is becoming more focussed on patient-centred care, not just eradicating the cancer. From new initiatives to embed patient and public involvement in cancer research to patient advocate organisations working
Survivorship will also continue to grow as a research field. Cancer treatments can lead to side effects ranging from long-term fatigue to infertility. Researchers are already talking to survivors to better understand these side effects and find ways to get everyone back to their normal life and health. This can be seen in the IPCOR (Irish Prostate Cancer Outcomes Research) study, funded by the Irish Cancer Society and the Movember Foundation. IPCOR is assessing whether newly diagnosed Irish prostate cancer patients see big changes in their quality of life during and after treatment, and how their care and outcomes compare internationally.
And at the heart of cancer research will continue to be the goal to save lives. The Irish Cancer Society is backing the goal through funding projects such as BREASTPREDICT, a ¤7.5 million countrywide collaboration among more than 50 breast cancer researchers across Ireland. Sharing skills and expertise, BREAST-PREDICT collects information and tumour specimens from breast cancer patients so that researchers can better understand this disease and find ways to individualise treatment for a better anti-cancer effect. Currently the Irish Cancer Society funds more than 100 cancer researchers in Ireland. Their work is forming the basis of new discoveries that could improve and save future lives. None of this would be possible without the public’s generosity on days like Daffodil Day. Biosimilar Initiative of the Year The Biosimilar Initiative of the Year is a recognition of all the pre-clinical and clinical development projects, alliances, distribution, sales and marketing being carried out within this rapid growing field in the biosimilar market.
Doctors make up majority of mental health referrals A new service, the Practitioner Health Matters Programme (PHMP), which supports health professionals who may have addiction or mental health issues, has confirmed it helped 47 practitioners in its first year of operation. Non Consultant Hospital Doctors, Consultants and GPs made up 86% of referrals to the new confidential Programme which is open to doctors, dentists and pharmacists. An independent charitable organisation, the PHMP has the support of the representative and training bodies for the Medical, Dental and Pharmacy professions as well as the three professional regulatory bodies. Clinical Lead of the programme Dr Íde Delargy says early intervention is key. Doctors’ high-stress work environments could make them vulnerable to mental health and addiction problems, she says. They can also be reluctant to seek help due to fear of being reported. The issues In its first annual report the PHMP said 30 practitioners presented with a single problem at registration while 17 had more than one problem. Substance misuse was the most common standalone presenting problem (15) followed by anxiety (6) and depression (4). Where practitioners presented with a combination of issues, depression was the most common presentation (13) followed by anxiety (10) with substance misuse in combination with other
Mr Hugh Kane, Chairperson and Dr Íde Delargy, Clinical Lead, PHMP
symptoms being found in a further seven cases. While women made up just under half of the total (23), they were the clear majority in both the youngest (24-29) and oldest (60-69) age groups. While there were eight women in the youngest age group, their highest representation, this was the group with the least number of men, with just three. Overall the largest number of registrations, 13, was represented in both the 30-39 and 50-59 age groups. Almost half of all referrals were self-referrals (22) while eight referrals were made by a consultant psychiatrist and six were referred by a colleague. The Outcomes Over half of all practitioners patients registered on the programme have continued working in their professions and with the support provided by PHMP, did not require to take time off work. Six were required to stop working for a period of time but have now either returned or are returning to work in the near future. Seven patients are not currently working; of these one has retired and the others are deemed unfit for practice and are under ongoing
review. Seven others are attending the Health Committee of the Medical Council. Dr Íde Delargy, the Clinical Lead for the new Programme said health professionals are very slow to come forward to declare that they may have a mental health or alcohol or drug related problems due to reputational/confidentiality issues. She said they also generally present when in crisis, often having tried to self-manage and self-medicate their problem. “Early intervention is key and while taking that first step can be extremely challenging, for the person involved or their friend or family, it can also be lifesaving. If practitioners come forward early and get the help they need the statistics show their chances of
getting back to work are very good. Practitioners who access a service from a designated programme like this do extremely well and about 80% recover and return to working well” she said. Mr Hugh Kane, the Chairperson of the PHMP said that with over 25,000 doctors, pharmacists and dentists in the country the PHMP would anticipate that in excess of 2,000 practitioners may require help on an annual basis. “One of our main aims for 2017 will be to engage in an awareness raising campaign of this service amongst health professionals. The other is to establish a sustainable funding model for the Programme.” For full details of the Programme go to www.practitionerhealth.ie
Updated Pain Management Clinical Practice Guidelines The Pre-Hospital Emergency Care Council (PHECC) in Ireland has issued its new pain management clinical practice guidelines for emergency care teams. The aim of these guidelines is to provide a comprehensive and co-ordinated approach to how patients receive optimal care in the pre-hospital setting, so these updated guidelines are a welcome development for healthcare professionals managing trauma pain across the Republic of Ireland.
Dr Conor Deasy, Consultant in Emergency Medicine, Cork University Hospital and Deputy Medical Director of the National Ambulance Service (IAEM) commented, “Treatments such as IV analgesia or gas and air can be cumbersome to set up and take time to administer. When reviewing the guidelines the PHECC committee is always looking to include new and innovative treatments, which have a proven benefit to patients and can directly improve the quality of service our emergency care teams can provide.”
The new guidelines now include the inhaled pain relief medication, Penthrox® (methoxyflurane). Penthrox® is a patient controlled, inhaled medication, which provides rapid relief from acute pain. Penthrox® has been extensively used for many years by emergency medicine teams in Australia and New Zealand to provide rapid and effective pain relief to patients with trauma related injuries.
moderate to severe pain quickly, allowing healthcare professionals to provide a more immediate and effective pain relief and a better patient experience.” He concluded, “Availability of Penthrox® in the Republic of Ireland and its inclusion on the new Pain Management Clinical Practice Guidelines is an important step forward towards achieving better acute pain relief for our patients.”
