Page 1

Issue 10


Hospital Pharmacy Awards 2013

The Finalists Issue



News: Galway University Hospital launch Antimicrobial Prescribing Guidelines App Page 4

XTANDI is a direct approach to treating metastatic castration – resistant prostate cancer post – docetaxel1-3. XTANDI directly & potently targets AR receptor signalling at three steps of the AR pathway: Blocking androgen binding; preventing nuclear translocation of the AR; impairing DNA binding – preventing modulation of gene expression.1-5 Take hold of mCRPC in a brand new way.

Report: Advances made in understanding childhood cancer neuroblastoma Page 12 Drug news: Twice daily dosing approval for Incivo Page 16 Awards: Presenting the Hospital Pharmacy Awards 2013 finalists Page 20

XTANDI (enzalutamide) 40 mg soft capsules. Prescribing Information: Please read the Summary of Product Characteristics (SPC) before prescribing.Presentation: XTANDI 40 mg soft capsules each containing 40 mg of enzalutamide. Indications: XTANDI is indicated for the treatment of adult men with metastatic castration resistant prostate cancer whose disease has progressed on or after docetaxel therapy. Dosage and administration: The recommended dose is 160 mg enzalutamide (four 40 mg capsules) as a single oral daily dose. For further details please refer to the SPC. Contra-indications: Hypersensitivity to the active substance or to any of the excipients. Women who are, or who may become, pregnant. Precautions and warnings: Caution should be used in administering XTANDI to patients with a history of seizures or other predisposing factors. The risk of seizure may be increased in patients receiving concomitant medicinal products that lower the seizure threshold. Caution is required in patients with severe renal impairment as enzalutamide has not been studied in this patient population. Caution is required in patients with moderate hepatic impairment. XTANDI contains sorbitol (E420). Patients with rare hereditary problems of fructose intolerance should not take this medicinal product. Interactions: Co-administration with warfarin and coumarin like anticoagulants should be avoided. If XTANDI is co administered with an anticoagulant metabolised by CYP2C9, additional monitoring should be conducted. CYP2C8 plays an important role in the

elimination of enzalutamide and in the formation of its active metabolite. Strong inhibitors (e.g. gemfibrozil) or inducers (e.g. rifampicin) of CYP2C8 are to be avoided or used with caution during enzalutamide treatment. If patients must be co administered a strong CYP2C8 inhibitor, the dose of enzalutamide should be reduced to 80 mg once daily. CYP3A4 plays a minor role in the metabolism of enzalutamide and no dose adjustment is necessary when XTANDI is co administered with inhibitors or inducers of CYP3A4. Enzalutamide is a potent enzyme inducer and increases the synthesis of many enzymes and transporters; therefore, interaction with many common medicinal products that are substrates of enzymes or transporters is expected. The reduction in plasma concentrations can be substantial, and lead to lost or reduced clinical effect. There is also a risk of increased formation of active metabolites. Food has no clinically significant effect on the extent of exposure to enzalutamide. In clinical trials, XTANDI was administered without regard to food. Pregnancy and lactation: Enzalutamide is not for use in women. Enzalutamide is contraindicated in women who are, or who may become, pregnant. If the patient engages in sexual intercourse with a woman of childbearing potential, a condom and another form of birth control must be used during and for 3 months after treatment. Side effects: Very Common (≥ 1/10): headache, hot flush; Common (≥ 1/100 to < 1/10): neutropenia, visual hallucinations, anxiety, cognitive disorders, memory impairment, hypertension,

dry skin, pruritus, fractures, falls; Uncommon (≥ 1/1,000 to < 1/100): leucopenia, seizure, amnesia, disturbance in attention. Please refer to the SPC for further details of other side effects. Legal category: POM/S1A Marketing Authorisation numbers: EU/1/13/846/001. Marketing Authorisation holder: Astellas Pharma Co., Ltd, 5 Waterside, Citywest Business Campus, Dublin 24. Ph +353 1467 1555 References: 1. XTANDI Summary of Product Characteristics, 2013. 2. Tran C et al. Science 2009; 324(5928): 787–790. 3. Hu R et al. Expert Rev Endocrinol Metab. 2010; 5(5): 753–764. 4. Scher H et al. N Engl J Med. 2012; 367(13): 1187–1197. 5. Heinlein CA, Chang C. Androgen receptor in prostate cancer. Endocr Rev. 2004: 25; 491 – 503 Date of preparation: June 2013. XTANDI/06 2013/447. Adverse events associated with this drug should be reported to the IMB or to Astellas at

CPD: Bipolar Affective Disorder Page 27 Feature: Small molecule inhibitors for the treatment of RA Page 40


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Issue 10



Research success for Tralee hospital pharmacist P4


Kelly Jo Eastwood

Exclusive interview with Pfizer Ireland’s new Managing Director Paul Reid P9

Henry Rollins once said, “We know that in September, we will wander through the warm winds of summer's wreckage. We will welcome summer's ghost.”

Over €9 raised to fund clinical trials in new class of drugs P14

As we all settle back into a daily working routine those feelings of despair brought about by the Summer’s end should be further away as we examine the submissions and nominations for the inaugural Hospital Pharmacy Awards 2013. And to echo the sentiments of Henry Collins, we should welcome the summer’s ghost and more aptly the submissions and nominations that were made pre the summer for this premier event.


Hospital Pharmacy Awards 2013 – The finalists! P20 Trinity pharmacy students cycle around Ireland P51

Regulars Pharmacist management of Bipolar Affective Disorder P27

Hospital Pharmacy News is delighted to announce the finalists for the Hospital Pharmacy Awards Ceremony to be held in Santry’s Crowne Plaza Hotel on September, 21st, 2013.


From one first to another and this month the Royal College of Surgeons of Ireland School of Pharmacy have announced a Memorandum of Understanding with the pharmacy department at Saint John of God Hospital.

Small molecule inhibitors for the treatment of RA P44 Natriuretic Peptide–Based Screening and Collaborative Care for Heart Failure P48 Clinical profiles P53 51

Appointments P54

This MoU, the first one to be undertaken with a psychiatric teaching hospital, aims to enhance the educational opportunities available to undergraduate pharmacy students and will witness the development of inter-professional, work-based educational initiatives between the two organisations.

Hospital Pharmacy News is Circulated to all independent, multiple and hospital pharmacist, pre reg pharmacists, students pharmacy student’s offi cial bodies, government officials and departments, Pharmacy Managers, Manufactures, Wholesalers. Buyers of pharmacy groups and healthcare outlets. Circulation is free to all pharmacists Subscription rate for Hospital Pharmacy News 60euro plus vat per year All rights reserved by Hospital Pharmacy News. All material published in Hospital Pharmacy News is copyright and no part of this magazine may be reproduced, stored in a retrieval system of transmitted in any form without written permission. Pharmacy Communication Ireland have taken every care in compiling the magazine to ensure that it is correct at the time of going to press, however the publishers assume no responsibility for any effects from omissions or errors.

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

SALES MANAGER Debbie Graham Mobile: 0044 7450274112

Never before has it been more critical to nurture and develop the opportunities available to pharmacy students as they enter a profession faced with such uncertainty and challenge. Howevr they are the future, and such a partnership must be welcomed.

Elsewhere in this issue, EAHP Scientific Committee member Gunar Stemer sets out some of the key aspects to be addressed when writing an abstract for conference or poster presentations, whilst Galway University Hospitals pharmacy department along with colleagues, have launched a new mobile app for Antimicrobial Prescribing Guidelines.

CONTRIBUTORS Ronan Sheridan Kay McNamee Fiona McCann Dr Mark Ledwidge

MANAGING DIRECTOR Natalie Maginnis EDITOR Kelly Jo Eastwood

ART DIRECTED BY Smart Page Design

ACCOUNTS Julie Daly HospitalPharmacyNews

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The treatment suitable for Adults, Children & Infants Formulated to control and reduce the symptoms associated with diarrhoea.

HPN • Issue 10

4 News

Pharmacy team develop new Antimicrobial App Connie Merrick, Hospital Speciality Representative, MSD; Dr Eithne McCarthy, Consultant Microbiologist, GUH; Dr Deirbhile Keady, Consultant Microbiologist, GUH; Marie Tierney, Antimicrobial Pharmacist, GUH; Mick Phelan, Business Unit Director, MSD; and Dr Pat Nash, Group Clinical Director, Galway and Roscommon University Hospitals Group.

Galway University Hospitals pharmacy department along with colleagues, have launched a new mobile app for Antimicrobial Prescribing Guidelines. Prof Martin Cormican, Consultant Microbiologist and member of antimicrobial stewardship team said, “Since

their development over 60 years ago, antibiotics have helped to treat millions of patients with bacterial infections. Many of the advances in modern medicine such as cancer, chemotherapy and organ transplants would not be possible without them. However antibiotics have often been misused; antibiotics are

often used when they are not needed and sometimes when antibiotics are needed the antibiotic used may not be best antibiotic for that situation. We have to take steps to improve the use of antibiotics otherwise we risk squandering one of the most important medical advances of the past 100 years. “Over the past number of years we have made significant inroads in improving antimicrobial prescribing by developing user friendly guidelines that benefit patient care. The mobile app we are launching here today was

developed by a team of people to provide a user friendly version of our antimicrobial guidelines which we give to our staff in print format, with one version for adults and one for children. The app means that staff have information on the best antibiotic to use for each infection at their fingertips, it is extremely easy to use and it also means that we can update the information very quickly.” The development of the app was kindly supported by an educational grant from healthcare company MSD.

IMB publish interchangeable medicines The IMB has published online the initial list of interchangeable medicines containing groups of atorvastatin products. This follows the completion of a consultation process as required under the Health (Pricing and Supply of Medical Goods) Act 2013. The role of the IMB under this legislation is to establish, publish and maintain a "List of Interchangeable Medicines" on its website.

There are 96 atorvastatin products included on the list in four separate groups. Products are grouped together according to their active substance, strength, pharmaceutical form and the route of administration. Those using the website can also search the list using this information. For patients, the publication of the list of interchangeable

atorvastatin products means that their pharmacist may now offer them an alternative atorvastatin medicine to the one named on their prescription. Pharmacists can only recommend an alternative if it is deemed interchangeable by the IMB and included on the list.

active substance is assessed, it will be added to the list and published on their website. It is the role of the HSE to establish a reference price for medicines on the published list. It is expected that the reference price for atorvastatin will be confirmed in November.

The IMB’s immediate priority will be to review a further 19 active substances. As each

Cardiovascular risk assessment training The Irish Heart Foundation and the Irish Pharmacy Union will hold a Cardiovascular Risk Assessment Training Day for Pharmacists 22nd October 2013. This one-day course will be held in the Clarion Hotel Liffey Valley. The cost of the Training Day is ¤250. Please see programme and registration available at

Issue 10 • HPN


Pharmacy Hospital Memorandum of Understanding Saint John of God Hospital, one of the leading providers of mental health treatment and care services in Ireland, has announced an official collaboration between its Pharmacy Department, and the School of Pharmacy at the Royal College of Surgeons in Ireland (RCSI). The Memorandum of Understanding aims to enhance the educational opportunities available to undergraduate pharmacy students. This is the first time that the RCSI School of Pharmacy has undertaken a Memorandum of Understanding with a psychiatric teaching hospital. The partnership will see the development of inter-professional, work-based educational initiatives between the two organisations. Clinical work placements and structured site visits will help give pharmacy students an insight

into the Hospital's multi-faceted approach to the treatment of mental illness and person-centred care. The agreement will also facilitate collaborative research between the two organisations. According to Dolores Keating, Head of Pharmacy at Saint John of God Hospital, the Memorandum is an important step forward for the Hospital: "As a teaching hospital, education is a core part of the ethos and mission of the organisation. Pharmacists have an important role to play in the delivery of high quality mental health services. I hope that this collaboration will help pharmacists support people with mental illness on their recovery journey." Speaking at the Hospital to mark the announcement, Professor Hannah McGee, Dean of the Faculty of Medicine and Health Sciences, RCSI said: "The Pharmacy Department here at

Prof McGhee Saint John of God Hospital has established, under the leadership of Ms. Dolores Keating, a record as leading in innovation in pharmacy services and facilitating multidisciplinary care. It is with the greatest of pleasure therefore that today I sign this Memorandum of Understanding between our School of Pharmacy

and this prestigious Hospital. This Memorandum will enable our undergraduate pharmacy students and interns to have more access to clinical patient care scenarios; to learn from the clinical expertise of Ms. Dolores Keating and Ms Audrey Purcell; and to facilitate clinical research opportunities between our two institutions."

The NCCP drug protocols are being developed based on the latest evidence, related to the management of specific cancers, under the guidance of a Medical Consultant. The intention is to develop these protocols on a collaborative basis with the health care professionals involved in the drug treatment of cancer patients.

To this end, the NCCP would like to invite all pharmacists, involved in the treatment of patients with cancer, to register their interest in collaborating in these landmark developments.

NCCP drug protocols The National Cancer Control Programme has announced that work is commencing on the development of national drug protocols, for the treatment of patients with cancer, for those drugs already in use. The aim of these protocols is to support the safe,

evidence-based, and cost-effective cancer treatment of all cancer patients in Ireland. Once the protocols have been developed and approved, they will be disseminated to the hospitals involved in the care of cancer patients, in addition to being published on the NCCPwebsite.

Expressions of interest should be emailed to:

Organ transplant regulations Alex White, Minister of State at the Department of Health has strongly endorsed the European Union (Quality and Safety of Human Organs Intended for Transplantation) Regulations 2012 (Statutory Instrument No. 325 of 2012) which transposed EU Directive 2010/53/EU into Irish Law and which came into effect on 27 August 2012. This is against the background of the recall of Seanad Éireann to meet on 20 August to discuss a motion calling for the annulment of this Statutory Instrument.

Minister White said that these Regulations set out a clear legal framework for the quality and safety standards for organs intended for transplantation, pointing out that the aim is to ensure the safety and quality of organs as well as the protection of organ donors and recipients. “The Regulations provide for the authorisation of procurement and transplantation centres and activities, for traceability systems, as well as for the reporting of serious adverse events and reactions” said the Minister. “Moreover”, he added “they

set requirements for the safe transportation of organs and for the characterisation of every donor and organ”. “There is absolutely no reason to annul this Statutory Instrument” said Minister White. Under the Regulations, every hospital or healthcare facility at which any activity relating to donation, testing, characterisation, procurement, preservation, transport or transplantation of organs takes place must be authorised by the Irish Medicines Board” said the Minister. “Following the granting

of an authorisation, the hospital or healthcare facility in question will be inspected by the IMB at regular intervals to ensure compliance” he added. Meanwhile, the Department of Health has launched a public consultation (details on www. on the system of consent for organ donation and interested parties are invited to submit their views by 20th September. However, the Minister stressed that the consent issue was totally outside the scope of the issues covered by the EU Directive.

HPN • Issue 10

6 News

¤12.3 million HRB investment in pharmaceutical programmes Are current increases in suicide rates linked to the recession? This question, and many more, will be examined through a ¤12.3 million investment by the Health Research Board (HRB) in Irish research programmes.

Prof Aransman

Professor Ella Arensman of the National Suicide Research Foundation in collaboration with the Department of Epidemiology and Public Health and the Department of General Practice, University College Cork, will examine psychosocial, psychiatric and work-related risk factors associated with suicide in Ireland. The aims of the study are to improve the knowledge base on specific risk factors associated with suicide in Ireland and to gain insight into specific protective factors that prevent people from engaging in suicide. A total of 40 projects were selected from 209 applications. These were assessed by international peer review panels

who believed the nature, scope and relevance of the proposals demonstrated great ambition and innovation that would lead to results that are relevant both nationally and internationally. Each project will receive up to ¤330,000 over the next three years. Selected summaries Professor Ella Arensman of the National Suicide Research Foundation will examine whether there is a link between suicide rates and the recession. Dr Sean Dineen, National University Ireland, Galway, is investigating an intervention that will improve outcomes for young adults living with Type 1 Diabetes. Professor Dermot Kenny in the Royal College of Surgeons in Ireland is investigating the role of blood groups as a risk for heart attack. Professor Anne McFarlane at University of Limerick will examine

how to reconfigure the Irish Primary Care service for maximum benefit to patients and their families in the community. Dr Patricia Fitzpatrick, University College Dublin, is evaluating the clinical and economic benefits of introducing the new-born screening programme for cystic Fibrosis. Professor Stewart Walsh, University of Limerick, will conduct trials to help prevent adverse events in major vascular surgery. Dr Lucy Norris, Trinity College Dublin, is developing a risk score model she believes will help accurately identify whether gynaecological cancer patients at high risk of blood clotting in the veins or lungs. Dr Thomas Ritter, National University Galway will develop a new topical treatment for skin inflammation using adult stems cells.

The FIP hospital programme Dublin looks forward to welcoming 3,000 international delegates to the International Pharmaceutical Federation (FIP) Congress which takes place later this month from August 31 until September 5 with a full and varied hospital pharmacy programme. This includes a symposium on healthcare data and safeguarding confidentiality. Health professionals, including pharmacists, have increasing

need for access to patient data for clinical review of complex patients. In parallel there are social changes which are tending to restrict access to patient data. This session has been intended to explore the legal and ethics relating to the issue and give participants pointers to help their own practice. In addition there are workshops including the role of compounding in therapeutic

gaps. Featuring sessions, symposia, workshops, discussions and exhibitions focused on global pharmacy practice and pharmaceutical sciences. Titled “Towards a future vision for complex patients – integrated care in a dynamic continuum”, the Congress represents ¤4 million in revenue to the Irish economy, before the added benefits of delegates’ families travelling and related tourist plans across Ireland are factored in.

HPAI Annual Conference 2014 The HPAI annual education conference will take place in April 2014. Registration will open in January 2014. Poster abstracts will be accepted from the start of Issue 10 • HPN

January, so start thinking about possible entries.

member of IMPACT to be a full HPAI member.

HPAI membership is due at the start of January – please renew your membership before registration. You need to be a

To contact the education subcommittee re any aspect of conference 2013, please e-mail:

The Congress also features an Exhibition which offers a unique opportunity to display the services of industry partners, both global and local, from Sunday, August 31 until Wednesday, September 4. In particular there will be a technology showcase featuring a number of innovative Irish and international start-ups providing cutting-edge products and technologies that are designed to enhance pharmacy and patient outcomes world-wide.

Cholestagel: an engineered BAS in a tablet formulation

When standard LDL-C treatments are not enough

Legal category: POM. Further information is available from: Sanofi 18 Riverwalk, Citywest Business Campus, Dublin 24 or contact Tel.: (01) 4035600. Please refer to the Summary of Product Characteristics which can be found at before prescribing. Information about adverse event reporting can be found at Adverse events should be reported to the Sanofi Drug Safety Department at the above address.

GBIE.COL.13.07.04 Date of preparation: July 2013

Sustain response. Reduce recurrence1,2

Treat C. difficile infection...

...and help release your patients from the threat of recurrence1,2 Abbreviated Prescribing Information - DificlirTM Presentation: DIFICLIR film-coated tablets containing 200 mg fidaxomicin. Indications: DIFICLIR is indicated in adults for the treatment of Clostridium difficile infections (CDI) also known as C. difficile-associated diarrhoea. Posology: Adults including elderly: 200 mg administered twice daily for 10 days with or without food. Children: no data available. Renal and hepatic insufficiency: No dose adjustment is considered necessary (see special warnings and precautions) Contraindications: Hypersensitivity to active substance or any of the excipients. Special Warnings and Precautions: Due to limited clinical data, fidaxomicin should be used with caution in patients with severe renal impairment or moderate to severe hepatic impairment, pseudomembranous colitis,

fulminant or life threatening CDI or concomitant inflammatory bowel disease. Co-administration of potent P-glycoprotein inhibitors, such as cyclosporine, ketoconazole, erythromycin, clarithromycin, verapamil, dronedarone and amiodarone are not recommended. Drug interactions: DIFICLIR is both a substrate and may be an inhibitor of intestinal P-glycoprotein. DIFICLIR had a small but not clinically relevant effect on digoxin exposure. However, a larger effect on P-glycoprotein substrates with lower bioavailability or which are more sensitive to intestinal P-glycoprotein inhibition such as dabigatran etexilat cannot be excluded. Pregnancy and Lactation: Pregnancy: There are no data available. Animal studies did not indicate direct or indirect harmful effects. It is preferable to avoid the use of DIFICLIR during

pregnancy. Breast-feeding: It is unknown whether fidaxomicin and its metabolites are excreted in human milk. Although no effects on the breastfed newborns / infants are anticipated, a risk cannot be excluded. Undesirable Effects: The most common treatment related adverse reactions were vomiting (1.2%), nausea (2.7%) and constipation (1.2%). Uncommon adverse events reported in clinical trials included decreased appetite, dizziness, headache, dysgeusia, abdominal distension, flatulence, dry mouth, alanine aminotransferase increased. Consult DIFICLIR Summary of Product Characteristics for a full list of side effects. Legal Classification: Prescription Only Medicine (POM). Packs: Blister cards: 20 x 1 film coated tablets (10 x 2 cards) EU Number (PA Number): EU/1/111/733/001004. MA holder: Astellas Pharma Europe B.V.

References: 1. Cornely O.A. et al. Lancet Infect Dis 2012;12:281-89. 2.Louie T.J. et al. New Engl J Med 2011 ;364 :422-31

Sylviusweg 62, 2333 BE Leiden, The Netherlands. Date of Preparation of API: January 2013 Summary of product characteristics and further information from: Astellas Pharma Co Ltd, 5 Waterside, Citywest Business Campus, Naas Road, Dublin 24. Tel: 01 4671555 Adverse Events should be reported to Astellas Pharma Co. Ltd.

Dificlir/02 2013/384



Largest ever survey of hospital pharmacy practice The European Association of Hospital Pharmacists (EAHP) has announced the publication of a new booklet which provides a detailed summary of the largest ever survey undertaken of hospital pharmacy practice in Europe. EAHP Survey 2010: Hospital Pharmacy Practice in Europe is the collected analysis of a comprehensive survey, conducted throughout 2010, which investigates the many facets of current practice in hospital pharmacies across 30 different countries. The booklet, published by BMJ, contains the full series of articles that were originally published in The European Journal of Hospital Pharmacy. The articles observe the differences of practice between countries, as well as prevailing common trends in practice, with the intention of providing thought-provoking stimulus for any reader involved in hospital pharmacy service development.

pharmacies in Europe producing sterile as well as non-sterile medicines has decreased significantly since 2000. In addition, the number of pharmacies preparing total parenteral nutrition, cytotoxics and intravenous admixtures (24.6%, 43.8% and 8.0% of pharmacies, respectively) is quite low and depends to a large extent on the size of the pharmacies, with larger units generally demonstrating significantly higher production activity. There are some

differences between eastern and western Europe. Quality control and good manufacturing practice (GMP) seem to be well implemented (61.3% of pharmacies have adopted GMP) and many pharmacies have external certification. This is especially the case for the production of stock sterile medicines, which the 2010 survey shows to be less than half of that recorded in the 2000 survey (decreasing from 66.8% to 29.9% of pharmacies).

However, the 2010 survey also recorded a 32% decrease (from 71.0% to 48.5% of pharmacies) since 2000 in pharmacy involvement in the production of individual sterile preparations. Production for all preparations is highly dependent on the size of the hospital with the larger units recording significantly more production activity. While reagents for laboratories are seldom produced in hospital pharmacies (16.5% of pharmacies), production

The results of the survey will also guide future work by EAHP in delivering its mission of developing the hospital pharmacy profession across Europe. Production and quality assurance Dr Frontini and colleagues submitted a paper on production and quality assurance. The pan-European survey of hospital pharmacy practice conducted by the European Association of Hospital Pharmacists (EAHP) is an important source of information for understanding future professional challenges and system development needs in Europe. The methodology and the background of the 2010 survey were previously described. In this article the authors present the production and quality assurance findings. The number of hospital

HPN â&#x20AC;˘ Issue 10

10 Report surveys. There were significant differences between countries in relation to the average number of beds served by one hospital pharmacy (only complete hospitalisations, figure 3).

