THE INDEPENDENT VOICE OF HOSPITAL PHARMACY Xarelto Combi HPN A5(F):Layout 1 13/08/2012 16:28 Page 1
Xarelto®: One Anticoagulant Protecting Against and Treating Many Clot Threats Widely approved Prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery1 •
Licenced since 2008 in this indication
Proven superiority versus enoxaparin in RECORD trial programme2,3
Newly approved Prevention of stroke and systemic embolism in adult patients with non valvular atrial fibrillation (AF) with one or more risk factors, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischaemic attack4 Treatment of deep vein thrombosis (DVT), and preventionof recurrent DVT and pulmonary embolism (PE) following an acute DVT in adult patients4 Xarelto 10 mg film-coated tablets (Rivaroxaban). Please refer to full SmPC before prescribing. Presentation: Film-coated tablet containing 10mg rivaroxaban. Indication: Prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery. Dosage and Administration: Recommended dose is 10 mg rivaroxaban taken orally once daily. The initial dose should be taken 6 to 10 hours after surgery, provided that haemostasis has been established. Duration of treatment depends on the individual risk of the patient for VTE which is determined by the type of orthopaedic surgery. For patients undergoing major hip surgery, treatment duration of 5 weeks is recommended. For major knee surgery, treatment duration of 2 weeks is recommended. Renal impairment: No dose adjustment is necessary in patients with mild or moderate renal impairment. Use with caution in patients with severe renal impairment. Not recommended in patients with creatinine clearance <15 ml/min. Hepatic impairment: Contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk, including cirrhotic patients with Child Pugh B and C. Paediatric population: Xarelto is not recommended for use in children below 18 years of age, no data is available in this population. Contraindications: Hypersensitivity to the active substance or to any of the excipients; clinically significant active bleeding; hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C hepatic impairment; pregnancy and breast feeding. Warnings and Precautions: Not recommended: in patients receiving concomitant systemic treatment with strong CYP3A4 and P-gp inhibitors, i.e. azole-antimycotics or HIV protease inhibitors; patients with severe renal impairment (creatinine clearance <15 ml/min); patients below 18 years of age (due to lack of data); patients undergoing hip fracture surgery (due to lack of data), in patients treated concomitantly with dronedarone. Use with caution: in patients with severe renal impairment (creatinine clearance 15 - 29 ml/min) or moderate renal impairment (creatinine clearance 30 49 ml/min) or with renal impairment concomitantly receiving other medicinal products which increase rivaroxaban plasma concentrations; patients treated concomitantly with medicinal products affecting haemostasis (such as NSAIDs, acetylsalicylic acid, platelet aggregation inhibitors, other antithrombotic agents) or with strong CYP3A4 inducers; in patients with increased bleeding risk; when neuraxial anaethesisa or spinal/epidural puncture is employed; patients with congenital or acquired bleeding disorders, uncontrolled severe arterial hypertension, active ulcerative gastrointestinal disease, recent gastrointestinal ulcerations, vascular retinopathy, recent intracranial or intracerebral haemorrhage, intraspinal or intracerebral vascular abnormalities, recent brain, spinal or ophthalmological surgery, bronchiectasis or history of pulmonary bleeding. In patients at risk of ulcerative gastrointestinal disease prophylactic treatment may be considered. There is no need for monitoring of coagulation parameters during treatment with rivaroxaban in routine clinical situations. If clinically indicated rivaroxaban levels can be measured by calibrated quantitative antiFactor Xa tests. Xarelto contains lactose. Undesirable effects: Common: anaemia (incl. respective laboratory parameters), dizziness, headache, syncope, eye haemorrhage, tachycardia, hypotension, haematoma, epistaxis, gastrointestinal tract haemorrhage (incl. gingival bleeding and rectal haemorrhage), abdominal and gastrointestinal pain, dyspepsia, nausea, constipation, diarrhoea, vomiting, pruritus (incl. uncommon cases of generalised pruritus), rash, ecchymosis, pain in extremity, urogenital tract haemorrhage (incl. haematuris and menorrhagia), fever, peripheral oedema, decreased general strength and energy (incl. fatigue and asthenia), increase in transaminases, post-procedural