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HPN June 2016

Issue 28

HOSPITAL PROFESSIONAL NEWS IRELAND Ireland’s Dedicated Hospital Professional Publication

IN THIS ISSUE: NEWS: Progress on medicines savings proposals Page 5 MEETING: Leading in to ASCO 2016 Page 8 REPORT: Lord Neill’s final AMR Report Page 23

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.

CPD: Drug Delivery Interactions Page 27

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HPN Issue 19.indd 49

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Best of Luck to the 2016 HPN Award Entrants

25/08/2015 17:23:24

AWARDS: 2016 Hospital Professional Awards Page 32 FEATURE: Management and Treatment of Type 2 Diabetes Page 40


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HPN June 2016 Issue 28

Contents

Foreword

HEA speaks out on medicines pricing negotiations P4

Editor

Guarded welcome for Health Vision P6

In leading news this issue, the Government has agreed to support a motion establishing an all-party committee to devise cross-party agreement on a single long-term vision for health care and the direction of health policy in Ireland.

Kelly Jo Eastwood

4

Prostate Cancer Meeting Report P14 Cancer Trials saves Government ¤6.5m P22 Latest report on Metastatic Breast Cancer P48

“I am pleased that the Government has agreed to move ahead quickly to establish this committee and to get it up and running in the coming weeks.

8

Regulars

Meanwhile, his replacement Health Minister Dr Leo Varadkar has a full menu to digest as he takes position in office. First up was the Irish Hospital Consultants Association, who have warned of serious capacity deficits.

CPD: DDI in HIV P27 Feature: Type 2 Diabetes P40

22

Feature: Urinary Incontinence P49 Event Gallery P52 Clinical R&D P54

40

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.

PUBLISHER IPN Communications Ireland Ltd Clifton House, Lower Fitzwilliam Street, Dublin 2 (01) 669 0562 MANAGING DIRECTOR Natalie Maginnis n-maginnis@btconnect.com EDITOR Kelly Jo Eastwood kjeastwood@hotmail.com 00447876548989 ACCOUNTS Jennifer Dunseath cs.ipn@btconnect.com

The then Health Minister Dr Leo Varadkar is quoted as stating that “One of the key proposals in the Programme for Government is the establishment of an Oireachtas Committee to develop cross-party consensus on the future of the health service. I believe the health service would benefit enormously from a single unifying vision that we can all get behind and that can help to drive reform and development of the system over the next 10 years.

COMMERCIAL MANAGER Ingrid Lyons Ingrid@ipnirishpharmacynews.ie + 353 1 669 0562 + 353 87 777 0480

Dr Gerard Crotty, President, recently met with the Minister to confirm the need for immediate investment in frontline services to address critical capacity deficits. This, Dr Crotty said, is because frontline resources were cut steeply during austerity and funding has not been provided to cater for the country’s increasing and ageing population. In particular, he added, there needs to be a significant increase in the number of hospital beds and operating theatre access. Dr Crotty says that there is no need for lengthy studies to confirm what is already very clear. Hundreds of patients are being treated on trolleys every day, over 74,000 patients were awaiting essential surgery at the end of April and the cancellation of surgical appointments is a regular occurrence because of the shortage of hospital beds. In the past decade 1,500 acute hospital beds have been closed. The number of intensive care unit (ICU) beds has declined from 289 in 2009 when the HSE commissioned Prospectus Report recommended that the number of ICU beds needed to be increased by 45% immediately and doubled to 579 by 2020. Dr Crotty said patients’ lives were being put at risk due to the lack of ICU beds. Turn to page 18 for the full story. We hope you enjoy this issue. If you haven’t already requested your Hospital Professional Awards 2016 application/nomination forms do so now; we are expecting a huge increase in entries surpassing even last year’s so turn to page 32 for all the category and entry details. Good Luck!

CONTRIBUTORS Dr Dominic Rowley Olwyn Deignan Dr Diarmuid Smith Dr Suzanne O'Sullivan DESIGN DIRECTOR Ian Stoddart Design Visual Communications www.pharmacynewsireland.com www.facebook.com/ HospitalProfessionalNews

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


4 News

Medicine pricing negotiations will only succeed if reformers are at the talk’s table Medicine pricing negotiations will only succeed if reformers with a track record of change are at the talk’s table, otherwise patients and taxpayers will get a bad deal, Ireland’s leading pharmaceutical players have said. The Healthcare Enterprise Alliance (HEA), comprising some of the biggest suppliers of medicines in the country, made the comments following reports that the current negotiations process – involving only a segment of the pharmaceutical industry – are stalling. HEA members, who have put forward proposals to save the State almost ¤130million in its medicines budget, have yet to engage with Government on the next medicines agreement which will set drug prices for the next four years.

Commenting, Sandra Gannon, HEA President, said, “The Department of Health and Department of Public Expenditure and Reform are seeking to strike a deal with branded pharma companies, excluding reformers who have a track record of delivering change. “The logic of segregating the pharmaceutical market into branded and generic companies is outdated. Most companies have a presence in both categories. The Government itself accepted that the distinction was outdated in its 2013 generic substitution changes. “Competition and innovation are the biggest drivers in delivering more sustainable and accessible medicines to patients. We have seen in recent years what can be achieved by bringing a reforming ethos to medicine prescribing, dispensing and pricing.

HEA President, Sandra Gannon

“Our concern is that the State risks repeating the mistakes of the past by taking a narrow approach to the current negotiating process. Ministers Harris and Donohoe have the opportunity to secure a better deal for taxpayers and

patients. We do not expect that we will agree on everything, but a more informed and inclusive negotiations process can achieve this objective.”

Additional ¤500 million for health The Minister for Health, Simon Harris has welcomed the Government approval of a Revised Estimate for the Department of Health of ¤500 million, saying that it would allow Programme for Government commitments to be met while also addressing financial pressures in the health service. “My top priority is addressing some immediate problems facing patients as well as seeing Programme for Government commitments for the first 100

days implemented,” he said. “I am pleased to say that as a result of today’s announcement I am confident that we will have confirmed funding for a winter initiative to help address overcrowding in Emergency Departments. As an integral part of this initiative, I will increase resources for home care services. I can also confirm that the revised estimate will allow us to restore the full ring-fenced mental health budget and provide more funding to school-leavers with disabilities. I expect Ministers McEntee &

McGrath will outline more detail on these initiatives in the coming days. “The allocation to address the budget overrun in the HSE will be underpinned by an improved governance and accountability framework. Health service management will be accountable for performing within the budget set by these additional resources. It is in acute hospitals that Government sees the greatest need for improved accountability and control.

“The Programme for Government commits to establishing a Performance Management Unit which will work with individual hospitals where there are difficulties in order to achieve improvement. Establishment of this Unit will contribute to a stronger focus on operational control and accountability within acute hospitals. There should be support and recognition for managers who rise to the challenge of leading performance improvement within the funding available.”

New research collaboration formed to study medicines shortages in Europe A new pan-European initiative has been formed to investigate causes, impacts and potential solutions to the shortages of medicines experienced across all European countries. Taking place under the longestablished EU programme "Co-operation in Science and Technology" (COST), the network of interested researchers and individuals so far spans 20 countries and a multiplicity of June 2016 • HPN

professional backgrounds and expertise. The programme will last for four years and will operate via a series of working groups investigating such issues as the landscape of medicines shortages; manufacturing-related shortages; logistics-related shortages; therapeutic options and substitutions; and the impact of shortages on outcomes.

The Chair of the "Action" is Professor Helena Jenzer from the Bern University of Applied Sciences, Switzerland, with Dr Roberto Frontini, the immediate past President of EAHP, as Deputy Chair. Commenting on the new Action, EAHP Board Member and spokesperson on medicines shortages, Aida Batista commented, "On behalf of EAHP, I send my strongest congratulations

to Professor Jenzer in bringing together this project on the pressing topic of medicines shortages. With patient care being harmed on a daily basis by supply shortages, this kind of collaboration to shine a light on the causes and available remedies is to be much welcomed.”


5

Progress on Proposals to save over ¤50 million on drugs The group pushing for further reforms in medicine spending has welcomed the publication (Tuesday, 31st May) of proposals from Fianna Fáil aimed at achieving ¤50 million in savings in the national drugs budget.

Medical Goods) (Amendment) Bill 2016. The main purpose of the Amendment to the 2013 Act is to allow for two changes to be made which will deliver substantial savings to the existing medicines budget.

The Healthcare Enterprise Alliance (HEA) said the proposals were timely given focus on access and affordability to life saving medicines.

Health professionals will be empowered to choose more affordable biosimilar drugs, which is currently the norm in many EU countries. The proposals also include measures to treat newly diagnosed patients with generic rather than branded medicines.

Fianna Fail Health Spokesperson, Bill Kelleher TD introduced the Health (Pricing and Supply of

This initiative would save the State up to ¤51 million. Commenting, Sandra Gannon, President of the HEA said, “These proposals are a positive step in reforming patient access and affordability of medicines. “Changes made in 2013 were a first step in bringing Ireland in line with our European counterparts in the prescribing of medicines. Yesterday’s proposals are the type of reforms required to continue the progress made to date.

“Only this week, we have heard of cancer patients being denied access to drugs due to exorbitant costs. In the last couple of years the Government and politicians have accepted this fact and championed the cause of generic drugs. It is essential that the Government continues in this manner and work cross party to accept this Bill as soon as possible in the interest of patient care.”

Hospital Managers urged to support systems to reduce medication error The latest results from EAHP's annual survey of hospital pharmacy practice are now available. A headline result from the almost 1000 responses from 33 countries is a perceived lack of support from hospital managers for the implementation of computerised decision support systems to reduce the risk of medication errors. "Computerised decision support systems" refers to hospital wide software applications with prescribing support software and other functionalities designed to tackle common causes of error. Such systems reduce risk by eliminating hand written transcriptions, providing semiautomated error-checking possibilities, drug dose recommendations, and alerts for serious drug-drug reactions. They can also be linked to life saving systems such as bedside scanning of medicines to reduce administration error, specialised hospital pharmacy softwares to support pharmacy preparations and compounding, and more. The latest findings emerged as part of a report into the extent to which the 44 European Statements of Hospital Pharmacy are being met in practice. Among the statements the October-December 2015 survey focused on was Statement 5.5 "Hospital pharmacists should help to decrease the risk of medication errors by disseminating evidence-based approaches

to error reduction including computerised decision support." This topic emerged as one of the most challenging of the 23 Statements surveyed. Implementation of computerised support goes beyond the scope of what hospital pharmacies can achieve alone. Instead, a whole system project management approach is required, including prescribers (typically doctors), pharmacists and the administrators of medicines in hospital (typically nurses), as well as health system managers and budget planners, at local, national and regional levels. Responding to the results, EAHP President Joan Peppard remarked, "These survey results provide clear information about hospital pharmacy development and where activity must be focused in order to achieve implementation of the European Statements. It is clear much work remains to convince those with responsibility for hospital management of the safety benefit and other returns available from computerised decision support systems. “When it comes to leveraging technology for patient safety, progress does not happen by itself. Hospital pharmacists, with support from fellow healthcare professionals and patients, must advocate for better. Knowing that technologies for reducing medication error exist, and that the evidence of their benefit is out

there, the ethics of our profession demands our action." Tony West, Statement Implementation Project Director, added, "It is clear from early reflections on statement implementation across Europe that hospital pharmacies face similar difficulties in securing new technology take up. Computerised decision support systems to prevent medication error are just one example. Keele University's report advises sharing business cases where success has been achieved, as well as strategies for winning hearts and minds of other clinicians and managers. EAHP's statement implementation team are already taking up these recommendations."

EAHP survey show a perceived lack of support from hospital managers for the implementation of computerised decision support systems to reduce the risk of medication errors HPN • June 2016


6 News

Health Vision 10-year plan given ‘guarded welcome’ The Government has agreed to support a motion establishing an all-party committee to devise cross-party agreement on a single long-term vision for health care and the direction of health policy in Ireland. The decision was made to establish an Oireachtas Committee to debate and agree a 10-year vision. The Minister Simon Hamilton said after the Cabinet meeting, “One of the key proposals in the Programme for Government is the establishment of an Oireachtas Committee to develop cross-party consensus on the future of the health service. I believe the health service would benefit enormously from a single unifying vision that we can all get behind and that can help to drive reform and

development of the system over the next 10 years. “I am pleased that the Government has agreed to move ahead quickly to establish this committee and to get it up and running in the coming weeks. “I have been in discussion with Deputies from across the House, and I believe that we have now arrived at a motion that can attract broad support in the Dáil, and which the government is backing. We will also allocate government time to debate the motion in the House. “I hope to table this motion in the near future, and to start the debate about how we can develop a single unifying vision for the future of healthcare.”

However, the Irish Medical Organisation (IMO) has given a guarded welcome to the decision. The organisation says it looks forward to presenting its vision for the future of our public health services to the new Committee, however, the IMO has expressed concern that this move could delay agreement on urgent action to tackle the current crisis in the health services so that an improvement in waiting times, GP services, bed numbers and retain our doctors in Ireland where they can treat patients, can be seen.

to tackle the pressing problems that are impacting on patients and staff today. A 10 year plan sounds excellent but we also need a realistic immediate plan to tackle current issues.”

Dr John Duddy, IMO President, said, “Attempts to develop a long term vision or plan for the health services are to be welcomed but must not in any way distract from the urgent need to increase resources immediately in order

The IMO will also seek to ensure that any report produced by this Committee is accompanied by a comprehensive financial analysis and a commitment that the required funds be ring fenced and protected.

The IMO says it will engage proactively with this Committee and will seek to ensure that it does not merely produce another report for the shelves but a positive roadmap for a world-class health services which can serve patients and the wider community, and create a service in which people are happy and proud to work.

Managing Delirium in Palliative Care On Wednesday June 8th, the Canada-based international palliative care physician Dr Peter Lawlor led a multidisciplinary masterclass at the Our Lady’s Hospice & Care Services Education and Research centre. Entitled Managing Delirium in Palliative Care - the need for knowledge, support and realistic goals, this event featured a

range of prominent international specialists who shared their expertise in this area. Professor Philip Larkin, Palliative Care (Nursing) said, “This event was designed to help people understand the importance and impact of delirium and to enable the development of prevention, assessment and management techniques. It is also promoting

improved communications amongst the caring team and helping them better support and educate families of patients.” Dr Lawlor is currently conducting a pilot study on the role of melatonin in the prevention of delirium. During the Masterclass he was involved in talks including: ‘The characteristics and impact of

delirium in palliative care settings’; ‘Predisposing and precipitation factors for delirium: who, why and how?’ and ‘What are the requirements for the optimal assessment of delirium’. The next issue of Hospital Professional News will feature an in-depth report by Professor Larkin on his talk.

All Ireland Pharmacy Conference Daire Osborne (left) and Mark Phelan (first right) of AbbVie with poster prize winner Marine Chalanqui (QUB) and oral prize winner David Walsh (RCSI)

Approximately 100 delegates attended the 38th All Ireland Schools of Pharmacy Research Conference hosted by RCSI and supported by AbbVie on March 21st and 22nd 2016. The attendees June 2016 • HPN

comprised postgraduate students and faculty from all five Schools of Pharmacy in Ireland; RCSI, Trinity College Dublin, University College Cork, Queen's University Belfast and Ulster University.

A total of 75 abstracts were included in the conference programme, with 18 oral presentations from postgraduate students scheduled over the two days. This year's conference programme also included two keynote speakers; Dr Margaret Watson (University of Aberdeen) and Professor Robbert Jan Kok (Utrecht University). Dr Watson's keynote address focussed on the importance of pharmacy practicebased research in informing evidence-based pharmacy practice and policy. Professor Kok's keynote address outlined how the safety and efficacy of drugs could be improved through selective targeting and localised delivery.

The winner of the best oral presentation was David Walsh, PhD in RCSI's Anatomy Department, who presented his research on novel gene-activated scaffolds for application in tissue engineering. The winner of the best poster presentation was Marine Chalanqui of Queen's University, for her research on a biologically loaded, thermo-sensitive hydrogel for the treatment of bone metastases. Speaking during the conferences prize-giving ceremony, Professor Paul Gallagher, Head of RCSI's School of Pharmacy, said, “The RCSI School of Pharmacy took great pleasure in hosting this year's All-Ireland Schools of Pharmacy Research Conference, which is a long established and important feature of the academic calendar. I'd like to thank all of those who participated in the conference proceedings and thanks to AbbVie for their sponsorship of the event.”


PP-PFE-IRL-0007 Date of Preparation: May 2016

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8 Clinical Synopsis

2016 ASCO Annual Meeting to highlight advances in cancer research The American Society of Clinical Oncology (ASCO) announced the official programme for the 2016 ASCO Annual Meeting as HPN was going to press. Featured studies that highlighted advances in precision medicine and immunotherapy, as well as new approaches that make conventional cancer therapies even more beneficial for patients. This year’s ASCO Annual Meeting, took place in Chicago, June 3-7, and attracted as many as 30,000 oncology professionals from around the world. The theme of the 2016 Annual Meeting is Collective Wisdom: The Future of PatientCentred Care and Research, emphasising that the combined knowledge from various disciplines, cancer types, treatment approaches, and big data technologies is essential to progress. More than 5,200 abstracts were accepted to the ASCO Annual Meeting. Below, Hospital Professional News takes a look at some of the clinical presentations which will feature and our July/August double issue will carry full coverage from the event. Clinical Presentations Left vs. Right: Primary Tumour Location Predicts Survival in Metastatic Colorectal Cancer Cancer Originating on the Left Side of the Colon Is Associated With Longer Survival, Versus the Right Side “This is the largest study to date of tumour location in colorectal cancer, and it strongly suggests that this unexpected factor could answer some long-standing questions about why certain patients do better than others,” says ASCO President Julie M. Vose, MD, MBA, FASCO, ASCO President. “It is also an important reminder, in this exciting era of precision medicine, that genomics is not the only source of insight into how cancers should be studied and treated.” A retrospective analysis of data from a large, federally funded clinical trial finds that the location of the primary tumour within the colon predicts survival and may help inform optimal treatment selection for patients with metastatic colorectal cancer. The study will be presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. The data show that patients whose primary tumours originate on the left side of the colon (the descending colon, sigmoid colon, and rectum) survive significantly longer than those whose tumours originate on the right side (the cecum and ascending colon). “While previous studies had suggested that tumour location may impact clinical colorectal cancer outcomes, the effect we observed in this analysis appears to be far greater than we expected,” says lead study author Alan P. Venook, MD, Professor of Medicine at the University of California, San Francisco. “These findings will likely change the way we approach colorectal cancer treatment and research, even as we seek to more deeply understand the biology driving the difference in outcomes between right- and left-sided cancers.” June 2016 • HPN

Researchers retrospectively evaluated data from the Phase III CALGB/SWOG 80405 clinical trial, a federally funded clinical trial designed to compare bevacizumab and cetuximab in combination with chemotherapy as initial therapy for metastatic colorectal cancer. For the primary analysis, researchers identified data from 293 patients with right-sided primary tumours and 732 patients with left-sided primary tumours. This analysis included only patients without a mutated KRAS gene, which is a known biomarker of response to certain colorectal cancer therapies (cetuximab is approved only for treating KRAS wild-type tumours). In this patient population, those with left-sided tumours had longer median overall survival (33.3 months), compared to those with right-side tumours (19.4 months). Among patients who received cetuximab, patients with left-sided tumours lived 36 months, while those with right-sided tumors lived 16.7 months. Similar trends were observed among patients receiving another treatment, bevacizumab: overall survival was 31.4 months and 24.2 months for patients with left- and right-sided tumours, respectively. While the original trial found no significant advantage in overall or progression-free survival in patients treated with bevacizumab or cetuximab, this analysis suggests that the relative effectiveness of cetuximab and bevacizumab may differ depending on primary tumour location. Researchers are in the process of examining the molecular biology that presumably underlies these findings. Among patients with right-sided tumours, treatment with bevacizumab was associated with longer survival than that of cetuximab (24.2 months vs. 16.7 months). Conversely, among patients with left-side tumours, treatment with cetuximab was associated with longer overall survival than bevacizumab (36 months vs. 31.4 months). Because the CALGB/SWOG trial was initiated before KRAS mutation status was known to be an important factor in use of cetuximab, there was a smaller population of patients who had KRAS mutations (an additional 213). In this separate analysis, researchers found that those with left-sided tumours also lived longer compared to patients with right-sided tumours (median overall survival: 30.3 months vs. 23.1 months). Precision Medicine Yields Better Outcomes for Patients in Phase I Clinical Trials “Precision medicine is not the future of cancer care, it is the present. This study reinforces that the more we personalise treatment to the patient and the tumour, the better the outcomes – even in the earliest phases of research,” says Don S. Dizon, MD, FACP, ASCO. “This is the same approach ASCO’s TAPUR trial is using, and we anticipate it will also bring new insights that lead to better therapies for patients in need.”

A meta-analysis of 346 phase I clinical trials involving more than 13,000 patients found that patients whose treatment was selected based on the molecular characteristics of their tumour had significantly better outcomes. This study will be presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. “Our study suggests that, with a precision medicine approach, we can use a patient’s individual tumour biomarkers to determine whether they are likely to benefit from a particular therapy, even when that therapy is at the earliest stage of clinical development,” says lead study author Maria Schwaederle, PharmD, of the Centre for Personalised Cancer Therapy, University of California-San Diego School of Medicine. “This strategy often results in good outcomes for patients, and I hope it will encourage and reassure doctors and patients considering enrollment in precision medicinebased phase I trials.” The study examined efficacy and safety data from 346 phase I trials published between 2011 and 2013. The analysis included 58 treatment arms that employed precision medicine – defined as using biomarkers to select patients for treatment – and 293 that did not (all but one of these precision medicine trials evaluated a targeted agent: the trial evaluated the chemotherapy drug topotecan, which is believed to inhibit hypoxia-inducible factor 1-alpha (HIF-1 alpha), and patients in that trial were tested for this marker). The researchers found that in treatment arms employing precision medicine, tumour shrinkage rates were 30.6%, compared to 4.9% in those that did not. Patients in precision medicine arms also had a longer time before the disease worsened (progression-free survival) compared to other arms (median 5.7 months vs. 2.95 months). Results were similar in a sub-analysis that included 57 trials of targeted therapies – drugs that target specific genes or proteins found in cancer cells. In this group, treatment arms using biomarkers to assign patients to treatments had tumour shrinkage rates of 31.1%, compared to 5.1% for those that did not. Additionally, researchers found that matching patients to therapy based on genomic (DNA) biomarkers resulted in higher tumour shrinkage rates (42%) compared to protein biomarkers (22.4%). PD-1 Inhibitor Pembrolizumab Provides Long-Term Survival Benefit for Patients With Advanced Melanoma First Report of 36-month Overall Survival Data from Patients in Early-Stage “New therapies that block the PD-1 are extending survival for many patients, and for some may offer the prospect of living longer than ever after a diagnosis with advanced melanoma. In a matter of a few years, these therapies have truly transformed the outlook for patients with melanoma and many other hardto-treat cancers,” says Don S. Dizon, MD, FACP, ASCO spokesperson.


Herceptin® SC

Less waiting time More free time 1

ABRIDGED PRESCRIBING INFORMATION (For full prescribing information, refer to the Summary of Product Characteristics [SmPC]) HERCEPTIN® (trastuzumab) 600mg solution for injection in vial Indications: Metastatic Breast Cancer (MBC): Treatment of adult patients with HER2 positive MBC: (i) as monotherapy following at least 2 chemotherapy regimens for MBC. Prior chemotherapy to include at least an anthracycline and a taxane, unless unsuitable for treatments. Hormone receptor positive patients must also have failed hormonal therapy, unless unsuitable for treatments. (ii) in combination with paclitaxel for patients who have not received chemotherapy for MBC and where anthracyclines not suitable. (iii) in combination with docetaxel for patients who have not received chemotherapy for MBC. (iv) in combination with an aromatase inhibitor for the treatment of postmenopausal patients with hormone-receptor positive MBC, not previously treated with Herceptin. Early Breast Cancer (EBC): Treatment of adult patients with HER2 positive EBC (i) following surgery, chemotherapy (neoadjuvant or adjuvant) and radiotherapy (if applicable) (ii) following adjuvant chemotherapy with doxorubicin and cyclophosphamide, in combination with paclitaxel or docetaxel. (iii) in combination with adjuvant chemotherapy consisting of docetaxel and carboplatin. (iv) in combination with neoadjuvant chemotherapy followed by adjuvant Herceptin therapy for locally advanced (including inflammatory) disease or tumours >2cm diameter. Herceptin should only be used in MBC or EBC patients whose tumours have either HER2 overexpression or HER2 gene amplification as determined by an accurate and validated assay. Dosage and Administration: HER2 testing is mandatory prior to Herceptin therapy. Only physicians experienced in cytotoxic chemotherapy should initiate Herceptin: The injection should be administered by a healthcare professional only. Herceptin subcutaneous (SC) formulation is not intended for intravenous (IV) administration and should be administered via a SC injection only. Check product labels to ensure correct formulation is being administered, as prescribed. In order to prevent medication error it is important to the check the vial labels to ensure that the drug been prepared and administered is Herceptin (trastuzumab) and not Kadcyla (trastuzumab emtansine). Not recommended in patients <18 years of age. Dedicated PK studies in older people and those with renal or hepatic impairment have not been carried out. Refer to SmPC for dose reduction and missed doses. Treat MBC patients until disease progression. Treat EBC patients for 1 year or until disease recurrence; whichever occurs first, extending treatment beyond one year in EBC is not recommended. Recommended dose is 600mg irrespective of the patient’s body weight. No loading dose is required. This dose should be administered subcutaneously over 2-5 minutes every three weeks, refer to SmPC for further information regarding administration. Patients should be observed for six hours after the first injection and for two hours after subsequent injections for signs or symptoms of administration-related reactions. Refer to SmPC for chemotherapy combination dosing and information on switching from Herceptin IV to Herceptin SC and vice versa. Contraindications: Hypersensitivity to trastuzumab, murine proteins, hyaluronidase or any excipients. Severe dyspnoea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy. Warnings and Precautions: In order to improve traceability, the trade name and batch number of the administered product should be clearly recorded (or stated) in the patient file. HER2 testing in a specialised laboratory is mandatory to ensure adequate validation of test. No trial data available on re-treatment of patients with previous exposure to Herceptin in the adjuvant setting. Cardiac dysfunction: Congestive heart failure or asymptomatic cardiac dysfunction observed in patients receiving monotherapy or in combination with paclitaxel or docetaxel, particularly following anthracycline-containing regimens: may be moderate to severe, has been fatal. Caution should be exercised in treating patients with increased cardiac risk, refer to SmPC. All candidates for treatment (especially those with prior anthracycline and cyclophosamide exposure) should undergo baseline cardiac assessment including history and physical examination, ECG, echocardiogram, and/or MUGA scan or magnetic resonance imaging. Monitor for identification of cardiac dysfunction. In all patients cardiac assessments should be repeated every 3 months during treatment and every 6 months following discontinuation until 24 months from the last dose. A careful risk-benefit assessment should be made before deciding to treat with Herceptin. Anthracycline therapy should be avoided for up to 7 months after stopping Herceptin, refer to SmPC. Formal cardiological assessment should be considered in patients with cardiovascular concerns following baseline screening. In all patients, monitor cardiac function e.g. every 12 weeks. Monitor patients who develop asymptomatic cardiac dysfunction more frequently (e.g. every 6-8 weeks). Consider discontinuing treatment in patients with asymptomatic decreased LVEF function if no clinical benefit seen. The safety of continuing or resumption of Herceptin in patients who experience cardiac dysfunction has not been studied. Caution in treating patients with symptomatic heart failure, history of hypertension, Coronary artery disease, and in EBC patients with LVEF of 55% or less. If LVEF % drops ≥ 10 points from baseline AND to below 50%, suspend treatment, repeat LVEF assessment within 3 weeks. If LVEF does not improve or further declines, or symptomatic CHF develops strongly consider discontinuation, refer to SmPC. All such patients should be reviewed by cardiologist and followed up. If symptomatic cardiac failure develops during therapy, treat with standard medications. Most patients in the pivotal trials who developed CHF or asymptomatic cardiac dysfunction improved with standard medication, refer to SmPC. MBC: Herceptin and anthracyclines should not be given concurrently in the MBC setting. Increased risk of cardiac dysfunction in patients who previously received anthracycline therapy. EBC: For EBC patients, cardiac assessment, as performed at baseline, should be repeated every 3 months during treatment and every 6 months following discontinuation of treatment for duration of 24 months from the last dose. Further monitoring is recommended for patients receiving anthracycline containing chemotherapy and should occur yearly up to 5 years from the last dose or longer if a continuous decrease of LVEF is observed. In EBC, no data on patients with history of MI, angina pectoris requiring medical treatment, existing or a history of documented CHF (NYHA Class II-IV), LVEF of <55%, other cardiomyopathy, cardiac arrhythmia requiring medical treatment, clinically significant cardiac valvular disease, poorly controlled hypertension and hemodynamic effective pericardial effusion therefore treatment not recommended in such patients. Herceptin and anthracyclines should not be given concurrently in the adjuvant treatment setting. In EBC adjuvant patients, the incidence of symptomatic and asymptomatic cardiac events increased when Herceptin (IV formulation) was administered after anthracycline-containing chemotherapy compared to administration with a non-anthracycline regimen of docetaxel and carboplatin and was more marked when Herceptin (IV formulation) was administered concurrently with taxanes than when administered sequentially to taxanes. Most symptomatic cardiac events occurred within the first 18 months, regardless of the regimen used, refer to SmPC for further details. Risk factors for cardiac event include age >50 yrs, LVEF< 55% at baseline declining by 10-15 points prior to or following initiation of paclitaxel treatment and prior or concurrent use of anti-hypertensive medicinal products. In patients receiving Herceptin after completion of adjuvant chemotherapy, risk of cardiac dysfunction was associated with a BMI > 25 kg/m2 and a higher cumulative dose of anthracycline therapy given prior to initiation of Herceptin. In EBC patients eligible for neoadjuvant-adjuvant treatment, low dose anthracycline regimens (maximum cumulative doses: doxorubicin 180 mg/m2 or epirubicin 360 mg/m2) can be administered concurrently with chemotherapy naïve Herceptin patients. If patients have been treated concurrently with low dose anthracyclines and Herceptin in the neoadjuvant setting, no additional cytotoxic chemotherapy should be given after surgery. Experience of concurrent administration with low dose anthracycline regimens is currently limited to two trials, MO16432 and BO22227, refer to SmPC for details. Clinical experience is limited in neoadjuvant-adjuvant patients above 65 years of age. Administration-related reactions (ARRs) and Pulmonary events: ARRs are known to occur with Herceptin SC formulation. Pre-medication may reduce risk, refer to SmPC. Serious ARRs were not reported in the clinical trial however ARRs have been associated with the IV formulation; exercise caution.