Figure 2

of nonsterile medicines is common, especially for individual prescriptions (65.8 of pharmacies). Across Europe, only 43.8% of pharmacies reconstitute cytotoxics: this practice occurs in around 80% of large hospitals but in <20% of small hospitals (as they may not need this service). Centralisation of admixtures is still quite low (max. 8.5% of pharmacies for all units and 23.5% for special units) but in contrast compounding of total parenteral nutrition (TPN) seems to be well developed (64.7% of the very large hospitals).This is not surprising considering the high costs of the facilities needed in particular for the aseptic production. In eastern Europe, only in the Czech Republic and Hungary are a large number of pharmacies (57.1% and 57.4%, respectively) licensed to produce investigational medicinal products (IMPs). In western Europe, Denmark (100%), Sweden (81.3%) and Spain (62.7%) have the highest percentages of IMP licences. Very few hospital pharmacies are involved in advanced therapies and only 1.9% have a gene therapy licence. Only Austria, Denmark, Germany, Hungary, Issue 10 • HPN

Italy, Norway, Portugal and Spain have issued such licences, with Denmark having the most (28.6%) licensed pharmacies. Only oncology hospitals are involved in advanced therapy (6.3%). Quality of production is high as 61.3% of pharmacies reported that GMP has been implemented (n=949) and 64.4% have a written procedure for the recall of their own products (n=964). However, the situation differs by country (figure 2).

compared with the USA and has not grown significantly since 1995. Therefore, it can be problematic to make direct comparisons between hospital pharmacy services in the USA and Europe. A total of 4748 heads of pharmacy were contacted in all member states through a network of national coordinators.

Comparisons with the survey from 2000 and 2005 showed that in most of the countries there was a trend towards increasing the number of beds served, which was probably caused by the closing and merging of pharmacies. Comparing staffing in hospital pharmacies in Europe and the USA highlights some important differences: a hospital pharmacy in USA has, on average, 19-fold the pharmacists in Europe (17.5 to 0.9 FTE/100 beds complete hospitalisations). Similar differences can also be observed for PT: in USA, on average, 15-fold greater numbers (1.0 to 15.0 PT FTE/100 beds complete hospitalisations). Even taking into account the different educational systems between the USA and Europe— which could have different staffing as a consequence— direct comparisons between hospital pharmacy services in the USA and Europe are problematic. You can view the document in full by visiting

In addition, a paper is published within the document on general frames and staffing.

The collected data were analysed by country (30 European countries), by size of the hospital (number of beds— 12 groups), by type of hospital (seven groups) and also in comparison with previous EAHP

The average number of beds served by one pharmacy had not changed since 2005 but there was a decrease in complete and an increase in partial hospitalisation. Pharmacists (27%) and qualified technicians (32%) make up 60% of the total staff. The number of pharmacists/100 beds varies from 0.24 (Bosnia and Herzegovina) to 4.35 (UK). Only a few countries did not experience shortages of pharmacists and technicians. European hospital pharmacy staffing (pharmacists and pharmacy technicians) remains, on average, low

Figure 3: Average number of beds served by one pharmacy by country (n=1139).

General frame and staffing

NOW, LESS IS MORE LESS DISRUPTION MORE FREEDOM New INCIVO twice-daily dosing The ONLY PROTEASE INHIBITOR to offer a simple morning and evening dose for your chronic hepatitis C genotype 1 patients1

MORE SIMPLICITY* INCIVO® 375mg film-coated tablets PRESCRIBING INFORMATION ACTIVE INGREDIENT(S): Telaprevir Please refer to Summary of Product Characteristics (SmPC) before prescribing. INDICATION(S): Only in combination with peginterferon alfa and ribavirin, for treatment of genotype 1 chronic hepatitis C in adult patients with compensated liver disease (including cirrhosis): treatment naïve or previously treated with interferon alfa (pegylated or non-pegylated) alone or combination with ribavirin, including relapsers, partial and null responders. DOSAGE & ADMINISTRATION: Adults: Three 375 mg tablets, orally twice daily. Alternatively, two 375 mg tablets orally every 8 hours. Take tablets with food, swallow whole (total daily dose: 6 tablets) for 12 weeks, in combination with peginterferon alfa-2a or -2b and ribavirin. Refer to peginterferon alfa and ribavirin SmPC for specific dosage instructions. Total treatment duration of peginterferon alfa and ribavirin either 24 or 48 weeks refer to INCIVO SmPC All patients: Patients with HCV  RNA >  1,000  IU/ml at week  4 or 12 should discontinue all therapy. In case of 48 weeks treatment, discontinue peginterferon alfa and ribavirin if HCV RNA detectable at week 24 or 36. Do not reduce or interrupt INCIVO treatment. Do not restart INCIVO treatment if discontinued for ADRs or insufficient virologic response. When taken twice daily, missed dose can be taken within 6 hours. When taken three times daily, missed dose can be taken within 4 hours. Otherwise skip dose and resume normal dosing schedule. Children: <18 years old - no data available. Elderly: Limited data ≥ 65 years old. Renal impairment: No dose adjustment . No data on moderate/severe Renal impairment (CrCl ≤  50  ml/ min) or haemodialysis. Hepatic impairment: Dose modifications not required in mild hepatic impairment (Child-Pugh A, score 5-6). Not recommended in moderate to severe impairment (ChildPugh  B or  C, score ≥  7) or decompensated liver disease. Peginterferon alfa and ribavirin are contraindicated in ChildPugh score ≥  6. CONTRAINDICATIONS: Hypersensitivity to INCIVO tablets. Combinations with strong inducers of CYP3A and active substances highly dependent on CYP3A for clearance where resulting elevated plasma concentrations associated with serious and/or life-threatening events. Do not use with medicines such as: alfuzosin, amiodarone, bepridil, quinidine, astemizole, terfenadine, cisapride, pimozide, ergot derivatives, lovastatin, simvastatin, atorvastatin, sildenafil or tadalafil (only when used for treatment of pulmonary arterial hypertension), oral midazolam and triazolam, rifampicin, St. John’s wort, carbamazepine, phenytoin, phenobarbital. Concomitant Class Ia or III antiarrhythmics, except intravenous (IV) lidocaine. Refer to SmPCs for peginterferon alfa and ribavirin for their contraindications. SPECIAL WARNINGS & PRECAUTIONS: Rashes: Severe, potentially life-threatening and fatal skin reactions have been reported with INCIVO combination

MORE CONVENIENCE* MORE ADHERENCE*2 treatment; inform patients. Monitor all rashes for progression. Consider consultation with dermatology specialist for moderate rash (≤ 50% of body surface area). If rash severe (> 50% of body surface area), discontinue INCIVO immediately; consult dermatology specialist; peginterferon alfa and ribavirin may need to be discontinued. Discontinue INCIVO, peginterferon alfa and ribavirin if generalised bullous eruption, Drug Rash with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson syndrome (SJS) /toxic epidermal necrolysis (TEN), acute generalised exanthematous pustulosis, erythema multiforme suspected/diagnosed; consult dermatology specialist. Fatal cases have been reported in patients who continued to receive INCIVO combination treatment after developing a severe of rash (TEN). Do not restart INCIVO if discontinued due to skin reaction. Anaemia: Incidence and severity of anaemia increased with INCIVO combination treatment. Regularly monitor haemoglobin prior to and during treatment. Management of anaemia, see SmPC for ribavirin. If ribavirin permanently discontinued, INCIVO must also be permanently discontinued. If INCIVO discontinued for anaemia, may continue treatment with peginterferon alfa and ribavirin. Do not reduce dose of INCIVO or restart if discontinued. Pregnancy and contraception: see ‘Pregnancy’ below, see also SmPC for ribavirin. Cardiovascular: Significance of modest increase in QTcF interval uncertain. Use with caution with Class Ic antiarrhythmics propafenone and flecainide and other QT prolonging medicines. Avoid in patients with congenital QT prolongation, or family history of congenital QT prolongation or sudden death. Caution in patients with: history of acquired QT prolongation; persistent heart rate < 50  bpm; history of heart failure with reduced left-ventricular ejection fraction; with medicinal products known to prolong QT interval. Clinical and ECG monitoring required. Monitor and correct electrolyte disturbances. Laboratory tests: Monitor HCV RNA levels at least at weeks  4 and  12. Prior to treatment, monitor complete blood count with white blood cell differential counts, electrolytes, serum creatinine, liver function tests, TSH, uric acid and at least at weeks  2, 4, 8 and 12. Combination with peginterferon alfa-2b: No clinical data on treatment-experienced patients and limited data in treatment-naïve patients. Thyroid disease: Risk of increased TSH. Monitor TSH levels before and during treatment. Possible dose adjustment of thyroid replacement therapy. No clinical data on retreating patients who have failed HCV NS3-4A protease inhibitorbased therapy; in pre/peri/post-liver or other transplants; with HCV/HBV co-infection. INCIVO is a strong inhibitor of CYP 3A4, refer to ‘Contraindications’ and ‘Interactions’. Limited data in HIV/ HCV co-infection. Tablets contain sodium. SIDE EFFECTS: Very common (≥ 1/10): anaemia, nausea, diarrhoea, vomiting, haemorrhoids, proctalgia, pruritus, rash. Common (≥ 1/100 to < 1/10): oral candidiasis, thrombocytopenia, lymphopenia, hypothyroidism, hyperuricaemia, hypokalameia, dysgeusia, syncope, anal pruritus, rectal haemorrhage, anal fissure,

1. INCIVO Summary of Product Characteristics, available at April 2013. 2. Sievert W et al. J Hepatol 2013; 58(Suppl 1): S373.

*Compared to INCIVO dosing every 8 hours. The total dose is 6 tablets per day.1 Adverse events should also be reported to Janssen-Cilag Ltd on 0044 1494 567447

hyperbilrubinaemia, eczema, swelling face, exfoliative rash, oedema peripheral, product taste abnormal. Serious side effects: DRESS, SJS, TEN, retinopathy. Refer to INCIVO SmPC for other side effects. Refer to peginterferon alfa and ribavarin SmPC for associated side effects. PREGNANCY: Not recommended. Males and females (of childbearing potential) and their partners must use 2 effective non-hormonal contraceptives during treatment and for 2 months after INCIVO treatment ended. Refer to peginterferon alfa and ribavirin SmPC. LACTATION: Discontinue breast-feeding prior to therapy. INTERACTIONS: Co-administration with CYP3A and/or P-gp inducers may markedly decrease telaprevir plasma concentrations; avoid use with mild/moderate CYP3A inducers. CYP3A and/or P-gp inhibitors may increase telaprevir plasma concentrations. INCIVO inhibits CYP3A4 and P-gp. Strong CYP3A4 inhibition is time dependant, intensifies over first 2 weeks and after discontinuation can take 1 week to disappear, may increase systemic exposure to substrates of CYP3A or P-gp. Refer to C/Is. Avoid domperidone. Rifabutin, darunavir/ritonavir, fosamprenavir/ ritonavir, lopinavir/ritonavir, salmeterol, vardenafil not recommended. Inhaled/nasal fluticasone/budesonide not recommended unless benefit/risk positive. Avoid colchicine in renal or hepatic impairment. Caution with: Class Ic antiarrhythmics propafenone and flecainide, trazodone, systemic dexamethasone, abacavir, zidovudine, ethinylestradiol/norethindrone. Caution and clinical monitoring with IV lidocaine, clarithromycin, erythromycin, telithromycin, troleandomycin, ketoconazole, itraconazole, posaconazole, voriconazole, parenteral midazolam, amlodipine, diltiazem, felodipine, nicardipine, nifedipine, nisoldipine, verapamil, bosentan, fluvastatin, pitvastatin, pravastatin, rosuvastatin, repaglinide, methadone. Clinical and concentration monitoring with: digoxin, dabigatran, atazanavir/ritonavir, tenofovir, disoproxil fumarate, cyclosporine, tacrolimus, sirolimus. Careful monitoring advised with warfarin (monitor INR), fentanyl and alfentanil, dose adjustment may be necessary. Use telaprevir 1,125 mg every 8 hours with efavirenz. Clinical relevance of changes unknown for alprazolam, escitalopram, zolpidem. LEGAL CATEGORY: Prescription only medicine. PRESENTATIONS, PACK SIZES, PRODUCT LICENCE NUMBERS- 375mg film coated tablets; pack of 42 tablets (1 week) EU/1/11/720/002 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 2013 Prescribing information last revised: May 2013 PIVER0513. Date of preparation: June 2013 PHIR/INC/0513/0004a.

12 News

National early warning scorecard An electronic early-warning scorecard to help medical staff identify deteriorating patients which may improve patient outcomes has been developed at University College, Cork. The electronic National Early Warning Scorecard is currently on trial across a number of acute hospital settings. The paper based version of the National Early Warning Scorecard was introduced by the Health Service Executive’s (HSE) across all acute hospitals in 2011/12 as a patient safety measure. This is to help overcome the potential for the late detection of patient deterioration. If not identified early enough there can be a number of serious consequences for patient care along with increased healthcare costs, medical staff workload, and greater strain on hospital resources. The electronic National Early Warning Scorecard (e-NEWS) enables staff to undertake a systematic approach to the

identification and management of deteriorating patients to improve their outcome. e-NEWS provides a suite of intelligent decision support interfaces, built on a number of mobile platforms, which can integrate signals from remote medical devices such as wireless body area networks and patient sensors developed by the Tyndall

National Institute along with patient devices from OmronTM, GE HealthcareTM and PhilipsTM. This will provide healthcare professionals with a more accurate and timely picture of the status of their patient, enabling them to implement clinical care earlier which will improve patient outcomes and recovery time.

The project is being led by Professor Frédéric Adam (Principal Investigator) and a team of researchers at the Health Information Systems Research Centre (HISRC), University College Cork including Dr John O’Donoghue, Dr Simon Woodworth, Dr Tom O’Kane, Siobhán O’Connor and Fred Creedon.

Advances in understanding the childhood cancer neuroblastoma A significant advance in the understanding of a childhood cancer called Neuroblastoma has been made by scientists from the Smurfit Institute of Genetics at Trinity College Dublin. The TCD group led by Dr. Adrian Bracken and funded by Science Foundation Ireland, has just published their findings in the leading international journal, Developmental Cell. Neuroblastoma is the most common cancer in children younger than two years. As its

name suggests, Neuroblastoma is a cancer of special nerve cells called neuroblasts, which are found throughout the body. Normally, these immature cells grow and mature into functioning nerve cells. However, in Neuroblastoma, they fail to mature and become cancer cells instead. This new research explored the function of CHD5. The CHD5 gene is deleted in children with the worst form of Neuroblastoma. Chris Egan,

the lead author on the study, and a post-doctoral fellow in the laboratory of Dr Bracken, together with colleagues at the Karolinska Institute in Stockholm, showed that without CHD5, neuroblasts are incapable of maturing or “differentiating” to mature neurons. Commenting on the study, Dr Adrian Bracken said: “Understanding the role of genes whose deletion or inactivation is associated with disease is central to designing intelligent

therapeutic strategies. Our work has unravelled the normal function of the CHD5 gene, and suggests that its inactivation in neuroblastoma leads to an inability of these cells to correctly mature or differentiate. Our future work will assess the potential benefit of reactivating CHD5 in neuroblastoma cells which usually retain one silenced copy of this gene. We hope that this research will lead to new and improved treatments for children with this disease.”

Pharmacy innovations showcased New technology innovations designed to enhance pharmacy and patient outcomes across the world will be showcased to 3,000 international delegates visiting Dublin as part of a major Issue 10 • HPN

pharmaceutical congress this month. The technology exhibition, part of the International Pharmaceutical Federation (FIP) Congress 2013 will feature a

number of innovative Irish and international start-ups supplying cutting-edge products and services in the pharmaceutical area. The event this year has the

aim of advocating increasing roles for pharmacists in the management of complex patients, and providing an extensive platform for learning and growth in this respect.

New Clexane® and Clexane® Forte safety lock syringes CLEXANE® CONFIDENCE AT YOUR FINGERTIPS Automatic release of the safety mechanism when the plunger is fully depressed

to gned Desi st again t c e prot ck le sti need 1 ies injur

Needle completely covered by the protection cap immediately after the injection

Clear product identification

Clear visibility of expiry date

Colour-coded labelling and clear identification of CLEXANE® syringes by dose



Over 350 million patients treated with Clexane worldwide

References: 1. CLEXANE® Summary of Product Characteristics. sanofi 2. Sanofi IMS data on file April 2012

CLEXANE® SYRINGES AND CLEXANE® FORTE SYRINGES PRESCRIBING INFORMATION Presentation: Clear, colourless to pale yellow solution of either 100mg enoxaparin per 1ml (anti-factor Xa activity of 10,000IU/ml with reference to the WHO First International LMW Heparin Reference Standard) or 150mg enoxaparin per 1ml (anti-factor Xa activity of 15,000IU/ml). Clexane® Syringes: single dose pre-filled syringes containing either: 20mg enoxaparin in 0.2ml (2,000IU), 40mg enoxaparin in 0.4ml (4,000IU), 60mg enoxaparin in 0.6ml (6,000IU), 80mg in 0.8ml (8,000IU) or 100mg in 1ml (10,000IU). Clexane® Forte Syringes: single dose pre-filled syringes containing either: 120mg enoxaparin in 0.8ml (12,000IU) or 150mg in 1ml (15,000IU). Indications: Prophylaxis of thromboembolic disorders of venous origin, in particular those associated with orthopaedic or general surgery and in medical patients bedridden due to acute illness. Treatment of venous thromboembolic disease presenting with deep vein thrombosis, pulmonary embolism or both. Treatment of unstable angina and non-Q-wave myocardial infarction, administered concurrently with aspirin. Prevention of thrombus formation in the extracorporeal circulation during haemodialysis. Clexane 100mg/ml syringes only: Treatment of acute ST-segment Elevation Myocardial Infarction (STEMI) including patients to be managed medically or with subsequent Percutaneous Coronary Intervention (PCI) in conjunction with thrombolytic drugs (fibrin or non-fibrin specific). Dosage & Administration: Prophylaxis: Patients with low to moderate risk of thromboembolism, e.g. general surgery, recommended dose of Clexane® is 20mg (2,000IU) once daily subcutaneously. Clexane® should be continued for 7 to 10 days or until risk of thromboembolism has diminished. Longer durations may be appropriate in some patients following hip replacement. Patients undergoing surgery, initial dose approximately 2 hours preoperatively. Patients with high risk of venous thromboembolism, e.g. orthopaedic surgery, the recommended dose is 40mg (4,000IU) once daily subcutaneously, initial dose being given approximately 12 hours preoperatively. Medical patients bedridden due to acute illness, the recommended dose is 40mg (4,000IU) once daily for a minimum of 6 days until return to full ambulation, for a maximum of 14 days. Longer durations may necessary if it is there is an ongoing significant risk of thromboembolic events beyond 14 days. Treatment: Subcutaneous administration either as a single injection of 1.5mg/kg (150 IU/kg) or as a twice daily injection of 1 mg /kg (100 IU/kg) usually for 5 days and until adequate oral anticoagulation is established. Unstable angina and non-Q-wave myocardial infarction recommended dose is 1mg/kg (100IU/kg) every 12 hours subcutaneously, administered concurrently with oral aspirin 100 to 325mg once daily. Treatment should be for minimum of 2 days and continued until clinical stabilisation, usual duration 2 to 8 days. Clexane 100mg/ml syringes only: Treatment of STEMI, the recommended dose is a single IV bolus of 30mg, plus a 1mg/kg SC dose followed by 1mg/kg administered SC every 12 hours (max 100mg for the first two doses only, followed by 1mg/kg dosing for the remaining doses) for 8 days or until hospital discharge, whichever comes first. For dosage in patients ≥75 years of age, see elderly section. When used with a thrombolytic (fibrin specific or non-fibrin specific) Clexane® should be given between 15 minutes before and 30 minutes after the start of fibrinolytic therapy. All patients should receive aspirin 75 to 325mg once daily unless contraindicated. For patients managed with PCI: If the last Clexane® SC administration was given less than 8 hours before balloon inflation, no additional dosing is needed. If the last SC administration was given more than 8 hours before balloon inflation, an IV bolus of 0.3mg/kg of Clexane® should be administered. During haemodialysis: 1mg/kg (100IU/kg) Clexane® introduced into arterial line of the circuit at beginning of dialysis. This dose is usually sufficient for a 4 hour session. If fibrin rings are found, e.g. after a longer session, a further 0.5 to 1mg/kg (50 to 100IU/kg) may be given. In patients with high risk of haemorrhage reduce the dose to 0.5mg/kg (50IU/kg) (double vascular access) or 0.75mg/kg (75IU/kg) (single vascular access). Elderly: Clexane 100mg/ml syringes only: For treatment of STEMI in patients ≥75 years of age, do not use an initial IV bolus. Initiate dosing with 0.75mg/kg SC every 12 hours (maximum 75mg for the first two doses only, followed by 0.75mg/kg dosing for the remaining doses). For other indications, no dosage adjustment necessary unless kidney function is impaired. Children: Not recommended. Renal impairment: Dosage adjustment required for patients with severe renal impairment. Contraindications: Acute bacterial endocarditis; active major bleeding and conditions with a high risk of uncontrolled haemorrhage, including recent haemorrhagic stroke or subdural haematoma; thrombocytopenia in patients with positive in vitro aggregation test in presence of Clexane®; in jaundice; active gastric/duodenal ulcer; hiatal ulceration; threatened abortion or retinopathy; hypersensitivity to enoxaparin, heparin or other LMWH. Warnings and Precautions: Clexane® must not be administered by the intramuscular route. Different low

molecular weight heparins may not be equivalent; alternative products should not be substituted during therapy. Neuraxial haematomas may occur when Clexane® is used concomitantly with spinal/epidural anaesthesia. Haemodynamically unstable patients with pulmonary embolism may require alternative treatment. Use in patients with prosthetic heart valves has not been adequately studied and is not recommended. Clexane® should be used with care in hepatic insufficiency, history of thrombocytopenia, and conditions or patients with increased bleeding potential (such as those with peptic ulcers, recent ischaemic stroke, uncontrolled severe arterial hypertension, diabetic retinopathy, renal impairment, elderly and extremes of weight). Platelet counts should be measured prior to initiation of Clexane® and regularly during treatment. Heparins can suppress adrenal secretion of aldosterone leading to hyperkalaemia. Following vascular instrumentation adhere precisely to recommended dose intervals. If a closure device is used, the sheath can be removed immediately. If a manual compression method is used, sheath should be removed 6 hours after the last IV/SC enoxaparin sodium injection. If treatment is to be continued, the next scheduled dose should be given no sooner than 6 to 8 hours after sheath removal. The site of the procedure should be observed for signs of bleeding or haematoma formation. Pregnancy: Clexane® should be used during pregnancy only if the physician has established a clear need. Lactation: Advise avoidance of breast-feeding. Interactions: Discontinue unless essential agents affecting haemostasis, e.g. oral anticoagulants, thrombolytics, systemic glucocorticoids, NSAIDs, aspirin, clopidogrel. If the combination cannot be avoided, careful clinical and laboratory monitoring is recommended. Adverse Reactions: Bleeding, including retroperitoneal and intracranial, with or without the presence of associated risk factors, such as invasive procedures or use of medications affecting haemostasis. Thrombocytopenia, including rare cases of immuno-allergic thrombocytopenia with thrombosis. Elevation of liver enzyme levels and platelet count, and cutaneous or systemic allergic reactions (including anaphylactic/ anaphylactoid reactions, and very rarely cutaneous vasculitis) have been reported. At site of injection: pain, haematoma, irritation, rarely hard inflammatory nodules and skin necrosis. Heparins can cause hypoaldsteronism which can increase in plasma potassium, and rarely, clinically significant hyperkalaemia. Rare reports of neuraxial haematoma when using spinal/epidural anaesthesia and post-operative indwelling catheter. Please consult SPC for full details of the recognised side effects with Clexane. Pharmaceutical Precautions: Do not mix with other injections or infusions. Do not store above 25°C. Do not refrigerate or freeze. PI revision: November 2012 Product Licence numbers: PA 540/97/1: Clexane® Syringes; PA 540/97/2: Clexane® Forte Syringes. Legal category: POM Marketing Authorisation Holder: Sanofi-Aventis Ireland Ltd., Citywest Business Campus, Dublin 24, Ireland. Further information is available from: Sanofi 18 Riverwalk, Citywest Business Campus, Dublin 24 or contact Tel.: (01) 4035600.