haemorrhage (incl. post-operative anaemia and wound haemorrhage), contusion, wound secretion. Uncommon: thrombocythaemia (incl. platelet count increased), allergic reaction, dermatitis allergic, cerebral and intracranial haemorrhage, haemoptysis, dry mouth, hepatic function abnormal, urticaria, cutaneous and subcutaneous haemorrhage, haemarthrosis, renal impairment (incl. blood creatinine increased, blood urea increased), feeling unwell (incl. malaise), localised oedema, increases in: bilirubin, blood alkaline phosphatase, LDH, lipase, amylase and GGT. Rare: jaundice, muscle haemorrhage, bilirubin conjugated increased (with or without concomitant increased ALT.) Frequency not known: pseudoaneurysm formation following percutaneous intervention, compartment syndrome secondary to a bleeding, renal failure/acute renal failure secondary to a bleeding sufficient to cause hypoperfusion. Prescription only. Marketing Authorisation Holder: Bayer Pharma AG, D13342 Berlin, Germany. MA numbers: EU/1/08/472/006 - 008 Further information available from: Bayer Ltd., The Atrium, Blackthorn Road, Dublin 18. Tel: 01 2999313. Date of Preparation: 6/2012.
Xarelto 15mg and 20mg film-coated tablets (Rivaroxaban). Please refer to full SmPC before prescribing. Presentation: Film-coated tablet containing 15mg or 20mg of rivaroxaban. Indication: Prevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischaemic attack. Treatment of deep vein thrombosis (DVT) and prevention of recurrent DVT and pulmonary embolism (PE) following an acute DVT in adults. Dosage and Administration: : Prevention of stroke and systemic embolism: The recommended dose is 20 mg once daily, which is also the recommended maximum dose. Treatment of DVT and prevention of recurrent DVT and PE: The recommended dose for the initial treatment of acute DVT is 15 mg twice daily for the first three weeks followed by 20 mg once daily for the continued treatment and prevention of recurrent DVT and PE. Renal impairment: No dose adjustment is necessary in patients with mild renal impairment. Patients with moderate or severe renal impairment, for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation, the recommended dose is 15mg once daily, and for the treatment of DVT and prevention of recurrent DVT and PE, treatment should be 15mg twice daily for the first 3 weeks, thereafter the recommended dose is 15mg once daily. Hepatic impairment: Contraindicated in patients with hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C. Contraindications: Hypersensitivity to the active substance or any of the excipients; clinically significant active bleeding; hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C hepatic impairment; pregnancy and breast feeding. Warnings and Precautions: Not recommended: in patients receiving concomitant systemic treatment with strong concurrent CYP3A4- and P-gp-inhibitors, i.e. azole-antimycotics or HIV protease inhibitors; in patients with severe renal impairment (creatinine clearance <15 ml/min); in the treatment of acute pulmonary embolism; in patients below 18 years of age or with prosthetic heart valves or in patients concomitantly treated with dronedarone due to lack of data. Use with caution: in patients with severe renal impairment (creatinine clearance 15 - 29 ml/min) or with renal impairment concomitantly receiving other medicinal products which increase rivaroxaban plasma concentrations; patients concomitantly treated with medicinal products affecting haemostasis (such as NSAIDs, acetylsalicylic acid, platelet aggregation inhibitors, other antithrombotic agents) or with strong CYP3A4 inducers; in patients with increased bleeding risk; patients with congenital or acquired bleeding disorders, uncontrolled severe arterial hypotension, active ulcerative gastrointestinal disease, recent gastrointestinal ulcerations, vascular retinopathy, recent intracranial or intracerebral haemorrhage, intraspinal or intracerebral vascular abnormalities, recent brain, spinal or opthalmological surgery, bronchiectasis or history of pulmonary bleeding. In patients at risk of ulcerative gastrointestinal disease an appropriate prophylactic treatment may be considered. Clinical surveillance in line with anticoagulation practice is recommended throughout the treatment period. There is no need for monitoring of coagulation parameters during treatment with rivaroxaban in routine clinical situations. If clinically indicated rivaroxaban levels can be measured by calibrated quantitative anti-Factor Xa tests. Xarelto contains lactose. Undesirable effects: Common: anaemia, dizziness, headache, syncope, eye haemorrhage, tachycardia, hypotension, haematoma, epistaxis, gastrointestinal tract haemorrhage, gastrointestinal and abdominal pains, dyspepsia, nausea, constipation, diarrhoea, vomiting, pruritus, rash, ecchymosis, pain in extremity, urogenital tract haemorrhage, fever, peripheral oedema, decreased general strength and energy, increase in transaminases, post-procedural haemorrhage, contusion, wound secretion. Uncommon: thrombocythemia, allergic reaction, dermatitis allergic, cerebral and intracranial haemorrhage, haemoptysis, dry mouth, hepatic function abnormal, urticaria, cutaneous and subcutaneous haemorrhage, haemarthrosis, renal impairment, feeling unwell, localised oedema, increases in: bilirubin, blood alkaline phosphatase, LDH, lipase, amylase, GGT. Rare: jaundice, muscle haemorrhage and conjugated bilirubin increased. Frequency not known: pseudoaneurysm following percutaneous intervention, compartment syndrome or (acute) renal failure secondary to a bleeding. Prescription only. Marketing Authorisation Holder: Bayer Pharma AG, D-13342 Berlin, Germany. MA numbers: EU/1/08/472/011-21. Further information available from: Bayer Ltd., The Atrium, Blackthorn Road, Dublin 18. Tel: 01 2999313. Date of Preparation: 6/2012.
References: 1. Xarelto® 10mg Summary of Product Characteristics. 2.Eriksson et al, Oral rivaroxaban for the prevention of symptomatic venous thromboembolism after elective hip and knee replacement. J Bone Joint Surg [Br] 2009;91-B:636-44. 3. Turpie G et al.Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009; 373: 1673–80. 4. Xarelto® 15/20mg Summary of Product Characteristics. L.IE.GM.07.2012.0030
IN THIS ISSUE: News: HPAI President elected to board of European Hospital Pharmacists Association Profile: South Infirmary Victoria University Hospital (SIVUH) pharmacists show what can be achieved through teamwork Plant Visit: An HPN exclusive as we take a look inside one of the biggest pharmaceutical plants in the world Report: What is the role of hospital pharmacists in tackling the growing Hep C issue? Feature: Hospital Service Focus with Uniphar Group News: Phamacist Sean Owens reports from Atlanta on novel therapies for breast cancer
A new perspective on life with MS 61%
begins with a reduction in relapse rates vs interferon beta-1a IM at 1 year, in licenced subgroups of patients with highly active relapsing remitting MS not responding to interferon treatment1* • Superior efficacy compared to placebo in a 2-year study2†
ABBREVIATED PRESCRIBING INFORMATION Please refer to the Summary of Product Characteristics before prescribing Presentation: GILENYA 0.5 mg hard capsules, each capsule containing 0.5mg fingolimod (as hydrochloride) Therapeutic indications: Gilenya is indicated as single disease modifying therapy in highly active relapsing remitting multiple sclerosis for the following adult patient groups: - Patients with high disease activity despite treatment with a bta-interferon.These patients may be defined as those who have failed to respond to a full and adequate course (normally at least one year of treatment) of beta-interferon. Patients should have had at least 1 relapse in the previous year while on therapy, and have at least 9 T2-hyperintense lesions in cranial MRI or at least 1 Gadolinium-enhancing lesion. A “non-responder” could also be defined as a patient with an unchanged or increased relapse rate or ongoing severe relapses, as compared to the previous year. Or - Patients with rapidly evolving severe relapsing remitting multiple sclerosis defined by 2 or more disabling relapses in one year, and with 1 or more Gadolinium enhancing lesions on brain MRI or a significant increase in T2 lesion load as compared to a previous recent MRI. Dosage: Adults: Treatment should be initiated and supervised by a physician experienced in multiple sclerosis. One 0.5 mg capsule to be taken orally once daily. Patients can switch directly from beta interferon or glatiramer acetate to GILENYA provided there are no signs of relevant treatment-related abnormalities, e.g. neutropenia. Use with caution in patients aged 65 years and over. Safety and efficacy of GILENYA in children up to 18 years has not been established. No dose adjustments required in patients with mild to severe renal impairment or mild to moderate hepatic impairment. Exercise caution in patients with mild to moderate hepatic impairment. Do not use in patients with severe hepatic impairment (Child-Pugh class C). Use with caution in patients with diabetes mellitus due to an increased risk of macular oedema. Regular eye