Dr Deasy added, “Penthrox® is easy to use and relieves
HPN • April 2017
Event Gallery 59 Research collaboration on blot clots CÚRAM, the Science Foundation Ireland Centre for Research in Medical Devices, based at National University of Ireland Galway (NUI Galway) has announced an agreement with Mayo Clinic in the United States to collaborate on research into blood clots that cause ischemic stroke. As part of this agreement, researchers will work at CÚRAM and Mayo Clinic, to analyze and characterise clots from stroke patients in both Europe and the United States. The goal of the research is to advance and improve therapies for stroke patients in the future.
An NUI Galway post-doctoral fellow will perform research on secondment at Mayo Clinic to facilitate collaboration on standardising protocols and setting up an international database. Mayo Clinic’s Applied Neuroradiology Lab is initiating a nationwide effort in the US to retrospectively and prospectively collect samples of clots removed from patients who have suffered a stroke in order to analyze them to inform treatment in the future. Through CÚRAM, NUI Galway will be establishing a dedicated clot pathology lab to conduct parallel clot research in Europe.
Professor Abhay Pandit, Scientific Director of CÚRAM at NUI Galway, commented, “With this partnership and postdoctoral fellow program with Mayo Clinic, we’re excited by the opportunity to advance research in this area. Researchers at CÚRAM have been working on the analysis and characterisation of clots through collaborative arrangements with Neuravi, and we’re delighted that they and Science Foundation Ireland are funding this postdoctoral fellow program. This convergence of interests and expertise has enabled us to structure a unique collaboration with Mayo Clinic. We hope this will lead to
Professor Abhay Pandit, Scientific Director of CÚRAM
ground-breaking research and drive significant improvements in outcomes for stroke patients in the future.”
European Palliative Care Academy 2017-2019 Applications for the European Palliative Care Academy Leadership Course 2017 – 2019 are being accepted now. The European Palliative Care Academy was initiated by the Robert Bosch Stiftung and is a joint project of the four academic centres: • University Hospital of Cologne/ Germany • King’s College London, Cicely Saunders Institute/ United Kingdom • Nicolaus Copernicus University Toruń / Poland • Hospice Casa Sperantei, Brasov/ Romania These institutions have worked closely together to develop a curriculum aimed at emerging palliative care leaders of all professional backgrounds from across Europe. The new course starts in September 2017. Deadline for applications is June 11th 2017. For further information on the European Palliative Care Academy and the application process, please visit EUPCA’s website http://www.eupca.eu/
Accord to grow generic and biosimilar market Irish market. This evolution of the generics and biosimilars market here is underpinned by numerous launches in existing and new therapy areas and a diverse biosimilar pipeline for 2017. Accord Healthcare will also continue to support retail and hospital customers with trusted products, excellent distribution channels and communications techniques that have been developed and honed by the Actavis Ireland team over the years.
Tracy Kivlehan, Country Manager Accord Healthcare, Padraic O’Brien, Head of Commercial Actavis Ireland and Tony Hynds Managing Director Actavis Ireland
The new combined company will continue to support the growth of the Irish generics market through positive policy changes for patients and pharmacists. Accord Healthcare is an active member of the Irish Generics Medicines Association and is dedicated to increasing the use of biosimilars and for the inclusion of high tech medicines to the generics interchangeable list.
Through the merger with Actavis Ireland, Accord Healthcare announce the retention of the over 27 experienced sales
“Actavis as Accord will strive to continue to be your preferred partner with our experienced people focused on outstanding customer service, efficient twice
and management people and the promise to bring a unique offering of high quality generic and biosimilar products to the
daily product delivery and a commitment to championing the pharmacy industry through high level stakeholder engagement”, says Tony Hynds, Managing Director, Actavis Ireland. “We remain dedicated to our customers with over 25 experienced staff from both organizations’ working towards delivering high quality generics and biosimilars, simple transparent and competitive pricing schemes, tailored business training programmes and flexible account management to support the growth of Irish pharmacies”. “We want to encourage all our customers to contact their Actavis or Accord sales representatives or call us in our Cork office if they have any queries about the merger or existing supply agreements”. For further information on the merger and your supply agreements with Actavis and /or Accord, contact: Marguerite Tierney, Accord Healthcare: marguerite_tierney@ accord-healthcare.com or call on 021 4619040.
HPN • April 2017
60 Event Gallery Bon Secours donates ¤10,000 to ChildVision As part of the Community Initiative Programme, the Bon Secours Hospital Dublin recently donated ¤10,000 to ChildVision – National Education Centre for Blind Children. The money will provide a program of Equine Assisted Occupational Therapy (EAOT) Visually impaired children will be able to avail of horse riding sessions with a Horse Riding Instructor and an experienced side walker. The children will benefit greatly from the connection with the horses, the sensory experience of the horse’s movement and the increased demand of their postural control and the increased confidence that will be gained through such an experience.
Sr Goretti Spillane of the Pastoral Care Team in the Bon Secours Hospital Dublin, Ruth Hickey of ChildVision and Mike Tonery Hospital Manager Bon Secours Hospital Dublin
Star Awards for UCC Pharmacy University College Cork (UCC)Pharmacy Society picked up a record number of awards at this year UCC Societies STARS Awards. In addition to being nominated for awards across five different categories, the Pharmacy Society were awarded Best Financial Management for the first time ever and the society's Chairperson, Máire O'Connell was awarded an Individual Bene Merenti, an honour which had never before been bestowed on a UCC Pharmacy student. Pictured are Best Financial Management Award Presentation: Paul Harte, Finance Officer for UCC Societies Executive, Máire O'Connell, Chairperson of UCC Pharmacy Society, Anna Reilly, Finance and Sponsorship Officer of UCC Pharmacy Society and Cassie MacUileagóid, Vice President of UCC Societies Executive.
Promoting diversity with #BeBoldForChange Leading healthcare company MSD organised an event at their Dublin office focused on the importance of diversity and inclusion in today’s working environment, as part of International Women’s Day celebrations. Organised by the MSD Women’s Network, the event was aimed at empowering MSD employees to realise their full professional and personal potential through networking, mentoring and sponsorship while also supporting MSD’s business strategies.