Please refer to the Summary of Product Characteristics which can be found on IPHA @ http:// before prescribing. Information about adverse event reporting can be found at Adverse events should be reported to the Sanofi Drug Safety Department References: 1. CLEXANE® Summary of Product Characteristics. sanofi 2. sanofi Data on file April 2012 GBIE.ENO.13.06.01

Date of preparation July 2013

14 News

Development of PH46A as potential new therapy Professor Neil Frankish

therapeutics, and recently announced the funding from new investors, Fountain Healthcare Partners and founding investor, the Wellcome Trust. Other investors in Trino include Enterprise Ireland and Growcorp. The company is developing PH46A, the lead candidate from a novel, proprietary, class of drugs which was inspired by the indane scaffold molecule derived from a Taiwanese fern. PH46A is a potential first-in-class oral small molecule drug for the treatment of inflammatory bowel disease (IBD), which could be used in both ulcerative colitis (UC) and Crohn’s disease (CD). Other molecules in Trino’s drug class show promise with broad anti-inflammatory activity that could be suitable for applications in dermatology, pulmonary and auto-immune disease and the company will work to develop these compounds internally and in partnership with major international research centres. Over ¤9 million has been raised to fund clinical trials in developing a new class of drugs to tackle inflammatory diseases.

The drug discovery and early drug development company, Trinity Therapeutics, is focused on anti-inflammatory

The additional funding from the Wellcome Trust is in the form of a prestigious, international and highly competitive Strategic Translation Award.

Head of Business Development at the Wellcome Trust, Dr Richard Seabrook commented, “Current treatments for inflammatory bowel diseases often have significant side effects and patients are faced with tough decisions in how to manage their condition. We are pleased to extend our successful partnership with Trino to support the development of PH46A as a potential new therapy for these debilitating disorders.” The company founded by Trinity pharmacologist Professor Neil Frankish and medicinal chemist Professor Helen Sheridan centres on their highly innovative work on pharmaceutical grade drugs based on the indane skeleton as derived from a Taiwanese fern, used historically in plant-based medicine. Commenting on this investment on behalf of the company Professor Frankish said, “This significant investment validates our research, enabling us to expand the Trino team and develop our clinical partnerships so that we can investigate the effectiveness of our research where it is needed – in patients with inflammatory diseases and ineffective drugs”.

Clinicians discuss AHC hospital model UCC recently hosted the inaugural meeting to establish an Academic Healthcare Centre (AHC) model for the new South/ South West Hospital Group. Health managers and senior clinicians from hospitals in the new South/South West Group gathered at the College of Medicine and Health UCC to discuss the new developments at the invitation of UCC President, Dr Michael Murphy. Discussions focused on the importance of growing the linkages between the Hospital and the University and Issue 10 • HPN

developing a collective ambition to deliver an AHC model in the South/South West hospital group. Dr Michael Murphy commented: “An Academic Healthcare Centre is a mutually beneficial partnership between a University and a Healthcare provider. Over time it will change how our hospitals relate to each other and integrate within the academic sector.” Attendees were also given a tour of the Cavanagh School of Pharmacy during the meeting.

Pictured are those who attended the recent inaugural meeting to establish an Academic Healthcare Centre model.

In bipolar disorder find the right balance



Rapid efficacy with a fast-dissolving sublingual tablet1,2

Abbreviated Prescribing Information: For full prescribing information refer to the Summary of Product Characteristics. Name: Sycrest 5 mg & 10 mg sublingual tablets. Active Substance: Asenapine (as maleate). Indication: Treatment of moderate to severe manic episodes associated with bipolar I disorder in adults. Dosage: Treatment is twice daily (one dose to be taken in the morning and one dose in the evening). Monotherapy: starting dose is 10 mg twice daily, may be reduced to 5 mg twice daily according to clinical assessment. Combination therapy: starting dose is 5 mg twice daily, may be increased to 10 mg twice daily depending on the clinical response and tolerability in the individual patient. Paediatric population: No recommendation on posology can be made. Elderly patients: Use with care. Renal impairment: No dose adjustment required (no data in severe renal impairment CrCL < 15 ml/min). Hepatic impairment: Mild: no dose adjustment required; Moderate: caution; Severe: not recommended. Administration: Sublingual, only to be used by patients who can comply with instructions (due to poor bioavailability when taken orally). Use dry hands and do not remove the tablet until just before it is to be taken. Peel back the coloured tab and remove gently. Place the tablet under the tongue and allow it to dissolve completely. Do not chew or swallow. Avoid eating and drinking for 10 minutes after administration. When using Sycrest in combination with other medication, take it last. Contraindications: Hypersensitivity to the active substance or any of the excipients. Pregnancy and Lactation: Pregnancy: Sycrest should not be used in pregnant women unless clearly necessary and only if the potential benefit outweighs the potential risk to the foetus. Neonates exposed to antipsychotics (including Sycrest) during the third trimester should be monitored carefully for extrapyramidal/withdrawal symptoms. Lactation: Women taking Sycrest should not breast-feed. Special Warnings and Precautions for use: Elderly patients with dementia-related psychosis: Not recommended. Neuroleptic Malignant Syndrome: Sycrest must be discontinued if signs or symptoms develop. Seizures: Caution in patients with a history of seizures or a condition associated with seizures. Suicide: Closely supervise patients at high risk. Orthostatic hypotension: Caution in early treatment, in the elderly, in patients with cardiovascular/ cerebrovascular disease or with conditions predisposing to hypotension. Tardive dyskinesia: Discontinue Sycrest if signs or symptoms develop. Hyperprolactinaemia: Some reports have been received. QT interval: Caution in patients with known cardiovascular disease, family history of QT

prolongation or concomitant use of other QT-prolonging medicinal products. Hyperglycaemia and diabetes mellitus: Clinical monitoring is advised for at risk patients. Dysphagia: Some reports have been received. Body temperature regulation: Appropriate care is advised in patients at risk of an elevation of core body temperature. Severe hepatic impairment: Not recommended. Parkinson’s disease and dementia with Lewy bodies: These patients are at increased risk of adverse events (including NMS), benefits and risks should be carefully considered. Interactions: Caution: in combination with other centrally acting medicinal products; with CYP1A2 inhibitors (e.g. fluvoxamine), CYP2D6 inhibitors or substrates (e.g. paroxetine), antihypertensive agents, levodopa, dopamine antagonists. Avoid: Alcohol & eating / drinking for 10 minutes after administration. Adverse reactions: Very common (≥1/10): anxiety, somnolence. Common (≥1/100 to <1/10): weight increased, increased appetite, dystonia, akathisia, dyskinesia, parkinsonism, sedation, dizziness, dysgeusia, hypoaesthesia oral, ALT increased, muscle rigidity, fatigue. Uncommon (≥1/1,000 to <1/100): hyperglycaemia, syncope, seizure, extrapyramidal disorder, dysarthria, sinus bradycardia, bundle branch block, electrocardiogram QT prolonged, sinus tachycardia, orthostatic hypotension, hypotension, swollen tongue, dysphagia, glossodynia, paraesthesia oral, sexual dysfunction, amenorrhoea. Rare (≥1/10,000 to <1/1,000): neutropenia, neuroleptic malignant syndrome, accommodation disorder, pulmonary embolism, rhabdomyolysis, gynaecomastia, galactorrhoea. Not known (cannot be estimated from available data): allergic reactions, restless legs syndrome, nausea, oral mucosal lesions, salivary hypersecretion, drug withdrawal syndrome (neonatal). Other findings: Cerebrovascular events have been reported. Asenapine has anaesthetic properties – oral hypoaesthesia/ paraesthesia may occur directly after administration and usually resolve within 1 hour. Post marketing reports of serious hypersensitivity reactions (including anaphylactic reactions e.g. swollen tongue & throat) have been received. Overdose: Cardiovascular monitoring & supportive therapy. Close monitoring advised until patient recovers. Legal Category: POM. Marketing Authorisation Holder: N.V. Organon, Kloosterstraat 6, NL-5349 AB Oss, The Netherlands. Marketing Authorisation Numbers: EU/1/10/640/002 Sycrest 5 mg sublingual tablets, 60 pack. EU/1/10/640/005 Sycrest 10 mg sublingual tablets, 60 pack. Further information may be obtained from: Lundbeck (Ireland) Ltd., 7 Riverwalk, Citywest Business Campus, Dublin 24. Date of Preparation: January 2013. The person depicted is a model and is used for illustrative purposes only.

* Sycrest is licensed for the the treatment of moderate to severe manic episodes in bipolar I disorder. References: 1. McIntyre R, et al. A 3-week, randomized, placebo-controlled trial of asenapine in the treatment of acute mania in bipolar mania and mixed states. Bipolar Disord 2009: 11: 673-686. 2. Sycrest Summary of Product Characteristics.


16 Drug News


Approval for Incivo twice daily Janssen Infectious Diseases-Diagnostics BVBA have announced that the European Commission (EC) has approved a new twice daily (BID) dosing of Incivo® (telaprevir), a direct acting antiviral (DAA) protease inhibitor, in combination with pegylated-interferon and ribavirin (PR) for naive and previous treatment experienced patients. The newly approved dosing regimen for Incivo® is now 1,125 mg twice daily in combination with PR, which aligns a morning and evening dose to the already twice daily dosing schedule for ribavirin versus 750 mg every 8 hours in combination with PR. The EC approval is based on results from OPTIMIZE, a randomized, open-label, multicenter Phase III study in treatment naive patients with genotype-1 chronic HCV infection, which demonstrated that twice daily dosing of Invico® 1,125mg in combination with PR was non-inferior to the previously approved dosing every 8 hours in the proportion of patients who achieved sustained virologic response (74% versus 73%).[2] Twice daily dosing also showed similar cure rates with twice daily or every 8 hours Incivo dosing in patients with cirrhosis.[3]

The availability of new DAAs like telaprevir has transformed treatment options for HCV.[4] Telaprevir has already played a significant role in improving treatment outcomes with more than 80,000 patients treated with telaprevir combination therapy worldwide since it was first approved in 2011.[5] It also offers the shortest total treatment duration of any available HCV therapy, for a high proportion of treatmentnaïve or relapse patients. [6],[7]

"The approval of INCIVO® twice daily is

"Before the availability of direct acting antivirals

References: 1. Sievert W et al. Adherence with Telaprevir BID vs. Q8h Dosing in Treatment Naive HCV-infected Patients: Results from the Phase III OPTIMIZE Study. J Hepatol 2013; 58(Suppl 1): S373. 2. Buti M, Agarwal K, Horsmans Y, et al. OPTIMIZE Trial: Noninferiority of twice-

Issue 10 • HPN

good news for patients with genotype-1 chronic HCV infection. Making treatments more simple and easier to manage, without compromising efficacy, will help to increase adherence and give patients an even greater chance of achieving a cure," said Dr Maria Buti, Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain.

daily telaprevir versus administration of every 8 hours in treatment-naïve, genotype 1 HCV infected patients. 2012. American Association for the Study of Liver Diseases (AASLD) Abstract. (Final ID: LB-8). 3. Horsmans Y, Brown Jr. RS, Buti M, et al. Safety and effi cacy of twice daily versus every 8 hour telaprevir with peginterferon/ribavirin

like telaprevir, the best clinicians could hope for was to cure only 4050% of our genotype-1 HCV patients. DAAs now offer us the chance to cure approaching 80% of these patients, for many in a shorter amount of time. Successful treatment is effectively a cure and causes a massive reduction in the complications of HCV, such as liver cancer and cirrhosis. As with many diseases early therapy is most effective and has the greatest impact on complications. “The twice daily dosing of telaprevir makes the treatment easier to administer and will make it easier for patients to take advantage of the opportunity for a cure. We now need to ensure that patients with HCV are identified and offered therapy, before their disease progresses," said Graham Foster, Consultant Hepatologist, Barts Health London. Incivo® (telaprevir), in combination with peginterferon alfa and ribavirin (PR), is indicated (PR) in patients with cirrhosis. 2013. European Association for the Study of the Liver (EASL) Abstract 862. 4. Casey L C, Lee W M. Hepatitis C Virus Therapy Update 2013. Curr Opin Gastroenterol. 2013;29(3):243-249. 5. Janssen data on fi le. 6. Sherman K, et al. Duration of Initial Telaprevir Treatment for

for the treatment of genotype-1 chronic HCV in adult patients with compensated liver disease (including cirrhosis) who are treatment naïve, and who have previously been treated with interferon alfa (pegylated or non pegylated) alone or in combination with ribavirin, including relapsers, partial responders and null responders.[7] Incivo® is a small molecule, selective inhibitor of the HCV serine protease, and a member of the new class of medicine for the treatment of genotype-1 chronic HCV, direct acting antivirals (DAAs). Unlike previous treatments, DAAs act directly on viral enzymes and prevent the virus from replicating. Incivo® was approved by the European Commission on the 19th September 2011. Incivo, 1,125 mg (three 375 mg film-coated tablets) should be taken orally twice daily (BID) with food. Alternatively, 750 mg (two 375 mg tablets) can be taken orally every 8 hours (q8h) with food. The total daily dose is 6 tablets (2,250 mg).[7]

HCV Infection: A phase 3 study of treatment duration. N Engl J Med. 2011;365:1014-24. 7. INCIVO® Summary of Product Characteristics updated 2013. 8. Centers for Disease Control and Prevention. Hepatitis C FAQs. Available at: http://www. cFAQ.htm#transmission (last accessed May 2013).

Xaluprine Xaluprine


Mercaptopurine Mercaptopurine oraloral suspension suspension

Xaluprine oral suspension offers your patients: • Accuracy of dosing to 2 mg • Flexibility of dosing • Consistent absorption • A palatable alternative to tablets • Natural raspberry flavour with no artificial colours, flavours or added sugar

18 News

The art of writing an abstract Gunar Stemer

EAHP Congress is the yearly rise in the number of abstracts submitted for consideration of display. From the EAHP Scientific Committee’s perspective this is an excellent development, as it provides evidence that more practitioners recognise the need and importance of hospital pharmacy practice research. By presenting such scientific work to colleagues and the public the visibility what the hospital pharmacist does, and the value and benefit of their input, can only be increased.

EAHP Scientific Committee member Gunar Stemer sets out some of the key aspects to be addressed when writing an abstract for conference or poster presentations. Scientific abstracts cover the main points of a study and its results. They represent condensed and clearly structured summaries that allow the reader to understand the most important aspects (e.g.

study rationale, methods, results) at a glance. The task of writing an abstract can be challenging, and several pitfalls may lead to impaired quality or even rejection of the abstract. First impressions matter! Raising the bar on abstract submission standards One of the areas of very noticeable annual growth in terms of the

However, with an ever increasing number of abstract submissions the Scientific Committee has also considered there is a need to clearly communicate to our colleagues what our expectancies are in terms of the format and information contained in abstracts, and to give some indication of common mistakes that may unfortunately lead to an abstract failing to meet the necessary standard. For the Scientific Committee, the poster abstracts displayed at the congress is not so much a question of quantity, but in fact a matter of quality. Here are a few brief pointers that can help ensure a smooth journey through the submission and appraisal process. 1. Clarity is key The basis of a good abstract is a well performed study. It is essential that there is a clear study question and clear study aims at the very

beginning. If this is clear, then it is far easier to present the results in an acceptable way and draw valid conclusions. It follows too that unclear study aims und unclear methodology can often lead to unclear results. It is essential that authors only present conclusions that they can really support with data. 2. Language matters A very simple, but easily correctable, reason that can lead to a decision to reject a submission is poor use of the English language, so that the content of the abstract is very difficult to understand. 3. Use a fresh pair of eyes to review Finally, a tip that can apply in many circumstances, not only abstract submission, is to ask colleagues who have not been closely involved in the study, to provide an honest review and cross-check of the content to ensure the key ideas are well communicated. Asking someone uninvolved in the study to conduct such a review can help to imitate the ‘fresh pair of eyes’ that will read the abstract after submission. If this does not happen before submission, there can be situations during the abstract review process when the Scientific Committee asks itself: what is the message that the authors are seeking to convey?

IPHA comments on medicines shortages Commenting on a survey released on the shortage of some key medicines, the Irish Pharmaceutical Healthcare Association (IPHA), which represents companies producing branded medicines in Ireland, stated that it is committed to ensuring that patients have access to the full range of

Issue 10 • HPN

modern medicines in a timely manner. “The Supply Agreement between IPHA and the State which was renewed last October defines the mechanisms for the supply of medicines to Irish patients. Key provisions in the Agreement are designed to ensure as far as is possible, continuity of supply,

but from time to time disruptions to supply in the market place can emerge with individual products. These arise as a result of manufacturing processes, but in more recent times, shortages have emerged due to the trading of products across European markets which occurs when

the price in one country has been pushed well below that in other countries. IPHA member companies work tirelessly to secure the availability of medicines for Irish patients, however, these cross border trading issues are beyond their control,” they said.

Clozapine Denzapine offers the most comprehensive range of treatment options for your patient with the only Clozapine 50mg and 200mg Tablets and 50 mg/ml suspension available on the market in Ireland¹

• Simplify treatment regimes • Reduce pill burden • Reduce drug costs 200mg


50mg 25mg

DENZAPINE Suspension offers an exclusive treatment option for: • Difficult to treat patients • Patients with swallowing problems • New patients - simple initiation DENZAPINE Abbreviated prescribing information. Clozapine 25mg, 50mg, 100mg, 200mg Tablets. 25mg, 50mg, 100mg: Round flat yellow bevel edged tabs marked with strength over a pressure sensitive breakline. 200mg: Large, oval-shaped yellow tablet, with strength on one side and a breakline on the other. ALSO DENZAPINE ORAL SUSPENSION: Clozapine 50mg/ml. Free-flowing yellow suspension. Indications: Treatment-resistant schizophrenia in patients unresponsive to or intolerant of conventional neuroleptics. Psychotic disorders occurring during the course of Parkinson’s disease, if standard treatment has failed. Adult: Schizophrenia: Initially 12.5mg once or twice on first day increasing by 25-50mg increments up to 300mg daily within 2-3 weeks; may be further increased in 50-100mg increments at half-weekly or, preferably, weekly intervals. Usual range: 200-450mg /day given in divided doses. Max. 900mg daily. Parkinson’s initially 12.5mg/day in the evening. Increase by 12.5mg increments with max, 2 increments a week up to 50mg once daily. Usually range: 25 -37.5mg/day. Max. 50mg/day, exceptionally 100mg/day. Elderly: Initially 12.5mg daily increasing gradually in increments of 25mg daily. Child: Not recommended. Contraindications: Patients unable to undergo regular blood tests. History of granulocytopenia/agranulocytosis (except if from chemotherapy). Impaired bone marrow function. Uncontrolled epilepsy, alcoholic and other toxic psychoses, drug intoxication, comatose conditions. Circulatory collapse and/or CNS depression. Severe renal or cardiac disorders. Active liver disease associated with nausea, anorexia or jaundice; progressive liver disease, hepatic failure. Paralytic ileus. Lactation. Special warnings: Can cause agranulocytosis, Initiation restricted to WBC counts>3500/mm3 and neutrophil count >2000/mm3). Monitor these counts weekly for first 18 weeks and at least 4 week intervals thereafter including 4 weeks after complete discontinuation (see SPC). Discontinue immediately if neutropenia or agranulocytosis. Caution: CVD or family history of QT prolongation, risk factor for stroke, liver disorders, prostatic enlargement, narrow-angle glaucoma. Reported: Myocarditis, pericarditis/ pericardial effusion, cardiomyopathy, impairment of intestinal peristalsis, neuroleptic malignant syndrome, hyperglycaemia, thromboembolism. Withdraw gradually over 1-2 weeks. Pregnancy. Driving/using machinery. Contains lactose. Drug interactions: Contraindicated: Drugs causing agranulocytosis (co-trimoxazole, chloramphenicol, sulphonamides, pyrazolone analgesics e.g. phenylbutazone, penicillamine, carbamazepine, cytotoxic agents); avoid depot antipsychotics, drugs causing electrolyte imbalance, drugs prolonging QT, alcohol. Caution: CNS depressants, drugs with anticholinergic, hypotensive, or respiratory depressant effects, norepinephrine, epinephrine, CYP1A2 inhibitors (caffeine) and inducers (omeprazole), smoking, fluvoxamine, paroxetine, carbamazepine, phenytoin, rifampicin, CNS – active agents. See SPC. Adverse reactions: Leucopoenia/decreased WBC/neutropenia, eosinophilia, leukocytosis, weight gain, drowsiness, dizziness, blurred vision, headache, tremor, rigidity, akathisia, extra pyramidal symptoms, seizures, tachycardia, ECG changes, hypertension, postural hypotension, syncope, GI disorders, dry mouth, elevated liver enzymes, urinary incontinence/retention, fatigue, fever, temperature regulation disturbances. Pack Size: 84 x 25mg tablets, 50 x 50mg tablets, 84 x 100mg tablets, 50 x 200mg tablets, 100ml x 50mg/ml. Supply of DENZAPINE is restricted to pharmacies registered with the DMS. Product Authorisation Numbers: DENZAPINE 25mg, 50mg, 100mg and 200mg tablets PA 126/235/1, 3, 2 and 4, DENZAPINE 50mg/ml suspension PA 126/235/5. Full prescribing information is available on request or go to Legal Category: Medicinal product subject to medical prescription. Marketing Authorisation Holder: Clonmel Healthcare Limited, Waterford Road, Clonmel, Co. Tipperary. Date last revised: April 2013. - 2013/ADV/CLO/030 References: 1. MIMS April 2013

Hospital Pharmacy Awards 2013 Hospital Pharmacy Awards 2013 – The Finalists! The Hospital Pharmacy Awards have been designed to serve as the standardbearer for professionalism and excellence throughout hospital pharmacy as they reward and encourage excellence in patient care, pharmacy operations and vision. These hospital pharmacy departments, pharmacists and their teams represent exceptional success over the past year. The environment has been tough; these are the professionals leading the way to growth. There’s a broad spectrum of hospitals represented, as well as those of very different sizes, reflecting the diversity of Ireland’s hospital pharmacy. Congratulations to all our finalists. The Hospital Pharmacy Awards are hosted by HPN to recognise outstanding examples of high standards, best practice, innovation and excellence throughout hospital pharmacy in Ireland. The HPN offices were inundated with submissions and nominations over the past few months and our elite judging panel have once again been called upon to refine this impressive list to a smaller number of outstanding finalists. Whilst the shortlisting process was extremely difficult – with some strong entries failing to make it as finalists – it’s important to highlight that it’s not just about winners and losers. Everyone who entered this year’s Awards deserves commendation. The quality was of an increasingly high level – but what struck the judges is the level of innovation and dedication hospital pharmacy professionals are displaying with enhanced care and

medicines advice. Our judging panel has so many dedicated professionals to choose from who are making a difference in health care and in the profession.” The shortlisted submissions will now be put forward for a second round of judging on – September 10th at Carton House, Maynooth - by a totally independent judging panel of professionals from within as well as outside the pharmacy industry, who will decide the winners of the coveted Hospital Pharmacy Awards 2013.

How to attend the gala evening Tables and individual tickets for the gala evening are on sale now. However, we anticipate a sell-out event in 2013 so please be sure to book your tickets promptly to secure your seats. Please contact Kelly Jo Eastwood on: 0044 7876548989 Email: or

The winners will be announced during a glittering gala evening at the Crowne Plaza Hotel, Santry, on September 21st, 2013 in front of an audience of over 300 representatives from across the country. Each finalist will be profiled in the October/November 2013 issue of Hospital Pharmacy News. Natalie Maginnis, Managing Director of IPN Communications Ltd commented: “We are extremely proud and are equally delighted to see the Hospital Pharmacy Awards 2013 come to life with the announcement of around 35 finalists being shortlisted in 10 different award categories, which truly shows excellence being recognised and rewarded. The evening will be what we envisaged from the inception of the Awards; a unique celebration of Ireland’s hospital pharmacy profession. “We would also like to thank all of our sponsors for their tremendous support which enables the industry to come together for this fantastic occasion.”