examinations should be conducted in these patients. See SmPC for full details on posology and method of administration. Contraindications: Known immunodeficiency syndrome. Patients with increased risk for opportunistic infections, including immunocompromised patients (including those currently receiving immunosuppressive therapies or those immunocompromised by prior therapies). Severe active infections, active chronic infections (hepatitis, tuberculosis). Known active malignancies, except for patients with cutaneous basal cell carcinoma. Severe liver impairment . Hypersensitivity to the active substance or to any of the excipients. Special warnings and precautions for use Warnings/ Precautions: Bradyarrhythmia: Initiation of treatment results in a transient bradycardia which may be associated with AV conduction delays, including isolated reports of transient, spontaneously resolving complete AV block. After the first dose, the decline in heart rate starts within one hour and is steepest within 6 hours. The negative effect on heart rate progressively attenuates over subsequent days of treatment and returns to baseline within one month. Conduction abnormalities were typically transient, asymptomatic and usually did not require treatment. If necessary, the decrease in heart rate can be reversed by IV atropine or isoprenaline. All patients should have an ECG and blood pressure measurement performed prior to and 6 hours after the first dose of GILENYA. Monitor all patients for 6 hours for bradycardia, with hourly heart rate and blood pressure measurement. Continuous (real time) ECG monitoring during this 6 hour period is recommended. In the event of post-dose bradyarrhythmia-related symptoms, initiate appropriate clinical management and observe until symptoms resolve. If pharmacological intervention is required, overnight monitoring should be instituted. If the heart rate at 6 hours is the lowest since the first dose was administered, monitoring should be extended by at least 2 hours and until heart rate increases again. Additionally, if after 6 hours, the heart rate is <45 bpm, or the ECG shows new onset second degree or higher grade AV block or a QTc interval ≥500 msec, or occurrence at any time of third degree AV block extended monitoring (at least overnight), should be performed. The same precautions apply if GILENYA is discontinued for more than 2 weeks. GILENYA should not be used in patients with second degree or higher AV block, sick-sinus syndrome, sino-atrial heart block, significant QT prolongation, ischaemic cardiac disease, cerebrovascular disease, congestive heart failure, uncontrolled hypertension, or severe sleep apnoea, a history of symptomatic bradycardia, recurrent syncope, MI or cardiac arrest. Seek advice from a cardiologist before initiation of treatment in these patients to determine appropriate monitoring (at least overnight). GILENYA should not be co-administered with class Ia (e.g. quinidine, disopyramide) or class III (e.g. amiodarone, sotalol) antiarrhythmics. GILENYA should not be used in patients receiving beta blockers, or other substances which may decrease heart rate (e.g. verapamil, digoxin, anticholinesteratic agents or pilocarpine) due to possible additive effects. Seek advice from a cardiologist before initiation of treatment in these patients to switch to non heart-rate lowering agents or, if not possible, to determine appropriate monitoring (at least overnight). Avoid medicinal products that may prolong QTc interval. Infections: Reduction of the lymphocyte count to 20-30% of baseline values occurs with GILENYA. Perform a CBC at baseline and periodically during treatment, and in case of signs of infection, stop GILENYA until recovery if absolute lymphocyte count <0.2x109/L is confirmed. Delay initiation in patients with active infection until resolution. Consider VZV vaccination of patients without a history of chickenpox or VZV antibody negative patients prior to commencing GILENYA. GILENYA may increase the risk of infections. Employ effective diagnostic and therapeutic strategies in patients with symptoms of infection while on GILENYA and for 2 months after discontinuation. Macular oedema: Macular oedema with or without visual symptoms has been reported in 0.4% patients taking GILENYA. Perform an ophthalmological evaluation 3-4 months after GILENYA initiation. Evaluate the fundus, including the macula in patients reporting visual disturbances. Perform ophthalmological evaluation prior to initiating therapy and periodically thereafter in patients with diabetes mellitus or a history of uveitis.