References 1. 2. 3. 4. 5.

Pivot X, Semiglazov V, Chen S, et al. Subcutaneous injection of trastuzumab – analysis of administration time and injection site reactions. Poster presentation at the 37th European Society for Medical Oncology conference, Vienna, Austria, 28 September – 2 October 2012 (Abstract 272P). Herceptin SC Summary of Product Characteristics, 18th February 2016. Herceptin IV Summary of Product Characteristics, 18th February 2016. Ismael G, Hegg R, Muehlbauer S, et al. Subcutaneous versus intravenous administration of trastuzumab in patients with HER2positive, clinical stage I–III breast cancer: phase 3, randomised, open-label, multicentre (neo)adjuvant HannaH study. Lancet Oncol 2012; 13:869–878. Jackisch C, Stroyakovskiy D, Muehlbauer S, et al. Subcutaneous administration of trastuzumab in patients with HER2-positive early breast cancer: Results from the Phase III randomised, open-label, multi-centre (neo)adjuvant HannaH study. Oral presentation at the 8th European Breast Cancer Conference, Vienna, Austria (Abstract 1BA). 21 – 24 March 2012.

Observe patients for 6 hours after first injection and for 2 hours after subsequent injections. ARRs can be treated with an analgesic/antipyretic, or antihistamine. In rare cases, ARRs have resulted in fatal outcome. Patients experiencing dyspnoea at rest due to complications of advanced malignancy and co-morbidities may be at increased risk of fatal ARR and pulmonary events, therefore these patients should not be treated with Herceptin. Refer to SmPC for delayed (including fatal) ARR and pulmonary events. Severe pulmonary events have been reported with use of the IV formulation, occasionally fatal therefore exercise caution with the SC formulation. Cases of interstitial lung disease reported: risk factors include prior or concomitant therapy with other anti-neoplastic therapies known to be associated with it such as taxanes, gemcitabine, vinorelbine and radiation therapy. Patients experiencing dyspnoea at rest due to complications of advanced malignancy and comorbidities may be at increased risk of pulmonary events – do not treat these patients with Herceptin. Exercise caution for pneumonitis, especially in patients treated concomitantly with taxanes. Drug Interactions: No formal drug interaction studies have been performed. Effect of Herceptin on the pharmacokinetics of other antineoplastic agents: Pharmacokinetic data (PK) from studies BO15935 and M77004 in women with HER2 positive MBC suggest that exposure to paclitaxel and doxorubicin (and their major metabolites 6-α hydroxylpaclitaxel, POH, and doxorubicinol, DOL) is not altered by Herceptin IV loading or maintenance dose, refer to SmPC. However Herceptin may elevate the overall exposure of one doxorubicin metabolite (7-deoxy-13 dihydro-doxorubicinone, D7D). The bioactivity of D7D and the clinical impact of the elevation of this metabolite is unclear. Study JP16003 in HER2 positive Japanese MBC patients suggest administration of Herceptin has no effect on the single dose PK of docetaxel. Study JP19959, a substudy of BO18255 performed in male and female Japanese patients with advanced gastric cancer studied the PK of capecitabine and cisplatin administered with or without Herceptin. Exposure to the bioactive metabolite 5 –FU of capecitabine was not affected by the concurrent use of cisplatin plus Herceptin. However, higher concentrations and a longer half-life of capecitabine were demonstrated when combined with Herceptin. The PK of cisplatin was not affected by concurrent use of capecitabine or by concurrent use of capecitabine plus Herceptin, refer to SmPC. Effect of antineoplastic agents on Herceptin pharmacokinetics: Study JPI6003 in Japanese HER2 positive MBC patients found no evidence of a PK effect on Herceptin with concurrent administration of docetaxel. Comparison of PK results from phase II & III clinical trials in HER2 positive MBC patients indicate that individual and mean Herceptin trough serum concentrations varied within and across studies however no clear effect of the concomitant administration of paclitaxel on the pharmacokinetics of Herceptin, refer to SmPC for further details. The administration of anastrozole did not appear to influence the pharmacokinetics of trastuzumab. Fertility, Pregnancy and Lactation: Avoid during pregnancy unless potential benefit for mother outweighs risk to foetus. Do not breast-feed during and for 7 months after last treatment. Cases of foetal renal growth and and/or function impairment in association with oligohydramnios (some associated with fatal pulmonary hypoplasia of the foetus) reported in pregnant women in the post-marketing setting. Use effective contraception during and for at least 7 months after treatment has concluded. Advise women who become pregnant of potential foetal harm and manage with a multidisciplinary team. Effects on ability to drive and use machines: Patients experiencing administration-related symptoms (see section 4.4) should be advised not to drive and use machines until symptoms abate. Side Effects and Adverse Reactions: Most serious and/or common adverse reactions (reported for IV and SC formulations) are cardiac dysfunction, ARRs, haematotoxicity (especially neutropenia), infections and pulmonary events. The safety profile of Herceptin SC formulation from the pivotal trial in EBC was overall similar to the known safety profile of the IV formulation. Adverse events reported more frequently for the SC formulation: serious adverse events which included post-operative wounds infections, ARRs (during treatment phase), hypertension. The following adverse reactions have been reported with Herceptin IV monotherapy or in combination with chemotherapy in trials and in the post marketing setting: Very Common (≥1/10): infection, nasopharyngitis, febrile neutropenia, anaemia, neutropenia, decreased WBC count/leukopenia, thrombocytopenia, weight decreased/weight loss, anorexia, insomnia, tremor, dizziness, headache, paraesthesia, dysgeusia, conjunctivitis, increased lacrimation, increased/ decreased BP, irregular heart beat, palpitation, cardiac flutter, decreased ejection fraction, hot flush, wheezing*, dyspnoea*, cough, epistaxis, rhinorrhoea, diarrhoea, vomiting, nausea, lip swelling, abdominal pain, dyspepsia, constipation, stomatitis, erythema, rash, face swelling, alopecia, nail disorder, palmar-plantar erythrodysaesthesia syndrome, arthralgia, muscle tightness, myalgia, asthenia, chest pain, chills, fatigue, influenza-like symptoms, IRR, pain, mucosal inflammation, peripheral oedema and pyrexia. Common (≥1/100 - <1/10): neutropenic sepsis, cystitis, herpes zoster, influenza, sinusitis, skin infection, rhinitis, upper respiratory tract infection, urinary tract infection, erysipelas, cellulitis, pharyngitis, hypersensitivity, anxiety, depression, abnormal thinking, peripheral neuropathy, hypertonia, somnolence, ataxia, dry eye, congestive cardiac failure*, supraventricular tachyarrhythmia*, cardiomyopathy, hypotension*, vasodilation, asthma, pneumonia*, lung disorder, pleural effusion*, pancreatitis, haemorrhoids, dry mouth, hepatocellular injury, hepatitis, liver tenderness, acne, dry skin, ecchymosis, hyperhydrosis, maculopapular rash, pruritus, onychoclasis, dermatitis, arthritis, back pain, bone pain, muscle spasms, neck pain, pain in extremity, renal disorder, breast inflammation/mastitis, malaise, oedema and contusion. Immunogenicity: Neutralizing anti-trastuzumab antibodies were detected in post-baseline samples in Herceptin intravenous and Herceptin subcutaneous patients. 20.0% of patients treated with Herceptin subcutaneous formulation developed antibodies against the excipient hyaluronidase (rHuPH20). The clinical relevance of these antibodies is not known; nevertheless the pharmacokinetics, efficacy and safety determined by occurrence of ARRs of Herceptin IV and SC do not appear to be adversely affected by these antibodies. Adverse reactions of lesser frequency: anaphylactic reaction*, anaphylactic shock*, pulmonary fibrosis*, respiratory distress*, lung infiltration*, acute respiratory distress syndrome*, bronchospasm*, hypoxia*, oxygen saturation decreased*, respiratory failure* and acute pulmonary oedema*. *Denotes adverse reactions that have been reported in association with a fatal outcome. Refer to SmPC for full listings of adverse events. See SmPC section 4.8 for instructions on reporting adverse events. Legal Category: Product subject to medical prescription which may not be renewed (A). Presentation and Marketing Authorisation Number: EU/1/00/145/002 - Pack of one 6mL vial containing 5mL of solution. Marketing Authorisation Holder: Roche Registration Limited, 6 Falcon Way, Shire Park, Welwyn Garden City, AL7 1TW, United Kingdom. Herceptin is a registered trade mark. Further information is available from Roche Products (Ireland) Limited, 3004 Lake Drive, Citywest, Naas Road, Dublin 24. Telephone: (01) 4690700. Fax: (01) 4690791. Date of Preparation: January 2016

If a pregnancy occurs while using Herceptin or within 7 months following the last dose of Herceptin, please immediately report pregnancy to the Roche Adverse Event Line at Tel: (01) 4690700, Fax: (01) 4690793, Email: ireland.drug_surveillance_centre@roche.com, Out of Hours: (01) 2910943. Additional information will be requested during a Herceptin-exposed pregnancy and the first year of the infant’s life. This will enable Roche to better understand the safety of Herceptin and to provide appropriate information to Health Authorities, Healthcare Providers and patients. IE/HERS/0915/0009(1)

Date of item: April 2016

All the benefits of Herceptin, now in a faster format1-5


10 Clinical Synopsis Long-term follow-up from a phase 1b trial (KEYNOTE-001) in newly diagnosed and previously treated patients with advanced melanoma, showed that 40% of patients were alive three years after starting pembrolizumab, with similar 36-month overall survival rates in both groups. The study will be presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. Notably, 15% of patients in this study experienced complete remissions according to immune-related response criteria; of these patients, 89% remain in remission. Before 2011, when ipilimumab was approved as the first drug to extend survival, patients with advanced melanoma had a median overall survival of less than one year. “Advanced melanoma is still a very challenging cancer, which is why it is so remarkable that such a large proportion of patients see a longterm survival benefit from this therapy,” says lead study author Caroline Robert, MD, PhD, Head of the Dermatology Unit at the Institute Gustave-Roussy in Paris, France. “The results of this study further demonstrate the potential for long-term benefit with pembrolizumab.” The phase I study included 655 patients diagnosed with advanced melanoma. Seventyfive percent of patients had previously received other treatments, including ipilimumab. Study participants received pembrolizumab at 2 or 10 mg/kg every three weeks, or 10 mg/kg every two weeks. During the trial, 2 mg/kg every three weeks was determined to be the optimal dose. Patients remained on treatment until disease progression, intolerable toxicity or investigator decision. The three-year overall survival rate for patients treated with pembrolizumab was 40%, and the median overall survival was 24.4 months. Survival rates differed slightly, however, based on prior melanoma therapy. Among patients who had not received any prior treatment, survival was slightly higher, at 45%. Three-year survival rates were the same among patients who had previously received ipilimumab and those who had not (41% in both groups). The average time on pembrolizumab was 11.3 months. A total of 61 (9%) patients stopped pembrolizumab after a complete response was achieved, and 97% remained in remission at time of analysis. For patients who remained in remission after stopping pembrolizumab, the median time they remained in remission after stopping pembrolizumab was 10 months and ongoing. According to the researchers, while it is difficult to make any definitive conclusions based on this single-arm, early phase trial, these encouraging survival data suggest that patients can benefit from pembrolizumab regardless of whether they received previous treatments.

disease progression than those who received only chemotherapy using novel agents. This is the largest study reported to date aimed at comparing ASCT with a bortezomib-based regimen alone in patients younger than 65. The study will be presented at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago. ASCT is an intensive procedure in which a patient’s blood-forming stem cells are harvested from the blood and stored. After treatment with high-dose chemotherapy, the stem cells are given back to the patient. The proteasome inhibitor bortezomib was approved by the FDA in 2008 for upfront treatment of multiple myeloma. Since then, bortezomib has been incorporated into the standard treatments for patients with newly diagnosed multiple myeloma, whether or not they are able to undergo ASCT. For patients younger than 65, however, the continued need for ASCT has been debated in the era of novel agents, such as bortezomib (note: patients older than 65 are often unable to undergo ASCT). “Our findings show that autologous stem cell transplant should remain the preferred treatment for patients with multiple myeloma age 65 and under,” says lead study author Michele Cavo, MD, Head of the Seràgnoli Institute of Haematology at the University of Bologna. “While transplant-free treatment with novel agents remains an intriguing prospect, the reality is that stem cell transplant remains a powerful and proven approach, and with novel agents playing a supporting role, it is more effective than ever.” The randomised phase III study included 1,266 patients who were newly diagnosed with multiple myeloma. Following induction therapy with bortezomib-cyclophosphamidedexamethasone, patients were randomly assigned to receive either bortezomibmelphalan-prednisone (VMP), or high-dose melphalan followed by single ASCT. (In treatment centres with a standard policy of performing two [double] ASCTs, patients were

randomly assigned to either VMP or single ASCT or double ASCT.) In the second stage of the study, patients in both groups were randomly assigned to consolidation therapy with bortezomiblenalidomide-dexamethasone or no consolidation therapy. All patients received maintenance therapy with lenalidomide until disease progression or intolerable toxicity. A planned interim analysis was performed in January 2016. At the time of the analysis, median followup after the first treatment randomization was two years (23.9 months). While median progression-free survival was not yet reached, the data showed that patients who received stem cell transplants progressed more slowly than those who received VMP therapy without transplant. Among patients who had not yet experienced disease progression, those in the ASCT arm had a 24% lower risk of progressing at any future time point compared to those not receiving transplant. The benefit of transplant was confirmed in a further multivariate analysis and was even greater among certain patients at high risk of early progression. Patients with advanced disease (according to International Staging System III) randomized to the ASCT arm had a 48% lower chance of progressing at the next analysis compared to those not receiving transplant; among patients with certain highrisk genetic factors, ASCT was associated with a 28% lower chance of future progression compared to VMP therapy without transplant. In comparison with patients who did not have a transplant, those receiving ASCT were also more likely to achieve a high quality response (at least 90% tumour cell mass reduction) to treatment (74% vs. 84%, respectively), which is an important indicator of longer survival. Interim analysis of data related to the second randomisation to consolidation therapy or no consolidation therapy is not yet complete. The study is ongoing, and future analyses will assess overall survival, toxicity and quality of life as well as other measures.

Stem Cell Transplant Remains Important for Multiple Myeloma, Even in Novel Agent Era “Even in an age of novel therapies, proven approaches can retain their value. This study demonstrated that combining the best of both worlds – initial therapy with a novel agent followed by stem cell transplant – resulted in the best patient outcomes,” says ASCO President Julie M. Vose, MD, MBA, FASCO. Early findings from a phase III clinical trial showed that patients with multiple myeloma who received an autologous stem cell transplant (ASCT) survived longer without June 2016 • HPN

This year’s ASCO Annual Meeting, took place in Chicago, June 3-7 and attracted as many as 30,000 oncology professionals from around the world under the theme 'Collective Wisdom: The Future of Patient-Centred Care and Research'


NOW LICENSED

NEW ONCE-DAILY LIXIANA® ANOTHER STEP AHEAD.

.

(edoxaban)

Only LIXIANA combines: ®

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

www.lixiana.ie

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

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


12 News

Review of Nutrition and Hydration Care in Hospital The HIQA at the end of last month (May) published their “Report of the Review of Nutrition and Hydration care in Public Acute Hospitals”. The first of its kind, this review uses the National Standards for Safer Better Healthcare to assess how public acute hospitals are ensuring that patient’s nutrition and hydration needs are being adequately assessed, managed and evaluated. Encouragingly the report notes that the majority of the 579 (86%) patients interviewed by HIQA expressed satisfaction with the meal services they received and confirmed that they received meals suitable to their individual dietary needs.

Many patients expressed surprise to inspectors about the high quality of the food and commented that prior to coming to hospital that they had low expectations of hospital food. Patients were very complimentary about staff and gave inspectors many examples of where staff had been friendly, helpful or went out of their way to accommodate their needs. The HSE says it remains fully committed to addressing the reports four key areas for further improvement. These are: 1. All hospitals should have a nutrition steering committee in place to implement systems to ensure that all patients admitted to hospital receive high quality nutrition and

hydration care. Thirty of the 42 hospitals reported that they had a nutritional steering committee in place. 2. All patients admitted to hospital should be screened for the risk of malnutrition. Twenty one of the 42 hospitals stated they had implemented screening in all wards. Improvement plans are being developed and screening will be implemented on a phased basis. 3. Hospitals must audit compliance with all aspects of patients’ nutritional care and share the findings with all relevant staff groups involved in food service and patient care. Standardised auditing tools will be shared between hospitals/hospital

groups. Hospitals are currently analysing their in-patient hospital menus and a forum for sharing of standardised menus is being developed 4. Hospitals should strive to improve patients’ experience of hospital food and drink by engaging with patients about food variety and choice. Patient satisfaction surveys are used and will be shared and implemented as part of the improvement plans. Quality Initiatives like “protected mealtimes” currently in place in some hospitals will be rolled out.

Importance of self-management in Asthma patients Despite more than 90% of people with asthma agreeing that managing their condition is important to them, 83% don’t have a personal asthma management plan according to new research revealed at the launch of the ‘Make Asthma Personal’ campaign. The national campaign focuses on the importance of people living with asthma working with their healthcare professional to develop an Asthma Management Plan in order to help take control of their condition. Ireland’s latest respiratory campaign encourages those with asthma to develop a personal asthma management plan to put them in control of their condition. Professor Pat Manning is a Consultant Respiratory Physician at Bon Secours Hospital and lead for the National Clinical Programme for Asthma. He says it is imperative those suffering with asthma in Ireland have to know about managing their condition. Just last month (May) Professor Manning launched the ‘Make Asthma Personal’ campaign with the view to focus on the importance of people living with the condition working with their healtgcare professional to develop a steady Asthma Management Plan in order to help take control of their condition. He says, “With almost half a million people living with asthma in the June 2016 • HPN

country, it is incredibly important that they understand their condition and take a proactive approach to managing it. We know that one of the best ways to manage asthma successfully is for individuals to work with their healthcare professional to develop an effective Asthma Management Plan, personal to them and which will help to put them in control of their condition.”

Professor Pat Manning, Consultant Respiratory Physician at Bon Secours Hospital

Ireland has the fourth highest prevalence of asthma in the world; it is a major cause of illness and disability. Failure to control asthma inflicts a considerable burden on patients, families, and on the HSE. For healthcare professionals who deliver care to individuals with asthma and their families, unplanned acute care visits for asthma also disrupt practice schedules. Clinical trials show that asthma control is within reach for most individuals who have asthma, yet this chronic inflammatory disorder of the airways remains underrecognised and under-treated. While the most recent research shows that, on average more than three quarters of people agree that they feel comfortable initiating a discussion about their asthma with their healthcare professional, many people living with asthma tend not to take a proactive approach to managing their condition; 6 in 10 have never heard of an Asthma Management Plan; 40% admit to

not recording their symptoms or how they feel, and more than one in 6 (17%) say they don’t know what triggers their asthma. Having uncontrolled asthma symptoms can put someone at risk of an asthma attack. The research confirms that many people living with asthma in Ireland are unaware that their asthma may not be well controlled. More than one in three people (35%) use their reliever medication more than twice a week which is higher than the guidelines recommend and could indicate that asthma symptoms that are not well controlled.

The survey also reveals how the condition affects people’s daily lives when not well controlled*:  More than a quarter (27%) agree that they feel embarrassed by their asthma  More than a third (35%) of people agree that their asthma negatively impacts their ability to complete simple, daily household tasks  43% agree that they can no longer participate in sports or physical activities


fluticasone furoate Allergic rhinitis relief

Relieving the symptoms of allergic rhinitis1

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

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

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

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

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

Not actual size


14 Meeting Report

Cancer Trials Ireland leading the way in prostate cancer trials By Olwyn Deignan B.Sc., Senior Clinical Project Manager, Cancer Trials Ireland

Professor Ray McDermott, Medical Oncologist and Vice Clinical Lead with Cancer Trials Ireland (formerly ICORG)

The 2nd John Fitzpatrick Irish Prostate Cancer Conference held in Dublin in April 2016, brought together leading Irish and UK health care professionals with an international faculty of oncology and urology experts from around the world. Prostate Cancer is the most commonly diagnosed cancer among men, affecting one in six men in Ireland and the US. This year it is estimated that more than 180,000 men will be diagnosed with prostate cancer in the US while more than 3000 men will be diagnosed in Ireland. Prostate cancer is treatable if detected early, however where the cancer has spread to other parts of the body, survival rates and outcomes are poorer.

Professor John Armstrong, Consultant Radiation Oncologist and Director of Research at St. Lukes Hospital Dublin

Professor. Christopher J. Sweeney MBBS, Medical Oncologist from the Dana Farber Institute

Speaking at the conference Professor Ray McDermott, Medical Oncologist and Vice Clinical Lead with Cancer Trials Ireland (formerly ICORG) chaired the trials and outcomes session and spoke of the first wave of newer hormonal agents. These newer hormonal therapies are expected to have better side effect profiles and to be more efficacious. Professor John Armstrong, Consultant Radiation Oncologist and Director of Research at St. Lukes Hospital Dublin and founding member of Cancer Trials Ireland gave a complete overview of the radiotherapy trials for prostate cancer in Ireland. Professor Armstrong has been instrumental in the roll out of new procedures involving high tech radiation therapy procedures such as Intensity Modulated Radiation Therapy (IMRT) and Stereotactic radiosurgery over the last 20 years. Cancer Trials Ireland through the support of the pharmaceutical industries in Ireland and our continued successful international collaborations

June 2016 â&#x20AC;˘ HPN

with other prominent cancer cooperative clinical trial groups and hospitals, has led to a significant increase in the number of prostate cancer trials currently active in Ireland in 2016. This in turn opens up opportunities for patients to get early access to treatments that would otherwise not be available to them. Cancer Trials Irelandâ&#x20AC;&#x2122;s current prostate cancer trials cover the following areas of disease: localised high risk prostate cancer (prostate cancer which has not spread to other parts of the body), metastatic prostate cancer (prostate cancer which has spread to other parts of the body) both hormone sensitive and castration resistant, these trials are introducing the newer hormonal therapies highlighted by Professor McDermott and therefore allow earlier access to these treatments for Irish patients. The results of these trials may have the power to change standard of care globally. A recent example of this, presented at the conference by Professor. Christopher J. Sweeney MBBS, Medical Oncologist from the Dana Farber Institute, were the results of the CHAARTED trial. This trial was carried out to determine if treatment with standard hormone therapy plus docetaxel would result in longer overall survival than that with hormone therapy alone. Standard hormone therapy had been the backbone of treatment for metastatic prostate cancer since the 1940s. The conclusion of the CHAARTED trial was that six cycles of docetaxel at the beginning of standard hormone therapy for metastatic prostate cancer resulted in significantly longer overall survival than that with hormone therapy alone. The results of this trial has changed standard of care and Cancer Trials Ireland adapted all of our


Experience changes everything

Prostap DCS is indicated in all stages of prostate cancer

We've done our thing, so he can do his. Prostap SR DCS PROSTAP® SR DCS (3.75mg), PROSTAP® 3 DCS (11.25 mg), PROSTAP® 6 DCS (30 mg) leuprorelin acetate depot injection PRESCRIBING INFORMATION. Refer to Summaries of Product Characteristics (SmPC) before prescribing. Presentation: powder and solvent for prolonged-release suspension for injection in pre-filled dual chamber syringe with safety device. Indications: Prostap SR DCS/Prostap 3 DCS: Management of prostatic carcinoma for which suppression of testosterone is indicated. Management of oestrogen dependent gynaecological disorders including the management of pain and lesions associated with endometriosis. Preoperative management of uterine fibroids to reduce their size and associated bleeding. Treatment of central precocious puberty (girls under 9 years of age, boys under 10 years of age). Prostap SR DCS is also indicated for: endometrial preparation prior to intrauterine surgical procedures including endometrial ablation or resection. Prostap 6 DCS: Metastatic prostate cancer. Locally advanced prostate cancer, as an alternative to surgical castration. As an adjuvant treatment to radiotherapy in patients with high-risk localised or locally advanced prostate cancer. As an adjuvant treatment to radical prostatectomy in patients with locally advanced prostate cancer at high risk of disease progression. Dosage & Administration: Men: Prostap SR DCS: 3.75mg administered every month as a single subcutaneous or intramuscular injection. Prostap 3 DCS: 11.25mg every 3 months as a single subcutaneous or intramuscular injection. Prostap 6 DCS: 30mg administered as a single subcutaneous injection every 6 months. Do not discontinue when remission or improvement occurs. Response should be monitored clinically and if sub-optimal, check serum testosterone is at castrate level. In patients treated with GnRH analogues for prostate cancer, treatment is usually continued upon development of castrate-resistant prostate cancer. Reference should be made to relevant guidelines. Women: Prostap SR DCS: 3.75mg administered as a single subcutaneous or intramuscular injection every month for a maximum of 6 months (endometriosis and uterine fibroids). For endometrial preparation prior to intrauterine surgery the recommended dose is a single 3.75mg subcutaneous or intramuscular injection during days 3 to 5 of the menstrual cycle, 5-6 weeks prior to surgery. Prostap 3 DCS: 11.25mg as a single subcutaneous or intramuscular injection every 3 months for a maximum of 6 months (endometriosis and uterine fibroids). If appropriate, hormone replacement therapy (HRT - an oestrogen and progestogen) should be co-administered with Prostap DCS to reduce bone mineral density loss and vasomotor symptoms. Elderly: as for adults. Children: Central precocious puberty: Prostap SR DCS: Children with a body weight ≥ 20 kg: 3.75 mg administered once a month as a single subcutaneous injection. Children with a body weight < 20 kg: 1.88 mg administered once a month as a single subcutaneous injection. The administration interval should be 30 ± 2 days in order to prevent the recurrence of precocious puberty symptoms. Prostap 3 DCS: Children with a body weight ≥ 20 kg: 11.25 mg administered every 3 months as a single subcutaneous injection. Children with a body weight < 20 kg: 5.625 mg administered every 3 months as a single subcutaneous injection. The administration interval should be 90 ± 2 days in order to prevent the recurrence of precocious puberty symptoms. Injection site should be varied periodically. Contraindications:

Prostap 3 DCS

Prostap 6 DCS*

hypersensitivity to the active substance, any of the excipients or to synthetic GnRH or GnRHderivatives. Men: Use in patients insensitive to endocrine therapy or post-orchidectomy. Women and in girls with central precocious puberty: Lactation; pregnancy; undiagnosed abnormal vaginal bleeding. Warnings & Precautions: Development or aggravation of diabetes may occur; therefore diabetic patients may require more frequent monitoring of blood glucose. Hepatic dysfunction and jaundice with elevated liver enzyme levels have been reported. Therefore, close observation should be made and appropriate measures taken if necessary. Spinal fracture, paralysis, hypotension and worsening of depression have been reported. Postmarketing reports of seizures have been observed in patients treated with leuprorelin acetate and these events have been reported in both children and adults, and in those with or without a history of epilepsy, seizure disorders or risk disorders for seizures. Men: Initial transient rise in levels of testosterone may be associated with tumour “flare” manifesting as systemic or neurological symptoms. In the rare event of an injection site abscess, testosterone levels should be monitored as there may be inadequate absorption of leuprorelin from the depot formulation. Patients at risk of ureteric obstruction or spinal compression should be carefully considered and monitored during initial weeks of treatment. An anti-androgen may be administered to reduce the risk of “flare”. Any urological or neurological complications which occur should be treated by appropriate specific measures. May increase risk of bone loss, particular caution in patients with additional risk factors for osteoporosis. Patients at high risk for metabolic or cardiovascular diseases should be appropriately monitored. May prolong QT interval - particular caution in patients with a history of /or risk factors for QT prolongation or receiving concomitant medicinal products that might prolong the QT interval. Women: Patient should notify her physician if regular menstruation persists. Spotting/breakthrough bleeding may occur with Prostap SR DCS and Prostap 3 DCS treatment. An increase in clinical signs and symptoms may be observed during the initial days of therapy as sex steroids temporarily rise above baseline. In the case of uterine fibroids, it is mandatory to confirm the diagnosis of fibroids and exclude ovarian mass, before therapy is instituted. May cause an increase in uterine cervical resistance. The induced hypo-oestrogenic state results in a clinically significant loss in bone density over the course of treatment, some of which may not be reversible. The generally accepted level of bone loss with LHRH analogues such as Prostap is 5%. During one 6 month treatment period, this bone loss should not be important. In patients with major risk factors for decreased bone mineral content such as chronic alcohol and/or tobacco use, strong family history of osteoporosis, or chronic use of drugs that can reduce bone mass, therapy may pose an additional risk. Treatment options for vasomotor symptoms and bone mineral density loss should be considered. In the treatment of endometriosis, the addition of HRT (an oestrogen and progestogen) has been shown to reduce bone mineral density loss and vasomotor symptoms. In girls with central precocious puberty: a precise diagnosis of idiopathic and/or neurogenic central precocious puberty is necessary. The occurrence of vaginal bleeding, spotting and discharge after the first injection may occur as a sign of hormone withdrawal in girls. Bone mineral density (BMD)

* 6 month formulation is licensed in high risk localised, locally advanced and metastatic prostate cancer

may decrease during GnRH therapy for central precocious puberty. Slipped femoral epiphysis can be seen after withdrawal of GnRH treatment. Interactions: No studies performed. Carefully evaluate use with medicines that prolong QT interval or induce Torsade de pointes. Undesirable effects: Refer to section 4.8 of the SmPC in relation to other side effects Very common: weight gain, hot flushes, impotence, decreased libido, orchiatrophy, sweating and fatigue. Common: anorexia, mood changes, depression (occasionally severe), headache (occasionally severe), nausea, vomiting, muscle weakness, arthralgia, gynaecomastia, peripheral oedema, insomnia, paraesthesia and increases in liver function test values (usually transient). Rare: alteration of glucose tolerance which may affect diabetic control and reactions at the injection site e.g. induration, erythema, pain, abscesses, swelling, nodules, ulcers and necrosis. Very rare: pituitary apoplexy and anaphylactic reactions. Men: If tumour flare occurs, symptoms and signs due to disease may exacerbate e.g. bone pain and urinary obstruction, which should subside on continuation of therapy. QT prolongation (frequency unknown). Women: Adverse events occurring most frequently with Prostap SR DCS and Prostap 3 DCS are associated with hypo-oestrogenism. In women who have submucous fibroids there have been reports of severe bleeding following the administration of Prostap SR DCS and Prostap 3 DCS as a consequence of the acute degeneration of the fibroids. Patients should be warned of the possibility of abnormal bleeding or pain in case earlier surgical intervention is required. In children: In the initial phase of therapy with Prostap SR DCS and Prostap 3 DCS, a shortterm increase as flare-up of the sex hormone level occurs, followed by a decrease to values within the pre-pubertal range. Due to this pharmacological effect, adverse events may occur particularly at the beginning of treatment. Commonly reported adverse events with use of are emotional lability, headache, abdominal pain/abdominal cramps, nausea/vomiting, acne, vaginal bleeding, spotting, discharge and injection site reactions. General allergic reactions (fever, rash e.g. itching, anaphylactic reactions) are very rare. As with other medicinal products of this class, very rare cases of pituitary apoplexy have been reported following initial administration in patients with pituitary adenoma. Legal Classification: POM. Marketing Authorisation Numbers: PROSTAP SR DCS PA 1547/3/3; PROSTAP 3 DCS PA 1547/3/4; PROSTAP 6 DCS PA 1547/3/5. Marketing Authorisation Holder: Takeda UK Limited Additional Iinformation is available on request from: Takeda UK Ltd. Building 3, Glory Park, Glory Park Avenue, Wooburn Green, Buckinghamshire, HP10 0DF. Tel: 1800 937 970 Fax: +44 1628 526617. PI Approval Code: IRE/PT/14/0002(1). Date of revision: March 2016.

Adverse Events should be reported to the Pharmacovigilance Unit at the Health Products Regulatory Authority (medsafety@hpra.ie). Information about Adverse Event reporting can be found on the HPRA website (www.hpra.ie). Adverse Events should also be reported to Takeda UK Ltd on 1800 937 970. Date of preparation: March 2016 IRE/PRS/15/0006(2)


16 Meeting Report in house ongoing metastatic prostate cancer trial protocols to include this as an allowed therapy. It was also evident through our role as European Sponsor on one of the ongoing collaborative metastatic prostate cancer trials how quickly this new treatment option became standard of care in IRL and the UK. Cancer Trials Ireland is also running cancer trials in the area of translational research which it is leading and which are specific to prostate cancer. These trials are contributing to the ongoing important research to make it possible to better select patients for a particular drug based on their prostate cancer phenotype. Professor Stephen Finn Pathologist and co-director of the Cancer Molecular Diagnostic Laboratory at St. James hospital and member of Cancer Trials Ireland presented new translational studies for prostate cancer patients involving exercise both of which are being run in conjunction with Cancer Trials Ireland. Cancer Trials Ireland is at the centre of prostate cancer

research in country-wide. We continue to strive for patient access to the best treatments available globally and keep up to date with changes in standard practice which is constantly evolving in the area of prostate cancer. Prostate cancer is the most common male cancer in the developed world, second only to lung cancer worldwide, and is the sixth most common cause of cancer death among men. This is a disease of increasing age (autopsy studies have noted up to 70% of men >80 years have asymptomatic disease) and high survival figures. In Ireland, prostate cancer accounted for 30% of all diagnosed invasive cancers during 2007-9 and 13% of deaths. The median age at diagnosis is 69 years. Although the incidence of prostate cancer in Ireland ranked highest of all 30 European countries during 2008, mortality rates were ranked 11th highest; the discrepancy is related to the use of prostatespecific antigen (PSA) testing. Men may present asymptomatically (i.e. an

abnormal PSA result) or with symptoms relating to the primary tumour (i.e. prostatic/ local symptoms) or less commonly with symptoms related to metastatic disease (e.g. pathological fracture, hypercalcaemia, anaemia). Local symptoms may include symptoms of bladder outlet obstruction such as nocturia, hesitancy or pain on passing urine, incomplete emptying and a diminished urinary stream; in many cases these reflect benign conditions such as BPH rather than malignancy. However, these symptoms should prompt examination to rule out prostate cancer. A recent landmark genetic study described as the “Rosetta stone” of prostate cancer has opened up a new era of hope for men with advanced forms of the disease. The findings could lead to a plethora of personalised medicines that target specific gene defects, some of which are already in use or undergoing trials. British and US scientists who drew up the first comprehensive map of genetic mutations

linked to different strains of deadly prostate cancer found that almost 90% of the men whose DNA they studied carried potentially treatable defects. They also learned that 8% of the men were born with genetic faults that predisposed them to prostate cancer, strengthening the case for screening people with a family history of the disease. Professor Johann de Bono, from the Institute of Cancer Research in London, who led the British team, said, “This map will guide our future treatment and trials for this group of different lethal diseases. We’re describing this study as prostate cancer’s Rosetta stone — because of the ability it gives us to decode the complexity of the disease, and to translate the results into personalised treatment plans for patients.”

References: http://www. irishprostatecancerconference.org/ programme.html http://www.nejm.org/doi/ full/10.1056/NEJMoa1503747

Investigating unexpected deaths in lead to new therapies Biomedical researchers from the Regenerative Medicine Institute (REMEDI) and CÚRAM at NUI Galway, in collaboration with clinicians from Our Lady’s Children’s Hospital Crumlin (OLCHC) have developed the first in Ireland synchronised beating heart cells from human pluripotent stem (iPS) cells made from skin biopsy. The research funded in partnership by REMEDI and the National Children's Research Centre (NCRC) aims to investigate the causes of unexpected sudden death from inherited cardiac conditions in young people, and to help test therapies that may reduce the risk of sudden death in survivors and relatives. The discovery of the genetic basis of inherited cardiac conditions, specifically the inherited rhythm disease known as Long QT Syndrome, has advanced understanding of disease mechanisms and provided an insight into how it’s possible to ultimately ‘repair’ the genetic defect. June 2016 • HPN

The stem cell scientists at REMEDI in NUI Galway are now in a position to generate patientspecific heart tissue in a dish to test new therapies and treatments. Stem cell-derived heart cells have revolutionised understanding of heart mechanical and electrical communication, co-ordination and function. Mature human heart cells cannot be grown outside the body under normal conditions, and do not lend themselves easily to scientific interrogation without placing the patient at potential risk. By utilising a skin biopsy sample from a particular patient, the scientists can engineer those same skin cells into heart cells through what is termed ‘re-programming’ and can then create an exact replica of that patients’ heart tissue in a laboratory dish. This allows researchers to understand in detail the particular patient’s disease and to test or develop therapies without placing the individual patient at any medical risk. New medicines can be tested on these cells for their effectiveness in preventing

arrhythmias. Similarly, the genetic defect in the heart cell can be repaired through genome editing and this repaired heart cell can be then directly compared to the diseased heart cell in the lab. The stem cell study was initiated by Professor Timothy O’Brien, Director of REMEDI and CoPrincipal Investigator at CÚRAM in NUI Galway and Dr Terence Prendiville, NCRC Principal Investigator and the Department of Paediatric Cardiology in OLCHC. The research was carried out by Professor Sanbing Shen, Professor of Fundamental Stem Cell Biology and Post-doctoral researcher Dr Min Liu in the Biomedical Sciences Building at NUI Galway. The researchers in NUI Galway have developed a highly skilled and technically specialised expertise in ‘re-programming’ skin cells into stem cells, and then, in turn, making heart cells out of those same patient’s stem cells. The beating heart tissue can be electrically and mechanically measured and recorded. The ultimate goal is to repair the

genetic defect in the affected heart cells using new CRIPSR/Cas9 technology and return the heart cells to normal function. Professor Timothy O’Brien from NUI Galway, said, “We are excited about the potential to develop new therapies for children at risk of sudden death using this technology. The complete translational infrastructure for this work is now present in Galway and will be extended nationally with our collaborators in Dublin and throughout Ireland.” Dr Terry Prendiville from Our Lady’s Children’s Hospital Crumlin added, “I meet families every week in the hospital from all over Ireland who have been affected by the sudden unexpected death of a loved one. Their first question to me is: “Could this affect my child?” Their next question is: “How do I keep them safe?” “Research such as this allows us to continue to push the envelope on developing medical therapies that safeguard against risk of sudden death.”


STILL EXPLORING

34.7 median OS1

MO N T H S

94.9%

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

reduction in the risk of

48% radiographic progression3 WITH

of median follow up

YEARS

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

4+

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

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


18 News Overwhelming capacity constraints highlighted to Minister The Irish Hospital Consultants Association (IHCA) has met with Mr Simon Harris T.D., new Minister for Health, to discuss the overwhelming capacity constraints which are preventing the provision of care to patients, leading to unacceptable delays with record numbers of patients being treated on trolleys and a growing number of patients on surgical and other waiting lists. Dr Gerard Crotty, IHCA President, said the Association’s discussions with Minister Harris confirmed the need for immediate investment in frontline services to address critical capacity deficits. This, Dr Crotty said, is because frontline resources were cut steeply during austerity and funding has not been provided to cater for the country’s increasing and ageing population. In particular, he added, there needs to be a significant increase in the number of hospital beds and operating theatre access. Dr Crotty said that there is no need for lengthy studies to confirm what is already very clear. Hundreds of patients are being treated on trolleys every day, over 74,000 patients were awaiting essential surgery at the end of April and the cancellation

Health Minister Simon Harris T.D.

New Health Minister Simon Harris, pictured, has been warned of Ireland's overwhelming capacity constraints of surgical appointments is a regular occurrence because of the shortage of hospital beds. In the past decade 1,500 acute hospital beds have been closed. The number of intensive care unit (ICU) beds has declined from 289 in 2009 when the HSE commissioned Prospectus Report recommended that the number of ICU beds needed to be increased by 45% immediately and doubled to 579 by 2020. Dr Crotty said patients’ lives were being put at risk due to the lack of ICU beds.

He added that it is acknowledged that Ireland is suffering a damaging medical brain drain which has resulted in one in four advertised consultant posts receiving no applicants last year. The combined impact in recent years is that there are now hundreds of approved hospital consultant posts which cannot be filled on a permanent basis. The IHCA President said these vacancies are exacerbating delays in treating patients and adversely impacting patient outcomes.

Dr Crotty has called on Minister Harris to end the discrimination against new entrant consultants and honour the 2008 Consultant Contract to restore trust and our international competiveness in recruiting consultants. The IHCA delegation highlighted to Minister Harris that there is an urgent need to reform Tort Law, implement without delay the PreAction Protocols enacted in 2015 and effect other essential changes, as the escalating cost of clinical indemnity is unsustainable. Dr Crotty said that indemnity costs are forcing consultants to cease practice and emigrate because of increases since 2012 of between 100% and 400% depending on the specialty. Dr Crotty welcomes Minister Harris’s commitment to work on a collaborative basis with the Association and its consultant members in developing the proposed 10-year Health Service Plan, which the Association said must be realistic and supported by the necessary resources and funding.

Major study good news for COPD exacerbations Results from a major study, the head-to-head FLAME study, comparing the efficacy of once-daily Ultibro® Breezhaler® (indacaterol/glycopyrronium bromide) 110/50 mcg to twice-daily Seretide® (salmeterol/fluticasone [SFC]) 50/500 mcg in reducing chronic obstructive pulmonary disease (COPD) exacerbations has shown positive results. In addition to meeting the primary endpoint (non-inferiority), findings demonstrated the superiority of Ultibro® Breezhaler® over the widely used inhaled corticosteroid (ICS)/LABA* combination on exacerbation outcomes. The published FLAME results are anticipated to impact the future management and treatment of COPD patients. Preventing exacerbations is one of the primary goals of long-term care for COPD patients. These episodes have a detrimental effect on quality of life and disease progression, contributing to further lung function decline and, in severe cases, hospitalisation and even death. June 2016 • HPN

"Reducing exacerbations is absolutely critical to improve outcomes and quality of life for COPD patients,” said Vasant Narasimhan, Global Head Drug Development and Chief Medical Officer for Novartis. “The FLAME study has clearly shown that Ultibro® Breezhaler® is superior to the current standard of care in reducing exacerbations, marking a shift away from therapies containing steroids for the optimal treatment of COPD patients.” The results of FLAME confirmed that Ultibro® Breezhaler® is superior to SFC in reducing exacerbation outcomes regardless of a patient’s disease severity and eosinophil levels (a type of white blood cell)1. Significantly, compared to SFC, Ultibro® Breezhaler® both reduced the rate of moderate or severe exacerbations with a 17% risk reduction (rate ratio, 0.83), and prolonged the time to the first of these episodes with a 22% risk reduction (hazard ratio, 0.78). The safety profiles of the two

treatments were consistent with their known profiles. Results confirmed that Ultibro® Breezhaler® 110/50 mcg met its primary endpoint (non-inferiority) and furthermore demonstrated superiority to SFC 50/500 mcg on the rate of all COPD exacerbations (mild/moderate/severe) over one year of treatment in COPD patients with a history of at least one exacerbation in the previous year. Against further secondary endpoints, Ultibro Breezhaler was also superior compared to SFC in reducing or improving the following:  Rate and time to first moderate or severe COPD exacerbation  Time to first COPD exacerbation (mild/moderate/severe)  Time to first severe COPD exacerbation  Lung function (trough FEV1)  Health-related quality of life (St. George’s Respiratory Questionnaire)

Chronic obstructive pulmonary disease (COPD) affects an estimated 210 million people worldwide and is the third leading cause of death. It is progressive, and can be a life-threatening disease. COPD makes it difficult to breathe, with symptoms that have a destructive impact on patients’ function and quality of life. Exacerbations are a sudden worsening of COPD symptoms that can be “frightening” for patients, causing distress, anxiety and the deterioration of quality of life. COPD exacerbations are also associated with significant healthcare resource burden and costs, particularly due to the frequent need for hospitalisation. Consequently, the prevention of exacerbations is an important goal in COPD management to improve long-term health status and conserve healthcare resources.


WITH ULTIBRO BREEZHALER EXACERBATION PREVENTION IS IN YOUR HANDS1 ®

®

One proven treatment for COPD patients, with1,2* or without 3,4† exacerbations ULTIBRO® BREEZHALER® is indicated as a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).5 * Patients had at least one moderate or severe exacerbation in the previous 12 months. † Patients had no moderate or severe exacerbation in the previous 12 months. Ultibro Breezhaler ▼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. ABBREVIATED PRESCRIBING INFORMATION Please refer to Summary of Product Characteristics (SmPC) before prescribing. Presentation: Ultibro® Breezhaler® 85mcg / 43mcg inhalation powder hard capsules containing indacaterol maleate and glycopyrronium bromide respectively and separate Ultibro® Breezhaler® inhaler.Indications: A maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD). Dosage and administration: Recommended dose is the inhalation of the content of one capsule once daily, administered at the same time of the day each day, using the Ultibro® Breezhaler® inhaler. Capsules must not be swallowed. No dose adjustment required in elderly patients, for patients with mild and moderate hepatic impairment or for patients with mild to moderate renal impairment. No data available for use in patients with severe hepatic impairment and should only be used in patients with severe renal impairment or end-stage renal disease requiring dialysis if the expected benefit outweighs the potential risk. No relevant use in the paediatric population. Contraindications: Hypersensitivity to the active substances or to any of the excipients. Warnings/Precautions: Not to be administered concomitantly with medicinal products containing other LABA’s or LAMA’s. Asthma: ♦ULTIBRO® BREEZHALER® SHOULD NOT BE USED FOR TREATMENT OF ASTHMA. Acute use: ♦Not indicated for treatment of acute episodes of bronchospasm. Hypersensitivity: ♦Immediate hypersensitivity reactions have been reported after administration of indacaterol or glycopyrronium. If signs suggesting allergic reactions occur (in particular, angioedema, difficulties in breathing or swallowing, swelling of the tongue, lips and face, urticaria or skin rash), treatment should be discontinued immediately and alternative therapy instituted. Paradoxical bronchospasm: ♦If paradoxical bronchospasm occurs, Ultibro® Breezhaler® should be discontinued immediately and alternative therapy instituted. Anticholinergic effects related to glycopyrronium: ♦To be used with caution in patients with narrow-angle glaucoma and in patients with urinary retention. Patients with severe renal impairment: ♦Should only be used in patients with severe renal impairment, including those with end-stage renal disease requiring dialysis, if the expected benefit outweighs the potential risk. These patients should be monitored closely for potential adverse reactions. Cardiovascular effects: ♦To be used with caution in patients with cardiovascular disorders (coronary artery disease, acute myocardial infarction, cardiac arrhythmias, hypertension), in patients with known or suspected prolongation of the QT interval or patients treated with medicinal products affecting the QT interval and in patients with unstable ischaemic heart disease, left ventricular failure, history of myocardial infarction, arrhythmia (excluding chronic stable atrial fibrillation), a history of long QT syndrome or whose QTc (Fridericia method) was prolonged. ♦LABA’s may produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, blood pressure, and/or symptoms, ECG changes. In case such effects occur, treatment may need to be discontinued. Hypokalaemia: ♦ LABA’s may produce significant hypokalaemia in some patients, which has the potential to produce cardiovascular effects. In patients with severe COPD, hypokalaemia may be potentiated by hypoxia and concomitant treatment which may increase the susceptibility to cardiac arrhythmias. Hyperglycaemia: ♦Inhalation of high doses of LABA’s may produce increases in plasma glucose. Upon initiation of treatment with Ultibro® Breezhaler® plasma glucose should be monitored more closely in diabetic patients. ♦ Ultibro® Breezhaler® has not been investigated in patients for whom diabetes mellitus is not well controlled. General disorders: ♦To be used with caution in patients with convulsive disorders or thyrotoxicosis, and in patients who are unusually responsive to LABA’s. Excipients: ♦ Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Pregnancy and Lactation: ♦Ultibro® Breezhaler® should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the foetus. ♦Not known whether indacaterol, glycopyrronium and their metabolites are excreted in human milk. Use of Ultibro® Breezhaler® by breast-feeding women should only be considered if the expected benefit to the woman is greater than any possible risk to the infant. Interactions: ♦Concomitant use is not recommended with beta adrenergic blockers, anticholinergics or sympathomimetic agents. ♦Concomitant hypokalaemic treatment with methylxanthine derivatives, steroids, or non-potassium-sparing diuretics may potentiate the possible hypokalaemic effect of beta2adrenergic agonists, therefore use with caution. ♦Inhibition of the key contributors of indacaterol clearance, CYP3A4 and P-gp, does not raise any safety concerns given the safety experience of treatment with indacaterol. ♦No clinically relevant drug interaction is expected when glycopyrronium is co administered with cimetidine or other inhibitors of the organic cation transport. Adverse reactions: ♦Very common: upper respiratory tract infection. ♦Common: nasopharyngitis, urinary tract infection, sinusitis, rhinitis, dizziness, headache, cough, oropharyngeal pain including throat irritation, dyspepsia, dental caries, gastroenteritis, musculoskeletal pain, pyrexia, chest pain. ♦Uncommon: hypersensitivity, angioedema, diabetes mellitus and hyperglycaemia, insomnia, paraesthesia, glaucoma, ischaemic heart disease, atrial fibrillation, tachycardia, palpitations, paradoxical bronchospasm, epistaxis, dry mouth, pruritus / rash, muscle spasm, myalgia, pain in extremity, bladder obstruction and urinary retention, peripheral oedema and fatigue. ♦Please refer to SmPC for a full list of adverse events for Ultibro® Breezhaler®. Legal Category: POM Pack sizes: Cartons containing 10 capsules (1x10 capsule blister strips) and one Ultibro® Breezhaler® inhaler or 30 capsules (3x10 capsule blister strips) and one Ultibro® Breezhaler® inhaler. Marketing Authorisation Holder: Novartis Europharm Limited, Frimley Business Park, Camberley GU16 7SR, United Kingdom. Marketing Authorisation Numbers: EU/1/13/862/007 & 003. Full prescribing information is available on request from Novartis Ireland Ltd, Vista Building, Elm Park Business Park, Dublin 4. Tel: 01 2601255 or at www.medicines.ie Date of Revision of API Text: 9th February 2016 References: 1. Wedzicha JA, Banerji D, Chapman KR, et al. Indacaterol–glycopyrronium versus salmeterol–fluticasone for COPD. N Engl J Med. DOI: 10.1056/NEJMoa1516385. 2. Wedzicha JA, et al. Lancet Respir J 2013:1:199–209. 3. Mahler DA, et al. Eur Respir J 2014;43:1599–1609. 4. Vogelmeier CF, et al. Lancet Respir Med; 2013:1:51–60. 5. Ultibro® Breezhaler®. Summary of Product Characteristics.Accessed on www.medicines.ie , May 2016.

Date of Preparation: May 2016 IE02/ULT16-CNF057f


20 News

Psoriasis on agenda at IAD Spring Meeting AAD scholarships were awarded to Dr Catherine Foley and Dr Dmitri Wall to attend 2016 Annual Meeting of the American Academy of Dermatology, March 4-8, 2016, Washington, D.C.

the “Psychological aspects of Psoriasis” which came before presentation of the Burrows Cup and Poster Prizes. The annual conference dinner took place in the Aula Maxima at University College Cork.

The Irish Association of Dermatologists hosted their Spring 2016 meeting recently in the Radisson Blu Hotel, Little Island, Cork. Under the theme of ‘Psoriasis’ the keynote address was delivered by Professor Chris Griffiths, Professor of Dermatology with the University of Manchester, Manchester Academic Health Science Centre who spoke on “A perspective on the natural history of psoriasis”

before later going on to discuss “Brain-Skin Axis in Psoriasis.” This was followed by Professor Brian Kirby, Consultant Dermatologist at St Vincent’s University Hospital, Dublin who talked on "The future of psoriasis treatment." Dr Sandy McBride, Consultant Dermatologist at the Royal Free London NHS Foundation Trust gave delegates an overview on

The July/August issue of Hospital Professional News will feature full coverage of the event. In other news, scholarships to attend the annual AAD event are now open. For several years, the American Academy of Dermatology has sponsored a free registration programme in the interest of furthering the relationships of the Academy with dermatologists and dermatological societies throughout the world.

The programme, which is administered by the Academy’s International Affairs Committee, is designed to give young dermatologists from other countries an opportunity to attend the Annual Meeting of the Academy. The two selected individuals from each society will also be provided with complimentary tuition to a one or two-day postgraduate course of their choice (subject to availability of space in the course). These scholarships are available only to those individuals who have not received a previous registration scholarship from this program. The Academy will provide grants for $1,000 to each of these physicians. The checks will be distributed at the International Scholarship Dinner Reception Applicants must be fully paid up Trainee members of the IAD. The closing date for receipt of applications is mid-August annually. You can read more about this by visiting www.irishdermatologists.ie

Diabetic foot disease E-book tops ‘bestsellers’ list upon release Wednesday, June 8th, 2016. Today, St. James’s Hospital officially launched an e-book to help those living with acute diabetic foot disease. The e-book aims to assist people with diabetes and their families to better understand the condition and to assist them on their journey of living with a hole in the foot.

Siobhan O’Meara, Diabetes Podiatrist and Professor Ceppie Merry, Consultant in Infectious Diseases The International Working group on the Diabetic foot, reports that every 20 seconds a leg is lost to diabetes somewhere in the world. Diabetes is associated with between 23 and 90% of all lower limb amputations globally. 86% of amputations are preceded by a foot ulcer (hole in the foot).

Patient involvement was a key component in the production of the e-book and a focus group of patients, their families, and an independent clinician informed the topics identified for the e-book. The e-book was also written to ensure its accessibility for those with lower levels of literacy. Pauline Wilson, Diabetes Podiatrist, highlighted the importance of publishing patient focused material. Pauline said, “This publication was inspired by our wish to produce not only medical focused material, but material relevant to patients.” Professor Merry, Infectious Diseases commented, “With the advancement of technologies and the move to online, we June 2016 • HPN

recognised the importance of producing a booklet that was accessible online.” Corey Gillen, Diabetes Podiatrist, highlighted the importance of involving patients in the production of the e-book, saying “The writing of this e-book illustrated that clinicians can sometimes pre-empt what we think patients want to know, and that our presumptions

can often be mistaken. That is why the involvement of patients and their families was key to ensuring the content was relevant to patients.” Siobhan O’Meara, Diabetes Podiatrist, said; “We wanted to make sure that information on diabetes and its impact on patients was not only easily accessible and relevant, but also jargon free.”

The authors of the book; Professor Ceppie Merry, Infectious Diseases, Pauline Wilson, Diabetes foot service and Corey Gillen, Diabetes Day Centre and Siobhan O’Meara, Diabetes Day Centre, all work in St. James’s Hospital. The e-book is available for purchase on amazon.co.uk for £2.07 and all proceeds from the sale will go directly to the provision of patient services. Upon release on amazon.co.uk the e-book reached #1 in the Chiropody and Podiatry category and #6 in the Kindle store Allied Health Professionals category.


Real world patients remain on Stelara over the long term versus any other 1st line anti TNF1-3 Newly published PSOLAR data demonstrates greater drug persistency* over 4 years for Stelara compared to any other anti-TNF therapy2 Persistence of Therapy in Biologic-Naïve Patients2

Proportion of patients continuing therapy

1.0

Stelara® 0.8

0.6 Infliximab† 0.4

Etanercept‡ Adalimumab‡

0.2 0.0

0

12

Adapted from Menter A et al. 2015

24

36 48 Time on therapy (months)

60

72

84

• A higher proportion of patients stayed on Stelara® over the

long term versus any other 1st line anti TNF.2

• Fewer patients discontinued Stelara® vs. adalimumab, etanercept and infliximab.2 • Higher drug persistency was observed for Stelara® compared to the other biologics based

on statistically significant differences in time to stop/switch for each biologic vs Stelara®.2

* Drug Persistence Reflects various factors including: Primary or Secondary Drug Effectiveness, Drug Safety, AE Profile, Tolerability.1 Persistency was assessed by Kaplan-Meier analysis for time to therapy stop/switch seperately for Stelara®, infliximab, adalimumab and etanercept Study Limitations: Data in the overall population were adjusted for possible differences amongst groups. Data were not adjusted for variability such as socioeconomic factors (e.g. access to medication), setting of administration (self- versus physician-administered), geographic region, and clinical characteristics.