"Whilst the shortlisting process was extremely difficult, with some strong entries failing to make it as finalists, it's important to highlight it's not just about winners and losers. Everyone who entered this year's Awards deserves commendation" Issue 10 • HPN

Debbie Graham on 0044 7450 274112 Email: For more information about the Hospital Pharmacy Awards 2013, or sponsorship opportunities, visit

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PHI/2013/002/1 April 2013

Hospital Pharmacy Awards 2013

Hospital Pharmacy Team of the Year Award Investing in education and the health of the nation

Excellence in Pharmacy There are many key elements to building a productive team, including communication and cooperation. Good communication means everyone is aware of their own responsibilities and

what the team's goals are whilst co-operation leads to increased productivity. 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 finalists are...

Name of entrant: St Vincent’s Hospital pharmacy team

Name of entrant: Our Lady’s Children’s Hospital Crumlin pharmacy team

Name of entrant: Mater Misericordiae University Hospital pharmacy team

Team overview: SVUH is a Joint Commission International (JCI) accredited hospital and is the only public hospital in Ireland to achieve this distinction. JCI is an international organisation which inspects and accredits healthcare institutions world-wide according to published standards, which strive towards excellence in healthcare. The JCI accreditation process demands an incredible amount of team work from start to finish, and afterwards. This requires enormous multi-disciplinary involvement from all staff in the hospital. The pharmacy staff was pivotal in ensuring that SVUH achieved accreditation and the reputation of the pharmacy department was greatly enhanced as a result

Team overview: The pharmacy team in OLCHC is a dedicated and enthusiastic team, whose members are highly motivated and committed individuals. Team members possess a shared goal; to deliver efficient, best quality pharmaceutical care to the children of Ireland. The motivation to deliver this goal is established and maintained by regular communication. The pharmacy team possess a range of experiences and skills. These skills have been developed and nurtured in the pharmacy department. Individual strengths are identified by management based on unique backgrounds and experiences.

Team overview: The pharmacy department had the additional challenge of the relocation of a number of wards and departments from outdated clinical configurations to the new, state of the art, Whitty building. When a department is already is working to capacity with a sustained reduction in staff numbers, such a change could be conceived as a negative and ‘quick fix’ options may be considered to the detriment of the service as a whole. However the pharmacy department team rose to the challenge and recognised that implementation of successful significant changes would require meaningful engagement with all grades of staff. Communication and consistently liaising with the staff who actually deliver the services and are experts in their field allowed the identification of the value and waste elements of services and what potential improvements could be made.

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Hospital Pharmacy Awards 2013

Name of entrant: Letterkenny General Hospital pharmacy team

Name of entrant: Bon Secours Hospital Tralee pharmacy team

Team overview: Good communication is vital for the efficient functioning of any team or organisation and the department at LGH has a once weekly meeting for all staff where any issue or topic can be discussed. The evolution and development of the pharmacy service has come almost exclusively from ideas and innovation of staff members.Projects are continuously underway in any progressive organisation. The catastrophic flood which occurred in Letterkenny Hospital recently demanded an immediate and an ongoing response and the work carried out by all members of pharmacy staff in the weeks since the occurrence has been remarkable.

Team overview: Under the leadership of Ann Oâ&#x20AC;&#x2122;Leary, the pharmacy team within Bon Secours in Tralee operate under a main focus, team work being the essence of all objectives. Regular communication and a shared goal of delivering the best possible care to patients has ensured the team move forward in innovation. Each team member possesses a skill set to compliment one another and are actively engaged in professional development and furthering their knowledge to the enhancement of the whole pharmacy department.

Name of entrant: Portiuncula Hospital pharmacy team

Name of entrant: St Jamesâ&#x20AC;&#x2122;s Hospital pharmacy team

Team overview: The team at Portiuncula Hospital pharmacy department have successfully implemented many clinical initiatives, despite even low staffing levels over the last number of years, including admission medicine reconciliation and a warfarin clinic achieving 78% Time in Range for patients. The team constantly work well within a multidisciplinary environment and most members undertake continuous professional development for their own self and for the betterment of the team. The success is down to each individual sharing a sense of purpose and common goals.

Team overview: The team here work as part of a multidisciplinary team to deliver patientcentric pharmaceutical care. Their focus is patient safety; one of the main roles is in screening chemotherapy prescriptions to ensure safety and appropriateness.

Excellence in Pharmacy

This patient-focused culture also demands efficient work practices to ensure a timely supply of medicine/ patient education/ medicines information. Each member takes a responsibility for a section of the workload on a day-to-day basis but this is a dynamic process. Team members move to ease pressure as the workload dictates. The challenges facing the team are always changing with a constant focus on needing to improve efficiencies and develop services to optimise patient care.

HPN â&#x20AC;˘ Issue 10

Hospital Pharmacy Awards 2013

Hospital Pharmacist of the Year Award Investing in education and the health of the nation

Excellence in Pharmacy

We Innovate Healthcare This aim of this award category is to recognise those who, through their service to patient care, education or research, to the profession and to the society, are

worthy of being rewarded. The winner will exhibit eagerness, dedication and a positive attitude toward the academic learning, the

practice, and the profession of hospital pharmacy.

The finalists are...

Name of nominee: Patricia Ging

Name of nominee: Bernard Carr

Name of nominee: Mairead Galvin

Hospital: Mater Misericordiae University Hospital

Hospital: St James's Hospital

Hospital: Naas General Hospital

Nomination overview: Bernard Carr is the Chief 2 Pharmacist responsible for Clinical Services in St. James’s Hospital Dublin. He has consistently demonstrated his loyalty and commitment to the pharmacy department and to his profession.Bernard is fastidious in his approach to patient care. Patient safety is paramount to Bernard as is the provision of safe, effective and evidence based pharmaceutical care. He represents the department in both a leading capacity and as a team member in pharmacy and multidisciplinary team initiatives to improve patient care and safety. Bernard is the recognised “face” of clinical pharmacy within the hospital.

Nomination overview: Mairead Galvin has played a key role in several aspects of the hospital pharmacy team, and wider multidisciplinary team, in Naas General Hospital for many years. One of her key strengths lies in her research work within the antimicrobial field and she has published widely. She has worked tirelessly over the years to promote the roles and responsibilities of the hospital pharmacist, often taking on research and pilot projects in addition to her day-to-day work within the hospital.

Nomination overview: Patricia Ging is a Chief II Pharmacist at the Mater Misericordiae University Hospital (MMUH). She has worked there for 12 years and is the pharmacist for Heart and Lung Transplantation and Pulmonary Hypertension services in the hospital. Since assuming this role in 2008 she has worked exceptionally hard to develop and enhance the role of the pharmacist in these diverse services. Multidisciplinary team working is extremely important in such a complex area. Since joining the team Patricia has been active in the multidisciplinary team, educating the rotating medical and nursing staff on both a formal basis in the cardiothoracic nursing course and on an informal basis by presenting conference abstracts at the weekly multidisciplinary meeting. She has also written the unit protocols for the perioperative management of the transplant patients so that management is optimised, streamlined and standardised. Issue 10 • HPN

Hospital Pharmacy Awards 2013

Hospital Pharmacy Representative of the Year Award Investing in education and the health of the nation

Excellence in Pharmacy

This aim of this award category is to recognise the sales representatives who excel in customer service, knowledge of their product base and a commitment to their profession in terms of future growth and development. The winner of this category must stand out in business ethics and

integrity. The Hospital Pharmacy Representative of the Year category offers the opportunity to demonstrate professional sales skills and to benchmark those skills across competency areas against other top sales representatives.

Critical to this category, it provides hospital pharmacy sales representatives with invaluable learning, provides their organisation with comparative data with and provides the industry with a snap-shot of the quality of customer interaction within current sales models.

The finalists are...

Name of nominee: Caroline Fitzgerald

Name of nominee: Patrick Tehan

Name of nominee: Yvonne Kavanagh

Company: Actavis Ireland

Company: Fannin Ltd

Company: Teva Pharmaceuticals Ireland

Nomination overview: Caroline has been nominated, in part, for her dedication and focus in going that extra mile for her customers. Since joining the Actavis team, Caroline has dedicated herself to developing and growing the company’s hospital business unit. Her commitment is not just to meet the target expectations of the company but to ensure 100% service is delivered to the Hospital Pharmacist. Caroline’s sole focus is meeting the needs and requirements of her customers, however big or small. She follows a query/issue through to the end to ensure the pharmacist receives a satisfactory outcome and has introduced many new products to market and achieved majority market share in many of these products.

Nomination overview: Patrick has been described as ‘exceeding expectation in his assistance with management of supply shortages” most notably his assistance in management of the shortage of adrenaline minijets. He has been of essential need in meeting with pharmacy staff regarding training on use of the adaptors, and facilitated supply, always keeping in close contact. Patrick is an excellent communicator, who always follows up any queries and promptly responds with the required information. He is efficient at communicating anticipated supply problems, solutions to supply difficulties and will also keep staff informed of the status of ongoing supply queries.

Nomination overview: Yvonne balances the need for commercial success and meeting customer needs very well. She will face all challenges head on. Continuity of supply has been one of many challenges globally but Yvonne has handled issues such as this with knowledge, professionalism and dedication. One of her key motivations is to ensure customers have the knowledge to assist them in making the best decisions for their patients. She is a fantastic mentor for her colleagues and is asked regularly by the company to work as a training support for all her new colleagues. One of the big challenges Yvonne has overcome is the Irish attitude to biosimilars. She has been the consistent voice for biosimilar filgrastim and epoetin in Ireland. Through Yvonne’s work she has delivered thousands in savings to the Irish state by promoting medicines at a very high level of ethics and compliance.

HPN • Issue 10

Issue 10 • HPN



Managing factors of Bipolar affective disorder Local brain connectivity 3-dimensional view of mean regional connectivity

Biography- Ronan Sheridan graduated from the Robert Gordon University, Aberdeen in 2009 with a Masters in Pharmacy with Distinction. Ronan worked as a preregistration and clinical pharmacist at the Chelsea and Westminster Hospital NHS Foundation Trust, London for three years. He currently works as a Pharmacist Manager at Market Point and Green Road Pharmacy, Mullingar, Co Westmeath. Ronan was recently awarded the 2012 Helix Health Young Pharmacist of the Year.

Bipolar disorder, also known as manic-depressive illness, is a brain disorder that causes unusual shifts in mood, energy, activity levels, and the ability to carry out day-to-day tasks1. Symptoms of bipolar disorder are severe. They are different from the normal ups and downs that everyone goes through from time to time. Bipolar disorder symptoms can result in damaged relationships, poor job or school performance, and even suicide2.

• Loss of interest in food, work, sex and other people

hypomanic symptom but no manic episodes

• Insomnia or over-sleeping

Bipolar III Periods that simultaneously involve the full symptoms of both a manic and a full depressive episode

With bipolar disorder, moods can swing between low, high and mixed. But bipolar disorder can be treated, and people with this illness can lead full and productive lives3.

• Too much energy and little need for sleep

Bipolar disorder is a relatively common condition with around one person in 100 being diagnosed with the condition1. In Ireland there is estimated that 40,000 people are diagnosed with bipolar affective disorder. A low mood involves feelings of intense depression and despair. This is known as a depression and symptoms include: • Sad, empty or anxious feelings

• Chronic aches or pains with no discernible cause, and • Thoughts of death or suicide. A high mood involves feelings of elation. This is also known as mania or a manic period. Symptoms include: • Impaired judgement • Over-spending

• Anger or irritability, and • Unrealistic beliefs in one’s own abilities. A mixed mood involves, for example, depressed mood with the restlessness and over activity of a manic episode5. TYPES OF BIPOLAR DISORDER Bipolar I One or more manic or mixed episodes and wide mood swings Bipolar II The most common form, one or more episodes of depression with at least one

Rapid-cycling bipolar disorder Characterized by four or more mood episodes that occur within a 12-month period. Episodes must last for some minimum number of days in order to be considered distinct episodes. Bipolar disorder often develops in a person's late teens or early adult years. At least half of all cases start before age 25. Often people have their first symptoms during childhood, while others may develop symptoms late in life7. Bipolar disorder can be influenced by a range of factors. Biological factors Bipolar disorder seems to be most closely linked to family history. For example, while bipolar disorder affects around 2 per cent of the general population at some stage of their lives, people who have a parent with bipolar disorder have a 10

HPN • Issue 10

28 Feature

Bipolar disorder seems to be most closely linked to family history. For example, while bipolar disorder affects around 2 per cent of the general population at some stage of their lives, people who have a parent with bipolar disorder have a 10 per cent chance of having the illness themselves

per cent chance of having the illness themselves9. Physical health issues which can also trigger bipolar disorder include: • Pregnancy and childbirth • Hormonal problems (hyper and hypothyroidism) • Brain problems (Parkinson's and Huntington's disease) • Autoimmune problems (Lupus, HIV) • Cancer (cancerous tumour and pancreatic cancer) Social and psychological factors While a major cause of bipolar disorder seems to be genetic, stress can also trigger symptoms. Common triggers include9: • Changing jobs • Changing living arrangements • Family and relationship problems • Being the victim of verbal, sexual, physical or emotional abuse or trauma • Other life transitions e.g. having a child • Death or loss of someone close DRUG THERAPY The mainstay of therapy for both mania and hypomania is drug treatment. Antipsychotics and

Issue 10 • HPN

mood-stabilisers are equally effective, with the addition of sedatives and anxiolytics on an acute basis. No one antipsychotic can be deemed greater than the other based on efficacy, often leading to difficulty on drug selection. For those relapsing a moodstabiliser- antipsychotic combination has proven clinical effectiveness, but no evidence suggests this to be appropriate for those presenting untreated 1,2,7 . Under the current guidance from NICE, lithium, olanzapine or valproate should be considered for long-term treatment of bipolar disorder. Valproate Valproic Acid binds to and inhibits GABA transaminase, thus inhibiting enzymes that catabolise GABA and also block the reuptake of GABA into glia and nerve endings. Valproic Acid may also work by suppressing repetitive neuronal firing through inhibition of voltage-sensitive sodium channels. Valproate is generally well tolerated but it can cause gastrointestinal disturbances, alteration in hair thickness and liver toxicity. Valproate is teratogenic and should not be prescribed routinely for women of child-bearing potential10.

Olanzapine Olanzapine's antipsychotic activity is likely due to a combination of antagonism at D2 receptors in the mesolimbic pathway and 5HT2A receptors in the frontal cortex. Antagonism at D2 receptors relieves positive symptoms while antagonism at 5HT2A receptors relieves negative symptoms of schizophrenia. Some common side effects of olanzapine include drowsiness, weight gain, metabolic syndrome and increased appetite 6,10. Lithium Lithium acts by inhibiting the formation of inositol triphosphate (as a result of protein kinase C activation) and mimicking intracellular Na2+, thus modifying cell membrane potential and ionic balance. Lithium has a narrow therapeutic index hence patients receiving lithium require regular monitoring of their lithium blood level to ensure it is within safe limits. The normal therapeutic range is between 0.4 – 1.2 mmol/L. Lithium can cause renal impairment and since it is predominantly renally excreted, monitoring of renal function is essential. In addition, as longterm use has been associated

with thyroid disorders, thyroid function also requires monitoring. Signs and Symptoms of Lithium Toxicity Acute toxic effects of lithium are more likely when serum levels exceed 1.5mmol/L. Signs of toxicity include nausea, vomiting, diarrhoea, slurred speech, drowsiness, ataxia, lethargy, coarse tremor, myoclonic jerks, confusion, seizures, coma, death. Lithium plasma levels may be increased by sodium/fluid depletion (e.g. from vomiting/ diarrhoea or dehydration), impaired renal function, certain medicines or using different brands or formulations of lithium. The most common medicines causing significant drug interactions with lithium include thiazide and related diuretics, NSAIDs and ACE inhibitors. These can increase lithium concentration and increase the risk of lithium toxicity. Lithium brands and formulations vary widely in bioavailability. It is important that the patient continues to take the same brand and formulation 10.

29 "The most common medicines causing significant drug interactions with lithium include thiazide and related diuretics, NSAIDs and ACE inhibitors. These can increase lithium concentration and increase the risk of lithium toxicity"

Mood Stabilisers Used for the prophylaxis in bipolar disorder, they can help control mood swings characteristic of the condition. As discussed both Lithium and Valproate are considered the mood stabilisers of choice by NICE, however Carbamazepine, Lamotrigine and Gabapentin, which have fewer side effects than Lithium, have also proven to be effective1.




400mg/day, increasing every 5-7 days


As sodium50mg three times a day, increasing according to tolerability As Valproate500mg/day increasing as per sodium

Antipsychotics The variability between individual antipsychotic drugs include antimanic and antidepressant properties, anxiolytic and the degree of sedation. The effective of antipsychotics is enhanced by mood stabilisers. The drugs commonly used are Risperidone, Quetiapine, Olanzapine and Aripiprazole, with Olanzapine being the drug of choice1.

Aripiprazole, increasing to max 30mg/day


10mg/day, increasing to max 20mg/day


2-3mg/day. Increasing to max 6mg/day


IR: 100mg/day increasing to max 800mg XL: 300mg/day, increasing to 600mg/day (even on day 2)


5-10mg/day, increasing to max 15mg/day


Dose as required to max 4mg in 24 hours

Currently SSRI’s or Quetiapine are the drugs of choice for bipolar depression. The second line treatment is to switch to Mirtazepine or Venlafaxine or to add Quetiapine, Olanzapine or Lithium to the antidepressant. If mania develops, reducing or stopping the antidepressant is advisable.

Clonazepam Dose as required to max 8mg/day

The SSRI’s are generally safer and have fewer side effects than other antidepressant groups; those that can occur include nausea and vomiting and sexual dysfunction2.


Withdrawal from Antidepressants

Generally the use of antidepressants is limited to treatment during depressive episodes. Antidepressants should not be used alone for treatment of bipolar disorder. Once the depressive state has passed, the antidepressant should be gradually decreased.

DISCONTINUATION SYMPTOMS Agitation, Irritability, Insomnia, Vivid dreams, Flu like symptom, Diarrhoea, Slow/ pressured speech, ‘Shock

HPN • Issue 10

30 Feature like’ sensations, Dizziness, Crying spells

• The onset of symptoms can be within 5 days of stopping the medication, and can last for 1-3 weeks

occur after administration of a neuroleptic drug. Symptoms may begin immediately or can be delayed hours to days. Although a wide variety of medications can elicit symptoms, the typical antipsychotics are most often responsible. Dystonic reactions are characterised by intermittent spasmodic or sustained involuntary contractions of muscles in the face, neck, trunk, pelvis, extremities, and even the larynx2.

Combination Therapies

Cardiovascular risks

If several medications are tried with no improvement, trying a combination of mood stabilisers is the next step. Two mood stabilizers together may be more effective in relieving symptoms than one alone2.

There is increased risk of heart disease with antipsychotic medicines. The risk is said to be reduced once the medicines are stopped and the risk is also dose dependant. Patients should have a full cardiovascular risk assessment carried out prior to initiating any therapy.

• Need to have taken antidepressant for at least 8 weeks to experience discontinuation syndrome • Discontinuation symptoms is not a sign of dependence

Lithium and Lamotrigine Lithium and Antipsychotic Valproate and Quetiapine Valproate and Antipsychotic Valproate and Lamotrigine Valproate and Lithim ADVERSE DRUG EFFECTS FROM ANTIPSYCHOTICS Neuroleptic Malignant Syndrome Is a rare, but life-threatening, reaction to a neuroleptic medication. The syndrome is characterised by fever, muscular rigidity, altered mental status, and autonomic dysfunction. All antipsychotic agents, typical or atypical, may precipitate the syndrome4. Antipsychotic-induced motor disturbances Dystonic reactions are reversible extrapyramidal effects that can

Diabetes Some of the newer antipsychotics can cause rapid weight gain, which can put patients at risk of developing type 2 diabetes, as well as raises the cholesterol levels. This should be explained to patients and discuss their diet with them. As well as pre-screening it is important that 6 monthly blood checks are carried out to monitor renal and hepatic function as well as thyroid levels and electrolyte levels. Other common side effects of antipsychotic medications include: blurred vision, dry mouth, drowsiness, muscle spasms or tremor, involuntary facial movement and weight gain PHARMACIST ROLE

Pharmacists have a very important role to play in monitoring patient compliance, discussing side effects and highlighting the importance of continued use of medicines and the risks of discontinuation of therapy. • Patients should be advised that poor compliance can lead to a relapse of symptoms. • Patients on mood stabilisers with a narrow therapeutic index should be encouraged to attend their GP every 6 months, once established on therapy, to have their levels checked. • Patients on Lithium should be counselled about signs of toxicity and to avoid over the counter medicines that could affect their Lithium levels. • Pharmacists can advise about side effects and how these can be minimised. Weight gain can be counter acted by a balanced diet and regular exercise. • By providing patients with information about their condition and how beneficial the prescribed medicines can be to them, adherence can to treatment is more likely and so a relapse can be avoided. USEFUL CONTACTS SHINE- supporting people affected by mental health 38 Blessington Street, Dublin 7. Tel: 1890621631 AWARE- supporting people with depression and bipolar disorder 72 Lower Leeson Street, Dublin 2. Tel: 1890303302 MENTAL HEALTH IRELAND - supporting positive mental health Mensana House, 6 Adelaide Street, Dun Laoghaire Tel: 012841166 PIETA HOUSE- for specialised support for suicidal ideation and self harm Tel: 01 6010000 HEADSTRONG- national centre for youth mental health 16 Westland Square, Pearse Street, Dublin 2. Tel: 014727010

Issue 10 • HPN

REFERENCES 1. The Maudsley Prescribing Guidelines. 10th Edition. D Taylor, C Paton, S Kapur. Informa Healthcare, UK 2009. 2. Psychotropic Drug Directory. 2010. Stephen Bazire. Healthcromm UK Ltd 3. ICD-10. Classification of mental and behavioural disorders, WHO publications Geneva, 1992. 4. P Kumar and M Clark. Clinical Medicine. Saunders Elsevier, 7th edition. 2009 5. R Walker & C Edwards. Clinical Pharmacy and Therapeutics. Churchill Livingstone, 3rd edition, 2004. 6. British National Formulary, March 2013 7. National Institute of Clinical Excellence. Bipolar disorder: The management of bipolar disorder in adults, children and adolescents, in primary and secondary care. 2006 8. National Institute of Clinical Excellence. Bipolar disorder: Psychosis with coexisting substance misuse: Assessment and management in adults and young people. 2011 9. National Institute of Mental Health. Bipolar Disorder. [accessed June 2013] 10. Rang, Dale, Ritter and Moore. Pharmacology. Elsevier, 5th edition, 2003.

Hospital Pharmacy Awards 2013

Hospital Innovation and Service Award Investing in education and the health of the nation

Excellence in Pharmacy This award will be presented to a practising hospital pharmacist and/or team in recognition of a project which could easily be accomplished regardless of hospital size or staff, which need

not be sophisticated, and which serves a useful purpose or has recently been published. The judges will be looking to award the title of Innovation and

Service Award to an inspiring team or individual who, from their own experience and project work motivates and supports others to become innovative.

The finalists are...

Name of nominee: Allison Dunne and team

Name of nominee: Audrey Purcell and team

Pharmacy: Galway University Hospital

Pharmacy: St John of God Hospital

Project overview: The Clozapine Clinic in Galway City has evolved over the years to bring the multidisciplinary team and the patient together to improve patient care. The clinic provides care for over 150 psychiatric patients. The majority of these are outpatients. The patients can attend at any time they choose, there are no fixed appointments.

Project overview: Audrey’s innovation was to develop a lithium information pack for use by patients on Lithium therapy in St John of God Hospital, pilot its use in the hospital and eventually launch this for national use for all patients on Lithium therapy in Ireland. This has proven to be a very valuable resource in St John of God Hospital for both health-care professionals and patients. It is transferable across the rest of the hospital pharmacy sector and many hospital pharmacists have requested access to these information packs. Audrey is also hopeful of launching hese packs nationally to improve the safety of lithium therapy, standardise provision of information on lithium and involve patients in their lithium therapy.