Pictured at #BeBoldForChange event at the MSD office in Dublin are from l-r are Mairead McCaul, MSD Women’s Network Lead & Business Unit Director; Liz O’Donnell, Director Policy, Government and Corporate Affairs, MSD; and Agustina Garcia Exposito, MSD Women’s Network
Keynote speaker, former government minister and now Director of Policy, Government Affairs and Communications at MSD, Liz O’Donnell, spoke about her experience of moving through the political ranks in Ireland as a TD and her role in a number of political and social initiatives and movements that aimed to empower women. Focusing on the 2017 International Women’s Day theme
April 2017 • HPN
#BeBoldForChange, Ms O’Donnell commented, “Part of International Women’s Day is ensuring we are doing our utmost to progress diversity and equality in all aspects of life, including the workplace. In many ways the healthcare sector is leading the way when it comes to gender equality in Ireland, with many organisations significantly enhanced by a wide range of cultures, abilities, experience and viewpoints. As an organisation that ultimately services the patient, it is important that MSD as a business continues to reflect the diversity of the society we operate in. “One noteworthy programme is the MSD for Mothers initiative, focused on improving the health and well-being of mothers during pregnancy and childbirth. A 10year, $500 million programme, MSD is supporting over 50 projects in more than 30 countries, using next-generation solutions to improve maternal health and end preventable deaths.”
Clinical R&D 61 NEW DATA SHOWS STELARA MAINTAINED CLINICAL RESPONSE AND REMISSION AFTER TWO YEARS OF TREATMENT Janssen-Cilag International NV (“Janssen”) have announced new two-year data from the ongoing IM-UNITI long-term extension (LTE) study evaluating the efficacy and safety of subcutaneous (SC) STELARA® (ustekinumab) in patients with moderate to severe Crohn’s disease. The data presented at the 12th Congress of the European Crohn’s and Colitis Organisation (ECCO) showed that treatment with ustekinumab maintained clinical response and remission for up to two years with no new safety signals observed. “Maintaining control of disease symptoms is paramount in the treatment of Crohn’s disease. The two-year clinical response and remission rates from the IM-UNITI study provide further evidence that ustekinumab can be an effective therapeutic option for people living with this chronic and often debilitating disease,” said Dr Eoin Slattery, Consultant Gastroenterologist and Clinical Lead for Endoscopy, University Hospital Galway. Of the 1,281 patients enrolled in the maintenance study, 397 patients who achieved a response to ustekinumab at week 8 following an induction phase were randomised to receive SC ustekinumab 90mg every 8 weeks (Q8W) or every 12 weeks (Q12W), or placebo during a maintenance (0–44 week) period, before entering the LTE (44–252 week) period. A one-time dose adjustment to ustekinumab 90mg Q8W was permitted in patients in the randomised group who met loss of response criteria between weeks 8–32. Clinical efficacy data were collected every 12 weeks and safety data were collected every 4 weeks from the end of the maintenance trial (week 44) until the maintenance study was unblinded and then at Q8W or Q12W dosing visits during the LTE period; data at week 92 are reported here. Among randomised patients who entered the LTE period and continued to receive ustekinumab through week 96, 79.2% of patients receiving ustekinumab Q12W and 87.1% of patients receiving ustekinumab Q8W were in remission, while 90.9% of patients and 94.3% of patients showed clinical response at week 92, respectively. Among all ustekinumab-treated patients who continued to receive ustekinumab
through week 96, remission and response rates at week 92 were 70.7% and 84.7%, respectively (as observed). Safety event rates per hundred years of follow up were comparable in ustekinukab-treated patients compared to placebotreated patients from week 44 through to week 96. Among all ustekinumab-treated patients, there were two deaths (sudden death, asphyxia). There were two non-NMSC (non-melanoma skin cancer) malignancies reported between weeks 44 and 96, a seminoma in a ustekinumabtreated patient and a papillary thyroid cancer in a placebo-onlytreated patient.1 “The 96 week data from the IM-UNITI study complement data previously presented from the UNITI programme. We look forward to sharing future results from the UNITI programme, and remain committed to improving overall outcomes for people living with Crohn’s disease,“ said Dr Leisha Daly, Country Director, Janssen Ireland.
POSITIVE RESULTS FOR RELVAR® ELLIPTA® LUNG FUNCTION STUDY GlaxoSmithKline plc (LSE/ NYSE:GSK) and Innoviva, Inc. (NASDAQ: INVA) have announced positive headline results from a non-inferiority lung function study, which demonstrated that patients with well-controlled asthma were able to switch to the once-daily Relvar® Ellipta® (fluticasone furoate/vilanterol, FF/VI) 100/25, an inhaled corticosteroid (ICS)/ long-acting beta2 agonist (LABA) combination, from the twice-daily Seretide® Accuhaler® (fluticasone propionate /salmeterol, FP/SAL) 250/50, without compromising their lung function. Patients randomised to FF/VI taken once-daily maintained lung function comparable with those randomised to the twice-daily FP/SAL [difference +19mL (95% CI: -11mL, +49mL], meeting the study’s primary endpoint, based on the lower bound (-11ml) of the 95% confidence interval falling above the non-inferiority margin of -100mL. A third treatment arm with fluticasone propionate (FP), ICS monotherapy, was included to detect a lung function difference between treatments. Results demonstrated statistically significant differences in favour of the ICS/LABA combinations to FP (p<0.001). The incidences of on-treatment
serious adverse events (SAEs) and adverse events (AEs) of special interest were consistent with the known safety profile of FF/VI, established in asthma patients from other studies. Study Design Following a 4-week open-label treatment period with FP/SAL 250/50 twice-daily, patients with well controlled asthma were randomised to receive either FF/VI 100/25 once-daily, FP/SAL 250/50 twicedaily or FP 250 twice-daily in a double-blind, double-dummy manner for 24 weeks at multiple centres in 12 countries. The primary objective of the study was to demonstrate non-inferiority of Relvar Ellipta 100/25 once-daily with Seretide Accuhaler 250/50 twice-daily in adult and adolescent subjects 12 years of age and older with persistent bronchial asthma, well controlled on twice-daily ICS/ LABA. The endpoint for the study was the change from baseline in clinic visit evening FEV1 (pre-brochodilator and pre-dose) at the end of the 24-week treatment period. To demonstrate the non inferiority of FF/VI vs FP/SAL the lower limit of the 95% confidence interval for the mean difference in change from baseline for evening FEV1 needed to be greater than the pre defined margin of -100mL. This was to rule out the possibility that FF/VI was more than -100mL inferior to FP/SAL.