Discontinue GILENYA if a patient develops macular oedema. Liver function: Do not use GILENYA in patients with severe pre-existing hepatic injury (Child-Pugh class C). Delay GILENYA initiation in patients with active viral hepatitis until resolution. Recent transaminase and bilirubin levels should be available before initiation of GILENYA. Monitor liver transaminases at months 1, 3, 6, 9 and 12 and periodically thereafter. Institute more frequent monitoring if transaminases rise above 5 times the ULN, including serum bilirubin and alkaline phosphatase (ALP) measurement. Stop GILENYA treatment with repeated confirmation of liver transaminases above 5 times the ULN and only re-commence once liver transaminase values have normalised. Patients with symptoms of hepatic dysfunction should have liver enzymes checked and discontinue GILENYA if significant liver injury is confirmed. Resume GILENYA only if another cause of liver injury is determined and if the benefits of therapy outweigh the risks. Exercise caution with GILENYA use in patients with a history of significant liver disease. Serological testing: Peripheral blood lymphocyte counts cannot be utilised to evaluate the lymphocyte subset status of a patient treated with GILENYA. Laboratory tests involving the use of circulating mononuclear cells require larger blood volumes due to reduction in the number of circulating lymphocytes. Blood pressure effects: GILENYA can cause a mild increase in blood pressure. Monitor blood pressure regularly during GILENYA treatment. Respiratory effects: Use GILENYA with caution in patients with severe respiratory disease, pulmonary fibrosis and COPD due to minor reductions in values for FEV1and diffusion capacity for cabon monoxide (DLCO). Prior immunosuppressant treatment: No washout is necessary when switching patientsfrom interferon or glatiramer acetate to GILENYA assuming any immune effects (i.e. cytopenia) have resolved. Exercise caution when switching patients from natalizumab to GILENYA owing to the long half life of natalizumab and concomitant immune effects. Stopping therapy: GILENYA is cleared from the circulation in 6 weeks. Caution is indicated with the use of immunosuppressants soon after the discontinuation of GILENYA due to possible additive effects on the immune system. Interaction with other medicinal products and other forms of interaction: Anti-neoplastic, immunosuppressive or immune-modulating therapies should not be co-administered due to the risk of additive immune system effects. Exercise caution when switching patients from long-acting therapies with immune effects, e.g. natalizumab or mitoxantrone. No increased rate of infection was seen in MS clinical trials with concomitant treatment of relapses with a short course of corticosteroids. Vaccination may be less effective during and for up to 2 months after GILENYA treatment. Avoid use of live attenuated vaccines due to infection risk. GILENYA should not be initiated in patients receiving beta blockers, or class Ia and III antiarrhythmics, heart rate lowering calcium channel blockers (e.g verapamil or diltiazem), digoxin, anticholinesteratic agents or pilocarpine. Caution is indicated with substances that may inhibit CYP3A4. Co-administration of fingolimod with ketoconazole increases fingolimod exposure. No interaction has been observed with oral