This process has improved waiting time for patients from four days to approximately fifteen minutes. This is a huge benefit for patients who have to travel long distances to the clinic, or who are at work or college. From a safety point of view, the immediate access to the result of the full blood count means that in the rare event of the patient having an abnormal blood result action can be taken straight away. This could mean stopping clozapine treatment or arranging a follow-up blood sample.

Name of nominee: Catriona Reilly and Elizabeth Collis Pharmacy: St Vincent's University Hospital Project overview: Several medications, notably insulin, are supplied in pen form, for patients to self-inject. However, the pharmacy dept at SVUH indentified that they could not fully guarantee the integrity of these pens, without a seal, once the out box had been opened. The pharmacy technicians looked to the food industry to explore a method of sealing medication pens directly in the pharmacy, before dispensing them to a clinical area. Pharmacy, nursing staff and patients can now be 100% sure that the integrity of each individual pen has not been compromised, when obtaining a new pen from the fridge. This has increased the level of patient safety implicit in the “one patient / one pen” policy, by eliminating of the risk of transmitting an infection through the use of an inadvertently shared pen.

HPN • Issue 10

Hospital Pharmacy Awards 2013

Aseptic Hospital Unit of the Year Award Investing in education and the health of the nation

Excellence in Pharmacy This award category was 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 the unit that can best demonstrate safety and quality within their department while incorporating initiatives. This could be through SOPs, cost saving projects, clinical

trials medication, interaction with other departments, identification and fulfilment to training needs or other.

Name of nominee: Aseptic Unit Mayo General Hospital

Name of nominee: Aseptic Unit Beaumont Hospital

Team lead: Blanaid O'Connell

Team lead: Grant Carroll

Nomination overview: The team at Mayo General Hospital have undertaken a number of projects over 2012 and 2013. As the incidence of cancer continues to increase, the team have ensured they have maintained a focus on providing optimum care and medication facilities for their patients. Each team member utilises their skills to the betterment of the whole team and as a result they operate effectively and efficiently with a direct vision both on staff safety and patient care. The team continue to strive to maintain a safer and more effective unit, despite the increased demands and restraints placed on them.

Nomination overview: Team work is key for the team within the aseptic unit at Beaumont Hospital. Multidisciplinary working between the pharmacists and colleagues ranging from nurses to consultants ensures the smooth running of a busy department. The aseptic unit ensures the manufacturing of chemotherapy injections in a sterile environment to maintain the highest possible standards. Strict procedures are also followed to ensure accuracy. The pharmacy department also participates in a number of hospital groups and committees, including the Drugs and Therapeutics Committee, the Infection Control Committee, and the Clinical Services Group, amongst others.

The finalists are...

Name of nominee: Aseptic Unit, St James's Hospital Team lead: Veronica Treacy Nomination overview: The Aseptic Compounding Unit (ACU) in St Jamesâ&#x20AC;&#x2122;s is the largest hospital unit in the country. The unit adheres to GMP and Good Clinical Practice. All staff are validated on an annual basis to assure consistency of approach to all aspects of their work. The Unit is responding to the growing needs of patients. Treatments are still intravenous based and need the expertise of local units to support timely treatment of patients and avoid wastage and delays. The team are preparing for the implementation of standards for compounding in hospitals , and also implementing new international standards for hospitals on needle free systems.

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Name of nominee: Aseptic Compounding Unit, Mater Misericordiae University Hospital Team lead: Brid Ryan Nomination overview: The Aseptic Compounding Unit (ACU) of the Mater Misericordiae University Hospital (MMUH) has been using electronic manufacturing software (ASCRIBE) for several years in the manufacture of cytotoxic chemotherapy. This has been complemented by publishing version controlled chemotherapy protocols on the hospital intranet to give oncology/haematology staff access to up to date clinical protocols and ensure the safe and accurate treatment of patients. The MMUH Aseptic Unit has taken the first step in introduced a fully integrated system for the prescribing, manufacture and administration of cytotoxic chemotherapy.

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Hospital Pharmacy Awards 2013

Antimicrobial Project of the Year Award Investing in education and the health of the nation

Excellence in Pharmacy

Due largely to the overuse and misuse of antibiotics, bacteria have become increasingly resistant to many of the compounds we rely on to treat serious infections in our hospitals. Antibiotic pharmacists have been shown to be effective in many situations and as they become more accomplished their

role is greatly expanding to include direct intervention in patient treatment. The judges within this category were looking for innovative projects promoting health development, including reviewing antibiotic orders (including

drug selection and duration of therapy), design and promotion of clinical practice guidelines, implementation and operation of antibiotic “switch “programmes and documenting the effectiveness of interventions.

The finalists are...

Name of nominee: Anne Harnett and team

Name of nominee: Catherine Mannion and team

Hospital: University Hospital Limerick

Hospital: St Luke’s General Hospital, Kilkenny

Nomination overview: This iPhone application was developed to promote and support rational prescribing of antimicrobial agents for adults. Information is available for common infections and includes advice on: investigations to carry out; probable pathogens involved and empiric antimicrobial therapy. Patients benefit from timely and appropriate antimicrobial therapy, reduced antimicrobial resistance and better health outcomes. Staff benefit from leaner and more productive systems of work and better health outcomes for their patients resulting in reducing healthcare costs. With the app, an updated version can be easily implemented without waiting for a new hardcopy print.

Nomination overview: Suspected penicillin allergy is common among hospitalised patients, but the accuracy of the information given by patients varies. Documented penicillin allergies are likely to be treated with more toxic, broader-spectrum and more costly antibiotics with effects on microbial resistance and the public economy as a result. In the 2011 National Antibiotic Point Prevalence Audit, St. Luke’s General Hospital Kilkenny (SLK) had a prevalence of penicillin allergy of 15.1% (n=8) which is above the national average of 11.4%(n=295).2 Their objective was o clarify the nature of the documented penicillin allergy in order to highlight the impact of incorrect classification of patients as penicillin allergic on patient’s antimicrobial therapy. The results show a significant number of patients who are documented as being allergic to penicillin are often treated as if they have pencillin anaphylaxis. After investigation to determine the nature of their penicillin allergy many of these patients can more effectively, safely and economically be treated with a beta-lactam antimicrobial.

Issue 10 • HPN

Name of nominee: Zulema Gonzalez Sanchez and team Hospital: St Vincent's University Hospital Nomination overview: SVUH already has intranet-based guidelines for anti-microbial drug use, but prior to this project, there was no ongoing overview of the totality of anti-microbial use in the organisation. The antimicrobial pharmacists (AMP) have been instrumental in setting up a mechanism for the systematic review of all in-patients on parenteral and oral anti-microbial drugs. These stewardship interventions result in the right drug for the right indication at an appropriate dose and duration, in accordance with the Basel statements on hospital pharmacy. The IV to PO switch is easier to implement with the support provided by the anti-microbial pharmacist. OPAT referrals are identified.

Hospital Pharmacy Awards 2013

Oncology Pharmacist of the Year Award Investing in education and the health of the nation

Excellence in Pharmacy

safe handling rdous drugs

Recognising those who provide quality patient care in relation to a patient’s oncologic diagnosis, prescribed treatment, age group and other identified needs and provides comprehensive pharmaceutical care to oncology patients to assure safe and effective drug therapy.

The judging panel will be looking for a high calibre individual who can demonstrate organisation, management and quality of care and services that optimise outcomes in patients with malignant diseases. This person will be able to show how they coordinate the drug

therapy process through drug selection, drug information, dosing, monitoring, outcomes management, and patient education/counselling.

The finalists are... 1

Name of nominee: Fionnuala King

Name of nominee: Evelyn Garvey

Name of nominee: Brid Ryan

Hospital: St James's Hospital

Hospital: Midland Regional Hospital Tullamore

Nomination overview: Fionnuala joined the staff of St James’s Hospital in 2000, and has been lead Pharmacist for Oncology/ Haematology and palliative care , as Chief 2 HOPe directorate. She is dedicated to her patients, her team and consistently provides comprehensive pharmaceutical care to this patient cohort. She focuses on patient safety , and also efficiency and effectiveness of drug therapy. She is the “go to” person amongst her colleagues, both within the hospital and external for up to date information on oncology. Fionnuala thinks outside the box and will look for simple solutions and trial before fully implementing.

Nomination overview: Evelyn Garvey is a recognised authority in the field of oncology, not just within Midland Regional Hospital in Tullamore but throughout Ireland and further afield. She has published widely in this specialist area and her opinion is sought after by colleagues and peers alike. Extremely highly considered as a valuable member of the pharmacy department team Evelyn has been described as innovation, hard working and displaying a dedication that goes beyond that expected from her daily role.

Hospital: Mater Misericordiae University Hospital Nomination overview: In 2011 the ACU, Brid and her pharmacy department colleagues identified CATO as a potential upgrade to the systems that were currently in place. This has clear workflow advantages for the aseptic unit and has the potential for improved and more efficient workflow for the whole Oncology Haematology Multidisciplinary team. In 2012, Phase 1 of CATO implementation was commenced. The workload for Brid in this phase was intense, and had to be undertaken without additional resources. Brid was extremely committed to the project and continued complete functioning Brid’s hard work in the department transfers to her personal life where she is Chairperson of the Civil Service Harriers Athletics Club, Dublin, leading to participation and success in many competitions and completion of full marathons.

HPN • Issue 10

Hospital Pharmacy Awards 2013

Lifetime Achievement Award Investing in education and the health of the nation The Evolution of Generics

Excellence in Pharmacy

The Lifetime Achievement Award recognises the career and achievements of a hospital pharmacist who has made an indelible impact on the pharmacy industry within Ireland as a whole. This award will be given to a hospital pharmacist that has made a major impact on the arena of pharmacy in Ireland and will honour those individuals who have made a difference.

The award provides special recognition to those who have provided outstanding service over a sustained period of years to the pharmacy/pharmacy academic community. The Award recognises the recipient’s dedication to promoting excellence in the pharmacy profession over a substantial period. A lifetime achiever serves as a superior role model to their peers.

The group’s vision is to be involved in all the aspects of bringing pharmaceuticals to patients. Our activities today encompass the entire pharmaceutical value chain and so create a truly integrated offering.

By being vertically integrated and owning all steps of the process, Accord can bring high quality medicines to patients faster, more economically and with greater efficiency than our rivals.

The finalists are...


An evolving company Part of the Intas Group, Accord Healthcare is a young and dynamic pharmaceutical company, involved in the development, manufacturing and distribution of pharmaceutical products to over 50 markets around the world.

The Lifetime Achievement Award winner will be either a current pharmacist or a retired pharmacist who was a member for 25 or more consecutive years. The adjudication panel will be particularly keen to reward long term achievements in developing and promoting clinical pharmacy, innovation, research and development, publication and dissemination of good practice, and peer recognition.

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Accord Healthcare Ltd. 24-26 Bullford Business Campus Kilcoole, County Wicklow - Ireland E-mail: Tel. +353 (0)1 2592020

The Evolution of Generics

Name of nominee: Professor Ciaran Meegan Pharmacy: Mater Misericordiae University Hospital Nomination overview: Professor Ciaran Meegan is a well known face within the pharmacy industry in Ireland. Within a short space of time he had made his mark in the Mater, becoming the Honorary Secretary of the Drugs and Therapeutics Committee and a member of the Research Ethics Committee - posts he still holds to date. From a hospital pharmacy advancement perspective, he introduced ward clinical pharmacy to the Mater in 1993, including the specialisation of clinical roles in cardiology, intensive care and oncology. In recent years Ciaran has developed a significant interest in patient safety, and more specifically medication safety.

Name of nominee: Andrew Barber Pharmacy: Galway University Hospital Nomination overview: Andrew has been instrumental in establishing the Home Chemotherapy Service at Galway Hospital, which has made an enormous and significant impact on the quality of life for cancer patients. To quote one patient: “I could be gone from half-nine until half-four or more… a trip is a day wasted, a day lost in my life.” The patient’s partner added: “Sometimes she wouldn’t sleep for two or three nights thinking about it”. The patient also com- mented: “When you’re at the hospital, you hear what the doctors and nurses are say- ing but it doesn’t always sink in. At home, you can listen to what you’re being told”. She is now more confident and her partner added: “… Sometimes the tension grows in the person who’s being treated… you don’t see that when she’s being treated at home”.

Issue 10 • HPN

The Evolution of Generics


Part of the Intas Group, Accord Healthcare is a young and dynamic pharmaceutical company, involved in the development, manufacturing and distribution of pharmaceutical products to over 50 markets around the world. The groupâ&#x20AC;&#x2122;s vision is to be involved in all the aspects of bringing pharmaceuticals to patients. Our activities today encompass

the entire pharmaceutical value chain and so create a truly integrated offering. By being vertically integrated and owning all steps of the process, Accord can bring high quality medicines to patients faster, more economically and with greater efficiency than our rivals.

Accord Healthcare Ltd. 24-26 Bullford Business Campus Kilcoole, County Wicklow - Ireland E-mail: Tel. + 353 (0)1 2592020

The Evolution of Generics


An evolving company

Hospital Pharmacy Awards 2013

Hospital Pharmacy Technician of the Year Award Investing in education and the health of the nation

Excellence in Pharmacy This Award category serves to recognise and salute those pharmacy technicians whose hard work quite often flies under the radar. If you know someone that has enriched the depth and broadened the scope of pharmacy

technicians then this award category is for you. Hospital pharmacy technicians have a vital role to play in supporting the team within hospital pharmacy departments.

In recognition of this, this award will be given to someone who has provided an outstanding support for the pharmacy profession within their department.

The finalists are...

Name of nominee: Orla Johnston

Name of nominee: Caroline Monaghan

Name of nominee: Laura Lyons

Hospital: Beaumont Hospital

Hospital: Tallaght Hospital

Nomination overview: During her time in the pharmacy department at Beaumont Orla has come into contact with staff and suppliers alike. In all her dealings with both she is always pleasant and courteous as she encounters many problems and always deals with them in a cool and efficient manner. She is described as professional in her duties and has earned her an excellent reputation which is well deserved and worthy of recognition.

Nomination overview: Despite cuts in staffing, resourcing and increased demands on all staff within hospital pharmacy, Caroline has worked constantly with fewer resources to deliver and improve this service. She has a vision for the future of pharmacy and will work constantly to bring about these quality improvements. She understands how important pharmacyâ&#x20AC;&#x2122;s role is in shifting from pill to patient and that being at ward level helps improve patient care. It is great for other pharmacy staff to see her motivation in these difficult times and it is inspiring to other pharmacy technicians.

Hospital: Mater Misericordiae University Hospital

Issue 10 â&#x20AC;˘ HPN

Nomination overview: Laura Lyons is a Senior Pharmaceutical Technician in the Pharmacy Department, MMUH. Having qualified in 1989, Laura worked in the Mater Private Hospital for 3½ years before moving to MMUH in February 1993. Since then she has contributed 20 years of outstanding service to the Pharmacy Department. Laura has always been an active Hospital Pharmaceutical Technician on a national level. Her key strengths lie in her relationship with department staff, other hospital staff, patients and representatives from outside the hospital.

Hospital Pharmacy Awards 2013

Hospital Pharmacy Manager of the Year Award Investing in education and the health of the nation

Excellence in Pharmacy A successful manager creates a productive environment to work in as well as the drive and impetus to make things happen. They must balance technical and management skills.

This Award was aimed at any individual who has made a significant contribution in the past year to their pharmacy department, to those pharmacy managers who have been instrumental in driving the department forward. This could

be through improving financial and clinical performance through effective medication management, inter department relations, reviews or clinical trials, developing a new service or development of staff

The finalists are...

Name of nominee: Louise Byrne

Name of nominee: Mariosa Kieran

Name of nominee: Gerladine Colohan

Hospital: Adelaide & Meath Children’s Hospital

Hospital: Mater Misercordiae University Hospital

Hospital: Portiuncula Hospital

Nomination overview: Pharmacy in general has been facing difficult times but Louise Byrne always leads her team at AMCH with a smile, encouragement and initiative. She has helped grow the success of the pharmacy team and developed and maintained a strong multidisciplinary work ethic. Louise shows a dedication beyond what is expected from her role and has helped to boost training, morale and motivation, empowering other members of the team.

Issue 10 • HPN

Nomination overview: Maríosa has successfully operated in three managerial roles in the Mater Misericordiae University Hospital pharmacy department over the last year, Medicines Information Service Manager, Clinical Pharmacy Service Manager and Deputy Head of Pharmacy Services. Maríosa has overseen the pharmacy department involvement in the relocation of a number of wards and departments from outdated clinical configurations to the new, state of the art, Whitty Building. In the current rapidly changing health service, Maríosa is thriving on the challenge of maintaining a productive work environment and implementing changes to drive the MMUH pharmacy department forward.

Nomination overview: It has been under Geraldine’s leadership that the team at Portiuncla have shown initiative, willing and innovation in improving the pharmaceutical care provided to their patients. She has led the team in successfully implementing many clinical services, often despite low staffing levels, including discharge medicine reconciliation and medication reconciliation. Geraldine always liaises closely with her team, identifying everyone’s key strengths and ensuring they are embodied within the wider multidisciplinary group. A ‘hard working, caring and passionate’ individual she has been described as an extremely worthy winner of the Hospital Pharmacy Manager of the Year award.

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Hospira is one of the major companies producing and marketing biologics globally With over 14,000 employees in 70 countries Hospira Biologics is built on strong foundations of excellence in innovation, service and support

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Our philosophy is simply to deliver more in everything we do

42 Arthritis

Small molecule inhibitors for the treatment of RA Kay McNamee PhD | Fiona McCann PhD The Kennedy Institute of Rheumatology Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, UK

Rheumatoid arthritis (RA) is a debilitating autoimmune condition that affects around 1% of the population. Disease is characterised by joint inflammation, cartilage damage, bone destruction and chronic pain, and if left untreated can result in profound disability. Pathophysiology is attributed to over-production of proinflammatory cytokines, with tumour necrosis factor alpha (TNFα), identified as a pivotal mediator. Control of RA has improved significantly in recent years with the development of drugs that target TNFα, namely infliximab, etanercept and adalimumab. Anti-TNFα biologics, usually taken in combination with methotrexate (MTX), are highly effective at reducing inflammation and restricting joint damage, thereby slowing disease progression, with approximately 70% of RA patients showing an American College of Rheumatology 20% improvement (ACR20). However, despite the unequivocal success of biologics, there remains a substantial subset of patients who do not adequately respond to this treatment strategy. A major disadvantage with biologic therapies is that they must be delivered either subcutaneously or intravenously, and are expensive to produce. Thus, there is a significant need for more cost-effective drugs that can be orally administered and target proinflammatory cytokines. Small molecular weight inhibitors (SMI compounds with a molecular weight of less than 1kDa), have been much explored for their potential to treat RA and other autoimmune disorders. Here, we discuss the SMI currently in development, their proposed

Issue 10 • HPN

mode of action and the impact on drug development in RA. PROTEIN KINASES SMI currently being investigated in inflammatory diseases are largely targeted to intracellular signalling pathways, the most explored of which target kinases. Imperative for cellular processes, kinases are attractive targets as they often act upstream of inflammatory mediators such as TNF and hence selective blockade can regulate inflammatory processes. The mitogen-activated protein kinases (MAPKs) are one such pathway well described in inflammation. They comprise three groups; p38, c-Jun N-terminal kinase (JNK) and extracellular-regulated protein kinase (ERK). There has been significant interest in p38 as therapeutic target as it is expressed in the RA synovium, and blockade of p38 reduces expression of cytokines implicit in the pathogenesis of RA. p38 Inhibitors have proved effective in suppressing disease in animal models of arthritis, providing a clear rationale for a trial in RA patients.(1) However, numerous p38 inhibitors have now been synthesised including SCIO-469 (Scios), pamapimod (Roche), VX-702 and VX-745 (Vertex) and so far none have progressed to a phase III clinical trial. The first generation p38 inhibitors failed in the clinic owing to toxicity in the liver and central nervous system(1,2) and subsequently substantial efforts have been made to enhance specificity. This increased their tolerability, but they have repeatedly failed to demonstrate efficacy in the treatment of RA. However, targets upstream of p38 might

yet prove fruitful. Despite the failure of targeting MAPKs to date, focus on other kinases important in immune responses has continued. The tyrosine kinases Janus (Jaks) and Syk kinases have emerged as front runners from recent RA clinical trials owing to favourable efficacy. Jak family members bind cytokine receptors which are crucial for mediating signal transduction of cytokines in immune regulation. CP-690 550 (tofacitinib, Pfizer) is a JAK family antagonist currently in clinical trials for RA and other autoimmune diseases including IBD, psoriasis and psoriatic arthritis.(3) The initial proof of concept monotherapy study was conducted in RA patients who had failed to respond to either biologics or MTX alone. At the end of the six-week study, patients receiving tofacitinib had shown a significant response (compared to placebo) for ACR20 from the first week for all doses and for ACR50 and ACR70 from week two for the highest dose.(4) This was followed up with two phase IIb 24-week studies designed to evaluate tofacitinib in combination with MTX in patients who had previously exhibited an inadequate response to MTX. The second trial compared the efficacy of tofacitinib as a monotherapy with the anti-TNF biologic adalimumab. In the MTX combination study, patients were treated with tofacitinib at either 1,3,5,10,or 15 mg twice daily or 20mg once daily and MTX or placebo. All doses, with the exception of the 1mg/ twice daily, showed significant ACR20 response by week 12, with the 5, 15 and 20mg doses

also demonstrating increased ACR50 and ACR70 responses. (4) In addition, the 3,10,15 and 20mg doses conferred significant DAS28 remission. In the second study, patients were given either adalimumab at 40mg every other week or tofacitinib at 1,3,5,10,or 15mg twice daily. Patients treated with adalimumab showed increased ACR20 response by week 12. When treated with tofacitinib, patients exhibited higher ACR20, ACR50 and ACR70 responses and a reduced DAS28 score with the 10 and 15mg doses. (4) These encouraging results have led to further evaluation of tofacitinib efficacy in five independent phase III trials, with all five successfully meeting their endpoints. One trial raised concern when four deaths were reported,(5,6) with one fatality due to respiratory failure attributed to tofacitinib. Most other adverse events incurred were mild, and largely due to infection.(6) Tofacitinib may present a promising alternative to biologics, but more long term safety analysis is warranted for further progress. Other Jak inhibitors currently in development are INCB-28050/ LY3009104 (Eli Lilly, Incyte) and VX-509 (Vertex), a JAK 1/2 and JAK 3 inhibitor respectively which are currently in phase II trials for RA.(6) Another SMI kinase targeted of interest is R788 (fostmatinib, Rigel). Fostmatinib acts by targeting spleen tyrosine kinase (Syk), an intracellular tyrosine kinase that is important in the regulation of signalling in many immune cells. Syk is also involved in osteoclast ‘bone-eating’ cells responsible for erosions seen within the

Oral dosing syringe provided

44 Arthritis arthritic joint. The first trial to assess fostmatinib in RA was conducted in 2008. The phase II trial compared three doses of fostmatinib (50, 100 or 150mg twice daily) to placebo in patients already taking MTX. The 100 and 150mg doses showed an improvement compared with the placebo at 12 weeks; with over 65% of patients achieving an ACR20 response (versus placebo response of 38%). (7) The next three-month trial considered how fostmatinib would perform in patients in which treatments with biologics had previously failed.(8) Discouraging results reported no significant differences between fostmatinib and placebo. However, fostmatinib did have an effect on MRI scores measuring synovitis, but ultimately this reduced synovitis did not prevent progressive bone erosion.(8) Despite this, fostmatinib has performed sufficiently well in the phase II trials to continue into phase