ASTEX PHARMACEUTICALS CELEBRATES AS CANCER DRUG RECEIVES US MARKETING APPROVAL Astex Pharmaceuticals (“Astex”), a pharmaceutical company dedicated to the discovery and development of novel small molecule therapeutics for oncology and diseases of the central nervous system, announced today that its long-standing pharmaceutical collaborator, Novartis, has received US Food and Drug Administration (FDA) marketing approval for Kisqali® (ribociclib, formerly known as LEE011) plus an aromatase inhibitor as a first-line treatment in post-menopausal women with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) advanced (metastatic) breast cancer.
into between Astex and Novartis in 2005. The partnership was struck to discover cell cycle inhibitors which represented a novel class of compounds that target the mechanisms of cell division in order to prevent or interfere with cancer growth. Under the collaboration, Astex scientists, based at the company’s research laboratories in Cambridge UK, were responsible for solving the crystal structure of the key cancer target protein CDK4. This was an important scientific breakthrough that no other group had previously been able to achieve, leading to a peerreviewed publication in PNAS(1). Working with the Novartis team at the Novartis Institutes for BioMedical Research (NIBR), Cambridge, Mass., USA, Astex then applied its structure-based drug discovery technology, part of its Pyramid™ platform, in the collaboration that led to the discovery of LEE011, (now known as Kisqali) which was then taken forward by Novartis into clinical trials. In total, a team of some 25 Astex scientists were involved in this research program. Kisqali® (ribociclib) is a selective cyclin-dependent kinase inhibitor, a class of drug that helps slow the progression of cancer by inhibiting two proteins (CDK4 & CDK6) which, when over-activated, can enable cancer cells to grow and divide quickly. Novartis received the approval under the FDA Breakthrough Therapy Designation and Priority Review programs, based on data from a first-line Phase III trial that met its primary endpoint at interim analysis, due to its superior efficacy compared to letrozole alone. The combination of Kisqali plus letrozole reduced the risk of disease progression or death by 44% over letrozole alone. There was a sustained separation of the progression free survival curves evident as early as 8 weeks and more than 53% of patients with measurable disease who took Kisqali plus letrozole saw their tumor size shrink by at least 30%. The combination also showed significant clinical benefit in all patient subgroups regardless of disease burden or tumour location(2).
Astex is eligible to receive a milestone payment in respect of this FDA marketing approval and on approval of additional regulatory filings in Europe and Japan, as well as royalty payments on annual sales of Kisqali, under the drug discovery alliance entered HPN • April 2017
62 Clinical R&D LANDMARK OUTCOMES STUDY ON REPATHA®
Amgen (NASDAQ:AMGN) have announced that the 27,564-patient Repatha® (evolocumab) cardiovascular outcomes study, FOURIER, established for the first time that substantially reducing low-density lipoprotein cholesterol (LDL-C) levels with evolocumab, beyond what is possible with the current best therapy alone, leads to a further reduction in major cardiovascular events, including heart attacks, strokes and coronary revascularisations when compared to optimised statin therapy. The study found a statistically significant 15 percent reduction (p<0.001) in the risk of the extended MACE composite (primary) endpoint, which included hospitalisation for unstable angina, coronary revascularisation, heart attack, stroke or cardiovascular death versus optimised statin therapy. The study was statistically powered around the hard major adverse cardiovascular event (MACE) composite endpoint of first heart attack, stroke or cardiovascular death (key secondary composite endpoint) and found that adding evolocumab to optimised statin therapy resulted in a statistically significant 20 percent (p<0.001) reduction in these events compared with optimised statin therapy alone. The robust benefit in this objective measure started as early as six months and continued to accrue through the median 2.2 years of the study. In fact, the magnitude of the risk reduction in the hard MACE composite endpoint grew over time, from 16 percent in the first year to 25 percent beyond the first year. Patients on evolocumab experienced a reduction in the risk of heart attack (27 percent, nominal p<0.001), stroke (21 percent, nominal p=0.01) and coronary revascularisation (22 percent, nominal p<0.001). Consistent with recent trials of more intensive LDL lowering, there was no observed effect on cardiovascular mortality.1-5 Similarly, there was no observed effect on hospitalisation for unstable angina. In an exploratory analysis, the relative risk reduction for fatal and non-fatal heart attack or stroke was 19 percent in the first year (p=0.003) and 33 percent beyond the first year (p<0.00001). When added to statin therapy, evolocumab reduced LDL-C from a median of 92 to 30 mg/ dL (2.38mmol/l to 0.78mmol/l), a reduction of 59 percent at April 2017 • HPN
week 48, which was sustained throughout the trial. At 48 weeks, the LDL-C was reduced to at least 25 mg/dL (0.65mmol/l) in 42 percent of patients treated with evolocumab, as compared with <0.1 percent in the placebo group (p<0.001). Additionally, treatment with Evolocumab had favorable effects on other lipid parameters. Evolocumab was developed from the breakthrough work of Amgen scientists who elucidated the interaction of PCSK9 and the LDL receptor (LDLR), including the site where the LDLR binds to PCSK9, and developed antibodies that bind to PCSK9 at that site and block the interaction of PCSK9 with the LDLR. These scientific advances resulted in the intellectual property to antibodies to PCSK9 that protect evolocumab. An extensive set of clinical trials subsequently demonstrated the effectiveness of evolocumab in lowering LDL-C, in regressing coronary atherosclerosis and finally now in reducing the risk of major adverse cardiovascular events. From its inception, the program has demonstrated the power of human validation of a drug target based on genetic insights, an approach which is playing an increasingly important role across Amgen’s therapeutic portfolio. No new safety concerns were identified in this large clinical trial with roughly 60,000 patientyears of follow-up; this included the assessment of patients who achieved very low levels of LDL-C. In particular, there were no notable differences seen between treatment arms in the overall rate of adverse events, serious adverse events or adverse events leading to study drug discontinuation. Likewise, rates of adjudicated new onset diabetes (8.1 percent evolocumab; 7.7 percent placebo), muscle-related side effects (5.0 percent evolocumab; 4.8 percent placebo), cataract (1.7 percent evolocumab; 1.8 percent placebo), neurocognitive adverse events (1.6 percent evolocumab; 1.5 percent placebo) and allergic reactions (3.1 percent evolocumab; 2.9 percent placebo) were similar between the two arms. Injection site reactions were more common with Evolocumab than with placebo (2.1 percent evolocumab; 1.6 percent placebo). In the evolocumab arm, postbaseline new binding antibodies were detected in 43 patients (0.3 percent) and neutralising antibodies in none. Detailed results from the evolocumab cognitive function study (EBBINGHAUS) will be presented in a separate LateBreaking Clinical Trial Session on Saturday, March 18 at 9 a.m. ET.