STELARA® solution for injection PRESCRIBING INFORMATION ACTIVE INGREDIENT(S): Ustekinumab. Please refer to Summary of Product Characteristics (SmPC) before prescribing. INDICATION(S): Plaque psoriasis adults: Treatment of moderate to severe plaque psoriasis in adults who failed to respond to, or who have a contraindication to, or are intolerant to other systemic therapies including ciclosporin, methotrexate or PUVA. Plaque psoriasis paediatrics: Moderate to severe plaque psoriasis in adolescent patients from the age of 12 years and older, who are inadequaely controlled by, or are intolerant to, other systemic therapies or phototherapies. Psoriatic arthritis: Alone or in combination with methotrexate for the treatment of active psoriatic arthritis in adult patients when the response to previous non-biological diseasemodifying anti-rheumatic drug (DMARD) therapy has been inadequate. DOSAGE & ADMINISTRATION: Under the guidance and supervision of a physician experienced in diagnosis and treatment of psoriasis or psoriatic arthritis. Subcutaneous injection. Avoid areas with psoriasis. Self-injecting patients or caregivers ensure appropriate training Physicians are required to follow-up and monitor patients. Plaque psoriasis, adults & elderly: Patients <100kg, 45 mg at week 0 followed by a 45 mg dose at week 4, then every 12 weeks. Patients >100 kg, 90 mg at week 0 followed by a 90 mg dose at week 4, then every 12 weeks (45 mg was less effective in these patients). Plaque psoriasis paediatrics (12 years and older): Patients <60 kg, 0.75 mg/kg at week 0, followed by 0.75 mg/kg at week 4 then every 12 weeks thereafter. Patients ≥60-<100kg, 45 mg at week 0 followed by 45 mg at week 4, then every 12 weeks. Patients >100 kg, 90mg at week 0, followed by 90mg at week 4, then every 12 weeks. Psoriatic arthritis, adults & elderly: 45 mg at week 0 followed by a 45 mg dose at week 4, then every 12 weeks. Alternatively, 90 mg may be used in patients with a body weight >100 kg. Consider discontinuation if no response after 28 weeks. Children <12 years: Not recommended. Renal & Hepatic impairment: Not studied. CONTRAINDICATIONS: Hypersensitivity to product; clinically important, active infection. SPECIAL WARNINGS & PRECAUTIONS: Infections: Potential to increase risk of infections and reactivate latent infections. Caution in patients with a chronic infection or history of recurrent infection, particularly TB. Patients should be evaluated for tuberculosis prior to initiation of STELARA. Consider anti-tuberculosis therapy prior

to initiation of STELARA in patients with past history of latent or active tuberculosis. Patients should seek medical advice if signs or symptoms suggestive of an infection occur. If a serious infection develops, they should be closely monitored and STELARA should not be administered until infection resolves. Malignancies: Potential to increase the risk of malignancy. No studies in patients with a history of malignancy or in patients who develop malignancy while receiving STELARA. Monitor all patients, in particular those older than 60, patients with a medical history of prolonged immunosuppressant therapy or those with a history of PUVA treatment for non-melanoma skin cancer. Concomitant immunosuppressive therapy: Caution, including when changing immunosuppressive biologic agents. Hypersensitivity reactions: Serious hypersensitivity reactions (anaphylaxis and angioedema) reported, in some cases several days after treatment. If these occur appropriate therapy should be instituted and, STELARA discontinued immediately. Latex sensitivity: Needle cover contains natural rubber (latex), may cause allergic reactions. Immunotherapy: Not known whether STELARA affects allergy immunotherapy. Serious skin conditions: Exfoliative dermatitis has been reported following treatment. Discontinue STELARA if a drug reaction is suspected. SIDE EFFECTS: Common: dental infections, upper respiratory tract infection, nasopharyngitis, dizziness, headache, oropharyngeal pain, diarrhoea, nausea, pruritus, back pain, myalgia, arthralgia, fatigue, injection site erythema, injection site pain, antibodies to ustekinumab. Other side effects include: cellulitis, serious hypersensitivity reactions (including anaphylaxis, angioedema), skin exfoliation, exfoliative dermatitis. Studies show adverse events reported in ≥12 year olds with plaque psoriasis were similar to those seen in previous studies in adults with plaque psoriasis. Refer to SmPC for other side effects. FERTILITY: The effect of ustekinumab has not been evaluated. PREGNANCY: Should be avoided. Women of childbearing potential: Use effective contraception during treatment and for at least 15 weeks posttreatment. LACTATION: Limited data in humans. INTERACTIONS: In vitro, STELARA had no effect on CYP450 activities. Vaccinations: Live vaccines should not be given concurrently with STELARA, and should be witheld for at least 15 weeks after last dose of STELARA. STELARA can resume at least 2 weeks after such vaccinations. No data on secondary transmission of infection by live vaccines

in patients receiving STELARA. Concomitant immunosuppressive therapy: Psoriasis: The safety and efficacy of STELARA in combination with other immunosuppressants, including biologics, or phototherapy have not been evaluated. Refer to SmPC for full details of interactions. LEGAL CATEGORY: Prescription Only Medicine. PRESENTATIONS, PACK SIZES, MARKETING AUTHORISATION NUMBER: 45 mg: 1 x vial. EU/1/08/494/001, 45mg: 1 x 0.5ml prefilled syringe. EU/1/08/494/003. 90mg: 1 x 1.0ml pre-filled syringe. EU/1/08/494/004. MARKETING AUTHORISATION HOLDER: JANSSEN-CILAG INTERNATIONAL NV, Turnhoutseweg 30, B-2340 Beerse, Belgium. FURTHER INFORMATION IS AVAILABLE FROM: Janssen-Cilag Ltd, 50 – 100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG UK. © Janssen-Cilag Ltd 2015 Adverse events should be reported. Healthcare professionals are asked to report any suspected adverse events via: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2, Tel: +353 1 6764971, Fax: +353 1 6762517, Website: www.hpra. ie, E-mail: medsafety@hpra.ie. Adverse events should also be reported to Janssen-Cilag Ltd on +44 1494 567447. Prescribing information last revised: 06/2015 References: 1. Warren RB et al. J Inv Dermatol. Accepted article: June 2015; doi: 10.1038/jid.2015.208. 2. Menter et al. P1705: Presented at the AAD annual meeting 2015. 3. Gniadecki R et al. Br J Dermatol. 2015 Jan; 172(1): 244-252. 4. Kimball AB et al. JEADV 2013; 37: 1535-1545. Date of preparation: April 2016 | PHIR/STE/0416/0002


22 News

Cancer Trials saves Government ¤6.5m annually Pictured at the launch of the ‘Just Ask’ campaign and New Name to mark International Clinical Trials Day (20th May) were Professor Bryan Hennessy, Clinical Lead for Cancer Trials Ireland, Sinead, Cliodhna and Alan Pearson, and Eibhlin Mulroe, CEO, Cancer Trials Ireland.

while a further 88 were in the follow up stage.

Our key objective is to build on this and increase the number of patients on cancer drug trials from the current 3% to 5% of all patients. We want to initiate and support more investigator led studies, work with pharmaceutical companies and broaden our impact across more cancer types An independent report commissioned by Cancer Trials Ireland (formerly ICORG) estimates that the ¤3.63m funding from the Exchequer, and other grants, allocated to cancer trials in 2016 will save the HSE at least ¤6.5m in cancer drugs cost, generate almost ¤6m in tax revenues, contribute ¤16.5m to Ireland’s GDP and support over 230 jobs, mostly high quality specialist positions. In addition, Cancer Trials Ireland is expected to generate more than ¤3.85m from international sources. These findings were announced to mark International Clinical Trials Day (20th May) and the roll out of ‘Just Ask’, a new campaign developed by Cancer Trials Ireland to encourage people diagnosed with cancer to just ask their doctor or healthcare professional about cancer trials. Based on a small sample of case studies, the report, prepared by DKM Economic Consultants, estimates that cancer trials can add 6 to 15 quality adjusted years June 2016 • HPN

of life (QALYs) collectively for trial participants with a related economic benefit ranging from ¤0.28m to ¤0.65m per trial. The report notes that subsequent benefits would be a multiple of these values when proven therapies are made available to patients generally. These benefits are in addition to the early access to drugs and treatments and the extra care cancer trials participants receive. A case study contained in the report demonstrated that in the breast cancer trial known as Tailor X, 110 Irish patients collectively avoided 27 years of chemotherapy which generated a saving of ¤0.766m for the HSE in avoided treatment costs. The test that resulted from this trial means that each year hundreds of patients do not have to undergo chemotherapy which saves the HSE over ¤0.5m annually. Another cancer trial in the area of advanced melanoma added a combined 6.3 quality years of life to the 27

participants which generated an economic benefit of over ¤0.28m. Speaking at the launch of International Clinical Trials Day, Eibhlin Mulroe, CEO, Cancer Trials Ireland, said, “This report highlights the impact our very well developed network of 14 Cancer Trials Units is having. They give patients early access to medicines not yet available. They can contribute significantly to their wellbeing all the while finding answers to cancer. They also represent a highly effective and efficient one stop shop network for investigator led studies and attracts cancer trials from around the world and from leading pharmaceutical companies.” The report showed that to date, Cancer Trials Ireland has opened over 350 cancer trials involving more than 15,000 cancer patients. During 2015, 14 hospitals which have Cancer Trials Units were working on 154 cancer trials involving 6700 patients; 66 were actively recruiting patients

Professor Bryan Hennessy, Clinical Lead for Cancer Trials Ireland and Consultant Oncologist, Beaumont Hospital, said, “Cancer Trials Ireland’s network offers a world class infrastructure. Our key objective is to build on this and increase the number of patients on cancer drug trials from the current 3% to 5% of all patients. We want to initiate and support more investigator led studies, work with pharmaceutical companies and broaden our impact across more cancer types. This growth will further bolster the huge reservoir of scientific knowledge and expertise that we have built over the past 20 years and ensure that people living with cancer continue to access the latest medicines not yet widely available.” The report also notes that Cancer Trials Ireland’s success with international collaborations helps the IDA build and broaden linkages with its existing clients and opens up opportunities for discussions with new clients interested in cancer. “These deepened relationships and positive perceptions of Ireland as an innovative location have the potential to increase our chances of winning high-value foreign direct investment in the biopharma space, especially as innovation in oncology is moving at such as fast pace,” Barry Heavey, Global Head of Life Sciences, Engineering & Industrial Tech at IDA. Currently, one in three people will be diagnosed with cancer during their lifetime in Ireland and according to the National Cancer Registry Ireland, there are just over 20,000 cancer diagnoses each year. However, the Strategy for Cancer Control in Ireland notes that cancer incidence is projected to double by 2040.


Report 23

Final recommendations to defeat superbugs

He is the Honorary Chair of Economics at Manchester University, as well as a Visiting Research Fellow at the international economic think tank, Bruegel, and a member of the economic advisory board to the IFC, the investing arm of the World Bank.

his influential Building Better Global BRICs research paper, which was credited with coining the BRIC (Brazil, Russia, India, China) acronym, and foresaw the radical shift in global economic power away from the established western economies towards these rapidly-expanding economies. Since then, Jim’s work has shone a light on the development of the next wave of emerging economies, including the ‘MINTs’ – Mexico, Indonesia, Nigeria and Thailand. This deep understanding of global patterns of growth and economic development means Jim is especially well-placed to understand the broad range of international interests and interdependencies at play within the issue of rising resistance to antimicrobial drugs.

Jim is particularly well-known for his work in relation to developing economies, having been one of the earliest (and most prominent) economic commentators to identify the enormous potential for growth by middle income countries during the first half of the 21st century.In 2001, Jim published

Lord O'Neill is currently the Commercial Secretary of the Treasury and his duties include leading the work for the Government on the Northern Powerhouse, city devolution and infrastructure. In May 2015 he was also made a Life Peer to the House of Lords.

About the Chairman Lord Jim O’Neill is an internationally published economist, and until 2013 was Chairman of Goldman Sachs Asset Management, having previously been the organisation’s Head of Economic Research. He joined Goldman Sachs in 1995, after 13 years working in the City of London for the Swiss Bank Corporation, the Marine Midland Bank, and Bank of America.

My Review not only makes it clear how big a threat AMR is to the world, with a potential 10 million people dying each year by 2050, but also now sets out a workable blueprint for bold, global action to tackle this challenge Lord Jim O’Neill has published his final Global Review on Antimicrobial Resistance (AMR), setting out final recommendations and providing a comprehensive action plan for the world to prevent drugresistant infections and defeat the rising threat of superbugs – something that could kill 10 million people a year by 2050, the equivalent of 1 person every 3 seconds, and more than cancer kills today. Building on eight interim papers, this report was established by the UK Prime Minister David Cameron in 2014 to avoid the world being “cast back into the dark ages of medicine”.

The costs of AMR The report sets out why AMR is such a huge problem and that it must be tackled. AMR is a problem that is getting worse. Antimicrobial drugs are becoming less effective and the world is not developing enough new ones to keep up. The global costs if we do not take action now could be 10 million people dying every year by 2050, and a cumulative economic cost of around 100 trillion USD. He states, “My Review not only makes it clear how big a threat AMR is to the world, with a potential 10 million people dying each year by 2050, but also now

sets out a workable blueprint for bold, global action to tackle this challenge. The actions that I’m setting out today are ambitious in their scope – but this is a problem which it is well within our grasp to solve if we take action now. I call on the governments of the G7, G20 and the UN to take real action in 2016 on the ten proposals made by my Review, to avoid the terrible human and economic costs of resistance that the world would otherwise face.” How AMR can be tackled The Review sets out ten areas where the world needs to take action to tackle AMR. Many of these measures focus on how we can reduce the unnecessary use of antimicrobials, and so the rate at which resistance increases, making current drugs last longer. Others look at how we can increase the supply of new antimicrobial drugs because, even if we reduce unnecessary use, our arsenal to defeat

superbugs is running out and needs to be replenished. The two most eye-catching proposals advanced by O’Neill are:  To force the pharmaceutical industry to “pay or play”. Drug companies must either research and develop new antibiotics or be prepared to fund other companies to do so. “We think there is a credible case for the pharmaceutical industry itself to pay, given how important antibiotics are for 7 billion people around the world,” he said.  To ban doctors from prescribing antibiotics until they have carried out rapid tests to prove the infection is bacterial. “We must stop treating antibiotics like sweets, which is what we are doing around the world today,” he said. However, there must be incentives to develop such tests which do not yet exist.

HPN • June 2016


24 Report Dr Virginia Acha, Director of Research, Medical and Innovation, ABPI

The Review fails to recognise the need for a collaborative response which this long-term review has consistently identified. Putting the onus on any one group will not solve the problem and is not a sustainable solution The pay or play idea was immediately rejected by trade body the Association of the British Pharmaceutical Industry. “The Review fails to recognise the need for a collaborative response which this longterm review has consistently identified,” said Dr Virginia Acha, director of research, medical and innovation at the ABPI. “Putting the onus on any one group will not solve the problem and is not a sustainable solution.” The Irish Pharmaceutical Healthcare Association was quick to agree with Dr Acha telling Hospital Professional News, “We welcome the final report of Lord O’Neill’s team and in particular the call for global action on what is an important issue of healthcare. The global pharmaceutical industry is already playing a key role in addressing the issue of antimicrobial resistance, including the development of new medicines and treatments – 34 antibiotics and infection preventing vaccines are currently in the global innovative pipeline. “In 2014, 13 Billion US Dollars was spent on R&D, with 3.7% focused on anti-infectives. It needs to be borne in mind

June 2016 • HPN

that the development of new antibiotics and vaccines for drug resistance is highly challenging in terms of risk and cost. “The potential imposition of a tax on the pharmaceutical industry to fund market entry rewards would be counterproductive and an unjust imposition on just one segment of the life sciences sector. A far more productive approach would be the introduction of incentives that support additional investment, rather than the imposition of penalties which would ignore the universal responsibility for finding a solution to this problem.” Other recommendations include:  An urgent and massive global awareness campaign as most people are ignorant of the risks  Establishing a $2bn ($1.4bn) Global Innovation Fund for early stage research  Improved access to clean water, sanitation and cleaner hospitals to prevent infections spreading  Improved surveillance of the spread of drug resistance

How solutions can be paid for The paper then discusses how these solutions would be paid for. The costs of action are dwarfed by the costs of inaction: the proposals made by the Review on AMR would cost up to 40 billion USD over 10 years. However, the cost of AMR between now and 2050 could be as much as 100 trillion USD. The solutions could be paid for by one or more of the following:  Allocating a very small percentage of G20 countries’ existing healthcare spending to tackling AMR  Reallocating a fraction of global funding from international institutions to AMR  Apply an antibiotic investment charge to pharmaceutical companies who do not invest in research for AMR  Implementing a tax on antibiotics  Introducing transferrable ‘vouchers’ to reward new antibiotics Next steps International collaboration for

real action via the World Health Assembly, G7, G20 and the UN is needed to deliver these policy proposals and turn discussions on AMR into action. This needs to build on promising steps made by governments, and by industry recently affirming its commitment to tackle AMR with a landmark declaration at Davos. With this momentum, and 700,000 people already dying every year from AMR, 2016 is a crucial year. Dr Jeremy Farrar, Director of the Wellcome Trust and Longitude Committee, added, “Over the past two years Jim O’Neill and his team have raised the global profile of drug-resistant infection to its rightful place as one of the most pressing economic and health security issues of our time. These recommendations offer a road map for stopping growing resistance to our best drugs from claiming millions of lives. It is now up to world leaders, business and civil society to respond to this vital call for action, and create the incentives for preserving existing drugs and developing new ones that we need to address this critical challenge.”


MSD is passionate about pursuing breakthrough science to combat infectious diseases.

There was a time when there were no medicines to fight some of the most common infections â&#x20AC;&#x201C; but the introduction of antibiotics in the 1940s changed that. MSD is proud of our legacy of progress in this fight, which includes producing penicillin to help American soldiers during World War II. Our commitment continues. Today, the rise in infections caused by resistant bacteria has become an urgent global health issue. Our researchers are hard at work developing the next generation of antibiotics â&#x20AC;&#x201C; and the best ways to use them. We believe that creating new medicines, and using them correctly, are essential in the fight against infectious diseases. And our determination does not stop there. Through engagement with global policy-makers we are working to ensure a sustainable antibiotic future, that not only welcomes innovation, but actively embraces it. Together we can ensure that these life-saving treatments are valued the world over and used appropriately to combat what is undeniably one of the greatest societal challenges of our age. Science will get us half way there,

We are willing to do our part, and continue to work with others. We are in this fight together.

Date of Preparation: December 2015

AINF-1169891-0000

but effective political and policy collaboration will take us over the line.


THE FIRST APPROVED

UNBOOSTED INTEGRASE INHIBITOR

Models

ISENTRESS® (raltegravir) ABRIDGED PRODUCT INFORMATION Refer to Summary of Product Characteristics before prescribing. PRESENTATION 400 mg film-coated tablet containing 400 mg of raltegravir (as potassium). 25 mg chewable tablets containing 25 mg of raltegravir (as potassium). 100 mg chewable tablets containing 100 mg of raltegravir (as potassium). INDICATIONS For use in combination with other anti-retroviral medicinal products for the treatment of human immunodeficiency virus (HIV-1) infection in adults, adolescents, and children weighing at least 11 kg. DOSAGE AND ADMINISTRATION Therapy to be initiated by a physician experienced in the management of HIV infection. Posology For use in combination with other active anti-retroviral therapies (ARTs). Adults: 400 mg (one tablet) twice daily. Elderly: Limited information therefore use with caution. Children and adolescents: If at least 25 kg, the recommended dosage is 400 mg (one tablet) twice daily. Children at least 11 kg: weight based to maximum dose 300 mg chewable tablets, twice daily. Because the formulations are not bioequivalent, the chewable tablets should not be substituted for the 400 mg tablet. The chewable tablets have not been studied in HIV-infected adolescents or adults. Renal impairment: No dosage adjustment required. Hepatic impairment: No dosage adjustment required for mild to moderate hepatic impairment. Safety and efficacy not established in patients with severe underlying liver disorders. Use with caution in patients with severe hepatic impairment. Paediatric population: Safety and efficacy of raltegravir in infants below 4 weeks of age have not yet been established. No data are available. Method of administration Oral use. ISENTRESS can be administered with or without food. The 400mg tablets should not be chewed, crushed or split due to anticipated changes in the pharmacokinetic profile. The 100 mg chewable tablet can be divided into equal 50 mg doses. However, breaking the tablets should be avoided whenever possible. CONTRA-INDICATIONS Hypersensitivity. PRECAUTIONS AND WARNINGS Advise patients that current ART does not cure HIV and has not been proven to prevent the transmission of HIV to others through blood contact. While effective viral suppression with antiretroviral therapy has been proven to substantially reduce the risk of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission should be taken in accordance with national guidelines. Considerable interand intra-subject variability was observed in the pharmacokinetics of raltegravir. Raltegravir has a relatively low genetic barrier to resistance. Therefore, whenever possible, raltegravir should be administered with two other active ARTs to minimise the potential for virological failure and the development of resistance. In treatment naïve patients, the clinical study data on use of raltegravir are limited to use in combination with two nucleotide reverse transcriptase inhibitors (NRTIs) (emtricitabine and tenofovir disoproxil fumarate). Depression, including suicidal ideation and behaviours, has been reported, particularly in patients with a pre-existing history of depression or psychiatric illness. Caution should be used in patients with a pre-existing history of depression or psychiatric illness. Monitor patients with pre-existing liver dysfunction including chronic hepatitis as they have an increased frequency of liver function abnormalities during combination anti-retroviral therapy. Consider interruption or discontinuation if evidence of worsening liver disease exists. Patients with chronic hepatitis B or C and treated with combination anti-retroviral therapy are at an increased risk for severe and potentially fatal hepatic adverse reactions. Osteonecrosis: Although etiology is multifactorial, cases of osteonecrosis have been reported. Advise patients to seek medical advice if they experience joint effects or difficulty in movement. Immune reactivation syndrome: In HIV-infected patients with severe immune deficiency at the time of institution of combination anti-retroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic pathogens may arise. Evaluate any inflammatory symptoms and institute treatment when necessary. Autoimmune disorders (such as Graves’ disease) have also been reported to occur in the setting of immune reactivation: however, the reported time to onset is more variable and these events can occur many months after initiation of treatment. Antacids Co-administration of ISENTRESS with aluminium and magnesium antacids resulted in reduced raltegravir plasma levels. Co-administration of ISENTRESS with aluminium and/or magnesium antacids is not recommended. Myopathy and rhabdomyolysis Myopathy and rhabdomyolysis have been reported. Use with caution in patients who have had myopathy or rhabdomyolysis in the past or have any predisposing issues including other drugs associated with these conditions. Severe skin and hypersensitivity reactions Severe, potentially life-threatening, and fatal skin reactions have been reported in patients taking ISENTRESS, in most cases concomitantly with other drugs associated with these reactions. These include cases of StevensJohnson syndrome and toxic epidermal necrolysis. Hypersensitivity reactions have also been reported and were characterized by rash, constitutional findings, and sometimes, organ dysfunction, including hepatic failure. Discontinue ISENTRESS and other suspect agents immediately if signs or symptoms of severe skin reactions or hypersensitivity reactions develop (including, but not limited to, severe rash or rash accompanied by fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, facial edema, hepatitis, eosinophilia, angioedema). Clinical status including liver aminotransferases should be monitored and appropriate therapy initiated. Delay in stopping ISENTRESS treatment or other suspect agents after the onset of severe rash may result in a lifethreatening reaction. Rash occurred more commonly in treatment-experienced patients receiving regimens containing ISENTRESS + darunavir compared to patients receiving ISENTRESS without darunavir or darunavir without ISENTRESS. Lactose ISENTRESS filmcoated tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. INTERACTIONS In vitro studies indicate that Raltegravir is not a substrate of cytochrome P450 (CYP) enzymes, does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A, does not induce CYP3A4 and does not inhibit P-glycoprotein-mediated transport. It is not expected to affect the pharmacokinetics of drugs that are substrates of these enzymes or P-glycoprotein. Raltegravir is eliminated mainly by metabolism via a UGT1A1-mediated glucuronidation pathway. Although in vitro studies indicated that raltegravir is not an inhibitor of the UDP glucuronosyltransferases (UGTs) 1A1 and 2B7, one clinical study has suggested that some inhibition of UGT1A1 may occur in vivo based on effects observed on bilirubin glucuronidation. However, the magnitude of the effect seems unlikely to result in clinically important drug-drug interactions. The following information is based on Geometric Mean values; the effect for an individual patient cannot be predicted precisely. Effect of raltegravir on the pharmacokinetics of other medicinal products: Raltegravir did not have a clinically meaningful effect on the pharmacokinetics of etravirine, maraviroc, tenofovir, hormonal contraceptives, methadone, midazolam, or boceprevir. In some studies, co-administration of ISENTRESS with darunavir resulted in a modest decrease in darunavir plasma concentrations; the mechanism for this effect is unknown. However, the effect of raltegravir on darunavir plasma concentrations does not appear to be clinically meaningful. Effect of other agents on the pharmacokinetics of raltegravir: Raltegravir is metabolised primarily via UGT1A1, therefore use caution when co-administering with strong inducers of UGT1A1 (e.g., rifampicin). Rifampicin reduces plasma levels of raltegravir; the impact on the efficacy of raltegravir is unknown. If co-administration with rifampicin is unavoidable, consider doubling the dose of ISENTRESS in adults. There are no data to guide co-administration of ISENTRESS with rifampicin in patients below 18 years of age. The impact of other strong inducers of drug metabolising enzymes, such as phenytoin and phenobarbital, on UGT1A1 is unknown. Less potent inducers (e.g., efavirenz, nevirapine, etravirine, rifabutin, glucocorticoids, St. John’s wort, pioglitazone) may be used. Coadministration with drugs known to be potent UGT1A1 inhibitors (e.g., atazanavir) may increase plasma levels of raltegravir. Less potent UGT1A1 inhibitors (e.g. indinavir, saquinavir) may also increase plasma levels of raltegravir, but to a lesser extent compared with atazanavir. Tenofovir may increase plasma levels of raltegravir too, but mechanism is unknown. The safety profile in patients who

used atazanavir and / or tenofovir in trials was similar to that of patients who did not use these agents. Therefore no dose adjustment is required. Co-administration of ISENTRESS with antacids containing divalent metal cations may reduce raltegravir absorption by chelation, resulting in a decrease of raltegravir plasma levels. Taking an aluminium and magnesium antacid within 6 hours of ISENTRESS administration significantly decreased raltegravir plasma levels. Therefore, co-administration of ISENTRESS with aluminium and/or magnesium containing antacids is not recommended. Co-administration of ISENTRESS with a calcium carbonate antacid decreased raltegravir plasma levels; however, this interaction is not considered clinically meaningful. Therefore, when ISENTRESS is co-administered with calcium carbonate containing antacids no dose adjustment is required. Co-administration of ISENTRESS with other agents that increase gastric pH (e.g., omeprazole and famotidine) may increase the rate of raltegravir absorption and result in increased plasma levels of raltegravir. Safety profiles in the subgroup of patients in Phase III trials taking proton pump inhibitors or H2 antagonists were comparable with those who were not taking these antacids. Therefore no dose adjustment is required with use of proton pump inhibitors or H2 antagonists. PREGNANCY AND LACTATION Do not use during pregnancy. An Anti-retroviral Pregnancy Registry has been established which physicians are encouraged to use. Breastfeeding is not recommended. SIDE EFFECTS Refer to Summary of Product Characteristics for complete information on side-effects. The safety profile was based on the pooled safety data from two Phase III clinical studies in treatment-experienced patients and one Phase III clinical study in treatment-naïve adult patients. The most frequently reported adverse reactions during treatment were headache and nausea, occurring at 5% or greater. The most frequently reported serious adverse reaction was immune reconstitution syndrome. In treatment-experienced patients, the two randomised clinical studies used the recommended dose of 400-mg twice daily in combination with OBT in 462 patients. In treatment-naïve patients, the multi-centre, randomised, double-blind, active-controlled clinical study used the recommended dose of 400 mg twice daily in combination with a fixed dose of emtricitabine 200 mg (+) tenofovir 245 mg in 281 patients, in comparison to 282 patients taking efavirenz (EFV) 600 mg (at bedtime) in combination with emtricitabine (+) tenofovir. In this pooled analysis of treatment-experienced patients, the rates of discontinuation of therapy due to adverse reactions were 3.9 % in patients receiving ISENTRESS + OBT and 4.6 % in patients receiving placebo + OBT. The rates of discontinuation of therapy in naïve patients due to adverse reactions were 5 % in patients receiving ISENTRESS + emtricitabine (+) tenofovir and 10% in patients receiving efavirenz + emtricitabine (+) tenofovir. Paediatric population Children and adolescents 2 to 18 years of age. Raltegravir has been studied in 126 antiretroviral treatment-experienced HIV-1 infected children and adolescents 2 to 18 years of age, in combination with other antiretroviral agents in IMPAACT P1066 (see sections 5.1 and 5.2). Of the 126 patients, 96 received the recommended dose of ISENTRESS. In these 96 children and adolescents, frequency, type and severity of drug related adverse reactions through Week 48 were comparable to those observed in adults. One patient experienced drug related clinical adverse reactions of Grade 3 psychomotor hyperactivity, abnormal behaviour and insomnia; one patient experienced a Grade 2 serious drug related allergic rash. One patient experienced drug related laboratory abnormalities, Grade 4 AST and Grade 3 ALT, which were considered serious. Clinical adverse reactions related to ISENTRESS (alone or in combination with other ART) are listed below. Any term that includes at least one serious adverse reaction is identified with a dagger (†). Adverse reactions identified from postmarketing experience are included in italics. Frequencies are defined as common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100) and not known (cannot be estimated from the available data). Common Decreased appetite, abnormal dreams, insomnia, nightmare, abnormal behaviour, depression, dizziness, headache, psychomotor hyperactivity, vertigo, abdominal distention, abdominal pain, diarrhoea, flatulence, nausea, vomiting, dyspepsia, rash, asthenia, fatigue, pyrexia, alanine aminotransferase increased, atypical lymphocytes, aspartate aminotransferase increased, blood triglycerides increased, lipase increased, blood pancreatic amylase increased. Uncommon genital herpes†, folliculitis, gastroenteritis, herpes simplex, herpes virus infection, herpes zoster, influenza, lymph node abscess, molluscum contagiosum, nasopharyngitis, upper respiratory tract infection, skin papilloma, anaemia†, iron deficiency anaemia, lymph node pain, lymphadenopathy, neutropenia, thrombocytopenia, immune reconstitution syndrome†,drug hypersensitivity, hypersensitivity, cachexia, diabetes mellitus, dyslipidaemia, hypercholesterolaemia, hyperglycaemia, hyperlipidaemia, hyperphagia, polydipsia, body fat disorder, mental disorder†, anxiety, suicide attempt†, confusional state, panic attack, suicidal ideation , suicidal behaviour (particularly in patients with a pre-existing history of psychiatric illness) ,amnesia, carpal tunnel syndrome, cognitive disorder, disturbance in attention,dysgeusia, hypersomnia, hypoaesthesia, memory impairment, migraine, neuropathy peripheral, paraesthesia, somnolence, tremor, poor quality sleep, visual impairment, tinnitus, sinus bradycardia, hot flush, hypertension, ventricular extrasystoles, dysphonia, epistaxis, nasal congestion, gastritis†, anorectal discomfort, constipation, epigastric discomfort, erosive duodenitis, eructation, gastrooesophageal reflux disease, gingivitis glossitis, pancreatitis acute, peptic ulcer, rectal haemorrahage, hepatic steatosis, hepatitis†, hepatitis alcoholic, hepatic failure, acne, alopecia, hyperhidrosis, lipoatrophy, dermatitis acneiforme, erythema, facial wasting, lipodystrophy acquired, lipohypertrophy, prurigo, pruritis, rash macular, rash maculopapular, rash pruritic, xeroderma, skin lesion, Stevens Johnson syndrome, drug rash with eosinophilia and systemic symptoms (DRESS), urticaria, arthralgia, arthritis, neck pain, flank pain, osteopenia, tendonitis, rhabdomyolysis, renal failure†, nephritis, nephrolithiasis, nocturia, renal cyst, renal impairment, tubulointerstitial nephritis, erectile dysfunction, gynaecomastia, menopausal symptoms, chest discomfort, face oedema, submandibular mass, oedema peripheral, fat tissue increased. Cancers were reported in treatment-experienced and treatment-naïve patients who initiated ISENTRESS in conjunction with other antiretroviral agents. The risk of developing cancer in these studies was similar in the groups receiving ISENTRESS and in the groups receiving comparators. Grade 2-4 creatine kinase laboratory abnormalities were observed in subjects treated with ISENTRESS. Patients co-infected with hepatitis B and/or hepatitis C virus: The safety profile of ISENTRESS in patients with hepatitis B and/or hepatitis C virus co-infection was similar to that in patients without hepatitis B and/or hepatitis C virus co-infection, although the rates of AST and ALT abnormalities were somewhat higher in the subgroup with hepatitis B and/or hepatitis C virus co-infection for both treatment groups. PACKAGE QUANTITIES 60 tablets. Legal Category: POM. Marketing Authorisation number: EU/1/07/436/001. EU/1/07/436/003. EU/1/07/436/004. Marketing Authorisation holder: Merck Sharp & Dohme Limited, Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, UK. Date of revision: December 2014. © Merck Sharp & Dohme Ireland (Human Health) Limited, 2014. 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: November 2015.