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III trials for RA, due to be completed in 2013. Although research for oral treatments has been largely dominated by kinase targets, there are alternative SMI in development including those targeting cell surface receptors, TLR antagonists and PDE4 inhibitors. Human CC chemokine receptor 5 (CCR5) is a chemokine cell surface receptor expressed by T cells and macrophages associated with the migration of immune cells to the rheumatoid synovium. CCR5 expression is elevated in T cells in active RA synovium and increased levels CCR5 ligands (MIP and RANTES) have been implicated in the pathogenesis of RA. Treatment of an animal model (non-human primate) of RA with a CCR5 antagonist resulted in reduced clinical score, joint swelling and bone erosion (referenced in 9). Maraviroc (Pfizer) is a non-competitive

antagonist of CCR5, previously assessed in HIV therapy clinical trials and most recently evaluated in a phase IIa study to assess safety and efficacy in RA patients receiving MTX. Maraviroc was well tolerated in patients at a dose of 300mg twice daily, and by week 12, ACR20 responses were 30% for maraviroc and 19.1% for placebo, though statistical significance was not reached. (9) The lack of efficacy observed concurred with another study where an alternative CCR5 antagonist also failed to show any evidence of therapeutic effect in RA.(10) Toll-like receptors (TLRs) are classified as pattern recognition receptors (PRRs) and are important in host defence by recognising pathogenassociated molecular patterns (PAMPs) from viruses, bacteria, protozoa and fungi. TLRs have been implicated in RA due to the elevation of several

family members (TLR2, 3 and 7) in synovial fibroblasts compared with healthy controls. Stimulation of TLR3 and TLR8 increases TNFα production from RA synovial membrane cultures and inhibition of myeloid differentiation protein 88 (MyD88) and TIR domaincontaining adapter protein (TIRAP), crucial for TLR2 and TLR function, reduces cytokine expression in RA synovial cultures (reviewed in 11). VTX763 (VentiRx Pharmaceuticals) is a SMI that has been shown to inhibit responses to TLR8 stimulation. VTX-763 suppresses TNFα in vitro, and is currently in pre-clinical evaluation for autoimmune disorders.(11) Other SMIs of TLRs currently in phase I trials are DV1179 (Dyanvax) and CPG52364 (Pfizer) for systemic lupus erythematosus. SMIs targeting TLRs are at a very early stage and their impact will not be evident for some time. Another therapeutic approach


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Bioequivalent to original brand with additional benefits1 Fentadur 12, 25, 50, 75 and 100 micrograms/hour transdermal patch (fentanyl) Prescribing information (refer to Summary of Product Characteristics for full prescribing information). Presentation: Tan coloured transdermal patches releasing 12, 25, 50, 75 or 100 micrograms / hour of fentanyl. Indications: Severe chronic pain which can only be managed with opioid analgesics. Dosage: Adults. Initial dose: This should be based on patient’s opioid history taking into account possibility of developing tolerance, patient’s current general condition, medical status and the degree of severity of the disorder. Assess dosage regularly after each administration. If changing from another opioid to fentanyl refer to the SPC for initial recommended doses. For opiate naive patients initiate treatment with patches releasing 12 micrograms/hour fentanyl. Elderly or weak patients: recommend initiate opiate treatment with immediate release morphine and prescribe fentanyl after determination of optimal dose. Dose titration and maintenance: Replace patch every 72 hours. Titrate dose until analgesic efficacy attained. Treatment discontinuation should be gradual in order to prevent withdrawal symptoms. Elderly, cachectic or debilitated patients: Observe carefully for signs of fentanyl toxicity and reduce dose if necessary. Hepatic and renal impairment: Observe carefully for signs of fentanyl toxicity and reduce dose if necessary. Children: Do not use in children under 2 years (12 µg/h strength only) or 12 years (25 - 100 µg/h strengths) of age as experience is limited. Administer only to opioid-tolerant paediatric patients already receiving at least 30 mg oral morphine equivalent per day. Please refer to SPC for initial dosage. Dose titration and maintenance: If analgesic effect is insufficient administer supplementary morphine or another short-duration opioid. Dose adjustments should be done in 12.5 mcg/hour increments. Apply patch to a clean, dry and non-hairy area of skin on the upper body (chest, back, upper arm). Remove hair at application site using scissors instead of shaving. The skin area to which the patch is applied should be free of microlesions (e.g. due to irradiation or shaving) and skin irritation. Contraindications: Hypersensitivity to fentanyl or any of the excipients. Acute or postoperative pain. Severe impairment of central nervous system. Warnings and Precautions: Use only if patient has been adequately assessed medically, socially and psychologically. Do not change from one fentanyl containing product to another without counselling. Treatment should only be initiated by an experienced physician familiar with the pharmacokinetics of fentanyl transdermal patches and the risk of severe hypoventilation. Potential for serious or life-threatening hypoventilation exists even if the lowest dose is used when initiating therapy in opioid-naïve patients. It is recommended that Fentadur be used in patients who have demonstrated opioid tolerance. After a serious adverse reaction monitor patient for 24 hours following removal of patch. Do not divide or cut patch. As respiratory depression may occur patients must be observed for this effect. Respiratory depression may persist after the removal of the patch. Drug dependence may occur. CNS active substances may worsen the respiratory depression. Use with caution in patients with existing respiratory depression, chronic obstructive or other pulmonary disease, increased intracranial pressure, impaired consciousness, coma, brain tumours, hypotension, hypovolemia or bradyarrhythmias. Patients with hepatic or renal impairment should be observed and dose reduced if necessary. Patients with fever should be monitored for opioid adverse reactions. Do not expose application site to direct external heat sources. Elderly or cachectic patients should be observed carefully for signs of fentanyl toxicity and the dose reduced if necessary. Do not administer to opioid naïve paediatric patients. Potential for serious or life-threatening hypoventilation exists regardless of the dose of transdermal fentanyl administered. Use of fentanyl patches may lead to a positive doping test. Use of fentanyl patches as a doping agent may be hazardous to the health. Exercise caution in patients with myasthenia gravis as non-epileptic (myo)clonic reactions can occur. Abuse or intentional misuse of Fentadur may result in overdose and/or death.Dispose of used patches in accordance with guidance within SPC. Drug Interactions: Barbituric acid derivatives. Concomitant use of buprenorphine, nalbuphine or pentazocine not recommended. CNS depressants (e.g. opioids, antipsychotics, hypnotics, general anaesthetics, skeletal muscle relaxants, sedating antihistamines and alcoholic beverages). MAO-inhibitors. CYP3A4 inhibitors (such as itraconazole. ritonavir, ketoconazole, itraconazole or macrolide antibiotics).Pregnancy & Lactation: Do not use in pregnancy unless clearly necessary as safety in pregnancy is not established. Studies in animals have shown reproductive toxicity. Long-term treatment during pregnancy may cause withdrawal symptoms in the infant. Use during labour and delivery not advised as fentanyl passes into the placenta. Discontinue lactation at least 72 hours after removal of patch. Side Effects: Respiratory depression is the most serious side effect. Long term use can lead to development of tolerance and physical / psychological dependence. Withdrawal symptoms (nausea, vomiting, diarrhoea, anxiety and shivering) may occur after switching from other opioids or following discontinuation of treatment. Very common (over 10%): constipation, dizziness, headache, nausea, pruritus, somnolence, sweating and vomiting. Common (1-10%): hypersensitivity, abdominal pain, anorexia, anxiety, asthenia, cold feelings, confusional state, conjunctivitis, depression, diarrhoea, drowsiness, dry mouth, dyspepsia, dyspnoea, erythema, fatigue, hallucinations, hypertension, influenza like illness, insomnia, itching, loss of appetite, malaise, muscle spasms, nervousness, oedema peripheral, palpitations, paraesthesia, rash, rhinitis, sedation, skin reactions at application site, stomach pain, tiredness, tachycardia, tremor, urinary retention, urinary tract infection, vertigo and yawning. Please refer to full SPC for other undesirable effects. Driving and operating machinery: May affect the ability to drive and use machines, especially at onset of treatment, following dosage change or if used with alcohol or antipsychotics. Overdose: Immediate management includes removing patch and physical / verbal stimulation of patient, followed by administration of an opioid antagonist such as naloxone. Respiratory depression due to overdose can persist longer than the effect of the opioid antagonist. Intensive care unit treatment may be required. If severe or persistent hypotension occurs consider use of hypovolemia with appropriate parenteral fluid therapy. Legal Category: CD (Schedule 2), POM (S1A).Marketing Authorisation holder: Pfizer Healthcare Ireland, Pfizer Building, 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24. Package quantities and Marketing Authorisation numbers: Fentadur 12 µg/h., each pack contains 5 transdermal patches, PA 822/70/5. Fentadur 25 µg/h., each pack contains 5 transdermal patches, PA 822/70/1. Fentadur 50 µg/h., each pack contains 5 transdermal patches PA 822/70/2. Fentadur 75 µg/h., each pack contains 5 transdermal patches, PA 822/70/3. Fentadur 100 µg/h., each pack contains 5 transdermal patches, PA 822/70/4. Further information is available on request from: Pfizer Healthcare Ireland, Pfizer Building, 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24. Medical Information Direct Line: 1 800 633 363. Date of Preparation: August 2012. Company reference: gxFE 2_0 IE References: 1. Data on file; Fentanyl Transdermal Patch Common Technical Document, Nov 2007. 2. Date of preparation: Jan 2013 FENT/2013/003/1

46 Arthritis

is via the inhibition of type 4 phosphodiesterases (PDE4), due to the capacity to suppress TNFα in vitro. PDE4 hydrolyses cAMP to AMP and is expressed in immune cells. By inhibiting PDE4, cAMP is elevated leading to suppression of TNFα production via the protein kinase A pathway (PKA). Due to their anti-inflammatory potential, PDE4 has been considered as a worthy target in the treatment of autoimmune conditions; however, issues with toxicity have prevented previous molecules from reaching the clinic. The development of many PDE4 inhibitors including filaminast, lirimilast, and piclamilast have been discontinued, with their lack of efficacy possibly due to lower dosing to enhance tolerability. SIGNIFICANCE OF APREMILAST Apremilast (CC-10004 Celgene) is a novel, orally available small molecule that specifically targets PDE4 that has shown efficacy in the treatment of psoriasis, psoriatic arthritis and animal models of arthritis. In a trial conducted into psoriatic arthritis, 43.5% of patients on apremilast (at 20mg twice daily) and 35.8% of patients (40mg apremilast once daily) achieved the ACR20 end point compared to 11.8% of patients taking placebo after a threemonth period.(12) Furthermore, in a plaque-type psoriasis trial, apremilast administered at 30mg twice daily met the primary end point of a 75% reduction in the psoriasis area and severity index (PASI) score in 41% of patients compared to 6% in the placebo group over a fourmonth treatment period.(13) In the murine models of arthritis (collagen induced arthritis (CIA) and collagen antibody induced arthritis (CAIA)), apremilast significantly reduced severity of disease.(14) Importantly, effects of apremilast on behaviour were compared to another PDE4 inhibitor, rolipram that had previously shown efficacy in

Issue 10 • HPN

CIA. Unlike rolipram, apremilast did not reduce locomotion or increase immobility in DBA/1 mice, indicating that this PDE4 inhibitor may be a suitable candidate due to its tolerability, noteworthy for this class of drugs. Indeed, phase II clinical trials are currently underway to assess efficacy of apremilast in Behcet’s disease and RA, with phase III trials for psoriasis and psoriatic arthritis ongoing,15 and phase III trials for ankylosing spondylitis expected in 2012, suggesting that PDE4 inhibition may indeed be an intriguing strategy for treating chronic inflammation. CONCLUSIONS In summary, SMI have been hailed as having the potential to revolutionise the treatment of chronic autoimmune conditions by providing better delivery routes through oral administration, highly desired by patients as well as reduced costs to healthcare providers via more cost-effective products. In effect, however, the majority of candidate treatments have failed to reach the clinic. This does not mean the end for SMIs in RA, since the targeting of Jak and Syk kinases and PDE4 may yet prove to be efficacious in the long-term, attaining favourable comparisons to established biologics in the clinic. Indeed, SMI may provide a clear alternative for the subset

of patients who fail to respond to anti-cytokine agents, but they are considered unlikely to usurp the dominance of biologics in the near future. REFERENCES 1. Hammaker D, Firestein GS. “Go upstream, young man”: lessons learned from the p38 saga. Ann Rheum Dis 2010;69 Suppl 1:i77–82. 2. Lindstrom TM, Robinson WH. A multitude of kinases – which are the best targets in treating rheumatoid arthritis? Rheum Dis Clin North Am 2010;36(2):367– 83. 3. Opar A. Kinase inhibitors attract attention as oral rheumatoid arthritis drugs. Nat Rev Drug Disc 2010;9(4):257–58. 4. Riese RJ, Krishnaswami S, Kremer J. Inhibition of JAK kinases in patients with rheumatoid arthritis: scientific rationale and clinical outcomes. Best Pract Res Clin Rheumatol 2010;24(4):513–26. 5. Yazici Y, Regens AL. Promising new treatments for rheumatoid arthritis – the kinase inhibitors. Bull NYU Hosp Jt Dis 2011;69(3):233–37. 6. Garber K. Pfizer’s JAK inhibitor sails through phase 3 in rheumatoid arthritis. Nat Biotechnol 2011;29(6):467–68. 7. Weinblatt ME et al. Treatment of rheumatoid arthritis with a Syk kinase inhibitor: a twelve-

week, randomized, placebocontrolled trial. Arthritis Rheum 2008;58(11):3309–18. 8. Genovese MC et al. An oral Syk kinase inhibitor in the treatment of rheumatoid arthritis: a three-month randomized, placebo-controlled, phase II study in patients with active rheumatoid arthritis that did not respond to biologic agents. Arthritis Rheum 2011;63(2):337– 45. 9. Fleishaker DL et al. Maraviroc, a chemokine receptor-5 antagonist, fails to demonstrate efficacy in the treatment of patients with rheumatoid arthritis in a randomized, double-blind placebo-controlled trial. Arthritis Res Ther 2012;14(1):R11. 10. van Kuijk AW et al. CCR5 blockade in rheumatoid arthritis: a randomised, doubleblind, placebo-controlled clinical trial. Ann Rheum Dis 2010;69(11):2013–16. 11. Goh FG, Midwood KS. Intrinsic danger: activation of Toll-like receptors in rheumatoid arthritis. Rheumatology (Oxford) 2012;51(1):7–23. 12. Schett G et al. Apremilast is active in the treatment of psoriatic arthritis (abstract). Proceedings of the ACR-ARHP Annual Meeting 2009;Oct 17–21:Abstr 1258. 13. Papp K, Hu A, Day R. Oral apremilast is active in the treatment of moderate to severe plaque psoriasis (abstract). Proceeedings of the 69th Annual Meeting of the American Academy of Dermatology 2011;Feb 4–8:Abstr P3308. 14. McCann FE et al. Apremilast, a novel PDE4 inhibitor, inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis. Arthritis Res Ther 2010;12(3):R107. 15. Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol 2012; Epub ahead of print:10 January.




Brian is meeting his most important benchmarks September 28

December 15

April 30

August 2

All Ireland Final

Family reunion

Easter holidays

Start cooking class


® is proven to extend overall2

(sunitinib malate)

survival beyond two years

SUTENT® Capsules (sunitinib malate) PRESCRIBING INFORMATION – IRELAND Please refer to the Summary of Product recommended in patients with severe hypertension Characteristics (SmPC) before prescribing SUTENT that is not controlled with medical management. 12.5mg, 25mg or 50mg. Presentation: Hard gelatin Decreased absolute neutrophil and platelet counts capsules containing sunitinib malate equivalent to occurred during clinical trials and complete blood 12.5mg, 25mg and 50mg sunitinib. Indications: For counts should be performed at the beginning of the treatment of unresectable and/or metastatic each treatment cycle. Cardiovascular events, malignant gastrointestinal stromal tumour (GIST) in including CHF, cardiomyopathy and myocardial adults after failure of imatinib treatment due to disorders, some of which were fatal, have been resistance or intolerance; advanced and/or reported. Closely monitor for clinical signs and metastatic renal cell carcinoma (MRCC) in adults; symptoms of CHF and consider baseline and unresectable or metastatic, well differentiated periodic evaluations of LVEF especially in patients pancreatic neuroendocrine tumours (pNET) with with cardiac risk factors and/or history of coronary disease progression in adults. Dosage: Therapy artery disease. If clinical manifestations of CHF should be initiated by a physician experienced in the present, discontinuation of sunitinib is administration of anti-cancer agents. The recommended. The administration of sunitinib recommended dose for GIST and MRCC is 50mg should be interrupted and/or dose reduced in taken orally, once daily, with or without food, for 4 patients without clinical evidence of CHF but with a consecutive weeks, followed by a 2-week rest period, LVEF <50% and >20% below baseline. Sunitinib to comprise a complete cycle of 6 weeks. For pNET should be used with caution in patients with a 37.5mg taken orally once daily without a scheduled known history of QT interval prolongation, patients rest period. Dose modifications in 12.5mg steps may who are taking antiarrhythmics, or patients with be applied based on individual safety and relevant pre-existing cardiac disease, bradycardia, tolerability. Daily dose should not exceed 75mg nor or electrolyte disturbances. Treatment related be decreased below 25mg for GIST or MRCC, the venous thromboembolic events have been reported. maximum daily dose administered during the phase Arterial thromboembolic events (ATE), sometimes 3 pNET study was 50mg. The use fatal, have been reported including cerebrovascular of sunitinib in children and adolescents is accident, transient ischaemic attack, and cerebral not recommended. Contra-indications: infarction. Respiratory events have been reported. Hypersensitivity to the active substance or to any of Baseline lab measurements and monitoring of the excipients. Special warnings and precautions thyroid function during treatment are required and for use: Co-administration of potent CYP3A4 patients treated as per standard medical practice. inhibitors or inducers should be avoided if possible, Pancreatitis and serious pancreatic events, some or the dose of sunitinib altered. Skin discolouration, with fatal outcome have been reported. depigmentation of the hair or skin and occasional Hepatotoxicity has been observed in patients treated rash affecting the palms of hands and soles of feet with sunitinib. Monitor liver function tests at commonly occur during treatment. Pyoderma baseline during each cycle of treatment, and as gangrenosum, generally reversible after drug clinically indicated. If symptoms of pancreatitis or discontinuation, has been rarely reported. Severe hepatic failure are present, treatment with sunitinib cutaneous reactions have been rarely reported, should be discontinued and the patient provided including cases of erythema multiforme (EM) and with appropriate supportive care. Sunitinib cases suggestive of Stevens-Johnson syndrome treatment may be associated with cholecystitis, (SJS) and toxic epidermal necrolysis (TEN). If signs including acalculous and emphysematous or symptoms of SJS, TEN, or EM are present, cholecystitis. Some cases with fatal outcome have sunitinib treatment should be discontinued. been reported. Cases of renal impairment, renal Haemorrhagic events, some of which were fatal failure and/or acute renal failure, in some cases have been reported. Serious, sometimes fatal with fatal outcome, have been reported. Baseline gastrointestinal complications have occurred rarely urinalysis is recommended. Patients should be in patients with intra-abdominal malignancies. monitored for the development or worsening of Treatment related hypertension has been reported. proteinuria. Sunitinib should be discontinued in Patients should be screened for hypertension and patients with nephrotic syndrome. If fistula controlled as appropriate. Temporary suspension is formation occurs, treatment with sunitinib should

be interrupted. Cases of impaired wound healing have been reported during sunitinib therapy and the decision to resume sunitinib therapy following a major surgical intervention should be based upon clinical judgment of recovery from surgery. Osteonecrosis of the jaw (ONJ) has been reported, the majority of cases occurred in patients who had received prior or concomitant treatment with IV bisphosphonates. Caution should therefore be exercised when sunitinib and IV bisphosphonates are used either simultaneously or sequentially. Prior to treatment with sunitinib either along with or subsequent to IV bisphosphonates, a dental examination and appropriate preventative dentistry should be considered. Invasive dental procedures are also an identified risk factor and should be avoided if possible. In case of angioedema due to hypersensitivity, treatment with sunitinib should be interrupted and medical care provided. Patients with seizures and signs/symptoms consistent with reversible posterior leukoencephalopathy syndrome should be controlled with medical management, including control of hypertension as above and temporary suspension of sunitinib is recommended. Cases of Tumour Lysis Syndrome, some fatal, have been reported. Patients should be monitored closely and treated as clinically indicated, and prophylactic hydration should be considered. Serious infections most commonly respiratory, urinary tract, skin infections and sepsis, with or without neutropenia, including some with a fatal outcome, have been reported. Other interactions: None. Fertility, pregnancy and lactation: Sunitinib should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the foetus and is not recommended during breastfeeding. Fertility may be compromised during treatment with sunitinib. Driving and operating machinery: Patients should be advised that they may experience dizziness during treatment with sunitinib. Undesirable effects: The most important treatmentrelated serious adverse reactions associated with sunitinib, some fatal, are renal failure, heart failure, pulmonary embolism, severe cutaneous reactions (EM, SJS and TEN), gastrointestinal perforation and haemorrhages (e.g. respiratory tract, gastrointestinal, tumour, urinary tract, and brain haemorrhages). Very common adverse events are neutropaenia, thrombocytopenia, anaemia, decreased appetite, taste disturbance, headache, hypertension, epistaxis, diarrhoea, stomatitis/

aphthous stomatitis, vomiting, nausea, dyspepsia, abdominal pain/distension, constipation, glossodynia, yellow skin/skin discolouration/ pigmentation disorder, palmar-plantar erythrodysaesthesia syndrome, rash, hair colour changes, dry skin, pain in extremity/limb, fatigue/ asthenia, mucosal inflammation, oedema. Commonly reported adverse events are leucopoenia, hypothyrodism, dehydration, insomnia, depression, paraesthesia, dizziness, neuropathy peripheral, hypoaesthesia, hyperaesthesia, lacrimation increased, eyelid oedema, flushing, hot flush, dyspnoea, oesophagitis, oropharyngeal pain, cough, dyspnoea exertional, nasal dryness, pleural effusion, nasal congestion, oral pain, flatulence, dry mouth, gastro-oesophageal reflux disease, dysphagia, gingival bleeding, mouth ulceration, cheilitis, proctalgia, haemorrhoids, oral discomfort, rectal haemorrhage, eructation, stomach discomfort, alopecia, erythema, skin reaction, skin exfoliation, pruritus, dermatitis, periorbital oedema, nail disorder/discolouration, skin lesion, blister, hyperkeratosis, acne, skin hyperpigmentation, myalgia, arthralgia, muscle spasm, back pain, muscular weakness, musculoskeletal pain, chromaturia, pyrexia, chills, chest pain, pain, influenza like illness, ejection fraction decreased/ abnormal, weight decreased, white blood cell count decreased, lipase increase, platelet count decreased, haemoglobin decreased, blood creatinine phosphokinase increased, amylase increased, aspartate aminotransferase increased, alanine aminotransferase increased, blood creatinine increased, blood pressure increased blood uric acid increased, respiratory infections, urinary tract infections, skin infections, abscess, viral infections, bacterial infections, fungal infections. Refer to SmPC for information on other adverse effects. Legal Category: S1A. The Marketing Authorisation Holder: Pfizer Limited, Sandwich, Kent, CT13 9NJ, United Kingdom. For further information on this medicine please contact: Pfizer Medical Information on 1800 633 363 or at EUMEDINFO@ For queries regarding product availability please contact: Pfizer Healthcare Ireland, Pfizer Building 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24 + 353 1 4676500. Last revised: April 2013. Ref: ST 18_1

Reference 1. SUTENT® Summary of Product Characteristics, March 2013. 2. Motzer et al. Overall survival and updated results for sunitinib versus interferon alpha in first line treatment of patients with metastatic renal cell carcinoma J Clin Oncology 2009;27:3584-90.