AFFIDEA ANNOUNCES NEW MEDICAL SCANNING CENTRE FOR WATERFORD Affidea, Ireland’s leading independent provider of diagnostic imaging services including MRI, Ultrasound and X-ray, has announced its plans to open a new medical scanning facility in Ardkeen, Waterford this June, to serve the people of Waterford and surrounding areas. The company is creating ten jobs and is investing ¤2.6m in opening the Waterford centre, as part of an overall ¤15m investment in the Irish healthcare sector. Last month, the company announced plans to open a new diagnostic centre in Tallaght this May, to service west Dublin. Construction work has already started at the Waterford centre, which will include a multi-modality scanning centre located at Holly House, Arkeen, Cove Roundabout, Waterford. It will serve as a diagnostic scanning facility, offering MRI, Ultrasound, Dexa and X-ray. Affidea anticipates that 9,000 patients will attend the centre for 12,000 scans each year. It is expected the new centre will be of particular benefit to patients at areas including Waterford, Wexford, Kilkenny and Tipperary. Affidea Waterford will be equipped with state of the art technology including the high-specification Aera Magnetom MRI scanner, providing the highest-quality scans and a much-improved patient experience, particularly for patients who experience claustrophobia or those who find it difficult to tolerate the noise of older scanners Affidea centres are accredited with the internationally recognised standard in ambulatory care from the Joint Commission International (JCI) and will operate the new centre in Waterford to the same exacting standards while undergoing the accreditation process. Tom Finn, CEO of Affidea, said, “Affidea currently caters for the South East of the country with our centres in Kilkenny and Naas, however, the Waterford centre will ensure local patients have greater accessibility to medical scans, quickly, professionally and to the highest of standards. The new centre will ensure patients can receive the timely attention they need in a primary care environment, rather than hospital based setting.” Affidea rebranded from Euromedic in 2015, to ensure a uniform identity across Europe, and to aid European growth and support the organisations aggressive global expansion plans. Affidea entered the Irish market in March 2007 through the acquisition of MRI Ireland. Over the past eight years,
six further locations have been added to the network in Ireland with more centres expected nationwide over the coming months.
MORE UNDERSTANDING OF BIPOLAR DISORDER ON WORLD BIPOLAR DAY In support of World Bipolar Day, mental health organisation Aware is calling for increased education, awareness and advocacy against the social stigma of mental health conditions, in particular bipolar disorder. Brid O’Meara, Director of Services with Aware commented, “World Bipolar Day is a great reminder to us all that help and support are available for those with mental health conditions. Bipolar disorder is a serious condition and typically consists of both manic and depressive episodes, separated by periods of normal moods.” Aware is a non-profit organisation which provides education, information and support to those affected by depression and bipolar disorder. The organisation runs a number of support services, such as a Support Line and Support Mail service, Life Skills Programme, a Relatives Education Programme and Support Groups. The nature of the peer-to-peer Support Groups for those affected by bipolar disorder mean that people can speak openly about their condition and listen to others going through similar experiences. Bipolar disorder can cause unusual shifts in mood, energy, activity levels, and the ability to carry out day-to-day tasks. The condition is characterised by extreme mood swings, which can range from extreme happiness (mania) to extreme sadness (depression). A key focus for Aware is to raise further awareness of the range of support and services they can offer to individuals and their loved ones affected by depression or bipolar disorder, whilst reinforcing that with the right support, it is possible to lead a normal life.
63 PANDEMIC RESEARCH PROJECT PRESENTS RECOMMENDATIONS TO EUROPEAN COMMISSION The European Union-funded pandemic project, Pandemic Risk and Emergency Management (PANDEM), has completed its research phase and produced a final report, identifying current needs and recommending innovative solutions to the European Commission. The 18-month project, coordinated by NUI Galway, was funded through the EU Horizon 2020 Secure Societies programme of research and innovation, to help improve pandemic preparedness across European Union member states and beyond. Throughout history, pandemics have had a major impact on the health and security of human populations. An outbreak of plague killed one third of Europe’s population in the Middle Ages, and Spanish flu killed 40-50 million people in the early 20th century. In 2003, a new disease called Severe Acute Respiratory Syndrome (SARS) emerged in China and spread from Hong Kong through international transport hubs to multiple countries within days causing major disruption with an estimated economic cost of US$80 billion. The most recent H1N1 influenza pandemic in 2009 spread around the world in weeks, affecting all countries with significant health, economic, political, social, cultural and environmental consequences. More recently, outbreaks of the Zika virus, Ebola and MERS-CoV have posed major threats to human health, and to global trade and trust. The threat analysis conducted by the project concluded that the risk of emergence of a pandemic is greater now than ever before. Influenza viruses continue to circulate between birds, pigs and humans, greater numbers of laboratories engaging in bioengineering work on dangerous pathogens increases the risk of accidental release if biosafety measures are not strictly implemented, and bioterrorism poses a threat with the increased availability of technology and knowledge to build a bioweapon. Antibiotic resistance is also a major threat to human health which could bring the management of infectious diseases back to the pre-antibiotic era. The objectives of the PANDEM project were to review best practice and identify tools and systems needed to strengthen pandemic preparedness and response at national, EU and global levels. From the beginning of the project in September 2015,
there has been a particular focus on identifying innovative solutions to build capacity of EU member states to collaborate on cross border risk assessment, response and recovery. These solutions aim to build the foundations for a multi-disciplinary, inter-sectoral network of experts, and contribute to the reduction of health, socio-economic and security consequences of future pandemics through improved preparedness at local, national, EU and global level. The project coordinated by NUI Galway included the World Health Organisation (WHO) Regional Office for Europe, the London School of Tropical Medicine and Hygiene, Swedish Defense Research Agency, Public Health Agency of Sweden, Université catholique de Louvain and IGS Strategic Communications. The PANDEM team at NUI Galway, a collaboration between the School of Medicine, the College of Engineering and Informatics and the Insight Centre for Data Analytics, demonstrated the cutting edge expertise in the University and the value of cross-disciplinary work to bring science and innovation to the next level in this important field of pandemic research. The PANDEM Final Conference was held in Brussels earlier this month, back-to-back with a meeting of DG HOME’s Community of Users for Safe, Secure and Resilient societies, which brought the recommendations of the PANDEM project and proposed next steps to more than 1,000 members of the Community of Users in crisis management, security and related fields in Europe.