contraceptives when co-administered with fingolimod. Fertility, Pregnancy and lactation: There is potential for serious risk to the foetus with GILENYA. A negative pregnancy test is required before initiation of GILENYA. Female patients must use effective contraception during treatment with GILENYA and for 2 months after discontinuation. Discontinue GILENYA if a patient becomes pregnant. Fingolimod is excreted into breast milk. Women receiving GILENYA should not breast feed. Fingolimod is not associated with a risk of reduced fertility. Undesirable effects: Very common (≥1/10); Influenza viral infections, headache, cough, diarrhoea, increased ALT, back pain. Common (≥1/100 to <1/10); herpes viral infections, bronchitis, sinusitis, gastroenteritis, Tinea infections, lymphopenia, leucopenia, depression, dizziness, parasthesia, migraine, blurred vision, eye pain, bradycardia, AV block, hypertension, dyspnoea, eczema, alopecia, pruritus, asthenia, increased GGT, increased hepatic enzymes, abnormal liver function test, increased blood triglycerides, decreased weight. Uncommon (≥1/1,000 to <1/100); pneumonia, depressed mood, macular oedema, decreased neutrophil count. Marketing Authorisation Holder: Novartis Europharm Ltd, Wimblehurst Rd, Horsham, W Sussex, RH12 5AB, UK. Marketing Authorisation Numbers: EU/1/11/677/001-005. Date of last revision of Abbreviated Prescribing Information: June 2012. Full prescribing information is available upon request from: Novartis Ireland Limited, Beech House, Beech Hill Office Campus, Clonskeagh, Dublin 4. Tel: 01-2601255, Fax: 01-2601263 or at www.medicines.ie Detailed information on this product is also available on the website of the European Medicines Agency http://www.ema.europa.eu
References: 1. Havrdová E. et al. Clinical outcomes in subgroups of patients with highly action relapsing-remitting multiple sclerosis treated with Fingolimod (FTY720): Results from the FREEDOMS and TRANSFORMS phase III studies. Poster presented at ECTRIMS, Amsterdam, October 2011. 2. Cohen J. et al. Oral Fingolimod vs. Intramuscular Interferon in Relapsing Multiple Sclerosis. N Eng J Med. Vol.362 No.5, Feb 4, 2010;362:402-415. *TRANSFORMS: A 1-year, randomised, double-blind, double-dummy, active (interferon beta-1a IM)-controlled study of 1292 people with RRMS. Patients received either a daily 0.5 mg dose of GILENYA or interferon beta-1a IM at a weekly dose of 30 μg. †
FREEDOMS: A 2-year, randomised, double-blind, placebo-controlled study of 1272 people with RRMS. Patients received either a 0.5mg daily dose or matching placebo.
NO071204 Date of Preparation: July 2012
Pharmacists voice concerns over Troika actions on HSE deficit P5
What does it take to win a Hospital Pharmacy Team national award? P9 Joan Peppard elected to board of European Hospital Pharmacists Association P16 HPN contributor Eamonn Brady pays a visit to the Novartis Pharmaceutical plant in Basle P22 The font of all knowledge with patient safety, we speak to Pharmacist of the Year Tim Delaney P36 Inappropriate prescribing identified in Munster nursing home patients P40
Regulars Feature - Antimicrobial Prophylaxis reducing urinary tract infections P18 Industry Profile - The team at Uniphar P29 Feature - The role of off label medicines and their usage defined P32 Clinical Profiles P43 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.