Date of preparation: July 2013


48 Cardiology

Natriuretic Peptide–Based Screening and Collaborative Care for Heart Failure The STOP-HF Randomized Trial Mark Ledwidge, PhD; Joseph Gallagher, MB; Carmel Conlon, PhD; Elaine Tallon, PGDip; Eoin O’Connell, MLitt; Ian Dawkins, DPhil; ChrisWatson, PhD; Rory O’Hanlon, MD; Margaret Bermingham, BSc(Pharm); Anil Patle, MBA; Mallikarjuna R. Badabhagni, RDCS; Gillian Murtagh, MD; Victor Voon, MB; Leslie Tilson, PhD; Michael Barry, MD; Laura McDonald; Brian Maurer, MD; Kenneth McDonald, MD

Mark Ledwidge, PhD

The increasing prevalence of heart failure (HF) remains a major public health concern underlining the need for an effective prevention strategy.1 Presentday approaches, focusing mainly on risk factor intervention, have brought about some reduction in new-onset HF.2-4 However, recent major reports in the United States and the European Union underline difficulties in achieving adequate risk factor control and show that present strategies will not be as effective as desired.5,6 This, in turn, may in part be explained by the uniform direction of resources to a population containing predominantly lower-risk patients and the lack of risk stratification beyond that calculated from standard risk factors. Refining risk prediction may be aided by the use of brain type natriuretic peptide (BNP), which has been shown in large general and American College of Cardiology Foundation/ American Heart Association stag A/B (asymptomatic) populations to identify those at highest risk of cardiovascular events and, more specifically, of newly diagnosedHF.7,8 Studies have shown advantages of using this peptide in this regard over conventional risk indicators.8,9 This may reflect the fact that BNP is a response to established cardiovascular damage whereas other conventional risk indicators reflect the potential for cardiovascular insult. New data suggest that more targeted Issue 10 • HPN

surveillance using a combination of risk factors and BNP may improve identification of those at greatest risk of newly diagnosed HF.10 Therefore, we hypothesized that BNP-based screening and intervention would target management to those at highest risk of HF and asymptomatic ventricular dysfunction, providing an approach to prevention of HF and cardiovascular disease that would be superior to standard care. The St Vincent’s Screening to Prevent Heart Failure (STOP-HF) study was designed as a pragmatic, prospective randomized trial in a broad community population characterized by collaborative care intervention between cardiovascular specialists and primary care physicians. METHODS Patient Population All primary care physicians in the catchment area of St Vincent’s University Hospital, Dublin, Ireland, participating in the Community Programme for Cardiovascular Risk Evaluation (COMPARE) study were invited to participate by mail and then at an initiation meeting. COMPARE was a nurse-provided primary care cardiovascular risk screening program. Patients were referred by their primary care physicians to the STOP-HF program between 2005 and 2009, with 39 participating practices. Patients from COMPARE were eligible to participate in the

STOP-HF study if they were older than 40 years and had a history of 1 or more of the following: (1) hypertension (medicated for ≥1month); (2) hypercholesterolemia, defined as total cholesterol greater than 193 mg/dL (5.0 mmol/L) (174 mg/Dl [4.5 mmol/L] in high-risk patients) and/or low-density lipoprotein cholesterol greater than 116 mg/dL (3.0 mmol/L) (97 mg/dL [2.5 mmol/L] in highrisk patients) or receiving lipid lowering lipid lowering therapy; (3) obesity, defined as body mass index (calculated as weight in kilograms divided by height in meters squared) greater than 30; (4) vascular disease, including coronary artery disease (confirmed by angiography or history of myocardial infarction), cerebrovascular disease, and peripheral vascular disease; (5) diabetes mellitus; (6) arrhythmia requiring therapy; or (7) moderate to severe valvular disease. We excluded those who refused to provide informed consent, had established evidence of left ventricular systolic dysfunction, had evidence or a history of symptomatic HF, or had a diagnosis compromising survival over the study period. Study Procedures The study protocol was approved by the St Vincent’s University Hospital Ethics Committee and conformed to the principles of the Declaration of Helsinki. The study nurse enrolled consecutive consenting patients and obtained written consent. Study group was assigned by the STOP-HF centre according to a computer-generated random number list created by the study statistician. An administrator in the study centre allocated patients consecutively to intervention or control group. The allocation sequence was concealed from the investigators until individuals were assigned. The randomization process assigned patients 1:1 to control group (receiving routine primary care physician management) or BNP-driven

collaborative care between the primary care physician and specialist cardiovascular centre. It was not possible to blind participants or clinical investigators to group assignment. All patients in the study underwent BNP blood testing (Triage, Biosite) at study commencement and annually thereafter. Primary care physicians did not have access to BNP testing outside of the study protocol. Enrollment commenced in January 2005 and ended in December 2009. Follow-up was completed in December 2011 (Figure 1). In the control group, patient care continued with advice on lifestyle modification and risk factor intervention as determined by primary care physicians without knowledge of BNP results and with at least an annual patient visit. At the annual review, the study nurse performed blinded BNP testing on all control-group patients as part of a structured cardiovascular risk and lifestyle review. Patients in the control group received specialist cardiologist care only if requested by the primary care physician as part of their usual care. In the intervention group, BNP results were made available to primary care physicians with protocol referral of all patients with a value of 50 pg/mL or higher (50 ng/L) to the specialist cardiovascular service. Those with BNP values less than 50 pg/ mL received the same care as provided in the control group, albeit with disclosure of BNP values to patients and primary care physicians. Participants with a BNP level of 50pg/mL or higher underwent Doppler echocardiography and review by a cardiologist at the study centre, who decided on further investigation and management. In addition to disclosure of BNP values to patients and the primary care physicians, the focus of the specialist intervention for those with elevated BNP was multidimensional. This approach included optimal

Research Original Investigation

Natriuretic Pept


Figure 1. Participant Flow Figure 1. Participant Flow

3123 Patients assessed for eligibility 1749 Excluded 1203 Did not meet inclusion criteria 546 Declined to participate

BNP indicates brain-type natriuretic peptide

1374 Randomized

risk factor management with the most appropriate therapy and complete investigation and treatment of abnormalities defined on examination or on Doppler echocardiography. In addition, all patients received further coaching by a specialist nurse who emphasized individual risk status and the importance of adherence to medication and healthy lifestyle behaviours. Patients with an initial BNP level of 50pg/mLor higher also received ongoing collaborative care with at least an annual specialized cardiovascular review, including repeat Doppler echocardiography, BNP measurement, and other investigations as appropriate. In all patients with an initial BNP of less than 50 pg/mL, annual BNP testing by their primary care physician resulted in specialist referral with management as outlined above if the value increased to 50 pg/mL or higher. Participants’ primary care physicians were informed of all clinical investigations performed by the specialist cardiovascular centre and were involved in any change in management strategy. At study termination, all control and intervention participants underwent clinical assessment by a cardiologist including Doppler echocardiography; the technician and reporting cardiologist were blinded to study group allocation. End Points The original protocol version from June 2004 specified newly diagnosed HF or left ventricular systolic dysfunction as the primary end point. However, slower-than-expected recruitment rates resulted in an extension of the study in April 2009 and the redefinition of the primary end point to include significant left ventricular diastolic dysfunction as determined by a ratio of mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (E′) greater than 15. This change in the study primary end point was approved by the institutional review board and occurred before completion of recruitment in December 2009.

697 Randomized to receive BNP screening and protocol referral for BNP ≥50 pg/mL to specialist cardiovascular center (collaborative care) 697 Received BNP screening as randomized 263 With BNP ≥50 pg/mL received Doppler echocardiography and collaborative care follow-up

677 Randomized to receive usual primary care physician management 677 Received usual care as randomized

535 Completed follow-up 70 Lost to follow-up (not contactable) 92 Withdrew from study 61 Not interested in further participation 17 Unable to attend study visits 9 Moved out of area or changed physician 5 Other reasons

476 Completed follow-up 69 Lost to follow-up (not contactable) 132 Withdrew from study 83 Not interested in further participation 34 Unable to attend study visits 8 Moved out of area or changed physician 7 Other reasons

697 Included in analysis

677 Included in analysis

treatment of abnormalities defined on examination or on Dop-

mented before the assessment o

STOP-HF investigators did not The change was approved and The calculations were then based which began in 2010, and prio echocardiography. In addition, all patients received on furimplemented pler implemented before a prevalence of left ventricular have any influence in the decision the assessment of the study by a specialist dysfunction (systolic and diastolic) to admit. nurse All clinical end points ring. Therefore, the primary e ther coaching who emphasized indiprimary end point, which began with or without HF expected to were assessed by a member ported herein is the prevalence vidual risk status and the importance of adherence to in 2010, and prior to any data be 19.6%in the control group at of the study team by reviewing tion (asymptomatic left ventric medication and healthy lifestyle behaviors. analysis occurring. study end. The treatment effect the primary care physician’s was expected to be similar toventricular d records and confirmed by hospital asymptomatic left Patients with an initial BNP level of 50 pg/mL or higher also Therefore, the primary end point that observed at 1 year with discharge summary. of the study as reportedongoing herein iscollaborative withoutintervention newly diagnosed HF at received care with at least an annual speantihypertensive in the prevalence of left ventricular process was carried outDoppler echThe inclusion of asymptoma cialized cardiovascularThis review, including repeat the LIFE study.11 This implies dysfunction (asymptomatic left by the same specialist nurse for a prevalence of 13.4%in the or significant diastolic ocardiography, and other investigations as function ventricular systolic dysfunctionBNP measurement, consistency of reporting over the intervention group and an absolute or asymptomatic left ventricular primary end point reflects appropriate. In all patients an initial BNPwho of less than 50 ofofthe studywith duration. The nurse reduction 6.2%. diastolic dysfunction) with or reviewed records to determine pg/mL, annual BNP testing by their primary care physician re- these abnormalities, specificall without newly diagnosed HF at With an OR of 0.63, anα=.05 outcomes was blinded to HF. Left ventricular sulted in specialist referral with management as outlined above study completion. (2-tailed), and a power level ofdysfunction participant allocation. Finally, we 80%, thetion revised total required of (1) left ventricular ejectio if the value increased to 50 pg/mL or higher. Participants’ prialso evaluated change in BNP over The inclusion of asymptomatic left sample size 1129. The than 15 in the s time. Other end points in E/E′was ratio greater marydysfunction care physicians were informed of all included clinical investigaventricular systolic or principal investigators agreed that the study protocol were evaluation significant diastolic dysfunction ejection fraction tions performed by the specialist cardiovascular center the andstudylarwould continue until on Doppler of the relationship between BNP as a component of the primary a sufficient number of patients ence of HF was defined as sym were involved in any change in management strategy. and severity of left ventricular end point reflects the heightened were followed up for at least dysfunction, hospital admissions particirisk status of theseAtabnormalities, gency admission to the hosp study termination, all control and intervention 1year (accounting for known specifically topants the later andassessment death, quality-of-life and discharge summary. underwent clinical by a cardiologist includpatient withdrawals) to exceed the development of HF. Left ventricular cost effectiveness analyses, numbers in the power calculation. Secondary end points rep ing Doppler echocardiography; the technician and reporting dysfunction was defined as any and evaluation of the clinical, Further assumptions were that combination of (1) left ventricular gency hospitalizations for any o cardiologist were blinded to study group allocation. demographic, biochemical, allocation to control or intervention ejection fraction less than 50% or pharmacological, genomic, cardiovascular events: arrhythm group was even and unbiased (2) E/E′ ratio greater than 15 in the proteomic, and metabolomic (ie, group membership was an stroke, myocardial infarction, pe Endleft Points setting of normal ventricular determinants of BNP. These will be independent random binomial ejection fraction onoriginal Dopplerprotocol version bosis/embolus, or HF. The from June 2004 specified newly reported in future analyses. variable with P = .50) and that All major a echocardiography. The presence classified based diagnosed HF or left ventricular systolic dysfunction as thecovariates pri- were account for 0%of theon the disc Sample Size Calculation of HF was defined as symptoms of variation in probability of HF or left the STOP mary endadmission point. However, slower-than-expected recruit- pitalization event, and HF requiring emergency Sample size calculations were ventricular dysfunction. to the hospital, confirmed by ment rates resulted in an extension ofon the study in April 2009 any influence in the decision to originally based the primary hospital discharge summary. and the redefinition ofend thepoint primary point sig- were assessed by a member of th of HFend and/or left to include RESULTS

Secondary end points reported ventricular dysfunction, Participants primary care physician’s records nificant left ventricular diastolicsystolic dysfunction as determined herein include emergency the prevalence of which was charge summary. This process w byfor a ratio of mitral peakassumed velocitytoofbe early filling (E) to early diaFrom the participating practices, hospitalizations any of 9.6% in the control 1374 patients randomized the following major cialistwere nurse for consistency of r stolicadverse mitral annular velocity (E′)5.9%in greater than 15. This change group and the treatment (Figure 1) and followed up for a cardiovascularinevents: arrhythmia, group. Thiswas yields an odds by ratiothe institution. The nurse who reviewed re the study primary end point approved mean of mean of 4.2 (SD, 1.2) transient ischemic attack, stroke, (OR) of approximately 0.59. Using was1blinded to participant alloc tional review board and occurred before completion of recruityears (Table and eAppendix in myocardial infarction, peripheral an OR of 0.59, an α=.05 (2-tailed), the Supplement). Hypertension or pulmonary ment thrombosis/ ated change in BNP over time. in December 2009. The change approved and impleand power levelwas of 80%, the total was the most prevalent risk embolus, or HF. All major required sample size was n=1644. factor, and most participants had adverse cardiovascular events size 1calculations were at least 2 risk factors in addition JAMA 2013 VolumeSample 310, Number were 68 classified basedJuly on3,the later adjusted when the primary to age. There were 37 deaths discharge summary from the hospitalization event, and the endpoint was changed. (5.5%) in the control group and 36

Downloaded From: by a University College Dublin User on 07/02/2013

HPN • Issue 10

50 Cardiology

Research Original Investigation

Natriuretic Peptide–Based Screening and Heart Failure

Table 1. Baseline Participant Characteristics

Table 1. Baseline Participant Characteristics

All Participants Intervention (n=697)

Control (n=235)

Age, mean (SD), y

65.4 (10.3)

64.1 (10.1)

70.8 (8.5)

67.9 (9.0)

Male, No. (%)

300 (44.3)

323 (46.3)

104 (44.3)

104 (44.9)

Hypertension, No. (%)

419 (61.9)

433 (62.1)

164 (69.8)

205 (78.0)

Diabetes mellitus, No. (%)

123 (18.2)

127 (18.2)

47 (20.0)

54 (20.5)

Obesity, No. (%)

193 (28.5)

180 (25.8)

69 (29.4)

63 (24.0)

54 (8.0)

48 (6.9)

32 (13.6)

31 (11.8)

7 (1.0)

2 (0.85)


Arrhythmia, No. (%) Valvular disease, No. (%) Lipid disorders, No. (%)

3 (0.44)

Intervention (n=263)

355 (50.9)

144 (61.3)

Vascular disease, No. (%)

23 (3.4)

32 (4.6)

13 (5.5)

21 (8.0)

Myocardial infarction, No. (%)

56 (8.3)

73 (10.5)

37 (15.7)

46 (17.5)

132 (50.2)


204 (30.1)

204 (29.3)

62 (26.4)

65 (24.7)


242 (35.8)

241 (34.6)

86 (36.6)

99 (37.6)


180 (26.6)

188 (27.0)

83 (35.3)

44.8 (57.5)

48.2 (84.9)

86.6 (73.2)


182.1 (40.6)

182.7 (39.9)

174.9 (42.3)

180.1 (40.4)

Low-density lipoprotein

101.4 (34.3)

103.1 (36.4)

95.7 (32.0)

100.1 (35.0)

High-density lipoprotein

50.5 (16.1)

49.3 (15.7)

50.6 (15.3)

48.9 (15.3)

Non–high-density lipoprotein

131.6 (38.4)

133.4 (38.2)

124.3 (39.8)

131.2 (36.6)


150.4 (78.8)

156.7 (82.6)

140.2 (72.0)

152.7 (82.9)

109.6 (37.6)

109.8 (37.8)

110.5 (40.2)

108.8 (28.41)

Creatinine, mean (SD), mg/dL

0.95 (0.22)

0.95 (0.23)

1.01 (0.27)

0.97 (0.25)

Body mass indexa

28.0 (5.5)

27.7 (5.0)

27.9 (6.1)

27.4 (4.5)

70 (12)

70 (12)

67 (12)

67 (12)


147.0 (22.5)

144.7 (20.9)

148.7 (23.7)

147.1 (23.7)


80.5 (11.9)

81.1 (12.0)

77.6 (12.3)

79.0 (12.1)

No. of risk factors, No. (%)

97 (36.9) 91.6 (118.0)

Cholesterol, mean (SD), mg/dL

Glucose, mean (SD), mg/dL

Heart rate, mean (SD), /min

renin-angiotensin-aldosterone system(RAAS). Diuretics were prescribed in approximately onefifth ofpatients in both groups as therapy for hypertension. There was an increase in RAASmodifying therapies in the intervention group, driven predominantly

5 (1.9)

376 (55.5)

BNP, mean (SD), pg/mL

Pharmacotherapy: At baseline, pharmacotherapy was well matched between the groups, with approximately half of the total population receiving statins, antiplatelet therapy, and agents that modify the

Participants With BNP ≥50 pg/mL

Control (n=677)

Blood pressure, mean (SD), mm Hg

Abbreviation: BNP, brain-type natriuretic peptide. by increased use of angiotensin SI conversions: To convert BNP receptor blockers (eTable 3 in the to ng/L, multiply Supplement). by 1.0. To convert total, low-density BNP and Risk Factor Control lipoprotein, highLevels of BNP increased in both density lipoprotein, groups over the duration of and non–high-BNP, brain-type Abbreviation: density lipoprotein the study, consistent with the natriuretic peptide. cholesterol to increasing age of the population. SI conversions: Toby convert BNP to mmol/L, multiply ng/L, multiply by 1.0. To convert total,subgroup with BNP levels of 0.0259. To convert In the low-density lipoprotein, high-density triglycerides to 50 pg/mL or higher, the increase lipoprotein, and non–high-density mmol/L, mulitply in BNP levels in the intervention lipoprotein to mmol/L, by 0.0113. cholesterol To group was approximately half multiplyglucose by 0.0259. convert to To convert of that observed in the control mmol/L, multiply by triglycerides to mmol/L, mulitply by 0.0555. Toconvert convertglucose togroup (mean, 12.5 vs 23.5 pg/ 0.0113. To creatinine to µmol/L, mmol/L, multiply by 0.0555.mL; To P = .24). In the subgroup with multiply 88.4. ato μmol/L,BNP levels less than 50 pg/mL, convert by creatinine Calculated weight therewas no change in BNP levels multiply by as 88.4. ina kilograms divided in either group or between groups Calculated as weight in kilograms by height in meters divided by height in metersover the follow-up period; absolute squared. mean changes were 0.4 pg/mL squared.

in the control group compared with0.5pg/mLin the intervention

formed in the intervention group, with more markedgroup, differ-respectively (P = .90). Secondary EndinPoints (5.2%) deaths the intervention 0.57; 95% CI, 0.38-0.86; P = .007). group with BNP levels of 50 pg/ ences in the group with BNP levels of 50 pg/mL or higher (496 Major Adverse Cardiovascular Events group. There were 309 all-cause Twenty-one cases of new-onset mL or higher, the incidence rates The details of cardiovascular risk vs 850 cardiovascular investigations per 1000for person-years in Seventy-one patients (10.5%) were admitted for major ademergency hospitalisations in the HF requiring hospitalization of emergency hospitalisation factor control at baseline and control group (106.6 per 1000 intervention groups, respectively; IRR, 1.71; 95% verse cardiovascular events in the control group and 51 (7.3%) the control andmajor adverse cardiovascular follow-up are presented in eTable 1 (14 in the control group and 7 patient years) and 269intervention all-cause events(eTable were 782 per 1.61-1.83; P<.001) in the Supplement). in the Supplement. were admitted in the group (OR, 0.69; 95% group) CI, CI, in the intervention were emergency hospitalizations in the 0.49-0.98; P = .04) (Table 2 and Figure 2). The ed, incidence rates of which identifi the majority 1000patient-years in the control intervention group (92.2 per 1000 Discussion: STOP–HF is the first of emergency cardiovascular events fraction. Pharmacotherapy preserved ejection groupand40per1000patientyears patient-years) hospitalization (eTable 9 in thefor major had prospective, randomized study, of those in vs the22.3 control Atgroup baseline, pharmacotherapy was well matched between theknowledge, to demonstrate were 40.4 perThe 1000 patient-years control group in the intervention group (IRR, Supplement). IRR was 0.85 in theTen to our were admitted once and groups, 6 of those 0.54; 95% CI, 0.37-0.77; = .002) with approximately half of thePtotal population reper 10000.72-1.00; patient-years in.05). the intervention group (IRR, 0.60; 95% (95%CI, P= A full a reduction in newly diagnosed in the intervention group were 3).Results for the list the cardiovascular andthe non HF, asymptomatic left ventricular ceiving statins,(Table antiplatelet therapy, andgroup agentswith that modify the CI, of 0.45-0.81; P = .002). In group with BNP levels of 50 once. BNP levels of less than 50 pg/mL cardiovascular emergency and rates ofadmitted dysfunction, and emergency were pg/mL or higher, the incidence emergency hospital- renin-angiotensin-aldosterone system (RAAS). Diuretics are presented in eTable 5 in the elective admissions and outpatient cardiovascular hospitalizations Theevents remainder prescribed in approximately groups ization for major adverse cardiovascular were in 78both per groups Supplement. one-fifth of patients in bothusing BNP-guided collaborative visits is presented in eTables 11 were admitted on 2 occasions. as therapy for hypertension. There was an increase in RAAS100012 patient-years in the control group and 40 per 1000 patientcare in a broad community cohort. and in the Supplement. Seventeen of the 21 admissions The most frequently observed modifying therapies in the intervention group, driven pre-rms BNP as a risk identifier years in the intervention group (IRR, 0.54; 95% CI, 0.37-0.77; It confi occurred in patients with at least clinical events were arrhythmia Primary End Point HF and cardiovascular events dominantly by increased use of angiotensin receptorfor blockP = .002) (Table 3). Results for the group1with BNP levels of lessresult BNP measurement of 50 (90% atrial fibrillation), transient and provides unique data on ers (eTable 3 inischemic the Supplement). thanprimary 50 pg/mL presented 5 in the The endare point of left in eTablepg/mL orSupplement. higher before diagnosis attack, and stroke the potential benefit of using ventricular dysfunctionobserved and HF clinical(eTable in the Supplement). The most frequently events 8 were arrhyth(Table 2 and eTable 10 in the levels of this peptide as a guide wasmetin 59 (8.7%)of 677 controlmia (90% atrial fibrillation), transientSecondary ischemic attack, and BNP and Risk Factor Control Supplement). for care. The positive clinical End Points group patientsand37 (5.3%) of Levels of BNP increased in both groups over the duration stroke (Table 2 and eTable 10 in the Supplement). effectofof this intervention was 697 intervention-group patients Diagnostic Investigations Major Adverse Cardiovascular associated with improved risk the study, consistent with the increasing age of the popula(OR, 0.55; 95% CI, 0.37- 0.82;P = Events: Seventy-one patients Electocardiography, cardiac tion. In the subgroup with BNP levels of 50 pg/mL or factor higher,control, increased use of Diagnostic Investigations .003).Asymptomatic left ventricular (10.5%) were admitted for major agents that modulate the RAAS imaging, ambulatory blood dysfunctionwas found in 45 (6.6%) the increase in BNP levels in the intervention group was apElectocardiography, cardiac imaging, ambulatory blood pres- events adverse cardiovascular in targeted at those with elevated pressure monitoring, and of 677 control-group and werethe proximately half of that observed in the control group (mean, sure monitoring, and patients stress testing more likely to be percontrol group and 51 (7.3%) BNP levels, and increased use of

stress testing were more likely 30 (4.3%) of 697 interventionwere admitted in the intervention to be per performed in the group patients (OR, 0.57; 95% CI, group (OR, 0.69; 95% CI, 70 JAMA July 3, 2013 Volume 310, Number 1 intervention group, with more 0.37-0.88;P = .01).Heart failure marked differences in the 0.49-0.98; P = .04) (Table 2 and occurred in14 (2.1%) of 677 group with BNP levels of 50 Figure 2). The incidence rates controlgroup patients and 7 (1.0%) pg/mL or higher (496 vs 850 of emergency hospitalization of 697 intervention-group patients oaded From: College Dublin Userevents on 07/02/2013 cardiovascular investigations for major cardiovascular (OR, 0.48; 95%CI, 0.20-1.20; P by a University per 1000 person-years in the were 40.4 per 1000 patient= .12) (Table 2 and eTable 4 in control and intervention groups, years in the control group vs the Supplement). The unadjusted respectively; IRR, 1.71; 95% CI, 22.3 per1000patient-years in the analyses and the covariate1.61-1.83; P<.001) (eTable 2 in the adjusted analyses were similar for intervention group (IRR,0.60;95% the primary outcome measure (OR, CI, 0.45-0.81; P = .002). In the Supplement).