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)

Red Oak North, South County Business Park, Leopardstown, Dublin 18, D18 X5K7 Ireland

INFC-1168533-0000

ENVISION A PATH FORWARD


CPD 22: HIV Infection & Diagnosis Continuing Professional Development

CPD

27

Grimes RM1, Hardwicke RL, Grimes DE, DeGarmo DS. Patients presenting with fever, pharyngitis, and lymphadenopathy are likely to have mononucleosis; however, patients with acute HIV infection may present with similar symptoms. Acute HIV infection should be considered as a differential diagnosis if test results for mononucleosis are negative. This article describes when to order HIV testing and discusses the importance of early intervention for acute HIV infection.

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 Any clinician is faced with a diagnostic challenge when a patient presents with fever, pharyngitis, and lymphadenopathy. Mononucleosis, the most likely of these conditions, can be diagnosed with a positive monospot: the heterophile antibody test; however, there are a number of diagnostic considerations when this test is negative. First, the heterophile test will yield a false negative in 25% of patients who are in the early stages of infectious mononucleosis, and 10% of those with the condition will always have a false negative. Traditionally, viral illnesses were managed by supportive care only; however, recent advances in treatment of acute HIV infection and its sequelae have greatly increased the importance of diagnosing this condition for early treatment. Acute HIV infection occurs almost immediately after a patient is infected with HIV and leads to two major events. Treatment with antiretroviral medications immediately after infection can greatly reduce this high level of circulating virus and can make the patient less infectious. This is extremely important because acute HIV infection is usually the result of recent unsafe sexual practices that are likely to continue after infection. There are important benefits to both the patient and the public’s health if the clinician recognises HIV infection as early as possible. The best guarantee for detecting acute HIV infection is the sensitivity to its possible presence. Given the severity of the symptoms of acute HIV infection, many of these individuals with acute HIV infection are likely to seek clinical care in secure settings– such as primary care practices, EDs, and public health clinics.

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.

When to consider acute HIV infection in the differential diagnosis Any clinician is faced with a diagnostic challenge when a patient presents with fever, pharyngitis, and lymphadenopathy. In a very well-researched review article, Hurt and Tammaro list eight possible conditions that may be found in a patient with these symptoms.1 Influenza is another potential diagnosis when these symptoms are present. Mononucleosis, the most likely of these conditions, can be diagnosed with a positive monospot: the heterophile antibody test; however, there are a number of diagnostic considerations when this test is negative. First, the heterophile test will yield a false negative in 25% of patients who are in the early stages of infectious mononucleosis, and 10% of those with the condition will always have a false negative.1 In addition to recognising that the negative test may be false, the clinician would consider the potential of other pathogens causing the symptoms. Suspecting a specific pathogen allows the clinician to determine whether the condition can be treated with specific therapy as opposed to supportive care. For example, strep throat is a relatively common condition that mimics mononucleosis and can be diagnosed with rapid antigen detection testing (RADT). A positive result can be considered diagnostic of streptococcal pharyngitis. Treatment with appropriate antibiotics is curative and can prevent further sequelae, such as rheumatic fever.3

There are a significant number of false-negative results with the RADT as well. Toxoplasmosis is difficult to diagnose but relatively easy to treat with anti-parasitic medications.4 ACUTE HIV INFECTION AND THE IMPORTANCE OF ITS RECOGNITION Traditionally, viral illnesses were managed by supportive care only; however, recent advances in treatment of acute HIV infection and its sequelae have greatly increased the importance of diagnosing this condition for early treatment. Acute HIV infection occurs almost immediately after a patient is infected with HIV and leads to two major events. The first is that the virus attacks and ravages the gastrointestinal (GI) tract associated lymphoid tissue, causing severe depletion of CD4+ cells in the GI tract within weeks of initial infection. Without these cells, there is a constant passage of intestinal microbes into the circulatory system, a process known as bacterial translocation. This, in turn, creates a constant inflammatory response as the immune system seeks to suppress the constant introduction of bacteria.5 Once the GI tract’s response is depleted, its capability can only be partially restored even after extensive treatment with anti-HIV medications. This occurs even if the patient has an undetectable HIV viral load in his or her plasma. Treatment is most effective in preserving the GI tract’s immune system when initiated as soon as possible after infection.6-8

Continuous Professional Development Modules are sponsored by MSD MSD has no editorial oversight of the CPD programmes included in these modules.


28

CPD 22: HIV Infection & Diagnosis

The second important event immediately following HIV infection is the extraordinary production of virus that can easily exceed 1,000,000 viral copies/mL in plasma.9,10 Very high levels of HIV also occur in the genital tract.11,12 Therefore, the patient in the early phases of HIV infection is highly infectious and much more likely to sexually transmit the virus to others. Studies suggest that individuals who are experiencing these high rates of viremia are 8 to 26 times more likely to transmit the virus to a sexual partner than at later stages in the infection.13,14 The risk of transmission from an infected male to a female sexual partner during this early period have been estimated at between 7% and 24% depending on the frequency of intercourse.9 The highest rates of transmission seem to occur at the earliest point in infection(up to 2 months after infection) and diminish over time as the body begins to produce HIV-specific antibodies that begin to suppress the virus.14 Treatment with antiretroviral medications immediately after infection can greatly reduce this high level of circulating virus and can make the patient less infectious. This is extremely important because acute HIV infection is usually the result of recent unsafe sexual practices that are likely to continue after infection. Additionally, there is increasing evidence that early treatment with anti-retroviral medications can also have the important long-term benefit by preventing the patient from losing circulating CD4+ cells that are essential to maintaining the integrity of the immune response.15 RECOGNISING ACUTE HIV INFECTION There are important benefits to both the patient and the public’s health if the clinician recognises HIV infection as early as possible. Most HIV-infected persons experience an acute viral syndrome, with symptoms similar to infectious mononucleosis, shortly after becoming infected. The frequency of symptoms has been estimated between 50% and 90%.16 The exact frequency is hard to estimate because identifying HIV infection may occur years after the syndrome has occurred, and the patient may not recall the acute viral event. The acute infection tends to occur within 2 to 3 weeks after transmission and will last 2 to 4 weeks. Acute HIV infection symptoms are often severe enough for the infected patient to seek

Table 1: Potential diagnoses and symptoms associated with mononucleosis-like presentations Condition Signs/symptoms (estimated frequency of occurrence) Adenovirus (1%)

Pharyngitis, conjunctivitis, high fever, enlarged anterior cervical lymph nodes, headache, general malaise, and weakness. Incubation period 5–9 days and typically occurs in 5- to 18-year olds.

Acute HIV infection (<2%)

Fever, fatigue, myalgia, or arthralgia, lymphadenopathy, weight loss/anorexia, pharyngitis, GI symptoms, rash, headache, mucocutaneous ulcers, meningitis-like symptoms.

Toxoplasma gondii (Toxoplasmosis) (3%)

Flu-like symptoms, lymphadenopathy, myalgia that may last for a month or more. History of eating undercooked meat or exposure to contaminated cat feces.

Group A, Beta hemolytic Streptococcus pyogenes (pharyngitis; rheumatic fever) (3%–4%)

Abrupt onset of sore throat, erythema, and possible exudative tonsils and/or pharynx; tender, swollen lymph nodes; infections of the skin, such as impetigo, cellulitis, erysipelas. Peak incidence is winter/spring.

Herpes simplex virus, Type 1 (Herpes labialis) (6%)

Cold sores/ fever blisters; painful ulcerative vesicular lesions of the lips, mouth, and or pharynx.

Cytomegalovirus Fatigue, low-grade fever (lasting days to weeks), (mononucleosis-like illness) (5%–7%) chills/ sweats, myalgia, anorexia, lymphadenitis, pharyngitis, headache. Exanthema subitum (roseola infantum): human herpesvirus 6 (HHV-6) (9%)

Sudden onset of high fever (104° F [40.0° C] or greater) lasting 3–5 days; followed by a maculopapular rash on the trunk, although rash not always present. Malaise, irritability, and tympanic membrane inflammation. Highest among infants 6-12 months of age.

Epstein-Barr virus (infectious mononucleosis) (50%-90%)

Extreme fatigue, low-grade fever and in some cases moderate to-high fever, palatal petechiae, pharyngitis, posterior cervical or auricular adenopathy, hepatosplenomegaly, atypical lymphocytosis.

Influenza (very common depending on the season of the year)

Fever, chills, cough, pharyngitis, rhinorrhea or nasal congestion, myalgia, and headaches. The fever and myalgia can last 3–5 days and the cough and fatigue may last for 2 or more weeks.

treatment either in a primary care or ED setting. The clinician who encounters these patients can, by early identification of the acute infection, intervene before these patients lose their GI-associated lymphoid tissue. They can also have a major impact

on preventing HIV transmission by arranging for early treatment and by counselling patients to avoid unprotected sex. Such tasks are possible when the clinician is aware of the potential for patients presenting with acute HIV infection and by ordering the appropriate diagnostic tests.

Acute HIV infection, like most acute viral infections, does not present a clear clinical picture to differentiate it from other conditions, nor does the literature on acute HIV infection provide the clinician with a clear picture. The studies of acute HIV infection symptoms have relatively small

Continuous Professional Development Modules are sponsored by MSD MSD has no editorial oversight of the CPD programmes included in these modules.


29 Table 2: Frequency and symptoms in acute HIV infection14,17-20

mononucleosis. The rash originates on the trunk but can spread to the limbs, including the palms and soles.

Symptom

Reported frequency

Fever

High

IMPORTANCE OF A PATIENT HISTORY AND DIAGNOSTIC TESTING

Fatigue

High

Myalgia or arthralgia

Medium

Lymphadenopathy

Medium

Weight loss/anorexia

Medium

Pharyngitis

Medium

GI symptoms

Medium

Rash

Medium

Headache

Medium

Mucocutaneous ulcers

Low

Meningitis-like symptoms

Low

samples (usually less than 100 patients). In addition, some of the studies have used patient reports, while others have reported clinician findings. Consequently, while clinicians may report lymphadenopathy, the patient may report soreness; the patient report of a severe headache may be diagnosed as aseptic meningitis, migraine, or other cranial malady14,17-20 (see Frequency and symptoms in acute HIV infection). Acute HIV infection presents like many viral infections: with diffuse symptoms that are more useful in alerting the clinician than in making a diagnosis. Acute HIV infection is usually described as “an acute flu-like illness.” The easiest way to differentiate acute HIV infection from influenza or viral upper respiratory tract infection is that acute HIV infection is not reported to have the respiratory symptoms (runny or stuffy nose) that are characteristic of these conditions. The absence of fever and fatigue increases the likelihood that the patient does not have acute HIV infection. However, if a patient has additional signs and symptoms even though he or she does not have a fever or report fatigue, there is still some likelihood that the patient has acute HIV infection, and it may need to be ruled out.

DIFFERENTIATING ACUTE HIV INFECTION FROM MONONUCLEOSIS Mononucleosis tests are diagnostic when positive but are associated with a significant level of false negatives; therefore, it is imperative to distinguish mononucleosis from acute HIV infection in the patient with a negative test. Patients with mononucleosis are likely to present with the classictriad of fever, pharyngitis, and lymphadenopathy, all of which are frequently found in those with acute HIV infection. However, there are characteristic differences between acute HIV infection and mononucleosis that are helpful in differentiation. Fever in mononucleosis is likely to be less than 100.0° F (37.7° C) and in some cases a moderate to high fever; however, fever in acute HIV infection tends to be much higher, ranging up to 104° F (40.0° C).1,14,15 Infectious mononucleosis is also frequently associated with petechiae of the palate, although this condition is seen less frequently in acute HIV infection. Acute HIV infection is occasionally accompanied with mucocutaneous ulcers in the mouth and the genitals, which do not occur in infectious mononucleosis. A non-pruritic, maculopapular rash can occur in acute HIV infection and not in infectious

Taking a history of recent sexual encounters and/or injection drug use is another method of determining if testing for acute HIV infection is warranted. Acute HIV infection testing should be done if the patient admits to these behaviours. Unfortunately, sexual and drug histories often yield false negatives, as patients are sometimes not truthful because of the stigma associated with these behaviours. THE NEW HIV TEST

or safer sex methods. Previous versions of HIV tests, including the oral swabs or other rapid tests, will not be useful in ruling out HIV infection. If these are all that is available, an HIV viral load test should be obtained. DEALING WITH THE POSITIVE TEST In the event that a patient is found to be HIV infected, they will need to be counselled regarding the importance of abstaining from sex due to the high infectiousness during this phase of the infection. If abstinence is not feasible, the patient should be counselled to use condoms for any sexual encounter. This counselling session is crucial to halting the spread of HIV.

In the past, HIV testing relied on HIV antibodies appearing in the blood as detected by an enzyme-linked immunosorbent assay (ELISA) test. Because of the possibility of false-positive results, the test results were confirmed by a second test, the Western blot assay, which might also give an indeterminate result. Antibody levels sufficiently high enough to be detected by an ELISA often did not appear until after the acute HIV infection had resolved. Therefore, the commonly used test for detecting HIV infection was not likely to be helpful in detecting acute HIV infection at the time of its occurrence.

The patient also needs to be referred for immediate treatment to preserve the GI-associated lymphoid tissue. In addition, HIV treatment is a lifelong process, and it is necessary to develop a long-term relationship.

However, there is a new, fourthgeneration test for HIV infection that detects HIV infection within 15 to 25 days of infection. This is usually around the time that a patient with acute HIV infection will be seeking care.21,22 Therefore, it is possible to diagnose HIV infection simultaneously with acute HIV infection.

A number of studies in Europe and in the United States suggest that acute HIV infection appears in 1% to 2% of patients appearing with mononucleosis-like symptoms in primary care.24-26 Acute HIV infection may not be diagnosed, as was reported in a North Carolina study of 32 adults diagnosed with acute HIV infection during voluntary HIV testing, and 24 of the adult participants reported that they had symptoms associated with acute HIV infection. Of these, 20 sought medical care for the symptoms, but only 3 were tested for HIV.27

When evaluating a patient for acute HIV infection, one can use the CDC’s new HIV diagnostic algorithm for HIV-1/HIV-2 antigen and antibody combination immunoassay.21 Because the test detects P24 antigen (a major core protein of HIV) that appears before antibodies appear, it is able to detect HIV infection several days earlier than with previous tests. This fourth-generation test also gives a definitive result of either infected or not infected. To definitively rule out infection, patients should be asked to return in a week or two to have a viral load test that will determine whether the virus is present. This should be accompanied with counselling regarding no sex

IMPLICATIONS FOR PRACTICE The best guarantee for detecting acute HIV infection is the sensitivity to its possible presence. Given the severity of the symptoms of acute HIV infection, many of these individuals with acute HIV infection are likely to seek clinical care in secure settings–such as primary care practices, EDs, and public health clinics.

Acute HIV infection is not a highprobability diagnosis, but it is a very important one. Patients who are detected early have much better outcomes and fewer HIVrelated diseases. Once treated, individuals have a decreased likelihood of transmission of the virus. Studies have shown that as much as 50% of all HIV transmissions occur during early HIV infection.6,28 Early detection and treatment can be crucial to control the HIV epidemic.

Continuous Professional Development Modules are sponsored by MSD MSD has no editorial oversight of the CPD programmes included in these modules.


30

CPD 22: HIV Infection & Diagnosis

REFERENCES 1. Hurt C, Tammaro D. Diagnostic evaluation of mononucleosis-like illnesses. Am J Med. 2007;120(10):911. e1-911.e8. 2. Centres for Disease Control and Prevention. Influenza symptoms and the role of laboratory diagnostics. www. cdc.gov/fl u/professionals/diagnosis/ labrolesprocedures.htm. Last updated: October 16, 2014. 3. Shulman ST, Bisno AL, Clegg HW, et al. Clinical Practice Guideline for the Diagnosis and Management of Group A Streptococcal Pharyngitis: 2012 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2012;55(10):e86–102. 4. Centres for Disease Control and Prevention. Parasites—Toxoplasmosis (Toxoplasma infection) www.cdc.gov/ parasites/toxoplasmosis/treatment. html. Last reviewed: January 10, 2013. 5. Marchetti G, Tincati C, Silvestri G. Microbial translocation in the pathogenesis of HIV infection and AIDS. Clin Microbiol Rev. 2013;26(1):2-18. 6. Chun TW, Nickle DC, Justement JS, et al. Persistence of HIV in gutassociated lymphoid tissue despite long-term antiretroviral therapy. J Infect Dis. 2008;197(5):714-720. 7. Ananworanich J, Schuetz A, Vandergeeten C, et al. Impact of multitargeted antiretroviral treatment on gut T cell depletion and HIV reservoir seeding during acute HIV infection. PLoS One. 2012;7(3):e33948. 8. Schuetz A, Phuang-Ngern Y, Rerknimitr R, et al. Early ART Initiation Prevents Disruption of the Mucosal Barrier and Subsequent T-Cell Activation. 21st Conference

on Retroviruses and Opportunistic Infections (CROI 2014). Boston, March 3-6. Abstract 77. 9. Pilcher CD, Tien HC, Eron JJ, et al. for the Quest Study and the DukeUNCEmory Acute HIV Consortium. Brief but effi cient: acute HIV infection and the sexual transmission of HIV. J Infect Dis. 2004;189(10):1785-1792. 10. Pilcher CD, Price MA, Hoffman IF, et al. Frequent detection of acute primary HIV infection in men in Malawi. AIDS. 2004;18(3):517-524. 11. Morrison CS, Demers K, Kwok C, et al. Plasma and cervical viral loads among Ugandan and Zimbabwean women during acute and early HIV-1 infection. AIDS. 2010;24(4):573-582. 12. Pilcher CD, Joaki G, Hoffman IF, et al. Amplifi ed transmission of HIV-1: comparison of HIV-1 concentrations in semen and blood during acute and chronic infection. AIDS. 2007;21(13):1723-1730. 13. Wawer MJ, Gray RH, Sewankambo NK, et al. Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda. J Infect Dis. 2005;191(9):1403-1409. 14. Hollingsworth TD, Anderson RM, Fraser C. HIV-1 transmission, by stage of infection. J Infect Dis. 2008;198(5):687-693. 15. Le T, Wright EJ, Smith DM, et al. Enhanced CD4+ T-cell recovery with earlier HIV-1 antiretroviral therapy. N Engl J Med. 2013;368(3):218-230. 16. Richey LE, Halperin J. Acute human immunodefi ciency virus infection. Am J Med Sci. 2013;345(2):136-142. 17. Yerly S, Hirschel B. Diagnosing acute HIV infection. Expert Rev Anti Infect Ther. 2012;10(1):31-41.

18. Vanhems P, Dassa C, Lambert J, et al. Comprehensive classifi cation of symptoms and signs reported among 218 patients with acute HIV-1 infection. J Acquir Immune Defi c Syndr. 1999;21(2):99-106. 19. Chu C, Selwyn PA. Diagnosis and initial management of acute HIV infection. Am Fam Physician. 2010;81(10):1239-1244. 20. Hightow-Weidman LB, Golin CE, Green K, Shaw EN, MacDonald PD, Leone PA. Identifying people with acute HIV infection: demographic features, risk factors, and use of health care among individuals with AHI in North Carolina. AIDS Behav. 2009;13(6):10751083. 21. Branson BM, Owen SM, Wesolowski LG, et al. Laboratory testing for the diagnosis of HIV infection: updated recommendations. 2014. http://stacks. cdc.gov/view/cdc/23447. 22. Eller LE, Manak M, Shutt A, et al. Evaluation of the Proposed US CDC Algorithm for Detection of Acute HIV Infection in Serial Samples. Conference on Retroviruses and Opportunistic Infections. Mar 3-6, 2014. San Francisco Abstract 619. 23. Centers for Disease Control and Prevention. HIV in the United States: at a glance. www.cdc.gov/hiv/statistics/ basics/ataglance.html. Last updated: December 3, 2013. 24. Hsu DT, Ruf M, O’Shea S, Costelloe S, Peck J, Tong CY. Diagnosing HIV infection in patients presenting with glandular fever-like illness in primary care: are we missing primary HIV infection? HIV Med. 2013;14(1):60-63.

tested for mononucleosis. N Engl J Med. 1999;360(12):969. 26. Pincus JM, Crosby SS, Losina E, King ER, LaBelle C, Freedberg KA. Acute human immunodefi ciency virus infection in patients presenting to an urban urgent care center. Clin Infect Dis. 2003;37(12):1699-1704. 27. Hightow-Weidman LB, Golin CE, Green K, Shaw EN, MacDonald PD, Leone PA. Identifying people with acute HIV infection: demographic features, risk factors, and use of health care among individuals with AHI in North Carolina. AIDS Behav. 2009;13(6):10751083. 28. Brenner BG, Roger M, Routy JP, et al. High rates of forward transmission events after acute/early HIV-1 infection. J Infect Dis. 2007;195(7):951-959. Richard M. Grimes is an adjunct professor, The University of Texas Health Science Center at Houston Medical School, Department of Internal Medicine and Baylor UT Houston Center for AIDS Research. Robin L. Hardwicke is an associate professor, The University of Texas Health Science Center at Houston Medical School, Department of Internal Medicine. Deanna E. Grimes is a professor, The University of Texas Health Science Center at Houston, School of Nursing, Department of Nursing Systems and Baylor UT Houston Center for AIDS Research. D. Sean DeGarmo is an instructor, The University of Texas Health Science Center at Houston, School of Nursing, Department of Family Health. The authors have disclosed that they have no financial relationships related to this article.

25. Rosenberg ES, Caliendo AM, Walker BD. Acute HIV infection among patients

Continuous Professional Development Modules are sponsored by MSD MSD has no editorial oversight of the CPD programmes included in these modules.


Forr the treatment of HIV, choosee a One core agent. Many different patients. 1

2

dolutegravir/abacavir/ lamivudine Simplicity of dolutegravir in a single-pill regimen

Flexibility to build a tailored treatment regimen

www.dolutegravir.com TRIUMEQ is indicated for the treatment of HIV-infected adults and adolescents above 12 years of age weighing at least 40 kg. Triumeq is contraindicated: in patients with hypersensitivity to dolutegravir, abacavir or lamivudine or to any of the excipients, and with co-administration with dofetilide1. Before initiating treatment with abacavir-containing products, screening for carriage of the HLA-B*5701 allele should be performed in any HIV-infected patient, irrespective of racial origin. Abacavir should not be used in patients known to carry the HLA-B*5701 allele1. TIVICAY is indicated in combination with other antiretroviral medicinal products for the treatment of HIV-infected adults and adolescents above 12 years of age. Tivicay is contraindicated: in patients with hypersensitivity to dolutegravir, abacavir or lamivudine or to any of the excipients, and with co-administration with dofetilide2. 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 abacavircontaining 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. Caution with ribavirin. 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. POM Triumeq is a registered trademark of the ViiV Healthcare Group of Companies Date of approval: February 2016 Zinc code: UK/TRIM/0037/14(4)

Tivicay® dolutegravir 50 mg tablets See Summary of Product Characteristics before prescribing Indication: HIV in > 12 years and ≥ 40 kg as part of combination therapy. Dosing: 50 mg once daily with or without food if no proven/suspected integrase resistance. 50 mg 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: 50 mg 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. POM Date of approval: August 2015 Zinc code: UK/DLG/0055/13(7)

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, medsafety@hpra.ie. Adverse events should also be reported to GlaxoSmithKline on 1800 244 255. References: 1. Triumeq SmPC 2. Tivicay SmPC

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.

TRIUMEQ and TIVICAY are registered trademarks of the ViiV Healthcare group of companies. ©2015 ViiV Healthcare group of companies All rights reserved.

February 2016 IE/572/0003/16


Awards 32 Awards

Hospital Professional

Hospital Professional Awards 2016

2016

Shire Excellence in Child Psychiatry Award 2016

The Hospital Professional Awards are now in their fourth consecutive year and their success has driven further growth as we open our entry process to encompass the greater hospital team, to now include Consultants, Specialists and clinical teams in addition to our leading base of hospital Pharmacists.

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. These Awards decorate best practice within secondary care, with Award Categories ranging from Consultant-led project and team initiatives to specialised therapeutic area innovations and leading Pharmacy and Pharmacist-driven excellence. 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. These Awards have raised the profile of the industry within Ireland. Our sponsors are amongst the elite of the industry, all of whom see the awards as the perfect vehicle to show their support in this arena. The winners across all our Award Categories will have their submissions and projects published within Hospital Professional News monthly publication to further highlight their excellence and provide an in-depth clinical overview as to their content, promoting further learning. With over 400 hospital industry professionals in attendance at the 2015 event we are anticipating next year’s to be an over-capacity event and so would advise booking your place now. Each of the 2016 Hospital Professional Award categories are featured over the following pages. Entry forms can be access by visiting www.pharmacynewsireland.com or by contacting Kelly Jo Eastwood directly via email at Kelly@ipnirishpharmacynews.ie or via telephone on 0044 7876548989.