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Kelly Jo Eastwood In the words of Lyman Beecher, "No great advance has ever been made in science, politics or religion, without controversy!" In this issue of Hospital Pharmacy News we open a debate on the cost of drugs in Ireland and the effect on the patient. A report in The Irish Times has revealed private patients in border counties are buying cheaper prescription drugs in Northern Ireland than they would in the Republic. Meanwhile, Dublin South West Sinn Féin TD Seán Crowe has blasted the pharmaceutical industry, along with the HSE for 'ripping off' taxpayers. He is emphatic that the Health Services Executive is 'failing to secure a fair price from the pharnmaceutical industry for drugs, with some costing up to 12 times more from what is available thorugh the North's health service.' He adds claims that the massive price differential is a result of specific packaging that is required for this State is an insult to people's intelligence. However the IPU has been quoted as saying: 'A report produced for the HSE expressed the view that international comparisons of prices cannot be relied on as each market is different in terms of size, structure and regulations.' It takes two to start an argument, but only one to end it. Now is the time for Dr James Reilly to take a stand on the issue as ultimately the only people to lose out will be the patients. The publication of the Health Bill is only aspect of this argument requiring resolve. There's another item to be added to his growing agenda! Our next issue of HPN will feature an open debate on this subject and we would welcome your views. Elsewhere in this issue we report on the many changes afoot for hospital pharmacists. From updates of the regulation of clinical trials to the use of the profession as managers. The final BEAM Summit held in Dusseldorf heard how hospital pharmacists have a role to play in managing people, performance and resources and should be able to facilitate innovation, improvement and transformation. The focus this month appears to be on raising the profile of the profession as a whole and building reltaionships with colleagues. I hope you enjoy the issue"
CONTRIBUTORS Eamonn Brady Paul M Walshe Julianne Byrne Michael Capra Harry Comber Sean Owens ART DIRECTED BY Smart Page Design
THE INDEPENDENT VOICE OF HOSPITAL PHARMACY HPN • Issue 5
Hospital monitoring a reality? Dr Tracey Cooper
New National Standards aimed at protecting patients and radically improving services, and which will form the basis for future licensing of all healthcare facilities in Ireland, have been launched by the Health Information and Quality Authority (HIQA). HIQA envisages that in time, hospitals will be "monitored" to demonstrate compliance with the standards. This may form the basis for licensing of hospitals in the future. Speaking at the launch of the Standards, HIQA Chief
Executive Dr Tracey Cooper said, “The National Standards are significantly important for patients, placing them at the heart of the care process, with a major focus on dignity, respect, efficiency and safety. They are a benchmark for change. Patients will have a clear expectation of the standard of care they can expect to receive and service providers will be clear on what is expected of them. The Standards provide, for the first time, a national and consistent approach to improving safety, quality and reliability in our health service.” The National Standards for Safer Better Healthcare contain 45 Standards, based on best international evidence, to ensure service providers protect patients from risk and from harm, inform patients of adverse events, acknowledge and support the key role of staff, promote good governance and make the best use of information and resources to deliver high quality and safe care within the resources available. They can be accessed at http://www.hiqa.ie/publications/ national-standards-safer-betterhealthcare
Drop in numbers waiting for opioid substitution treatment There has been a 19 per cent reduction in the number of people waiting for opioid substitution treatment in the 13-month period to the from the end of March 2011 to the end of April 2012, according to the latest HSE figures. “I welcome the reduction in numbers from 230 to 187 on the waiting lists for opioid substitution treatment,” said Róisín Shortall, Minister of State at the Department of Health Issue 5 • HPN
with responsibility for Primary Care. “The provision of timely treatment greatly increases the likelihood of successful outcomes for the patients involved.” The HSE reported that 22 of its 48 clinics have no waiting times and that 33 of the 48 have waiting times of less than one month. The longest waiting times are in the Midlands, the NorthEast and in pockets of Dublin. However, even in areas where
waiting times remain high, there was a very significant downward trend – from 10 months to three months in Athlone, from 7.5 months to less than a month in Dublin’s City Clinic, from seven months to one month at the Dr Steven’s Clinic, from seven months to four in Louth, and from seven to two months in Waterford. “Over the past two years, additional services have been provided in Wexford, Waterford,
Kilkenny, Cork, Tralee, Limerick and Dundalk. Apart from reducing the numbers on waiting lists, the provision of such services encourages more people to come forward for treatment,” said the Minister. She acknowledged the need to develop services further to ensure the provision of access to drug misuse treatment for all within one month of assessment, in line with the aims of the National Drugs Strategy.