Issue 10 • HPN

some cardiovascular diagnostics. suggest that a targeted strategy for HF prevention using BNP and collaborative care in a community population may be effective and that benefits extend beyond prevention of HF to an overall reduction in emergency cardiovascular admissions.

These data

References available on request

Every day and every beat counts


Twice daily

Heart failure management has moved up a gear Procoralan: Abbreviated Prescribing Information. Please refer to the Summary of Product Characteristics (SmPC) before prescribing. PRESENTATION AND COMPOSITION*: Procoralan 5 mg: film-coated, scored tablet containing 5 mg ivabradine; Procoralan 7.5 mg film-coated tablet containing 7.5 mg ivabradine. INDICATIONS*: Treatment of coronary artery disease: Symptomatic treatment of chronic stable angina pectoris in coronary artery disease adults with normal sinus rhythm. Procoralan is indicated: - in adults unable to tolerate or with a contra-indication to the use of beta-blockers, or - in combination with beta-blockers in patients inadequately controlled with an optimal beta-blocker dose and whose heart rate is >60 bpm. Treatment of chronic heart failure: ivabradine is indicated in chronic heart failure NYHA II to IV class with systolic dysfunction, in patients in sinus rhythm and whose heart rate is 竕・75 bpm, in combination with standard therapy including beta-blocker therapy or when beta-blocker therapy is contra-indicated or not tolerated. DOSAGE AND ADMINISTRATION*: The starting dose in coronary artery disease patients and in patients with stable heart failure is 5 mg orally, twice daily during meals: breakfast and dinner. Depending on the therapeutic response, the dose may be increased to 7.5 mg twice daily after 3 to 4 weeks of treatment in coronary artery disease patients, and after 2 weeks in heart failure patients for whom heart rate is persistently above 60 bpm. In heart failure patients: to preferably be initiated by a physician experienced in the management of chronic heart failure: if heart rate is between 50 and 60 bpm, the dose of 5 mg twice daily should be maintained. If heart rate decreases persistently below 50 bpm at rest or in the presence of symptoms related to bradycardia such as dizziness, fatigue or hypotension, treatment should be downtitrated from 7.5 mg to 5 mg or from 5 mg to 2.5 mg twice daily. Treatment must be discontinued if heart rate is below 50 bpm or symptoms of bradycardia persist. CONTRAINDICATIONS*: Hypersensitivity to the active substance or to any of the excipients; resting heart rate below 60 bpm prior to treatment; cardiogenic shock; acute myocardial infarction; severe hypotension (< 90/50 mmHg); severe hepatic insufficiency; sick sinus syndrome; sino-atrial block; unstable or acute heart failure; pacemaker dependent (heart rate imposed exclusively by the pacemaker); unstable angina; AV-block of 3rd degree; combination with strong cytochrome P450 3A4 inhibitors such as azole antifungals (ketoconazole, itraconazole), macrolide antibiotics (clarithromycin, erythromycin per os, josamycin, telithromycin), HIV protease inhibitors (nelfinavir, ritonavir) and nefazodone (see interactions section); pregnancy, lactation (see fertility, pregnancy and breast- feeding section). WARNINGS*: Special warnings: Cardiac arrhythmias: ivabradine is not recommended in patients with atrial fibrillation and other cardiac arrhythmias that interfere with sinus node function, monitor regularly ivabradine-treated patients for the occurrence of atrial fibrillation. The risk of developing atrial fibrillation may be higher in chronic heart failure patients treated with ivabradine. Monitor also closely patients with chronic heart failure and intraventricular conduction defects; AV-block of 2nd degree: use not recommended; low heart rate: treatment must not be initiated below 60 bpm, during treatment, if resting heart rate decreases persistently below 50 bpm or in case of symptomatic bradycardia, the dose must be down-titrated or treatment discontinued if it persists; combination with calcium channel blockers (e.g. verapamil, diltiazem): not recommended; chronic heart failure: heart failure must be stable before considering ivabradine treatment: chronic heart failure NYHA class IV patients: use with caution; stroke: not recommended immediately after a stroke; visual function: use with caution in patients with retinitis pigmentosa. Precautions for use: Hypotension: use with caution; atrial fibrillation - cardiac arrhythmias: non urgent DC-cardioversion should be considered 24 hours after the last dose of ivabradine; patients with congenital QT syndrome or treated with QT prolonging medicinal products: use should be avoided; hypertensive patients requiring blood pressure treatment modification: blood pressure should be monitored; creatinine clearance below 15ml/min: should be used in caution as there is no data available in these patients: potassium depleting diuretics (thiazide diuretics and loop diuretics): to be used with caution, hypokalemia can increase the risk of arrhythmia; excipients: contains lactose. INTERACTIONS*: Contra-indicated: strong CYP3A4 inhibitors. Not recommended: QT prolonging medicinal products, moderate CYP3A4 inhibitors (verapamil and diltiazem). With precautions: Potassium-depleting diuretics (thiazide diuretics and loop diuretics), other moderate CYP3A4 inhibitors, grapefruit juice, CYP3A4 inducers. FERTILITY*. PREGNANCY and BREASTFEEDING*: contra-indicated. DRIVE AND USE MACHINES*: Possible occurrence of transient luminous phenomena should be taken into account. UNDESIRABLE EFFECTS*: Very common: Luminous phenomena (phosphenes). Common: Headache, blurred vision, dizziness, bradycardia, AV 1st degree block (ECG prolonged PQ interval), ventricular extrasystoles, uncontrolled blood pressure. Uncommon: Eosinophilia, hyperuricaemia, syncope, vertigo, palpitations, supraventricular extrasystoles, hypotension, dyspnoea, nausea, constipation, diarrhoea, angioedema, rash, muscle cramps, asthenia, fatigue, elevated creatinine in blood, ECG prolonged QT interval. Rare: Erythema, pruritus, urticaria, malaise. Very rare: Atrial fibrillation, AV 2nd degree block, AV 3rd degree block, sick sinus syndrome. OVERDOSE*. PROPERTIES*: Procoralan is a pure heart rate竏値owering agent which acts by selective inhibition of the cardiac pacemaker If current which controls spontaneous depolarization in the sinus node and regulates heart rate. Procoralan dose-dependently reduces heart rate, and provides a significant anti-ischaemic and anti-angina efficacy. PRESENTATION*: Pack of 56 film-coated tablets of Procoralan 5 mg, Pack of 56 film-coated tablets of Procoralan 7.5 mg. Legal Category: POM. Marketing Authorisation Numbers and Holders: EU/1/05/316/001-014 LES LABORATOIRES SERVIER, 50 rue Carnot, 92284 Suresnes cedex France. Date of Preparation or Last Review: July 2013. Full prescribing information is available from: Servier Laboratories, Block 2, West Pier Business Campus, Old Dunleary Road, Dun Laoghaire, Co Dublin. Tel: (01) 6638110, Fax (01) 6638120. *For complete information, please refer to the summary of product characteristics.

in Ar e d a M

Reference 1. Procoralan Summary of Product Characteristics November 2012. 2. Swedberg et al. for the SHIFT Investigators. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 2012; 376:875-885. 3. ESC Guidelines for diagnosis and treatment of acute heart failure 2012, Eur Heart J doi:10.1093/eurheartj/ehs104 Date of preparation: September 2013

Procoralanツョ is also effective for the treatment of Coronary Artery Disease1


52 Out & About Sharing ideas on product use and safety

A forum for sharing the latest information on product usage and safety was held recently in Prague; the annual Actavis Packaging and Safety Symposium. The event organized by the Actavis Hospital Business Unit, brought together industry experts and end users from across the world to share.

Speakers included Professor Graham Sewell, Head of School of Health Professions and Associate Dean, Plymouth University, who spoke on “Dose Branding”. Dr Ana Clopés, Head, Pharmacy Department, Catalan Institute of Oncology, spoke on “Barcode Technology in Hospitals”. Ewelina Korczowska, Hospital

Pharmacist, Clinical Hospital of Lord’s Transfiguration, Poznan, spoke on the “Management and Risks of Handling Cytotoxics”. Other topics included “Improving the safety of injectable drugs”, “Commercial Compounding-UK Experience” and “Ethical and Environmental Considerations of Manufacturing Pharmaceuticals”.

Pictured Left: Nuno Silva, Head of ACU/Chief II pharmacist, St. Vincent's Private Hospital, Eimear Mc Gowan, Chief ll Pharmacist, Waterford Regional Hospital, Caroline Fitzgerald, Hospital Business Manager, Actavis Ireland, Jonathan Ody, Vice President Hospital Business Unit, Actavis, Lisa Hammond, Acting Chief II Pharmacist (Aseptics),St. Vincent's University Hospital Conor Sadlier, Key Account Executive, Actavis Ireland.

Speaking at the event in Prague, Actavis Ireland Hospital Business Manager, Caroline Fitzgerald said “Actavis actively works towards reducing the risks associated with the handling and administration of chemotherapeutic and other high potency drugs. Focusing on areas such as contamination, packaging protection systems and innovative preparation methods; we are continually striving to maximise the safety of our products and those who interact with them. Through the Packaging and Safety Symposium we hope to facilitate a better understanding of how high potency hospital products are manufactured, packaged, transported and used.” If you would like further information about the Packaging and Safety Symposium or would be interested in attending next year’s event please contact Caroline Fitzgerald, Hospital Business Manager on 087 0545 344 or email

Trinity pharmacy students cycle 1400km around Ireland In July, three pharmacy students from Trinity College took on a ten-day 1400km cycle around Ireland. The motivation for the cycle stemmed from a freak accident their friend and classmate Jack Kavanagh suffered last year that left him paralysed from the chest down. Seeing the stellar work the National Rehabilitation Hospital does for patients with spinal cord injuries and how their work has helped Jack come closer to his immediate goal of continuing his Pharmacy degree this coming September is what prompted them all to undertake this mammoth challenge. The Cycle covered 1400km passing through all four provinces and all major cities and towns on the route. The three students leading The Cycle were joined along the route by a great number of other cyclists. Their aim was to raise ¤15,000 for the National Rehabilitation Hospital, The Jack Kavanagh Trust and the JP O’Brien trust. Donations, which can start from ¤2, can be made at

Issue 10 • HPN

Cyclists Joe Coffey, Jamie Byrne and Niall Barnwell with Jack Kavanagh

Out & About


Malnutrition time bomb brought into focus A number of international experts attending a two-day conference have urged the Minister for Health to recognise malnutrition as a major health issue and to prioritise awareness, detection and screening of the condition as other European countries have done, including Greece. The conference, organised by the Irish Society of Clinical Nutrition and Metabolism (IrSPEN), focused on health economics, policy and nutrition as well as providing continuous educational support for healthcare professionals with an interest in nutrition. Conference attendees were told how the Greek government have prioritised malnutrition, despite the country being in a far graver financial situation than Ireland. Malnutrition is a major cause and consequence of disease and frailty in older people and is common in hospital and community patients. It costs the state almost ¤1.42 billion annually in direct health and social care costs, which is greater than the costs associated with obesity and overweight combined. The cost of malnutrition is the equivalent of 10% of the total healthcare bill. These very high costs are due to the pressure that poorly nourished patients place on

1 the healthcare system. Niamh Rice, Consultant Nutritionist and Director of IrSPEN told the conference there needs to be a greater focus on identifying patients at-risk of malnutrition and ensuring that these patients are adequately treated. This approach has been successfully adopted by a host of European countries and most recently enshrined into legislation in Greece. “In Ireland, the implementation of a national screening programme has the potential to deliver clinical improvements and net savings, as it ensures that nutritional supplements and other forms for nutritional support are directed at those who need and will

2 benefit from it most. Despite this, screening is not routinely conducted in the majority of Irish hospitals and healthcare settings, nor is there a national strategy in place to manage malnutrition in patients, once identified.”

1) Chairman of the Irish Society for Clinical Nutrition and Metabolism, Professor John V Reynolds, welcomed attendees to the 2013 annual conference, Integrating Nutrition into Medicine and Healthcare

“Given that malnourished patients and their medical care costs the state over ¤1.4 billion per year, any potential saving that can be made will have a substantial positive impact on our health system. Even a 1% reduction would deliver ¤14 million in savings. In fact, significantly greater cost savings are possible based on the experience of the Dutch, in which screening has reduced hospital malnutrition by nearly 20% in the last 8 years. It begs the question:

2) Pictured at the 2013 annual conference of the Irish Society for Clinical Nutrition and Metabolism, Integrating Nutrition into Medicine and Healthcare, were, left to right, Jean Redmond (Medical Research Council UK) & Suzanne Doyle (TCD) & Prof. John Reynolds (TCD) & Dr.Laura Healy (James’s Hospital) & Anne-Marie Lynam (TCD).

can Ireland afford not to act?” she added.

Gobal Respiratory Infection Partnership Pictured attending the GRIP (Global Respiratory Infection Partnership) Summit 2013 were members of the Respiratory Tract Treatment Forum (RTTF). The RTTF is a multi-disciplinary educational initiative aiming to reduce inappropriate prescribing for upper respiratory tract infections (URTIs). From L-R: Dr Camilla Carroll, ENT Specialist, UPMC Beacon and Mount Carmel Hospitals, Dublin; Dr Martin Henman, Senior Lecturer in the Practice of Pharmacy, Trinity College Dublin and Dr Laura Noonan, GP, Mullingar.

The GRIP summit aims to unite experts around the world in the promotion of appropriate symptomatic management of RTIs, such as sore throats, and will focus on the implementation of measures that facilitate behaviour change at a country level; taking into account different cultures and healthcare provision systems. The event was supported by Reckitt Benckiser, makers of Strepsils Intensive and Plus ranges.

Bristol-Myers Squibb address change Bristol-Myers Squibb would like to announce that from Monday 16th September the office of the pharmaceutical division will relocate from the current

address in Leopardstown, to Swords in north Dublin. The new address and contact details are: Bristol-Myers Squibb Pharmaceuticals

Watery Lane Swords Co. Dublin Tel: 01 2913800 Fax: 01 8139040

HPN • Issue 10

54 Appointments

Mr Brian McEnery Minister for Health James Reilly, T.D. announced the appointment of Mr Brian McEnery as the new Chairperson of the Health Information and Quality Authority (HIQA). Welcoming Mr McEnery to his new role the Minister said “I am delighted that a man of the calibre of Brian McEnery has decided to accept this position as Chairperson of HIQA. With his professional background in healthcare consulting, Mr McEnery brings vast experience and understanding to his new role and I have no doubt he will carry on the excellent work commenced by outgoing Chairperson Pat McGrath.”

Mr Colam O’Neill Three new non-Executive Directors of the Board of the Hospital Group for the West/North West have been approved by the Minister for Health, Dr James Reilly. The three new members complete the Board, which now has eight non-executive members, four executive members and a chairman. The three new members are, Mr Gerry McManus, Ms Sharon Moohan and Mr Colam O’Neill. Mr O’Neill has a BSc in Chemistry and Biology and until his retirement was Managing Director of Allergan Ireland and Vice President of European Operations, Allergan Pharmaceuticals Ltd – based in Westport, Co. Mayo. In addition to the Irish operation which grew during Colam’s 28 years continuous service from 5 employees to 1100 employees, he also had responsibility for European operations including plants in Spain and France.

Dr Sathish Kolli Dr Sathish Kolli has been appointed as LEO Pharma's new Medical Director. Dr Kolli brings extensive NHS and pharmaceutical industry experience to LEO Pharma, gained from a career in both the NHS and a range of senior global Medical Affairs and Compliance roles, including at Astra Zeneca and Schwarz Pharma. Most recently Dr Kolli was Acting Global Medical Affairs Director, Neuroscience Centre of Excellence at Glaxo SmithKline.

Mr Ian Carter The HSE announced that, Mr Ian Carter National Director Designate of Acute Hospitals in the HSE and former CEO of St James’s Hospital has taken over responsibility for the Special Delivery Unit (SDU). The SDU was established by Minister for Health, Dr James Reilly to reduce the numbers of patients on hospital trolleys and on waiting lists.

Professor Andrew Deeks The Governing Authority of the University College, Dublin, has appointed Professor Andrew Deeks as President of UCD from January 2014. Professor Deeks with success Professor Hugh Brady,whose ten year tenure finishes at the end of December 2013.

Send your appointments announcements to Hospital Pharmacy News Have you taken up a new position recently or moved job roles? Get in touch to feature your new appointment on this page. Contact Kelly Jo Eastwood on 0044 7876548989 / E-mail: or Debbie Graham on 0044 / E-mail:

Issue 10 • HPN

Are you ready for the EU Sharps Directive?

One handed recapping is identified as an appropriate method to implement the EU Sharps Directive*

What does this mean for you?

5mm 6mm Mini

Solution 1... Injecting insulin 0.25mm (31G) x 5mm Box of 100: AN3650

Your ONE-HANDED recapping solution

Ultra Short 0.25mm (31G) x 6mm

Box of 100: AN3690

Unifine® Pentips® Plus is compatible with ALL diabetes injection pens

Solution 2... Blood sampling Gauge: 28G Box of 100: AT1042

Depth: 1.8mm Box of 200: AT1044

Gauge: 23G Box of 100: AT1002

Depth: 1.8mm Box of 200: AT1004

Unistik 3® is a single-use safety lancet making it the ideal lancet when doing blood sampling for your glucose testing.

* Health and Safety Excecutive: Draft Regulations to implement UK HSE Consultation Document CD244 2012 on preventing sharp injuries in the hospital and healthcare sector, published 21 August 2012. Risk control measure.

Two easy solutions to protect yourself from needlestick injuries when caring for people with diabetes:

For FREE samples contact:

Unfine® Pentips® Plus and Unistik® 3 are available from: J.S Dobbs and Co Ltd

T: 01-839-1071

Cahill May Roberts Group T: 01-630-5555

United Drug Distributors T: 01-463-2300 UniPhar Group

T: 01-428-7777



Olmesartan medoxomil

Benefit from Benetor® For the Effective Management of Essential Hypertension Greater BP reduction vs. other ARBs*1-7 Effective BP control maintained over 24 hours1,8 Proven achievement of recognised BP targets9,10 * vs. losartan, valsartan and candesartan

ABBREVIATED PRESCRIBING INFORMATION. Benetor 10, 20, 40mg film-coated tablets (olmesartan medoxomil). Refer to Summary of Product Characteristics (SPC) before prescribing. Presentation: Film-coated tablets containing 10mg, 20mg, 40mg olmesartan medoxomil. Contains lactose. Uses: Treatment of essential hypertension. Dosage: Adults: Recommended starting dose 10mg daily. If required the dose may be increased to 20mg daily. Maximum dose 40mg daily. Elderly: No dose adjustment generally required. Patients with moderate renal or hepatic impairment: Maximum daily dose is 20mg. Children, adolescents (below 18 years) and patients with severe hepatic impairment or severe renal impairment: Not recommended. Contra-indications: Hypersensitivity to any component. Second and third trimesters of pregnancy. Patients with biliary obstruction. Warnings and Precautions: Correct intravascular volume depletion before administering. In patients with other conditions associated with stimulation of renin-angiotensin-aldosterone system, possible side effects include acute hypotension, azotaemia, oliguria or, rarely, acute renal failure. Increased risk of severe hypotension and renal insufficiency in patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney. Periodic monitoring of serum potassium and creatinine levels is recommended in patients with impaired renal function. No experience in kidney transplantation or end-stage renal impairment. Hyperkalaemia (which may be fatal), risk factors include diabetes, renal impairment, age (> 70 years), combination with medicines which increase potassium potassi levels, potassium supplements, intercurrent events. Close monitoring of serum potassium in at risk patients is recommended. Not recommended for combination use with lithium. Special caution is recommended in patients suffering from aortic or mitral valve stenosis, or obstructive hypertrophic cardiomyopathy. Not recommended in patients with primary aldosteronism. The blood lowering effect of olmesartan medoxomil is somewhat less in black patients than non-black patients. Do not initiate during pregnancy. Excessive blood pressure decrease in patients with ischaemic heart disease or ischaemic cerebrovascular disease could result in a myocardial infarction or stroke. Interactions: Concomitant use with potassium supplements, potassium sparing diuretics and drugs that increase serum potassium levels (e.g. heparin) is not recommended. The blood pressure lowering effect of olmesartan medoxomil can be increased by concomitant use with other antihypertensive medications. Risk of acute renal failure with concomitant use of NSAIDs and angiotensin II antagonists. Monitoring of renal function and regular hydration of the patient is recommended. Use with NSAIDs can reduce the effect of olmesartan maedoxomil. Coadministration of warfarin and digoxin had no significant effect on the pharmacokinetics of olmesartan, warfarin or digoxin. Use in combination with lithium not recommended. If necessary, careful monitoring of serum lithium levels recommended. No clinically relevant interactions between olmesartan and drugs metabolised by cytochrome P450 enzymes 1A1/2, 2A6, 2C8/9, 2C19, 2D6, 2E1 and 3A4 are expected. Pregnancy and Lactation: Contraindicated in second and third trimesters of pregnancy. Not recommended in first trimester and during breast feeding. Discontinue as soon as possible if pregnancy occurs during therapy. Undesirable Effects: Market experience: The following have been reported very rarely (<1/10,000): Thrombocytopenia, hyperkalaemia, dizziness, headache, cough, abdominal pain, nausea, vomiting, pruritus, rash, allergic conditions such as angioneurotic oedema, dermatitis allergic, facial oedema, urticaria, muscle cramp, myalgia, acute renal failure, renal insufficiency, asthenia, fatigue, malaise, lethargy, abnormal renal function tests, increased hepatic enzymes. Clinical Trials: Common side effects include dizziness, bronchitis, cough, pharyngitis, rhinitis, abdominal pain, diarrhoea, dyspepsia, gastroenteritis, nausea, arthritis, back pain, skeletal pain, haematuria, urinary tract infection, chest pain, fatigue, influenza-like symptoms, peripheral oedema, pain, increased creatinine phosphokinase, hypertriglyceridaemia, hyperuricaemia, and liver enzyme elevations. Less common side effects include vertigo, hypotension, angina pectoris, rash, hyperkalaemia. Overdosage: Most likely effect is hypotension. In the event of overdosage, monitor the patient carefully and give symptomatic and supportive treatment. Pack Sizes: Blister containing 28 film-coated tablets. Legal Category: POM. Product Authorisation Numbers: PA 1595/1/1-3. Product Authorisation Holder: Daiichi Sankyo Ireland Ltd., Riverside One, Sir John Rogerson’s Quay, Dublin 2. Additional information is available on request from: Daiichi Sankyo Ireland Ltd., Telephone: (01) 489 3000, Fax: (01) 489 3033, E-mail: Date of Preparation: November 2009. References: 1. Smith D et al. Am J Cardiovasc Drugs 2005; 5(1):41-50. 2. Oparil S et al. J Clin Hypertens 2001;3;283−291,318. 3. Brunner HR et al. Clin Drug Invest 2003;23(7):419−430. 4. Brunner H and Arakawa K. Clin Drug Invest 2006;26(4):185−193. 5. Ball KJ et al. J Hypertens 2001;19(Suppl 1):S49−S56. 6. Stumpe KO and Ludwig M. J Hum Hypertens 2002;16(Suppl 2):S24−S28. 7. Giles TD et al. J Clin Hypertens 2007;9:187−195. 8. Fabia M J et al. J Hypertension 2007, 25:1327-1336. 9. Püchler J et al. J Hypertension 2001, 19(Suppl 1):S41-48. 10. Barrios V et al. Vascular Health and Risk Management 2009:5 723-729. Date of item: July 2013 DSIE/BEN54


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