June 2016 • HPN

This Award is open to Psychiatric Specialists and their teams. This is a new Award for 2016. The Shire Excellence in Child Psychiatry Award seeks to recognise the pivotal role that psychiatric professionals and teams play in improving or innovating psychiatric services and care for children and adolescents. 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 child psychiatry throughout Ireland. JUDGES WILL BE LOOKING FOR:  Excellence and leadership within child psychiatry and its development  Evidence of working effectively across organisational and departmental boundaries to deliver excellence in child psychiatry  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 child psychiatry  A multidisciplinary approach to clinically using medicines HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com


Awards 33

Roche Oncology Pharmacist of the Year 2016

Idis Hospital Pharmacist of the Year Award 2016

Part of the Clinigen Group

This Award is open to all Oncology Pharmacists working within an Irish hospital setting.

This Award is open to any Hospital Pharmacists working within an Irish hospital setting.

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 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 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.

The winner will demonstrate significant contributions to the pharmacy industry overall resulting in meaningful improvements in the quality of patient care and improved delivery models and pharmacy’s role on the health care team.

JUDGES WILL BE LOOKING FOR:  Evidence of a clinical role or a project that combines with developing a clinical service  A new approach to managing a clinical team, delivering a service or producing outstanding clinical work within oncology  Development of a new service or technique that refines/ changes clinical oncology practice  Research involving a clinical oncology service/setting or a new method of teaching oncology skills  Examples of a multi-disciplinary approach to oncology services

JUDGES WILL BE LOOKING FOR:  Evidence of long-term, consistent dedication and outstanding achievements that have led to the advancement of the profession of pharmacy and public health  Evidence of a large variety of skills, attributes and accomplishments  Evidence of an individual strong in character, cumulative professional accomplishments and the ability to properly represent and model what pharmacy as a profession encompasses  Evidence of an understanding the goals of pharmacy, and significantly contributing to how these goals may be achieved

HOW TO ENTER:

HOW TO ENTER:

For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions.

For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions.

For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

HPN • June 2016


Awards 34 Awards

Hospital Professional

MSD Antimicrobial Pharmacist of the Year Award 2016

2016

Medisource Hospital Pharmacy Technician of the Year 2016

This Award is open to any Antimicrobial Pharmacist working within an Irish hospital setting.

This Award is open to any Hospital Pharmacy Technicians working within an Irish hospital setting.

The MSD Antimicrobial Pharmacist of the Year Award will seek to recognise those pharmacy professionals that have displayed levels of excellence and dedication within antimicrobials in Ireland.

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.

Key roles for the antibiotic pharmacist include educating pharmacy, nursing and medical staff, auditing prescribing patterns and trends, monitoring antibiotic use, ensuring compliance with good antibiotic practices and managing infection control issues, all of which contribute to reducing hospital associated infections.

The shift in emphasis from dispensing to healthcare provision has meant that the wider pharmacy team has to pull together – pharmacy technicians capture the essence of this in everything that they do. This Award will recognise the winner’s important contribution to the hospital pharmacy technician profession.

Having a dedicated antibiotic pharmacist within the team can ensure better monitoring and compliance with hospital antibiotic guidelines, which are based on good practice and local assessment of microbiology in the hospital setting.

The judges will be looking for those who can demonstrate promotion of the role of the Pharmacy Technician and those who continue to champion excellence through forward thinking and innovation.

JUDGES WILL BE LOOKING FOR:  Evidence of long-term, consistent dedication and outstanding achievements that have led to the advancement of the profession of pharmacy and public health  Evidence of a large variety of skills, attributes and accomplishments  Evidence of an individual strong in character, cumulative professional accomplishments and the ability to properly represent and model what pharmacy as a profession encompasses  Evidence of an understanding the goals of pharmacy, and significantly contributing to how these goals may be achieved HOW TO ENTER:

The winners’ achievements will be an inspiration to those pursuing innovative practice; to those striving to raise standards; and to pharmacists who, through their professionalism, provide models for others within pharmacy. JUDGES WILL BE LOOKING FOR:  Evidence of long-term, consistent dedication and outstanding achievements that have led to the advancement of the profession of pharmacy and public health  Evidence of a large variety of skills, attributes and accomplishments  Evidence of an individual strong in character, cumulative professional accomplishments and the ability to properly represent and model what pharmacy technicians as a profession encompasses  Evidence of an understanding the goals of pharmacy, and significantly contributing to how these goals may be achieved HOW TO ENTER:

For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions.

For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions.

For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

June 2016 • HPN


Awards 35

Musculoskeletal Health & Pain Award 2016

Neurology Project of the Year 2016

This Award is open to Musculoskeletal Specialist individuals or teams working within an Irish hospital setting.

This Award is open to Neurology Specialist individuals or consultant-led teams working within an Irish hospital setting.

This Award will recognise efforts to improve efficiency, value and patient experience in musculoskeletal conditions and pain associated with them.

This Award will be given to an individual and/or team who is recognised by their colleagues for their selfless and outstanding service to the Neurology field. This Award will represent clinical excellence in neurology and will be looking for those who have demonstrated clinical expertise in neurologic therapeutics, contributed to the overall development of neurology therapy as a caring and scientific profession and shared their clinical expertise by mentoring others.

Entries are welcomed from teams and specialists creating, implementing and benefiting from new approaches and changed practices. This Award redresses that, celebrating those individuals and teams providing the highest quality care to this group of patients. The category is open to all those involved in musculoskeletal services –working within the hospital sector in Ireland. The judges will want to see entries that can demonstrate excellence in transforming the lives of patients, initiatives demonstrating innovation and resourcefulness in changing clinical practice alongside novel approaches making a real impact to patient care. They will want to see how innovative work has improved patient experience, health care value, and outcomes, potentially offering examples of ways in which rheumatology services can be improved.

At the heart of every great project, is a great story; this Award is for the team whose project demonstrates the most effective use of project management, the greatest results and the greatest benefit and innovations to the profession. The judges are looking for programmes demonstrating the most effective use of programme management techniques, the greatest results, and the innovation and lessons learned for the profession. JUDGES WILL BE LOOKING FOR:

JUDGES WILL BE LOOKING FOR:

 Service improvement which has benefited clinicians, healthcare organisations, and patients alike

 Improved performance. This could be demonstrated through, for example, reduced readmissions or reduced length of stay

 Innovative methods of delivering care

 A strong focus on patient safety and patient experience

 A patient-focused approach, with service users engaged in any redesign

 A dedication to innovative methods of improving efficiency and value, including through the better use of IT  A focus on sustaining performance improvements  Improved patient experience, and a commitment to improving it further still HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

 Strong connections between specialist services and other providers and professionals  Demonstrable improvements in value and patient satisfaction HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

HPN • June 2016


Awards 36 Awards

Hospital Professional

Hospital Specialist of the Year 2016

This Award is open to a Clinician working across any Speciality within an Irish hospital setting.

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. Their contribution may be at local, regional or national level in the past three years. This new Award for 2016 will seek to recognise exemplary leadership within a speciality that demonstrates a positive and sustained impact on patients, service users, carers and staff. Judges will want to see evidence of speciality skills and leadership which are focused on improvement, and enhancing the quality of experience. JUDGES WILL BE LOOKING FOR:  Evidence of key competencies across areas such as team working, innovation, research and education  Excellence in clinical work and/or medical education  Parity of esteem  Commitment to improving services for service users and/ or staff alongside evidence of measurable improvement as a result of the entrants/nominees work

2016

Excellence in Respiratory Initiative of the Year 2016

This Award is open to any Respiratory Specialist or Consultant-led respiratory team working within an Irish hospital setting. This new Award category for 2016 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. 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  Clearly described respiratory interventions  Clear evidence of innovation and new ways of working  Clarity of leadership and how the qualities have affected the team  Quantifiable improvements in patient care, including clinical outcomes

HOW TO ENTER: HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

June 2016 • HPN

For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com


Awards 37

Young Hospital Professional of the Year 2016 This Award is open to any Hospital Professional working across any speciality under the age of 30 working within an Irish hospital setting. The Young Hospital Professional of the Year 2016 Award recognises rising talent – those individuals who despite being in the early stages of their hospital careers are already demonstrating that they can make a difference to the profession and the companies for whom they work and the patients they serve. This award is open to hospital professionals aged up to 30 - at the date of entry submission - who are working within any hospital department where their involvement has been greater than six months. It is the individual qualities that will be evaluated, rather than those of any of the projects worked on. JUDGES WILL BE LOOKING FOR:  Judges will want to see effective communication skills with both staff and patients  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 HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

Patient Organisation Educational Project of the Year 2016 This Award is open to patient organisation-led patient service initiative or project within Ireland. This is a new Award for 2016. This Award seeks to recognise the innovative projects or campaigns undertaken by patient organisations within Ireland which are designed and implemented to improve the lives of patients and their families and address their health needs. Judges will be looking for an outstanding patient engagement project or initiative that is a collaboration with the hospital healthcare team, contributing to the improvement of care and overall health well-being for public, patients and caregivers. JUDGES WILL BE LOOKING FOR:  A project or initiative that has delivered improvement(s) to healthcare delivery and overall well-being of patients and caregivers  A project or initiative should be established and/or ongoing in the past 3 years  Only healthcare institutions, establishments involved in patient care or caregiving resources and patient support/volunteer groups may apply HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

HPN • June 2016


Awards 38 Awards

Hospital Professional

Innovation and Service Development Award 2016

2016

Excellence in Patient Safety Award 2016

This Award is open to an individual or team working within any department within an Irish hospital setting.

This Award is open to an individual or team working within any department within an Irish hospital setting.

The Innovation and Service Development Award is defined as the successful introduction of an idea, method or device that makes a genuine difference or positive change for the hospital department or patients, or both.

This Award will seek applicants who have shown commitment and dedication to improving patient safety/medication safety amongst patients in the secondary care setting.

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

June 2016 • HPN

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 sector in Ireland and invites applications from those who have recently undertaken patient safety initiatives to the betterment of the profession; those who are or who have offered patient safety expertise to the profession perhaps in the line of lecturing; or even those who have undertaken a recent patient safety innovation or initiative within a field pertinent to the hospital that will have a positive effect on the whole profession. JUDGES WILL BE LOOKING FOR:  Evidence of safety improvements and enhancements through collaborative working, introduction of new services, improved systems of work and/or new training standards  Innovative application of new standards, systems, protocols or services  Evidence of benefits to patients and colleagues  Examples of potential roll-out across Ireland HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com


Awards 39

Cardiology Project of the Year Award 2016

Consultant-Led Hospital Team of the Year Award 2016

This Award is open to a Cardiology Specialist or Consultantled team working within an Irish hospital setting.

This Award is open to a Consultant-led team working across any speciality within an Irish hospital setting.

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 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. This award will look for the individual and/or team who is an inspiration to hospital colleagues throughout Ireland via their research, education, training and development of the profession. They will be instrumental in motivating and encouraging others to achieve their aims. 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  Innovative methods of delivering care  A patient-focused approach, with service users engaged in any redesign  Strong connections between specialist services and other providers and professionals  Demonstrable improvements in value and patient satisfaction HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

This Award will be given to the hospital team that demonstrates the best combination of team spirit and enhancement of patient care at all levels. The judges will be looking for those who encourage and support each other and those who have collectively demonstrated innovation and forward thinking. The key to any successful hospital department is team work and this award recognises the power and potential of a focused and unified approach to health care initiatives. Teams can be based within one organisation or spread over multiple organisations; but they must comprise individuals working towards the same objective or goal 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 HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

HPN • June 2016


Awards 40 Awards

Hospital Professional

Hospital Pharmacy Team of the Year Award 2016

2016

Multidisciplinary Award 2016

This Award is open to any Hospital Pharmacy team working within an Irish hospital setting.

This Award is open to any teams working across disciplines either inside or outside of the hospital setting.

There are many key elements to building a productive team, including communication and co-operation. Good communication means everyone is aware of their own responsibilities and what the team's goals are whilst co-operation leads to increased productivity.

Treatment teams in healthcare establishments can be comprised of a number of different specialities and professions working together for the enhancement and betterment of patient care, combining expertise and processes to improve therapeutic outcomes and the quality of work flow.

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. The Award is open to any hospital pharmacy team with a minimum of three team members. JUDGES WILL BE LOOKING FOR:  Judges will want to see effective communication skills with both staff and patients  Demonstration of a commitment to mentoring or other leadership activities  Operation within their own pharmacy liaising with key staff members and management and developing key communication skills  A dedication and commitment to furthering the profession into the future HOW TO ENTER:

Obviously, pharmacists are part of treatment teams in healthcare establishments. With expertise of product and processes, they improve the therapeutic outcome and the quality of work flow. This Award will seek to recognise that a pharmacist form part of a team, this Award will seek to recognise those who can demonstrate added value by their contribution. The judging panel will want to see actual multidisciplinary healthcare working and actual examples of it in practice as well as an outline of what lessons have been learnt from its implementation. JUDGES WILL BE LOOKING FOR:  Evidence of how the applicant/team has shown exemplary teamwork  A clear dissemination of why this project as initiated, market research conducted on identifying need  Details of the challenges/innovations they overcome/initiated. Judges will expect to see evidence of results  A demonstration of the impact this applicant/project has had on the wider hospital team  Demonstration of how this initiative might be rolled out in hospitals across Ireland HOW TO ENTER:

For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

June 2016 • HPN

For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com


Awards 41

Actavis Innovation in Aseptic Compounding Award 2016

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. JUDGES WILL BE LOOKING FOR:  Why did you initiate the project?  What innovation did you incorporate to your pharmacy department and what was the outcome?  What was the most important element?  How does it fit with the Award criteria? HOW TO ENTER: For each award category you wish to enter you must fill in your full contact details in the spaces provided and ensure you answer all the questions. For an application form please contact Kelly Jo Eastwood via email on: kelly@ipnirishpharmacynews.ie or by telephone on +353 1 6690562 / 0044 7876548989 or by visiting our website at www.pharmacyawardsireland.com

HPN • June 2016


42 Feature

Management and Treatment of Type 2 Diabetes in Ireland Criteria for Testing for Diabetes in Asymptomatic Adult Individuals 1. Testing for diabetes should be considered in all adults who are overweight (BMI ≥ 25kg/m2) and who have one or more additional risk factors: • Physical inactivity • First-degree relative with diabetes • Are hypertensive (≥140/90mmHg) or on therapy for hypertension • Dyslipidaemia – HDL< 0.9 and/or triglycerides >2.82 • Have established arterial disease (IHD, CVA, PVD) Dr Diarmuid Smith, Former Clinical Lead for the National Clinical Diabetes Programme; Consultant Endocrinologist at Beaumont Hospital

It is estimated that there are approximately 190,000 people in Ireland with diabetes, with type 2 diabetes accounting for approximately 90% of all cases.1 In 2010, the Institute of Public Health in the report ‘Making Chronic Conditions Count’ revised their previous prevalence forecast upwards and now predict a 62% (up from 37%) increase in the number of people with diabetes by 2020. It also predicts that the prevalence of diabetes will increase from 4.5% in 2007 to 5.9% of the population in 20202. The overall prevalence of type 2 diabetes among adults aged 50 years and over in Ireland is 8.5% and is increasing in line with global trends, driven primarily by rising levels of obesity and ageing populations.3 The true prevalence of Type 2 is underestimated and many cases are undiagnosed because hyperglycemia develops gradually and at earlier stages is often not severe enough for the patient to notice any of the classic symptoms of diabetes. Recent data shows 5.5% adults aged 50 years and over

June 2016 • HPN

in Ireland have pre-diabetes, placing them at increased risk of developing type 2 diabetes in the future.4 It’s known that active intervention will greatly delay or reverse pre diabetes and should be a major focus of maintaining health and well-being. Classification Type 2 is the commonest type of diabetes and is characterised by disorders of insulin action and secretion, either of which may be the predominant feature. Both are usually present at the time that type 2 diabetes is clinically manifest. The specific reasons for the development of these abnormalities are not yet known.6 Type 2 diabetes has a long pre-clinical phase and may be asymptomatic until well after long term microvascular and macrovascular complications have occurred. Type 2 diabetes can be detected before the onset of symptoms and clinical signs by identifying people who are at risk, and performing diagnostic testing.

• High-risk ethnicity (e.g. African, Asian, Hispanic etc.) • Members of the Travelling Community • Have delivered a baby weighing >4.1kgs or have a history of gestational diabetes mellitus (GDM) • On previous testing had Impaired Glucose Tolerance (IGT) or impaired Fasting Glucose (IFG) • Have other clinical conditions associated with insulin resistance (e.g. polycystic ovary syndrome, acanthosis nigricans, longterm steroid use or severe obesity). 2. In the absence of the above additional risk factors, testing for diabetes should begin at age 45 years 3. If the results are normal, testing should be repeated at least at 3 year intervals. Patients with IFG or IGT should be tested annually (Adapted from the ADA Clinical Practice Recommendations 2015 Diabetes Care) Source: National Clinical ProgrammeDiabetes Working Group)

Diagnosis In 2011 WHO6 approved HbA1c as a diagnostic test for diabetes and some international guidelines have updated to reflect this.7,11 To aid screening and early detection of diabetes the HbA1c can now also be used to diagnose diabetes. For diagnosis of Type 2 diabetes probably the best combination of specificity and sensitivity is afforded by the first test being fasting blood glucose. If this is above 5.6mmol/L, the second test should be HbA1c or 75g OGTT. This will allow for identification of impaired fasting glucose, impaired glucose tolerance, and Type 2 diabetes. CRITERIA FOR DIAGNOSIS Diabetes is diagnosed using one of the following criteria Symptoms of diabetes plus random plasma glucose concentration > 11.1 mmol/L. Random is defined as any time of day without regard to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss. or Fasting plasma glucose ≥ 7.0 mmol/L.* Fasting is defined as no caloric intake for at least 8 hours7. or 2-hr plasma glucose > 11.1 mmol/L during a 75g Oral Glucose Tolerance Test. The test should be performed as described by W.H.O., using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water. or A HbA1c ≥ 48mmol/mol (≥ 6.5%)* † The test should be performed using a standardised assay.


MAKE THE SWITCH TO BYDUREON® PEN

Out with the old

In with the improved

Instead of Bydureon Injection (Single-Dose Tray), prescribe BYDUREON® Pen for your patients with type 2 diabetes BYDUREON® Pen offers your type 2 diabetes patients: 4 sustained Hba1c reductions3 4 sustained secondary benefit of weight loss+1,2

4 low hypoglycaemia risk4 4 convenient administration

+ BYDUREON is not indicated for the management of weight loss, and weight change was a secondary endpoint in clinical trials.

References: 1. Buse JB, Drucker DJ, Taylor K, et al. Exenatide once weekly produces sustained glycaemic control and weight loss over 52 weeks. Diab Care 2010;33:1255–61. 2. Drucker DJ, Buse JB, Taylor K, et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. 2008;372(9645):1240-1250 3. Klein EJ, Henry RR, Malloy J, et al. DURATION-1 extension: efficacy and tolerability of exenatide once weekly over 6 years in patients with type 2 diabetes mellitus. Poster presented at the 50th Annual Meeting of the European Association for the Study of Diabetes; September 15-19, 2014; Vienna, Austria. 4. BYDUREON® Summary of Product Characteristics available at www.medicines.ie.

Approval ID: 964265.011 Date of preparation: March 2016

BYDUREON® (exenatide) 2MG POWDER AND SOLVENT FOR PROLONGED-RELEASE SUSPENSION FOR INJECTION Consult Summary of Product Characteristics (SmPC) before prescribing. Use: Treatment of type 2 diabetes mellitus in combination with metformin, sulphonylurea, thiazolidinedione, or combinations of metformin and sulphonylurea or metformin and thiazolidinedione, in adults who have not achieved adequate glycaemic control on maximally tolerated doses of these oral therapies. Presentation: Powder and solvent for prolonged-release suspension for injection containing 2mg exenatide. Dosage and administration: Adults: The recommended dose is 2mg exenatide once weekly, on the same day each week, at any time of day, with or without meals. Administer as subcutaneous injection in the thigh, abdomen, or back of the upper arm immediately after suspension of powder in the solvent. If dose is missed, administer as soon as practical, then resume once weekly dosing schedule. Two injections should not be given on the same day. Prolonged-release exenatide is for selfadministration, appropriate training is recommended. Patients switching from immediate-release to prolonged-release exenatide may experience transient elevations in blood glucose concentrations, which generally improve within first two weeks after therapy initiation. When prolonged-release exenatide is added to existing metformin and/or thiazolidinedione, the current dose of these oral therapies can be continued. Increased risk of hypoglycaemia when prolonged-release exenatide is added to sulphonylurea. Consider reduction in dose of sulphonylurea to reduce the risk of hypoglycaemia. Blood glucose self-monitoring may be necessary to adjust the dose of sulphonylurea. If a different glucose-lowering treatment is started after the discontinuation of prolonged-release exenatide, consideration should be given to the prolonged release of the product. Elderly: No dose adjustment required. >75 years: Very limited clinical experience. Consideration should be given to the patient’s renal function. Renal or hepatic impairment: No dose adjustment required for patients with mild renal impairment (creatinine clearance 50-80 ml/min) or hepatic impairment. Very limited experience in moderate renal impairment (creatinine clearance 30 50ml/min). Not recommended in patients with moderate renal impairment, severe renal impairment (creatinine clearance <30 ml/min) or end-stage renal disease. Children and adolescents: <18 years old: Safety and efficacy not established. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Warnings and precautions: Not to be used in patients with type 1 diabetes mellitus or for diabetic ketoacidosis. Must not be administered by intravenous or intramuscular injection. Renal impairment: Uncommon events of altered renal function with exenatide, including increase serum creatinine, renal impairment, worsened chronic renal failure and acute renal failure, sometimes requiring haemodialysis. Some occurred in patients experiencing events that may affect hydration and/or receiving medicinal products known to affect renal function/hydration status, including angiotensin converting enzyme inhibitors, angiotensin-II antagonists, non-steroidal anti-inflammatory medicinal products and diuretics. Reversibility observed with supportive treatment and discontinuation of potentially causative medicinal products, including exenatide. Severe gastrointestinal disease: Not recommended. Acute pancreatitis: Use of GLP-1 receptor agonists has been associated with a risk of developing acute pancreatitis. Spontaneously reported events of acute pancreatitis. Resolution of pancreatitis has been observed with supportive treatment, but very rare cases of necrotising or haemorrhagic pancreatitis and/or death have been reported. Inform patients of the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain. If pancreatitis suspected, discontinue use; if acute pancreatitis is confirmed, prolonged-release exenatide should not be restarted. Caution should be exercised in patients with a history of pancreatitis. Concomitant medicinal products: Concurrent use of prolonged-release exenatide with insulin, meglitinides, alpha-glucosidase inhibitors, dipeptidyl peptidase-4 inhibitors or other GLP-1 receptor agonists have not been studied. The concurrent use of prolonged-release and immediate-release exenatide has not been studied and is not recommended. Weight loss: Rapid weight loss at a rate of >1.5kg per week has been reported with exenatide, which may have harmful consequences. Monitor for signs and symptoms of cholelithiasis. Discontinuation of treatment: The effect of Bydureon may continue as plasma levels of exenatide decline over 10 weeks. Choice of other medicinal products and dose selection should be considered accordingly until exenatide levels decline. Drug interactions: No dose adjustment required for medicinal products sensitive to delayed gastric emptying. Warfarin and cumarol derivatives: Increased INR (International normalised ratio) spontaneously reported during concomitant use of warfarin and prolonged-release exenatide. INR should be monitored during initiation of prolonged-release exenatide. HMG CoA reductase inhibitors: Concomitant use with exenatide was not associated with consistent changes in lipid profiles. Lipid profiles should be monitored as appropriate. Pregnancy and lactation: Women of childbearing potential should use contraception during treatment with prolonged-release exenatide. Discontinue at least 3 months before trying to get pregnant. Avoid use during pregnancy and breast-feeding. Undesirable Effects: Consult SmPC for full list of side effects. Very common (≥1/10): Hypoglycaemia (with sulphonylurea), diarrhoea, nausea. Common (≥1/100 to <1/10): Decreased appetite, dizziness, headache, vomiting, abdominal distention, abdominal pain, dyspepsia, constipation, flatulence, gastroesophageal reflux disease, pruritus and/or urticaria, injection site pruritus, fatigue, injection site erythema, asthenia. Uncommon (≥ 1/1000 to < 1/100): Dehydration, somnolence, intestinal obstruction, eructation, altered renal function (including acute renal failure, worsened chronic renal failure, renal impairment, increased serum creatinine), injection site rash. Rare (≥1/10,000 to <1/1000): Anaphylactic reaction. Frequency not known: Acute pancreatitis, angioneurotic oedema, macular and papular rash, injection site abscesses and cellulitis. INR ratio increased with concomitant warfarin use (some reports associated with bleeding). Patients may develop anti-exenatide antibodies following treatment with prolonged-release exenatide. These patients tend to have more injection site reactions (e.g. skin redness, itching). Small subcutaneous injection site nodules observed very frequently, consistent with the known properties of PLGA polymer microsphere formulations. Legal category: POM. Marketing authorisation number: EU/1/11/696/001 (single dose kit) and EU/1/11/696/003 (pre-filled pen). Further product information available on request from: Freephone 1800 800 899 or contact AstraZeneca UK Limited, Horizon Place, 600 Capability Green, Luton, Bedfordshire, LU1 3LU, United Kingdom. Bydureon is a trade mark of the AstraZeneca group of companies Date of API preparation: 03/2016.


44 Feature The following conditions will interfere with the HbA1c assay and exclude its use as a test to diagnose diabetes – plasma glucose criteria should be used instead to diagnose diabetes in the following conditions: 1. Haemoglobinopathies 2. Sickle cell disease 3. Haemolytic anaemia 4. Recent blood transfusion 5. Recent blood loss 6. Iron deficiency anaemia. Prevention/Delay of Type 2 Diabetes (T2DM) There is now substantial evidence that the development of Type 2 diabetes can be prevented or delayed. Individuals at high risk of developing diabetes can be identified easily. Knowledge of the early stages of hyperglycemia and research into the prevention of Type 2 diabetes clearly show that individuals at high risk can be identified and diabetes delayed, if not prevented. The American Diabetes Association (ADA) note that the cost- effectiveness of intervention strategies is unclear, but the huge burden resulting from the complications of diabetes and the potential ancillary benefits of some of the interventions suggest that an effort to prevent diabetes may be worthwhile.12 Studies have shown that in patients with pre-diabetes, IFG or IGT or both, their risk of developing Type 2 diabetes can be significantly reduced by following intensive lifestyle modification programmes. Medications, including metformin, have been shown to reduce the risk of diabetes in people with pre-diabetes. Thus individuals at high risk for developing diabetes and particularly those with IGT or IFG should be made aware of the many benefits of modest weight loss and regular physical activity and should be counselled and instructed in these areas. Follow up counselling and monitoring for the development of diabetes by glucose tolerance testing should be performed every 1-2 years. Screening for undiagnosed or new (gestational) diabetes in pregnancy

June 2016 • HPN

Gestational diabetes mellitus (GDM) is defined as the onset or first recognition of glucose intolerance during pregnancy. GDM is associated with increased risks for mother and baby during pregnancy and longer term risk of diabetes in both mother and baby. Women known to be at high risk of developing gestational diabetes include those who: • Have had previous gestational diabetes, • Have had a baby weighing over 4.5kilos, • Have a strong family history (parent or sibling with diabetes), • Are overweight or obese • Are members of a population group with a high prevalence of diabetes • Have a macrosomic foetus, polyhydramnios or glycosuria in their current pregnancy. Diabetes Care For most people diagnosed with Type 2 diabetes their condition is life-long and while new types of medication and medical devices are constantly being produced, the basic foundation for good diabetes care still focuses on healthy eating and physical activity, monitoring blood glucose levels and taking medication. The management of Type 2 diabetes involves behavioural change best achieved through integrated care and education. Integrated Care Three of the key components of a comprehensive diabetes service are patient registration, recall and regular review. Integrated care also includes allocation of protected time and adherence to a standard management protocol.14 An annual and comprehensive review is regarded as the crucial element of integrated diabetes care.15 Routine integrated care involves the patient, GP, practice nurse, diabetologist, clinical nurse specialist in diabetes, dietitian, ophthalmologist and podiatrist. All patients with Type 2 diabetes should have access to specialist services such as endocrinology, vascular, cardiology, nephrology and

psychology as needed. Care provision begins with initial assessment and follows with regular review that includes a comprehensive annual review. In order to provide this level of care, protected time is required and this has funding implications for all levels of service (primary, secondary and tertiary care). National Integrated Model of Care Under a proposed National Integrated Model of Care patients with uncomplicated T2DM will be seen 3 times a year in primary care in a structured fashion. The visits will be every 4 months with an annual review occurring every 12 months. Patients who develop complications will be referred from primary to secondary or tertiary care for an expert specialist opinion and their care will become shared between primary and secondary or tertiary care. These patients will be seen at least once a year in secondary care for their annual review or more frequently according to the severity of the diabetes related complication and up to twice a year in primary care at 4-monthly intervals. Lifestyle Management The main lifestyle management issues for people with Type 2 diabetes are healthy eating and physical activity and there is ample evidence (of varying levels) to support this. The Scottish Intercollegiate Guideline Network (SIGN) recommend that • Patients with diabetes should be offered lifestyle interventions based on a valid theoretical framework • Education programmes, computer assisted packages and telephone prompting should be considered as part of a multidisciplinary lifestyleintervention programme.18 Diet Nutritional advice and information is an essential component of the overall management of Type 1 and Type 2 diabetes. The aim is to keep blood glucose, cholesterol, triglycerides and weight within a normal range. Healthy eating is recommended

as it is encouraged for the entire population. Some of the most successful programmes for long-term weight control have involved combinations of diet, exercise and behaviour modification.19 Patients should be advised to maintain a healthy weight in order to maintain a BMI of between 20 and 25 kg/m2. The following are general recommendations in relation to referral to the dietetic service »» Ideally all newly diagnosed patients need to be advised by a dietician within 4 weeks of diagnosis.20 »» It is advisable that all people with type 2 diabetes should have an annual dietetic review.20 »» All patients with diabetes should be offered a structured diabetes education programme Physical Activity Along with diet and medication, exercise has long been considered as a key component of diabetes management. There is consistent evidence that programmes of increased physical activity and modest weight loss reduce the incidence of Type 2 diabetes in individuals with IGT.21, 22, 23, 24 Physical activity also helps those diagnosed with Type 2 diabetes to maintain a healthy weight and reduce the risk of CVD. Before beginning a programme of physical activity more vigorous than brisk walking, people with diabetes should be assessed for conditions that might be associated with increased likelihood of CVD or that might contraindicate certain types of exercise or predispose to injury, such as severe autonomic neuropathy, severe peripheral neuropathy, and pre-proliferative or proliferative retinopathy. The patient’s age and previous physical activity level should be considered.25 The universal recommendation with regard to physical activity is that all individuals should aim to accumulate at least 30 minutes of moderate intensity physical activity on most days of the week.26 This has been adopted as the minimum requirement for health benefits. However, 30 minutes spread over the entire


ANNOUNCING RESULTS FROM TECOS — A LONG-TERM CARDIOVASCULAR (CV) SAFETY TRIAL

Actor portrayals.