BAYER NOTICE OF DISCONTINUATION OF BONEFOS 800MG TABLETS (X60) FROM THE IRISH MARKET Bayer Ltd wishes to announce the planned discontinuation of Bonefos 800mg Tablets (x60) from the Irish market. The Hi Tech code for this product is 88006 and the PA number is PA 1410/2/1. The discontinuation is from July 1st 2017. Stock remaining in circulation is expected to last until 30th June 2017 however it is difficult to predict with certainty when stocks will be depleted as abnormal buying patterns may arise following the announcement of this planned discontinuation. For queries regarding availability of stock please contact customer service at 01 2999313 or email@example.com For other queries regarding this product please contact Bayer Ltd,
The Atrium, Blackthorn Road, Dublin 18; Tel: +353 1 2999313; Fax: +353 1 2061456; E-mail: info. firstname.lastname@example.org
LONG-TERM SAFETY AND EFFICACY EXTENSION STUDY DATA OF ALPROLIX® PUBLISHED Swedish Orphan Biovitrum have announced that interim results from the B-YOND extension trial, which studies Alprolix® [Coagulation Factor IX (Recombinant), Fc Fusion Protein] in previously treated subjects with severe haemophilia B, were published in the March 2017 issue of Thrombosis and Haemostasis. The study results reinforce the long-term safety and efficacy of prophylactic treatment with Alprolix over a median duration of more than three years in adults/ adolescents and more than a year and a half in children under 12 years of age. The primary outcome measure was development of inhibitors (neutralising antibodies that can interfere with activity of the therapy); no patients treated with Alprolix in the study developed inhibitors. “The interim data from B-YOND confirm the safety profile of Alprolix, and show that adult, adolescent and paediatric subjects maintained low annual bleed rates with prophylactic dosing of Alprolix every 1-2 weeks,” said John Pasi, MD, PhD, principal investigator of the study, Professor of Haemostasis and Thrombosis at The Royal London Hospital, Barts and the London School of Medicine and Dentistry. “These results come from the longestterm study of an extended half-life therapy for haemophilia B and provide physicians across the globe with important insights and information about the treatment of haemophilia B.” B-YOND is an ongoing open-label, nonrandomised extension study, and eligible previously-treated patients who completed B-LONG or Kids B-LONG could enrol in one of three treatment groups: weekly prophylaxis, individualised prophylaxis, and modified prophylaxis. An episodic treatment arm is also available only to adult and adolescent participants. At the time of the interim data cut, 116 male subjects (93 from B-LONG and 23 from Kids B-LONG) were enrolled in the study. “These results confirm the longterm safety and efficacy profile of Alprolix and show that a majority of the participants in the study were able to dose once weekly or less frequently while maintaining adequate protection,” said Maha Radhakrishnan, MD, senior vice president of medical at Bioverativ.
In the individualised prophylaxis treatment group, as of the B-YOND interim data cut, a total of 26 adolescent/adult subjects out of 30 (86.7%) had a dosing interval longer than one week with a median dosing interval of 13.7 days, and paediatric subjects aged 6 to < 12 years had a median dosing interval of 10.0 days. Fifteen of 26 (57.7%) adult/adolescent subjects in the individualised prophylaxis treatment group had a dosing interval of every 14 days or longer. “Together with Bioverativ, we remain focused on advancing research to better understand the underlying science and potential benefits of Alprolix for people with haemophilia B,” said Krassimir Mitchev, MD, PhD, vice president and medical therapeutic area head of Haemophilia at Sobi. The overall median annualized bleeding rate (ABR) at the time of the B-YOND interim data cut was 2.3 for adult/adolescent participants in both the weekly and individualised prophylaxis treatment groups, and 2.4 for those in the modified prophylaxis study arm. Participants receiving on-demand therapy, or treatment when a bleeding episode occurred, had a median ABR of 11.3. Among children under age six (n=9), the median ABR in the weekly prophylaxis group was zero. For children between six and 12 years old, the median ABR was similar in the weekly (2.7; n=10) and individualized (2.4; n=5) prophylaxis groups. The one participant from the 6 to < 12 years cohort who was in the modified prophylaxis group had an ABR of 3.1. In the B-YOND study as of the interim data cut, Alprolix was well tolerated and adverse events (AEs) were typical of the haemophilia B populations studied. The most common AEs were headache (n=14, 12.1%) and common cold (n=13, 11.2%), and the majority of AEs were considered by the investigator to be unrelated to Alprolix treatment. A total of 39 serious AEs (SAEs) were reported in 23 participants (19.8%) treated with Alprolix. All SAEs were assessed by the investigator as unrelated to Alprolix, with the exception of one SAE of renal colic in an adult/adolescent participant with a medical history of previous clot colic; the event resolved and did not lead to study discontinuation. In the study as of the interim data cut, there were no reports of serious allergic reactions or anaphylaxis associated with Alprolix, no vascular thrombotic events, and no deaths.
HPN • April 2017
In adult patients with moderate to severe active Ulcerative Colitis who have had an inadequate response to conventional therapy including corticosteroids and 6-mercaptopurine (6-MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies.1
EFFICACY THAT LASTS1-2,a thursday
The first and only subcutaneous anti-TNF with 4-week efficacy during maintenance treatment1,2,b
Please consult the Summary of Product Characteristics before prescribing. a
Based on results of PURSUIT Maintenance study. Patients with body weight less than 80 kg: Simponi given as an initial dose of 200 mg, followed by 100 mg at week 2, then 50 mg every 4 weeks, thereafter. Patients with body weight greater than or equal to 80 kg: Simponi given as an initial dose of 200 mg, followed by 100 mg at week 2, then 100 mg every 4 weeks, thereafter.1
(AZA) or 6 mercaptopurine (6–MP). The potential risk with the combination of AZA or 6 MP and Simponi should be carefully considered. A risk for the development for HSTCL in patients treated with TNF-blockers cannot be excluded. Colon dysplasia/carcinoma - Screen for dysplasia in all patients with UC who are at increased risk or had a prior history for dysplasia or colon carcinoma. In newly diagnosed dysplasia patients the risks and benefits of continued Simponi use should be carefully assessed. Melanoma (all TNF-blocking agents including Simponi) and Merkel cell carcinoma (other TNF-blocking agents) have been reported, periodic skin examination is recommended, particularly for patients with risk factors for skin cancer. Heart Failure: Simponi should be used with caution in patients with mild heart failure (NYHA class I/II). Patients should be closely monitored and Simponi must be discontinued in patients who develop new or worsening symptoms of heart failure. Some cases had a fatal outcome. Neurological events: Use of antiTNF therapy, including Simponi, has been associated with cases of new onset or exacerbation of clinical symptoms and/or radiographic evidence of central nervous system demyelinating disorders, including multiple sclerosis and peripheral demyelinating disorders. Discontinuation of Simponi should be considered if these disorders develop. Carefully consider the benefits and risks before initiation of therapy in patients with a history of demyelinating disorders. Surgery: Patients requiring surgery whilst on Simponi therapy should be closely monitored for infections. Autoimmune processes: If a patient develops symptoms suggestive of a lupus-like syndrome following treatment with Simponi and is positive for antibodies against double-stranded DNA, treatment should be discontinued. Haematological reactions: There have been post-marketing reports of pancytopenia, leukopenia, neutropenia, aplastic anaemia, and thrombocytopaenia in patients receiving TNF-blockers. Cytopenias including pancytopaenia have been reported infrequently in clinical trials. Patients should be advised to seek medical attention if they develop signs and symptoms suggestive of blood dyscrasias. Discontinuation should be considered in patients with significant haematologic abnormalities. Vaccinations/therapeutic infectious agents: It is recommended that live vaccines or any therapeutic infectious agents should not be given concurrently. Allergic reactions: If an anaphylactic reaction or other serious allergic reaction occurs, administration of Simponi should be discontinued immediately, and suitable treatment initiated. The needle cover of the pre-filled pen contains latex and may cause allergic reactions in those sensitive to latex. Special populations: Adverse events, serious adverse events and serious infections in patients aged ≥65 were comparable to those observed in younger patients. However, caution should be exercised when treating the elderly, particular attention should be paid to infections. There were no patients age 45 and over in the nr-Axial SpA study. Excipients: Simponi contains sorbitol (E420). Patients with rare hereditary problems of fructose intolerance should not take Simponi. Interactions: Combination of Simponi and other biological therapeutics used to treat the same conditions as Simponi, including anakinra and abatacept is not recommended. Pregnancy and Lactation: Administration of Simponi is not recommended during pregnancy or breast-feeding. Women of childbearing potential should use adequate contraception and continue its use for at least 6 months after the last Simponi treatment. Side-effects: Refer to SmPC for complete information on side effects Very Common (≥ 1/10): upper respiratory tract infection; Common (≥1/100): bacterial infections, lower respiratory tract infections, viral infections, bronchitis, sinusitis, superficial fungal infections, abscess, anaemia, allergic reactions, autoantibody positive, depression, insomnia, dizziness, headache, paraesthesia, hypertension, asthma and related symptoms, dyspepsia, gastrointestinal and abdominal pain, nausea, gastrointestinal inflammatory disorders, stomatitis, alanine aminotransferase increased, aspartate aminotransferase increased, pruritus, rash, alopecia, dermatitis, pyrexia, asthenia, injection site reaction, chest discomfort, bone fractures were reported. Serious, including fatal adverse events have been reported including septic shock, lymphoma, leukaemia, melanoma, Merkel cell carcinoma*, hepatosplenic T-cell lymphoma*, leukopenia, thrombocytopaenia, pancytopaenia, aplastic anaemia, serious systemic hypersensitivity reactions (including anaphylactic reaction), skin exfoliation, vasculitis (systemic), sarcoidosis, demyelinating disorders, congestive heart failure, arrhythmia, ischaemic coronary artery disease, thrombosis, interstitial lung disease and lupus-like syndrome. *Observed with other TNF-blocking agents, but not observed in clinical studies with golimumab Package quantities: 1 50 mg pre-filled pen containing 50 mg of golimumab in 0.5 ml solution for injection or 1 50 mg pre-filled syringe containing 50 mg of golimumab in 0.5 ml solution for injection or 1 100 mg pre-filled pen containing 100 mg of golimumab in 1 ml solution for injection. Legal Category: Prescription Only Medicine. Marketing Authorisation Number: 50 mg Pre-filled Pen EU/1/09/546/001; 50 mg Pre-filled Syringe EU/1/09/546/003; 100 mg Pre-filled Pen EU/1/09/546/005. Marketing Authorisation Holder: Janssen Biologics B.V., Einsteinweg 101, 2333 CB Leiden, The Netherlands. Date of Revision of Text: December 2015. Further information is available on request from: MSD, Red Oak North, South County Business Park, Leopardstown, Dublin D18X5K7 or from www.medicines.ie. Date of preparation: May 2016. Adverse events should be reported. Reporting forms and information can be found at www.hpra.ie Adverse events should also be reported to MSD (Tel: 01-299 8700) References: 1. EU Summary of Product Characteristics for SIMPONI 12 Jan 2016. 2. Sandborn WJ, Feagan BG, Marano C, et al. Subcutaneous Golimumab Maintains Clinical Response in Patients with Moderate-To-Severe Ulcerative Colitis, Gastroenterology. 2014;146:96-109.