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 LONGESTa CV SAFETY TRIAL WITH A DPP-4 INHIBITOR1

NOW EVEN MORE REASONS TO CHOOSE JANUVIA ® FIRST AS A PARTNER TO METFORMIN • No increased CV risk (primary end point) in a clinical trial of >14,000 patients with type 2 diabetes and CV disease1* • Met all secondary CV end points

TO COMPLEMENT YOUR PATIENTS’ EFFORTS TO ACHIEVE THEIR GOALS * When sitagliptin is added to usual care compared to placebo plus usual care

ing 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 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. DRUG 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. Sitagliptin with metformin: Common: hypoglycaemia, nausea, flatulence and vomiting; Uncommon: somnolence; upper abdominal pain, diarrhoea, and constipation. 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 and exfoliative skin conditions including Stevens-Johnson syndrome (see precautions); 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, 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. 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, Januvia 50 mg: EU/1/07/383/008, Januvia 100mg: EU/1/07/383/014. Janumet 50 mg/850 mg: EU/1/08/455/003, Janumet 50 mg/1000 mg: EU/1/08/455/010. Marketing Authorisation Holder Merck Sharp & Dohme Limited, Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, UK. Date of revision: March 2015. © Merck Sharp & Dohme Ireland (Human Health) Limited, 2015. 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: June 2015.

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) Median follow-up: 3 years. Reference: 1. Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes [published online ahead of print June 8, 2015]. N Engl J Med. 2015;1–11. doi:10.1056/NEJMoa1501352.

a

Red Oak North, South County Business Park, Leopardstown, Dublin 18, Ireland.

DIAB-1154814-0000

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. Elderly ≥ 75 years: Exercise care as there are limited safety data in this population. 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 administer-

(sitagliptin/metformin)


46 Feature • Rapid addition of medications and transition to new regimens when target glycaemic goals are not achieved or sustained • Early addition of insulin therapy in patients who do not meet target goals.28 Treatment/Control with Oral Agents Many organisations recommend that the patient is started on a single oral agent. The ADA, IDF and NICE recommend metformin as an option for first-line or combination therapy. • In addition NICE 29 also recommend metformin both for those who are overweight (BMI>25.0kg/m2) and not overweight as the first-line glucose-lowering therapy where blood glucose is inadequately controlled using lifestyle interventions alone (A)

day is equally beneficial as one 30-minute walk. Activities of daily living such as housework and using stairs are valuable in increasing physical activity.27 SIGN 55 recommend that exercise and physical activity involving aerobic and/or resistance training, should be performed on a regular basis. They also recommend that advice about exercise and physical activity should be individually tailored and diabetes specific and should include implications for glucose management.18 Achieving Glycaemic Control Type 2 Diabetes is a progressive disease with worsening glycaemia over time; therefore the addition of medications is the rule, not the exception, if treatment goals are to be met. The limited long-term success of lifestyle programmes to maintain glycaemic goals suggests that a majority of patients require medication. Baseline glycaemia, duration of diabetes, previous therapy and other factors affect the glucose-lowering effectiveness of individual therapies and combinations.28 Tight control of blood glucose with diet, physical activity and/ or medication reduces long term diabetes related complications

June 2016 • HPN

and is central to the overall management of diabetes.

benefits, for example, people with reduced life expectancy

Targets7,11

-- For whom tight blood glucose control poses a high risk of the consequences of hypoglycaemia, for example, people who are at risk of falling, people who have impaired awareness of hypoglycaemia and people who drive or operate machinery a part of their job

• The target HbA1c for the majority of patients with Type 2 diabetes should be ≤53mmol/mol (≤7.0%) • Targets should be set in consultation with the patient. The targets should be seen as guides, as a patient’s individual circumstances need to be considered when setting and agreeing targets. • More stringent A1C goals such as < 48mmol/mol (<6.5%) may be considered for selected individual patients if this can be achieved without significant hypoglycemia or other adverse effects of treatment. Appropriate patients might include those with short duration of diabetes, type 2 diabetes treated with lifestyle or metformin only, long life expectancy, or no significant cardiovascular disease (CVD). • Consider relaxing the target HbA1c level such as < 58mmol/mol (<8%) on a case by case basis, with particular consideration for people who are older or frail for adults with type 2 diabetes; -- Who are unlikely to achieve longer term risk reduction

-- For whom intensive management would be appropriate, for example people with significant co-morbidities Clinical Monitoring

Metformin is contraindicated in those with renal impairment (eGFR <30ml/min), and with end stage cardiac and hepatic failure. Metformin should be stopped in patients with eGFR <30ml/min and at possibly higher values in patients prone to dehydration. It should be noted that glitazones are under suspicion of precipitating acute cardiac events and current recommendations contraindicate the use of glitazones in patients with a history ischaemic heart disease. References available on request.

• The HbA1c should be checked four monthly and treatment adjusted as appropriate if the target HbA1c is not achieved. Treatment Diet and exercise are the cornerstones of type 2 diabetes management but frequently patients require medications to be added in. The following are medications recommended for patients who are having difficulty meeting the HbA1c agreed targets: The ADA recommend (E) • Achievement and maintenance of normal glycaemic goals • Initial therapy with lifestyle interventions and metformin

Dr Diarmuid Smith is the Former Clinical Lead for the National Clinical Diabetes Programme and is a Consultant Endocrinologist at Beaumont Hospital. He is now a member of the 3U Diabetes Partnership, which brings together the academic strengths of Dublin City University, Maynooth University and the RCSI to enhance education and research opportunities across the three partner institutions.


No w that I HAVE YOUR

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

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

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

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

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

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


48 News

Global Report amidst calls for increased focus on Metastatic Breast Cancer Professor John Crown, Consultant Medical Oncologist, St. Vincent’s University Hospital

A new report - The Global Status of Metastatic Breast Cancer (mBC) Decade Report which looks at the unique challenges facing metastatic breast cancer patients has been launched by a group of leading experts at the Royal College of Physicians in Ireland. The report confirms the extent of misconceptions and misunderstandings surrounding the most advanced stage of breast cancer – metastatic breast cancer (mBC) - as well as the level of isolation and helplessness felt by patients.2 The report was developed in collaboration with the European School of Oncology (ESO). Despite advances in the treatment of breast cancer, approximately 30% of women initially diagnosed with earlier stages of breast cancer eventually develop recurrent advanced or metastatic disease. [iii] Early detection does not help survival for metastatic breast cancer patients and average survival is only 2-3 years – although many women can live for much longer.1 The report showed that in most countries, a majority optimistically believed that patients who are diagnosed and treated early would not progress to develop mBC and that up to 76% believed that metastatic breast cancer is curable.[iv] “Irish cancer research has provided many new medicines and diagnostics which are improving the outcome for Irish women with Breast Cancer,” commented Dr Robert O’Connor, Head of Research for the Irish Cancer Society. “Our aim is to ensure all June 2016 • HPN

Irish women have the appropriate information about their condition, the best and most modern treatments available including access to clinical trials, and all the necessary supports to help them become more engaged in treatment decisions and thrive the greatest possible extent from that treatment.” The report highlights that progress in mBC has not nearly kept pace with the evolution witnessed in managing early breast cancer.2 In addition, the report confirms the many misconceptions and misunderstandings surrounding the metastatic breast cancer as well as the level of isolation and helplessness felt by patients.2 “While metastatic breast cancer remains a usually incurable disease, most patients are now achieving years of survival. With this expectation of longer life come special challenges. The physical toll of the illness and it treatment is frequently compounded by the psychological effects of loss of independence, change in body image, and an uncertain future,” says Professor John Crown, Consultant Medical Oncologist, St. Vincent’s University Hospital. “Society needs to recognise the unique needs of these women who will live every remaining day of their lives under the shadow of this serious illness”, said Tara Byrne, Europa Donna Ireland. “While newer, less toxic treatments offer the promise of longer and better life, more also needs to be done to provide support for a condition which can be notoriously isolating and indeed stigmatising.

“We believe that our role as a patient advocate organisation is to campaign to ensure that specialist breast units address mBC in a coordinated way and that from the time of diagnosis of mBC, patients should be offered appropriate psychosocial and supporting care as routine and this care should be personalised to meet the needs of individual patients.” “In addition we will continue to work with research organisations to ensure that the pace of research into mBC is increased given the global report has shown a decline in the last decade.” The general public knowledge of breast cancer issues often comes from survivor stories by patients with early breast cancer, which receive considerable attention and ensure that breast cancer is a disease familiar to many people.2 In contrast, the report reveals that there is a lack of public knowledge about mBC compared with early breast cancer (eBC) that leads to widespread misperceptions and which can have a negative impact on the lives of patients and their families.2 According to National Cancer Registry of Ireland there are over 30,000 women living with breast cancer in Ireland.[v] The incidence of female breast cancer in Ireland is 12.5% higher than the EU average[vi] with over 2800 new cases of breast cancer diagnosed each year.5 Irish mortality rates are the 3rd highest in the EU6 with over 680 Irish women dying from breast cancer each year.5 Substantial resources have been directed toward breast cancer -

education, research and advocacy effects which has resulted in gains that have mainly benefited those with early breast cancer.2 The goal of this report is to shed light on the challenges and gaps in mBC to inspire change within the breast cancer community and beyond, including physicians, researchers, policymakers, industry, advocates, caregivers, patients, and the public. It is one of the most far-reaching analyses of the key factors that contribute to the care and well-being of those with mBC and provide insight on areas in need of improvement. The Global Status of Metastatic Breast Cancer (mBC): A 2005 – 2015 Decade Report was developed by Pfizer Oncology, working collaboratively with the European School of Oncology (ESO) under the framework of the International Consensus Conference for Advanced Breast Cancer (ABC). A steering committee of global multidisciplinary mBC advisors comprised of physicians, patients support organisation leaders, and patients advised on the development of this report. The report assesses the status of mBC in terms of patient care, the wider breast cancer environment and scientific advances and developments. The analysis is based on three newly commissioned primary surveys examining current perceptions of the state of breast cancer among the general public, patient advocacy groups, Breast Cancer Centres, oncologists and nurses in 34 countries around the world.


Feature 49

Urinary Incontinence â&#x20AC;&#x201C; Disease & Pharmacological Management Urinary incontinence (UI) is an extremely common complaint in every part of the world. It causes a great deal of distress and embarrassment, as well as significant costs, to both individuals and societies. Estimates of prevalence vary according to the definition of incontinence and the population studied. However, there is universal agreement about the importance of the problem in terms of human suffering and economic cost. According to a survey carried out in the late 90â&#x20AC;&#x2122;s, urinary incontinence is amongst the top three health problems which embarrass Irish people. In 2015, it was estimated that over 28% of the Irish population are affected by urinary incontinence at some stage in their lifetime. The reported incidence of urinary incontinence varies depending on the population in question. For example, in the UK a 9% incidence of UI was found in the adult population. However, a similar Irish study found the figure to be much higher, at 33%.What is known is that UI affects more women than men and that the prevalence of incontinence increases with age. The exact prevalence of FI is difficult to determine due to the under-reporting of its symptoms, the lack of a standard scoring scale and variations in populations. It is estimated to affect approximately 3% of the population over 65 years. Whatever the exact incidence or population affected, incontinence has devastating consequences on the individual and also burdens the carers of those who require personal care. Guidelines from the European Association of Urology (EAU) Working Panel on Urinary Incontinence were written this year by a multidisciplinary group, primarily for urologists, and are likely to be referred to by other professional groups. They aim to provide sensible and practical evidence-based guidance on the clinical problem of UI rather than an exhaustive narrative review. Such a review is already available from the International Consultation on Incontinence[1], and so the EAU Guidelines do not describe the causation, basic science,

epidemiology and psychology of UI. The focus of these Guidelines is entirely on assessment and treatment reflecting clinical practice. The Guidelines also do not consider patients with UI caused by neurological disease, or in children, as this is covered by complementary EAU Guidelines.[2,3] Taking a careful clinical history is fundamental to the clinical process. Despite the lack of formal evidence, there is universal agreement that taking a history should be the first step in the assessment of anyone with UI. The history should include details of the type, timing and severity of UI, associated voiding and other urinary symptoms. The history should allow UI to be categorised into stress urinary

incontinence (SUI), urgency urinary incontinence (UUI) or mixed urinary incontinence (MUI). It should also identify patients who need rapid referral to an appropriate specialist. These include patients with associated pain, haematuria, a history of recurrent urinary tract infection (UTI), pelvic surgery (particularly prostate surgery) or radiotherapy, constant leakage suggesting a fistula, voiding difficulty or suspected neurological disease. In women, an obstetric and gynaecological history may help to understand the underlying cause and identify factors that may impact on treatment decisions. The patient should also be asked about other ill health and for the details of current medications, as these may impact on symptoms of UI.

Similarly, there is little evidence from clinical trials that carrying out a clinical examination improves care, but wide consensus suggests that it remains an essential part of assessment of people with UI. It should include abdominal examination, to detect an enlarged bladder or other abdominal mass, and perineal and digital examination of the rectum (prostate) and/or vagina. Examination of the perineum in women includes an assessment of oestrogen status and a careful assessment of any associated pelvic organ prolapse (POP). A cough test may reveal SUI if the bladder is sufficiently full and pelvic floor contraction together with urethral mobility can be assessed digitally.

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50 Feature Voiding diaries Measurement of the frequency and severity of LUTS is an important step in the evaluation and management of lower urinary tract (LUT) dysfunction, including UI. Voiding diaries are a semiobjective method of quantifying symptoms, such as frequency of UI episodes. They also quantify urodynamic variables, such as voided volume and 24-hour or nocturnal total urine volume. Voiding diaries are also known as micturition time charts, frequency/ volume charts and bladder diaries. Discrepancy between diary recordings and the patient rating of symptoms, e.g. frequency or UI, can be useful in patient counselling. In addition, voided volume measurement can be used to support diagnoses, such as overactive bladder (OAB) or polyuria. Diaries can also be used to monitor treatment response and are widely used in clinical trials. In patients with severe UI, a voiding diary is unlikely to accurately report 24-hour urine output and so voided volume may be lower than total bladder capacity. Post-voiding residual (PVR) volume is the amount of urine that remains in the bladder after voiding. It indicates poor voiding efficiency, which may result from a number of contributing factors. It is important because it may worsen symptoms and, more rarely, may be associated with UTI, upper urinary tract (UUT) dilatation and renal insufficiency. Both bladder outlet obstruction and detrusor underactivity contribute to the development of PVR. Post-voiding residual can be measured by catheterisation or ultrasound (US). The prevalence of PVR in patients with UI is uncertain, partly because of the lack of a standard definition of an abnormal PVR volume. Most studies investigating PVR have not included patients with UI. Although some studies have included women with UI and men and women with LUTS, they have also included children and adults with neurogenic UI. In general, the data on PVR can be applied with caution to adults with non-neurogenic UI. The results of studies investigating the best method of measuring PVR[31-36] have led to the consensus that US measurement of PVR is preferable to catheterisation. In peri- and postmenopausal women without significant LUTS or pelvic organ symptoms, 95% of women had a PVR < 100 mL.[37] In women with UUI, a PVR > 100 mL was found in 10% of cases.[38] Other research has found that a high PVR is associated with POP,

June 2016 • HPN

voiding symptoms and an absence of SUI.[37,39-41] Conservative management In clinical practice, it is the convention that non-surgical therapies are tried first because they usually carry the least risk of harm. They are often used in combination which makes it difficult to determine which components are effective. Containment devices play an important role, especially for individuals who prefer to avoid the risks of interventional treatments, or in whom active treatment is impossible for any reason. Urinary incontinence, especially in the elderly has been associated with multiple comorbid conditions including • cardiac failure • chronic renal failure • diabetes • chronic obstructive pulmonary disease • neurological disease including stroke and multiple sclerosis • general cognitive impairment • sleep disturbances, e.g. sleep apnoea • depression • metabolic syndrome It is possible that improvement of associated disease may reduce the severity of urinary symptoms. However, this is often difficult to assess as patients often suffer from more than one condition. In addition, interventions may be combined and individualised, making it impossible to decide which alteration in an underlying disease has affected a patient’s UI. There is compelling evidence that the prevalence of UI in women with type 2 diabetes is higher. One study showed no correlation between earlier intensive treatment of type 1 diabetes mellitus and the prevalence of UI in later life vs. conventional treatment. Adjustment of other (non-incontinence) medication Although UI is listed as an adverse effect of many drugs in drug compendia, this mainly results from uncontrolled individual patient reports and post-marketing surveillance. Few controlled studies have used the occurrence of UI as a primary outcome or were powered to assess the occurrence of statistically significant UI or worsening rates against placebo. In most cases, it is therefore not possible to be sure that a drug causes UI. In patients with existing UI, particularly the elderly, it may

be difficult or impossible to distinguish between the effects of medication, comorbidity or ageing on UI. Although changing drug regimens for underlying disease may be considered as a possible early intervention for UI, there is very little evidence of benefit.[49] There is also a risk that stopping or altering medication may result in more harm than benefit. Containment is important for people with UI when active treatment does not cure the problem, or when it is not available or not possible. Some individuals may prefer to choose containment rather than undergo active treatment with its associated risks. This includes the use of absorbent pads, urinary catheters, external collection devices, penile clamps for men and intravaginal devices for women. Studies of catheter use are not specific to patients with non-neurogenic UI. Detailed literature summaries can be found in the current ICUD monograph[1] and in European Association of Urological Nurses guidance documents. [95-97] A useful resource for health care professionals and patients can be found at: www. continenceproductadvisor.org Lifestyle interventions Examples of lifestyle factors that may be associated with incontinence include obesity, smoking, level of physical activity and diet. Modification of these factors may improve UI. Many drinks contain caffeine, particularly tea, coffee and cola. Anecdotal evidence of urinary symptoms being aggravated by excessive caffeine intake has focused attention on whether caffeine reduction may improve UI. However, a cross-sectional population survey found no statistical association between caffeine intake and UI.[112] Lack of knowledge about caffeine content of different drinks has made the role of caffeine reduction in alleviating UI difficult to assess. Fluid intake Modification of fluid intake, particularly restriction, is a strategy commonly used by people with UI to relieve symptoms. Advice on fluid intake given by healthcare professionals should be based on 24-hour fluid intake and urine output measurements. Form a general health point of view it should be advised that fluid intake should be sufficient to avoid thirst and that low or high 24-hour urine output should be investigated. Behavioural and Physical therapies Terminology relating to behavioural

and physical therapies remains confusing because of the wide variety of ways in which treatment regimens and combinations of treatments have been delivered in different studies [153]. The terms are used to encompass all treatments which require a form of self-motivated personal retraining by the patient and also include techniques which are used to augment this effect. Approaches include bladder training (BT) and pelvic floor muscle training (PFMT), but terms such as bladder drill, bladder discipline and bladder re-education and behaviour modification are also used. Almost always in clinical practice, these will be introduced as part of a package of care including lifestyle changes, patient education and possibly some cognitive therapy as well. The extent to which individual therapists motivate, supervise and monitor these interventions is likely to vary but it is recognised that these influences are important components of the whole treatment package. Bladder Training Bladder training (also referred to in the past as bladder drill, bladder discipline, bladder re-education, bladder re-training): A programme of patient education along with a scheduled voiding regimen with gradually adjusted voiding intervals. Specific goals are to correct faulty habit patterns of frequent urination, improve control over bladder urgency, prolong voiding intervals, increase bladder capacity, reduce incontinent episodes and restore patient confidence in controlling bladder function. The ideal form or intensity of a BT programme for UI is unclear. It is also unclear whether or not BT can prevent the development of UI. Efficacy of PFMT in SUI, UUI and MUI in women This question has been addressed by several systematic reviews,[152,157,161] all report inconsistency between studies because of poor reporting of technique and different outcome measures. Meta-analysis showed that PFMT was effective for cure or improvement of incontinence, and improvement in QoL. The effect applies in women with SUI, UUI and MUI though the effect in MUI is lower than in women with pure SUI. A Cochrane review comparing different approaches to delivery of PFMT (21 RCTs) concluded that increased intensity of delivery of the therapy improves response and that there is no consistent difference between group therapy and individualised treatment


51 sessions.[162] No other consistent differences between techniques were found. With regard to the durability of PFMT, another RCT reported 15-year follow-up outcomes of an earlier RCT, showing that long-term adherence to treatment was poor and half of patients had progressed to surgery.[163] Numerous systematic reviews have addressed the question of whether the effects of PFMT and BT are additive.[152,157,164] These reviews are confounded by differences in patient selection and have arrived at conflicting conclusions leaving uncertainty about the extent to which one treatment may augment the other. Similarly, there remains uncertainty about the additional value of biofeedback with systematic reviews reaching differing conclusions.[157,164] Comparison of PFMT to other treatments was extensively reviewed by both AHRQ and the 2010 UK HTA,[152,157] which considered additional nonrandomised data as part of a mixed treatment comparison. The UK HTA resulted in a number of different findings from those based solely on direct comparisons. In conclusion, the HTA, using a revised methodology, supported the general principle that greater efficacy was achieved by adding together different types of treatment and by increasing intensity. Pharmacological management Antimuscarinic (anticholinergic) drugs are currently the mainstay of treatment for UUI. They differ in their pharmacological profiles, e.g. muscarinic receptor affinity and other modes of action, in their pharmacokinetic properties, e.g. lipid solubility and half-life, and in their formulation. The evaluation of cure or improvement of UI is made harder by the lack of a standard definition of improvement and the failure to use cure as a primary outcome. In general, systematic reviews note that the overall treatment effect of drugs is usually small but larger than placebo. Dry mouth is the commonest side effect, though constipation, blurred vision, fatigue and cognitive dysfunction may occur.[157] The immediate release (IR) formulation of oxybutynin is the archetype drug in the treatment of UUI. Oxybutynin IR provides maximum dosage flexibility, including an off-label â&#x20AC;&#x2DC;on-demandâ&#x20AC;&#x2122; use. Immediate-release drugs have a greater risk of side effects

than extended release (ER) formulations because of differing pharmacokinetics. A transdermal delivery system (TDS) and gel developed for oxybutynin gives a further alternative formulation. Comparison of antimuscarinic agents Head-to-head comparison trials of the efficacy and side effects of different antimuscarinic agents are of interest for decision making in practice. There are over 40 RCTs and five systematic reviews. [157,176,187,189,191] Nearly all the primary studies were industry sponsored. Upward dose titration is often included in the protocol for the experimental arm, but not for the comparator arm. In general, these studies have been designed for regulatory approval. They have short treatment durations (12 weeks) and a primary outcome of a change in OAB symptoms rather than a cure of, or an improvement in, UUI, which were generally analysed as secondary outcomes. The clinical utility of these trials in real life practice in questionable. Most trials were of low or moderate quality.[189] The 2012 Agency for Healthcare Research and Quality (AHRQ) review included a specific section addressing comparisons of antimuscarinic drugs. No antimuscarinic agent improved QoL more than another agent [189]. Dry mouth is the most prevalent adverse effect. Good evidence indicates that, in general, higher doses of any drug are likely to be associated with higher rates of adverse events. Also, ER formulations of short-acting drugs, and longer-acting drugs are generally associated with lower rates of dry mouth than IR preparations.[189,191] Oxybutynin IR showed higher rates of dry mouth than tolterodine IR and trospium IR, but lower rates of dry mouth than darifenacin, 15 mg daily. [189,191] Overall, oxybutynin ER has higher rates of dry mouth than tolterodine ER, although the incidence of moderate or severe dry mouth were similar. Transdermal oxybutynin had a lower rate of dry mouth than oxybutynin IR and tolterodine ER, but had an overall higher rate of withdrawal due to an adverse skin reaction.[189] Solifenacin, 10 mg daily, had higher rates of dry mouth than tolterodine ER.[189] Fesoterodine, 8 mg daily, had a higher rate of dry mouth than tolterodine, 4 mg daily.[192,193] In general, similar discontinuation rates were observed, irrespective

of differences in the occurrence of dry mouth.* *Doses have been given were the evidence relates to a specific dose level typically from trials with a dose escalation element. Antimuscarinic drugs vs. non-drug treatment The choice of drug vs. non-drug treatment of UUI is an important question. More than 100 RCTs and high-quality reviews are available.[158,176,189,190,194,195] Most of these studies were independent. A US HTA[176] found that trials were of a low- or moderate-quality. The main focus of the review was to compare the different drugs used to treat UUI. In one study, multicomponent behavioural modification produced significantly greater reductions in incontinence episodes compared to oxybutynin and higher patient satisfaction for behavioural vs. drug treatment. One RCT showed a substantial benefit for sacral neuromodulation compared with medical therapy [196]. In men with storage LUTS no difference in efficacy was found between oxybutynin and behavioural therapy.[197] The combination of BT and solifenacin in women with OAB conferred no additional benefit in terms of continence.[198] Two small RCTs,[199,200] reported a similar improvement in subjective parameters with either transcutaneous electrical nerve stimulation or T-PTNS. However, only oxybutynin treated patients showed significant improvements in objective urodynamic parameters (bladder capacity). The oxybutynin-treated group had more side effects. One study compared tolterodine ER to transvaginal/anal electrical stimulation without differences in UI outcomes.[201] One small RCT found that the addition of P-PTNS to tolterodine ER improved UI and QoL.[202] Mirabegron Mirabegron is the first clinically available beta 3 agonist, available from 2013. Beta 3 adrenoceptors are the predominant beta receptors expressed in the smooth muscle cells of the detrusor and their stimulation is thought to induce detrusor relaxation.

mirabegron[251,252] reported that mirabegron at doses of 25, 50 and 100 mg, results in significantly greater reduction in incontinence episodes, urgency episodes and micturition frequency/24 hrs than placebo, with no difference in the rate of common adverse events.[251] The placebo dry rates in most of these trials are between 35-40%, and 43 and 50% for mirabegron. In all trials the statistically significant difference is consistent only for improvement but not for cure of UI. Similar improvement in frequency of incontinence episodes and micturitions/24 hrs was found in people who had previously tried and those who had not previously tried antimuscarinic agents. The most common treatment adverse events in the mirabegron groups were hypertension (7.3%), nasopharyngitis (3.4%) and UTI (3%).[251] In a 12-month, active-controlled RCT of mirabegron 50/100 mg vs. tolterdine ER 4 mg, the improvement in efficacy seen at 12 weeks was sustained at 12-month evaluation in all groups. The reported dry rates at 12 months were 43%, 45% and 45% for mirabegron 50 mg, 100 mg and tolterodine 4 mg respectively.[253] No risk of QTc prolongation on electrocardiogram[254] and raised intraocular pressure[255] were observed up to 100 mg dose, however patients with uncontrolled hypertension or cardiac arrhythmia were excluded from these trials. There is no significant difference in rate of side effects at different doses of mirabegron.[253] Evaluation of urodynamic parameters in men with combined BOO and OAB concluded that mirabegron (50 or 100 mg) did not adversely affect voiding urodynamic parameters compared to placebo.[256] Equivalent adherence was observed for tolterodine and mirabegron at 12 months (5.5% and 3.6%), although the incidence of dry mouth was significantly higher in the tolterodine group.[253] In mirabegron treated patients, improvement in objective outcome measures correlates directly with clinically relevant PROMs (OAB-q and PPBC).[257,258] References available on request

Mirabegron has undergone evaluation in industry-sponsored phase 2 and phase 3 trials. Two systematic reviews of all currently reported studies assessing the clinical effectiveness of

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52 Event Gallery US Research Award for Cormac Taylor The American Physiological Society (APS) has announced that Professor Cormac Taylor, a leading University College Dublin (UCD) researcher, is to be presented with the 2017 Takeda Distinguished Research Award by the Society’s Gastrointestinal and Liver Physiology Section. The prestigious award is presented annually to an outstanding investigator who is internationally recognised for his/her contribution to physiological research in these areas. This is the first time that this award will be presented to a scientist located outside the United States since it was established in 2007. The announcement of the Award to Professor Taylor, Professor of Cellular Physiology at the UCD School of Medicine, was made at the 2016 APS Experimental Biology meeting held in San Diego. The award will be presented to Professor Taylor at the 2017 meeting to be held in Chicago. UCD’s Professor Cormac Taylor said, “I am delighted and honoured with the announcement that I am to be the recipient of the 2017 Takeda Distinguished Researcher Award. This honour is a testament to the hard work of all of the PhD students and postdocs who have trained over the years in my lab at University College Dublin. I believe that the award underscores the importance of investigator-led basic research in medicine." Professor Taylor leads a research group at the UCD Conway Institute investigating the

mechanisms by which epithelial cells respond to low oxygen levels (hypoxia). The group explores the regulation of gene expression in hypoxic conditions and the potential of

targeting of oxygen-sensitive cellular pathways in inflammation as a means of treating conditions such as inflammatory bowel disease (IBD).