Red Oak North, South County Business Park, Leopardstown, Dublin D18 X5K7, Ireland.
SIMPONI 50 MG, 100 MG SOLUTION FOR INJECTION IN PRE-FILLED PEN SIMPONI 50 MG SOLUTION FOR INJECTION IN PRE-FILLED SYRINGE(GOLIMUMAB) Prescribing Information [Refer to full SPC text before prescribing Simponi (golimumab)] Indications: Rheumatoid Arthritis (RA): Simponi, in combination with methotrexate (MTX), is indicated for: the treatment of moderate to severe, active rheumatoid arthritis in adults when the response to disease-modifying anti-rheumatic drug (DMARD) therapy including MTX has been inadequate; the treatment of severe, active and progressive rheumatoid arthritis in adults not previously treated with MTX. Simponi, in combination with MTX, has been shown to reduce the rate of progression of joint damage as measured by X-ray and to improve physical function; Psoriatic Arthritis (PsA): Simponi, alone or in combination with MTX, is indicated for the treatment of active and progressive PsA in adults when the response to DMARD therapy has been inadequate. Simponi has been shown to reduce the rate of progression of peripheral joint damage as measured by X-ray in patients with polyarticular symmetrical subtypes of the disease and to improve physical function. Ankylosing Spondylitis (AS): Simponi is indicated for the treatment of severe, active AS in adults who have responded inadequately to conventional therapy. Non-radiographic axial spondyloarthritis (nr-Axial SpA): Simponi is indicated for the treatment of severe, active nr-Axial SpA who have had an inadequate response to or are intolerant to NSAIDS. Ulcerative colitis (UC): Simponi is indicated for treatment of moderately to severely active UC in adult patients who have had an inadequate response to conventional therapy including corticosteroids and 6 mercaptopurine (6 MP) or azathioprine (AZA), or who are intolerant to or have medical contraindications for such therapies. Dosage and administration: Simponi should be injected subcutaneously. Treatment should be initiated and supervised by qualified physicians experienced in the diagnosis and treatment of RA, PsA, AS, nr-Axial SpA or UC. After proper training in subcutaneous injection technique, patients may self-inject, if their physician deems it appropriate. RA: Simponi 50 mg given once a month, on the same date each month, concomitantly with MTX. PsA: Simponi 50 mg given once a month, on the same date each month, alone or in combination with MTX. AS and nr-Axial SpA: Simponi 50 mg given once a month, on the same date each month. Clinical response is usually achieved within 12-14 weeks of treatment (3 or 4 doses). Continued therapy should be reconsidered in patients who show no evidence of therapeutic benefit within this time period. In patients weighing more than 100 kg who do not achieve an adequate clinical response after 3 or 4 doses, increasing the dose of golimumab to 100 mg once a month may be considered, taking into account the increased risk of certain serious adverse reactions with the 100 mg dose compared with the 50 mg dose. UC: Patients weighing < 80 kg: Simponi given as an initial dose of 200 mg, followed by 100 mg at week 2, then 50 mg every 4 weeks. Patients weighing ≥ 80 kg: Simponi given as an initial dose of 200 mg, followed by 100 mg at week 2, then 100 mg every 4 weeks. During maintenance treatment, corticosteroids may be tapered, following clinical practice guidelines. Clinical response is usually achieved within 12-14 weeks of treatment (after 4 doses). Missed dose: If a patient forgets to inject Simponi on the planned date, the forgotten dose should be injected as soon as the patient remembers. The patient should be instructed not to inject a double dose. Older patients (≥ 65 years): no dose adjustment required. Paediatric patients (<18 years) and patients with renal and hepatic impairment: Simponi is not recommended in these populations. Contraindications: Patients with a hypersensitivity to golimumab or any of the excipients; Patients with active tuberculosis (TB) or other severe infection such as sepsis and opportunistic infections; patients with moderate or severe heart failure (NYHA class III/IV). Precautions and Warnings: Infections: Patients must be monitored closely for infection before, during and for 5 months after cessation of treatment. Exercise caution when considering Simponi in patients with chronic infection or a history of recurrent infection including use of concomitant immunosuppressive therapy. Simponi should not be given to patients with clinically important active infection. Patients should be advised of the potential risk factors. Bacterial infections (including sepsis and pneumonia), mycobacterial (including TB), invasive fungal and opportunistic infections, including fatalities, have been reported. The invasive fungal infection should be suspected if they develop a serious systemic illness. There was a greater incidence of serious infections, including opportunistic infections and TB, in patients receiving golimumab 100 mg compared with patients receiving golimumab 50 mg. Serious infections have occurred in patients on concomitant immunosuppressive therapy that, in addition to their underlying disease, could predispose them to infection.There have been reports of active TB in patients receiving Simponi, including patients previously treated for latent TB. Patients should be evaluated for active or latent TB before Simponi treatment. All such tests should be recorded on the Patient Alert Card provided with the product. If active TB is diagnosed, treatment with Simponi should not be initiated. If latent TB is diagnosed, treatment with anti-TB therapy must be initiated before initiation of Simponi. Patients on Simponi should be monitored closely for signs and symptoms of active TB and advised to seek medical advice if signs and/or symptoms of TB appear. Hepatitis B (HBV) reactivation: Reactivation of HBV occurred in patients receiving Simponi who were chronic carriers. Some cases had a fatal outcome. Patients should be tested for HBV infection before initiating treatment with Simponi Malignancies and lymphoproliferative disorders: Caution is advised when considering Simponi treatment in patients with history of malignancy or continuing treatment in patients who develop a malignancy, additional caution should be exercised in patients with increased risk for malignancy due to heavy smoking. A risk for the development of malignancies in children and adolescents cannot be excluded. Rare cases, usually fatal, of hepatosplenic T-cell lymphoma (HSTCL) have been reported, the majority of cases occurred in adolescent and young males nearly all on concomitant treatment with azathioprine
Published on Jun 13, 2017