Tallaght Hospital joins community groups for Green Ribbon Tallaght Hospital recently held a unique and exciting event about the importance of happiness in order to promote positive mental health. The event, entitled How to Stay Happy, took place on May 11th at 10am in the Fettercairn Community Centre in Tallaght. The initiative is part of Tallaght Hospital’s programme of activity for the Green Ribbon campaign on mental health, which takes places throughout the month of May. It also underlines Tallaght Hospital’s continued commitment to providing the best possible care and advice to patients, as highlighted by the 2014 Health Assets and Needs Assessment Report.

Dr Siobhán Ni Bhriain, Catherine Heaney, Emma Freeman and Professor Brendan Kelly, Tallaght Hospital

June 2016 • HPN

Dr Siobhán Ni Bhriain, Consultant Psychiatrist and Chair of the Medical Board at Tallaght Hospital said, “This is the first time we have tried to organise an event like this and the reaction from community groups is extremely positive. I believe the event will be a very valuable contribution to the national Green Ribbon campaign and the open conversation we all need to have about mental health, this is essential if we are to ever remove the stigma from it. People experience lots of stresses and strains in their daily lives and therefore is it so important to appreciate the importance of happiness and how to be happy. Positive mental health does not always happen automatically. It is important to work at it every day. With this public talk we hope to be able to provide some useful advice to people on how to do this.”


53 Professor Steinhoff Receives 2016 SFI-Pfizer Innovation Award

Professor Martin Steinhoff, UCD Charles Institute (2nd Left) along with Professor Mark Ferguson, Director General of Science Foundation Ireland and Chief Scientific Adviser to the Government of Ireland, Dr Paul Duffy, Vice President, Biopharmaceutical Operations and External Supply, Pfizer, Mr Damien English, TD, Minister for Research, Skills and Innovation

underlying skin inflammation and associated chronic itch, for which there remains a significant unmet clinical need. His team hopes to generate targeting molecules that will block the activation of key players involved in chronic itch and pain. Professor Steinhoff and his team will have the unique opportunity to work with the Pfizer Global Biotherapeutics Technology (GBT) group, at Grangecastle in Dublin, as well as Pfizer’s R&D innovation engine, the Centers for Therapeutic Innovation, focusing on the application of cutting edge technologies for next generation protein therapies. Professor Martin Steinhoff (UCD Professor of Dermatology and Director of the UCD Charles Institute) has been awarded one of three recipients of the 2016 SFI-Pfizer Biotherapeutics Innovation Award which were announced recently by Science Foundation Ireland.

discoveries for patients of unmet needs in the areas of immunology, oncology, cardiovascular and rare diseases. Awards were made to researchers from only three Irish academic institutions including the Royal College Surgeons (RCSI), University College Cork (UCC) and University College Dublin (UCD).

This prestigious funding award provides qualified academic researchers with an opportunity to deliver important potential

Professor Martin Steinhoff (MD, PhD) leads a translational research team attempting to understand the molecular mechanisms

Placing the award in context, Professor Steinhoff noted, “Science Foundation Ireland has early recognised the huge potential of strong academic industry partnerships. My group is very happy to partner for a second time with Pfizer, a world-wide key player in innovative drug development, to develop new innovative drugs in a medical field with a significant unmet medical need, which will hopefully help hundreds of million people with chronic pain or itch.”

Spotlight shone on stories of cancer survivorship The Marie Keating Foundation supported by Roche unveiled their mediumsized garden - ‘Out the Other Side: A Garden of Hope’ - at Bord Bia’s Bloom over the June Bank Holiday weekend. The garden’s aim was to shine a light on cancer survivorship and was inspired by the ‘Out the Other Side: Stories of Breast Cancer Survival’ photographic exhibition, which received an overwhelmingly positive response from the public during its time in St. Stephen’s Green in October of last year. The Garden of Hope’s colour scheme symbolised the emotions often experienced by women at various stages of their breast cancer journey. The beginning of the path was lined with dark purple and red foliage, plants and flowers, representing the feelings women may experience when they are first diagnosed or when they face difficulties during treatment. Towards the end of the path, the plants gradually lighten with lots of white appearing at the end as a colour that reflects new beginnings, protection and encouragement. The original ‘Out the Other Side’ photographic exhibition, created by Roche in partnership with the Marie Keating Foundation, has already visited University Hospital Galway and Mater Misericordiae University Hospital earlier this year as part of the national roadshow.

Liz Yeates, CEO of the Marie Keating Foundation, Country Medical Director, Roche Products (Ireland) Limited, Dr Michal Starnawski and garden designer Tünde Szentesi

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54 Clinical R&D 12TH ANNUAL CONGRESS OF THE EUROPEAN CARDIAC ARRHYTHMIA SOCIETY (ECAS) 2016 Bayer AG and its development partner Janssen Pharmaceuticals, Inc. have announced results from a new real-world study, REVISIT-US. In REVISIT-US reduced rates of ischemic stroke accompanied by reduced rates of intracranial haemorrhage (ICH) were seen with Xarelto® (rivaroxaban) versus warfarin in patients with non-valvular atrial fibrillation (AF). These results complement and reaffirm findings from the Phase III ROCKET AF clinical trial as well as the noninterventional XANTUS study. Results from REVISIT-US, which analysed nearly 23,000 real-world patients in the United States, were presented at the 12th Annual Congress of the European Cardiac Arrhythmia Society. REVISIT-US was a retrospective claims analysis performed using US MarketScan claims data evaluating the real-world occurrence of ischemic stroke and intracranial haemorrhage (ICH) in patients with non-valvular AF taking either rivaroxaban or warfarin. In this real-world setting rivaroxaban (n=11,411) was seen to be associated with a non-significant 29% decrease in ischemic stroke accompanied by a significant 47% reduction in ICH vs. warfarin (n=11,411). Looking at the combined endpoint of ICH and ischemic stroke, rivaroxaban resulted in a significant 39% reduction vs. warfarin in REVISIT-US. These results confirm the positive benefit-risk-profile of Xarelto as determined in the Phase III ROCKET AF clinical trial as well as the non-interventional XANTUS study. “In the management of patients with AF, ischemic stroke and intracranial haemorrhage are the two events both physicians and patients fear most,” said Professor Craig Coleman, Professor of Pharmacy Practice at the University of Connecticut, U.S. who presented the REVISITUS results at ECAS. “Finding the appropriate balance of benefit and risk is always the goal. It is therefore highly reassuring to see that results from the real world continue to confirm that rivaroxaban is striking the appropriate balance of reducing stroke whilst at the same time also reducing the risk of intracranial haemorrhage in patients with non-valvular AF.” June 2016 • HPN

“Although pivotal Phase III studies like ROCKET AF remain the gold standard to evaluate the efficacy and safety of a drug, real-world evidence plays an important role in complementing the knowledge about the use and impact of our medicines in everyday clinical practice,” said Dr Michael Devoy, Head of Medical Affairs & Pharmacovigilance of Bayer AG’s Pharmaceuticals Division and Bayer Chief Medical Officer. “We are pleased that study after study evaluating Xarelto in the real world across the spectrum of approved indications continues to confirm the positive benefit-risk profile of Xarelto.” REVISIT-US adds to the extensive investigation of rivaroxaban, which by the time of its completion, is expected to include more than 275,000 patients in both clinical trials and real-world settings.

EUROPEAN COMMISSION APPROVES TREVICTA® (PALIPERIDONE PALMITATE A 3-MONTHLY INJECTION) Janssen-Cilag International NV announced that the European Commission (EC) has approved the use of TREVICTA® (paliperidone palmitate a 3‑monthly injection) for the maintenance treatment of schizophrenia in adult patients. TREVICTA will provide the longest dosing interval available for an antipsychotic medication in the European Union, allowing patients to maintain an optimal level of treatment in their blood with fewer administrations, compared to currently available antipsychotic treatments. This may improve outcomes for patients, carers and healthcare professionals. TREVICTA is indicated for the maintenance treatment of schizophrenia in adult patients who are clinically stable on XEPLION®­, a 1-monthly paliperidone palmitate product that was approved in 2011 for the maintenance treatment of schizophrenia in the European Union. “Non-adherence to medication is a significant contributor to relapse and progression of schizophrenia in patients,” said Dr Roy Browne, consultant psychiatrist, Phoenix Care Centre, Dublin. “As a threemonthly treatment Trevicta increases the time between treatments, compared to current therapies, helping to relieve the burden of taking daily medication and greatly reducing the risk of

non-adherence. It also offers healthcare professionals and carers reassurance that the person with schizophrenia is benefiting from continuous delivery of medication between administrations, while allowing patients, when stable, less frequent attendances at outpatient clinics.” The marketing authorisation for TREVICTA is based on two Phase 3 studies. The first was a randomised, multi-centre, double-blind, placebo-controlled relapse prevention study in more than 500 patients with schizophrenia.3 The second was a randomised, multi-centre, double‑blind study comparing the efficacy and safety of paliperidone palmitate 3‑monthly and 1-monthly formulations. TREVICTA was found to be at least as effective in preventing relapse as the paliperidone palmitate 1‑monthly formulation and was not associated with any new or unexpected safety signals. As with all medications, some patients may experience side effects. The most frequently observed adverse drug reactions reported in ≥ 5% of patients in the two double-blind controlled clinical trials of paliperidone palmitate 3-monthly injection were: increased weight, upper respiratory tract infection, anxiety, headache, insomnia and injection site reaction. The decision from the EC follows a Positive Opinion recommending the approval of TREVICTA from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) in April 2016.1 This approval allows for the marketing of TREVICTA in all 28 member states of the European Union as well as the European Economic Area countries (Norway, Iceland and Liechtenstein).

SUPERIOR EFFICACY SEEN WITH ROCHE’S INVESTIGATIONAL COMPOUND OCRELIZUMAB VERSUS COMPARATORS Roche in Ireland has announced that investigational multiple sclerosis (MS) therapy ocrelizumab has shown superior efficacy across clinical and subclinical outcomes compared with interferon beta- 1a in people with Relapsing MS (RMS) and compared with placebo in Primary Progressive MS (PPMS). The new data from three Phase

III studies of the investigational medicine ocrelizumab was presented during the American Academy of Neurology (AAN) Annual Meeting, which took place from 15th to 21st April 2016 in Vancouver, Canada. The latest data, which investigate a composite endpoint, No Evidence of Disease Activity (NEDA), were presented from two Phase III studies in RMS. A composite of key measures of disease activity that assesses level of disease control, patients were considered to have achieved NEDA if they have no relapses, no disability progression and no new or enlarging MRI lesions over 96 weeks of clinical trial. It was also demonstrated that ocrelizumab significantly and consistently suppressed inflammatory and neurodegenerative markers of disease on MRI vs interferon beta- 1a in OPERA I and OPERA II over 96 weeks, with nearcomplete elimination of new T1 gadolinium-enhancing lesions following the first dose. The majority of new/enlarging T2 lesions and new T1 hypointense lesions occurred before week 24 and significantly declined thereafter. Pooled analyses of OPERA I and OPERA II efficacy endpoints showed that ocrelizumab significantly suppressed disease progression and increased the proportion of patients with disability improvement over 96 weeks compared with interferon beta- 1a. The efficacy demonstrated by ocrelizumab in the new analyses further substantiate the Confirmed Disability Progression (CDP) results from the OPERA trials. The data also show that CD20+ B-cell targeting with ocrelizumab has a robust effect in reducing disability progression in MS.


55 DISCONTINUATION NOTICE Notice of Discontinuation of the following products from the Irish Market: · Lariam (mefloquine) 250 mg Tablets (PA 50/73/1) · Roferon-A solution for injection in pre-filled syringe (PA 50/68/20 - PA 50/68/23) · Cymevene 500 mg Powder for Concentrate for Solution for Infusion (PA 50/125/2) Roche Products (Ireland) Limited (“Roche”) wish to inform you of the planned discontinuation of the following products from the Irish market: · Lariam 250 mg Tablets (PA 50/73/1) · Cymevene 500 mg Powder for Concentrate for Solution for Infusion (PA 50/125/2) · Roferon-A 3 million international units (IU) solution for injection in pre-filled syringe (PA 50/68/20) ·

Roferon-A 4.5 million international units (IU) solution for injection in pre-filled syringe (PA 50/68/21)

· Roferon-A 6 million international units (IU) solution for injection in pre-filled syringe (PA 50/68/22) · Roferon-A 9 million international units (IU) solution for injection in pre-filled syringe (PA 50/68/23) The discontinuation is effective from 31 July 2016. Stock remaining in circulation is expected to last until end of August 2016 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. Pharmacists are also being advised to advance warning to patients (with repeatable prescriptions) when they have their supply dispensed so that patients can visit their doctor and make alternative arrangements.

CANCER PERCEIVED AS SECOND MOST SEVERE HEALTH CONDITION BEHIND CHRONIC PAIN Pfizer Healthcare Ireland recently released cumulated data on cancer as derived from an analysis of 10 years of the Pfizer Health Index study. In total, a cumulated sample of 9,178 interviews over the period 2006 to 2015 was analysed. Cancer is among the most severe and debilitating of the medical conditions studied as part of the Pfizer Health Index. When we look at how cancer patients perceive their own health, 51% describe themselves as being in poor health, 39% feel that

their health is average with 10% considering themselves to be in good health. In this regard they have quite a similar perspective to those with chronic pain, heart disease and depression. 64% categorise their illness as severe or moderately severe, placing cancer second only to chronic pain in terms of perceived severity. Those experiencing cancer under the age of 50 are more likely to regard their illness as mild. Those who have cancer are slightly more likely to be women than men: 55% of cancer patients are women and the balance (45%) men. There is a heavy concentration of cancer patients over the age of 50, with a median age of incidence of 61 years. The data also illustrates that as many as 68% of cancer patients have been for a scheduled check-up in the past month. As such, cancer patients have the highest level of planned medical interaction across the full survey, having seen doctors more recently for check-ups than any other patient group. According to National Cancer Registry of Ireland there are approximately 27,000 women living with breast cancer in Ireland. [ii] The incidence of female breast cancer in Ireland is 12.5% higher than the EU average[iii] with over 2800 new cases of breast cancer diagnosed each year. Unfortunately, women diagnosed with earlier stages of breast cancer have a nearly 30 percent chance that their cancer will eventually progress to metastatic disease. [iv] Irish mortality rates are the 3rd highest in the EU with over 680 Irish women dying from breast cancer each year. “In addition to the clinical and emotional burden posed by mBC, there is compelling evidence that women with mBC often lack the information, support and care they need” said Michael Riordan, Oncology Lead, Pfizer Healthcare Ireland. “Later this year Pfizer plan to conduct research into the specific challenges facing metastatic breast cancer patients with the aim to develop initiatives that close the gap on information, support and awareness.” “There is much to be celebrated in the tremendous progress that has been made in fighting breast cancer in the past several decades. But metastatic breast cancer is not part of that celebration. It remains, to this day, largely an incurable condition” said Paul Reid, Country Manager, Pfizer Healthcare Ireland. “Pfizer is committed to ongoing research in oncology and in the area of metastatic breast cancer where

Anna Meagher, Senior Brand & Customer Manager, Cardiovascular, MSD and Clinical Nurse Specialist Shauna Connolly there remains an unmet need for innovative treatments.”

PATIENT BOOKLETS ROLLED OUT TO CARDIAC REHAB CLINICS ACROSS IRELAND The Cardiac Rehab Team in St. Columcille’s Hospital, Loughlinstown, Dublin and healthcare company MSD have developed two Cardiac Rehab Booklets, to help support patients who are recovering from a heart attack, a stent or heart surgery, which are being distributed to clinics across Ireland. The booklets contain educational information around cardiac rehab, risk factors, symptoms and treatment of cardiovascular disease, types of exercise to start as well as the do’s and don’ts of training, and ways to increase physical activity. Cardiac Rehab is a series of care that provides education and exercise sessions to patients to help increase physical fitness, improve general health and reduce the rise of future heart problems. The two booklets; Your Guide to Cardiac Rehab and Exercise and Your Heart Health are designed to complement the cardiac rehab programme delivered in hospital and give patients and their families useful and practical information that they can use at home. Anna Meagher, Senior Brand & Customer Manager, Cardiovascular at MSD, is pictured on cardiac rehab exercise equipment with Clinical Nurse Specialist Shauna Connolly, at the launch of the Cardiac Rehab Booklets in St. Columcille's Hospital, Loughlinstown, Dublin.

ACTELION’S UPTRAVI (SELEXIPAG) GRANTED EUROPEAN MARKETING AUTHORISATION Actelion Pharmaceuticals UK have announced that Uptravi (selexipag), a selective IP prostacyclin receptor agonist,

has been granted marketing authorisation for the long-term treatment of pulmonary arterial hypertension (PAH) in the EU by the European Commission. Uptravi has been licensed for the long-term treatment of PAH in adult patients with WHO functional class (FC) II-III, either as a combination therapy in patients insufficiently controlled with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor, or as monotherapy in patients who are not candidates for these therapies. PAH is a chronic, life-threatening disorder affecting between 6,000-7,000 people in the UK. The condition is characterised by abnormally high blood pressure in the arteries between the heart and lungs of an affected individual. Advances in research mean the prognosis and treatment of PAH today has shifted to that of a long-term condition, however it remains a progressive, potentially devastating disease with high rates of morbidity and mortality. The efficacy of Uptravi has been demonstrated in the GRIPHON trial, a long-term Phase III study in PAH patients with idiopathic and inherited PAH (58%), PAH associated with connective tissue disorders (29%) and PAH associated with corrected simple congenital heart disease (10%). The GRIPHON trial evaluated Uptravi’s safety and efficacy in a long-term, placebo-controlled study enrolling 1,156 patients with symptomatic PAH. The exposure to Uptravi was up to 4.2 years with a median duration of exposure of 1.4 years. The most commonly reported adverse reactions related to the pharmacological effects of Uptravi were headache, diarrhoea, nausea and vomiting, jaw pain, myalgia, pain in extremity, arthralgia and flushing.

HPN • June 2016


THE POWER TO MOVE YOU DEMONSTRATED POWERFUL PAIN RELIEF1,a For the symptomatic relief of1 Osteoarthritisb

30-60mg once daily

Rheumatoid Arthritis Ankylosing Spondylitis

90mg once daily

For the short-term treatment of1 Postoperative Moderate Dental Surgery Pain

90mg

Acute Gouty Arthritis

120mg

once daily, maximum 3 days

once daily, maximum 8 days

90mg once daily

ARCOXIA® Film-coated Tablets Prescribing Information Refer to the Summary of Product Characteristics (SmPC) before prescribing. Presentation: Arcoxia 30 mg (blue-green), 60 mg (dark green), 90 mg (white), 120 mg (pale green) film-coated tablets containing 30 mg, 60 mg, 90 mg and 120 mg etoricoxib respectively. Indication: Adults and adolescents 16 years of age and older for the symptomatic relief of osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis (AS), and pain and signs of inflammation associated with acute gouty arthritis. Adults and adolescents 16 years of age and older for short-term treatment of moderate pain associated with dental surgery. Dosage and method of administration: Shortest duration of treatment and lowest effective dose should be used as cardiovascular risk may increase with dose and duration of exposure. Need for symptomatic relief and response to therapy should be re-evaluated periodically especially in patients with OA. Administer orally with or without food. OA: 30 mg o.d. If insufficient relief, 60 mg once daily (o.d.) may increase efficacy. RA and AS: 90 mg o.d. Acute gouty arthritis: 120 mg o.d., maximum 8 days treatment. Postoperative dental surgery pain: 90 mg o.d., limited to maximum of 3 days. Do not exceed recommended dose or duration of treatment. Elderly: No dosage adjustments necessary. Exercise caution. Hepatic impairment: do not exceed 60 mg dose in mild dysfunction. Do not exceed 30 mg dose in moderate dysfunction. Renal impairment: No dosage adjustments required in creatinine clearance ≥ 30 ml/min. Contraindications: Hypersensitivity to ingredients, active peptic ulceration or active gastro-intestinal (GI) bleeding, patients who after taking acetylsalicylic acid or non-steroidal anti-inflammatory drugs (NSAIDs) including cyclooxygenase-2 (COX-2) inhibitors experience bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticarial or allergic-type reactions, pregnancy and lactation, severe hepatic dysfunction, estimated renal creatinine clearance < 30 ml/min, children and adolescents under 16 years, inflammatory bowel disease, congestive heart failure, patients with hypertension whose blood pressure is persistently elevated above 140/90 mmHg and has not been adequately controlled, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. Special warnings and precautions: Gastrointestinal effects: Upper GI complications, some resulting in fatal outcome have occurred with etoricoxib. Caution in patients at risk of developing GI complications with NSAIDs; elderly using other NSAID or acetylsalicyclic acid concomitantly or patients with history of GI disease. Increased risk of GI adverse effects when taken concomitantly with acetylsalicyclic acid. Cardiovascular effects: Class of drugs may be associated with risk of thrombotic events. Careful consideration in patients with significant risk factors for cardiovascular events (hypertension, hyperlipidaemia, diabetes mellitus, smoking). Do not discontinue anti-platelet therapies. Renal effects: Consider monitoring of renal function in patients with pre-existing significantly impaired renal function, uncompensated heart failure or cirrhosis. Fluid retention, oedema and hypertension: Caution in patients with history of heart failure, left ventricular dysfunction or hypertension and in pre-existing oedema. Take measures to discontinue treatment if deterioration of condition. Control hypertension before initiating treatment and monitor blood pressure within two weeks after initiation and periodically thereafter. Hepatic Effects: Monitor patients with symptoms and/ or signs of liver dysfunction, or in whom abnormal liver test has occurred. Discontinue if signs of hepatic insufficiency or persistent abnormal liver function test. General: Caution when initiating treatment in patients with dehydration. Serious skin reactions, some fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported very rarely in association with NSAIDs and some selective COX-2 inhibitors. Serious hypersensitivity reactions (anaphylaxisis and angioedema) have been reported. Discontinue at first appearance of skin rash, mucosal lesions or any other sign of hypersensitivity. Etoricoxib may mask fever and other signs of inflammation. Caution when coadministering with warfarin or other oral anticoagulants. Contains lactose. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take Arcoxia. Interactions: Pharmacodynamic Interactions: Oral anticoagulants: Closely monitor for increase in prothrombin time International Normalised Ratio in patients also receiving oral anticoagulants, particularly in first days of treatment initiation or etoricoxib dose change. Diuretics, ACE inhibitors and Angiotension II antagonists: Effectiveness of diuretics and other antihypertensive drugs may be reduced. Caution when combining ACE inhibitor or Angiotensin II inhibitor with cyclooxygenase inhibitors due to possible deterioration of renal function, including acute renal failure, especially in the elderly. Consider monitoring renal function after initiation of concomitant therapy, and periodically thereafter. Acetylsalicyclic acid: Not recommended with doses of acetylsalicylic acid above those for cardiovascular prophylaxis (low dose) or with other NSAIDs due to possible increased rate of GI ulceration

or other complications. Cyclosporin and tacrolimus: Coadministration of cyclosporine or tacrolimus with any NSAID may increase nephrotoxic effect. Monitor renal function if concomitantly used. Pharmacokinetic (PK) Interactions: Effect of etoricoxib on other drugs: Lithium: NSAIDs decrease lithium renal excretion and therefore increase lithium plasma levels. If necessary monitor blood lithium closely and adjust lithium dosage. Methotrexate: Monitor for methotrexate-related toxicity when administered concomitantly. Oral contraceptives: Etoricoxib has shown to increase concentration of ethinyl estradiol when coadministered with oral contraceptives; this can increase the incidence of adverse events associated oral contraceptives. Hormone Replacement Therapy: Evidence of increases in estrogenic concentration in concomitant use; consider when selecting post-menopausal hormone therapy for use with etoricoxib. Prednisone/prednisolone: No clinically important effects. Digoxin: Monitor patients at high risk for digoxin toxicity when administered concomitantly due to possible increase of digoxin Cmax. Drugs metabolised by sulfotransferases: Etoricoxib inhibits human sulfotransferase. Care when concomitantly administering with other drugs primarily metabolised by human sulfotransferases (e.g. oral salbutamol, minoxidil). Drugs metabolised by CYP isoenzymes: Not expected to inhibit cytochrome P450 enzymes. Effect of other drugs on Etoricoxib: Etoricoxib is metabolised by CYP enzymes. Ketoconazole: 400mg o.d. for 11 days did not have clinically important effect on single dose PK of 60 mg etoricoxib. Voriconazole (oral) and Miconazole (oral gel): Co-administration of either with etoricoxib caused slight increased exposure of etoricoxib but not clinically significant. Rifampicin: Co-administration produced decrease in etoricoxib concentrations. Etoricoxib doses higher than those studied are not recommended. Antacids: Does not affect PK of etoricoxib. Pregnancy and lactation: Not recommended. If woman becomes pregnant during treatment, etoricoxib must be discontinued. Do not use during breast feeding. Not recommended when attempting to conceive. Driving and using machines: Patients who experience dizziness, vertigo or somnolence when on treatment should refrain from driving or operating machinery. Undesirable effects: Very common (≥1/10): Abdominal pain. Common (≥1/100, <1/10): Alveolar osteitis, oedema/fluid retention, dizziness, headache, palpitations, arrhythmia, hypertension, bronchospasm, constipation, flatulence, gastritis, heartburn/acid reflux, diarrhoea, dyspepsia/epigastric discomfort, nausea, vomiting, oesophagitis, oral ulcer, ALT increase, AST increased, ecchymosis, asthenia/ fatigue, flu-like disease. Other important undesirable effects: Upper respiratory infection, leukopenia, hypersensitivity, atrial fibrillation, tachycardia, congestive heart failure, angina pectoris, myocardial infarction, cerebrovascular accident, transient ischaemic attack, hypertensive crisis, vasculitis, gastroduodenal ulcer, peptic ulcers including gastrointestinal perforation and bleeding, pancreatitis, hepatitis, hepatic failure, StevensJohnson syndrome, toxic epidermal necrolysis, angioedema/ anaphylactic/ anaphylactoid reactions including shock. Additional information available on request. Overdose: Remove unabsorbed material from GI tract, clinical monitoring, institute supportive therapy, if required. Not dialyzable by haemodialysis; not known whether dialyzable by peritoneal dialysis. Legal classification: POM. Marketing Authorisation numbers and pack sizes: Arcoxia 30 mg film-coated tablets: PA1997/1/1 28 pack, 60 mg film-coated tablets: PA1997/1/2 28 pack, 90 mg film-coated tablets: PA1997/1/3 5 and 28 pack, 120 mg film-coated tablets: PA1997/1/4 7 and 28 pack. Marketing Authorisation Holder: Merck Sharp & Dohme BV, Waarderweg 39, 2031 BN Haarlem, The Netherlands. Date of Preparation: December 2015. Ref: IRE/A15 0002(1)a References: 1. Arcoxia SmPC, www.medicines.ie. a. Doses greater than those recommended for each indication have either not demonstrated additional efficacy or have not been studied. Due to cardiovascular risks, the shortest duration possible and the lowest effective daily dose of ARCOXIA® should be used. b. The recommended dose for osteoarthritis is 30 mg once daily. An increased dose of 60 mg once daily may increase efficacy. The dose for osteoarthritis should not exceed 60 mg daily.1 Date of Preparation: February 2016. IRE/A16 0001c

Grünenthal Pharma Ltd., Dublin, Ireland, www.grunenthal.ie

HPN June 2016  
HPN June 2016  
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