Reilly comes under fire over deficit The Health Minister Dr James Reilly has come under further criticism as it was revealed the HSE overspend is nearing €300m and questions are now being asked over the potential impact on pharmacy and broader healthcare services.
with €151m of a deficit. Hospital pharmacists are now voicing concerns over recent HSE circulars calling for hospitals to have a zero- tolerance policy on overtime, the use of agency workers and employing new staff unless strictly required.
An HSE report on financial performance by the service has shown an overspend of €298.7m with hospitals the worst affected
One source told us: "The rumour mill has gone into overdrive but movements point to the possibility of
temporary contracts being terminated and the question of intern placements is very much up in the air." The Troika has reportedly told the HSE to also target a reform of drug prescribing by doctors. In June of this year, HSE Chief Executive Cathal Magee claimed the Department of Health mislead the Dail over the financial position of the health
service as they were aware of its deterioation for months. It was claimed Mr Magee asked for decisions to be taken and policy directions given to deal with the financial crisis from the Department of Health and in addition asked for guidance on how cost cutting would affect services but these were not met and he is still 'awaiting a response.'
Hospital pharmacist as manager Hospital Pharmacists should know how to manage people, performance and resources and be able to facilitate innovation, improvement and transformation. That was the take-away message from the final BEAM summit event on Management.
The Dusseldorf summit was attended by 44 hospital pharmacists from 24 different countries and was the fourth and final part of the EAHP’s BEAM programme. BEAM has been a series of4 training events aimed at raising the skills and knowledge of hospital pharmacists across Europe
in the key competency areas of Biotechnology, Evidencebased medicine, Aspects of compounding and Management. BEAM is part of the EAHP’s Academy Programme of educational events.
their self-awareness and build and maintain professional relationships with colleagues. There was also a strong focus on critical evaluation, impact assessment and how to effectively deliver improvement in a hospital pharmacy.
Participants at the management summit learned how to develop
Open call for abstracts The European Association of Hospital Pharmacists (EAHP) has issued a call for abstracts for its 2013 Congress in Paris. The Abstract Poster Walk is a highlight of EAHP’s Congress, displaying concise information about: hospital pharmacy
practice innovation; the introduction and assessment of new technologies; new understandings about pharmacotherapy issues; and the key findings of many other evaluative exercises from hospital pharmacies across Europe and beyond.
Any hospital pharmacist may submit an abstract to the EAHP’s Scientific Committee who will then consider its inclusion in the Congress poster display. Accepted abstracts will be published in the official Abstract Book that is issued to all Congress attendees, will
be available to view via the EAHP website following the Congress, and will be included in the Congress edition of the European Journal of Hospital Pharmacy (EJHP).
IMB Echinacea guidance The Irish Medicines Board (IMB) today advises that children's herbal products containing echinacea will no longer be recommended based on the lack of scientific data to support their use. This new advice follows a review by the IMB of available data on the safety and effectiveness of echinacea and it is now advising that such products should not be used for children under 12 years of age. The IMB is communicating with retailers and others within the supply chain to inform them of this recommendation and to request that children's echinacea-containing products are removed from sale.
HPN • Issue 5
Drug companies in 'rip off' criticism Dublin South West Sinn Féin TD Seán Crowe is being quoted as saying Irish taxpayers are being ripped off. A Sunday Business Post survey showing the high price of "generic drugs" in this State is further compelling evidence, he says. He adds that the Health Service Executive was failing to secure a fair price from the Pharmaceutical Industry for drugs with some costing up to 12 times more from what is available through the North’s Health Service. disturbing to Irish taxpayes is the fact that many of the actual drug products are made in Ireland and shipped abroad to be sold there signifcantly reduced cost to their respective Health ServIces under more favourable "sweetheart deals."
"Sinn Féin has repeatedly raised this matter with the Irish Health Minister James Reilly who should be doing more to reduce costs by ensuring the greater use and availability of generic drugs. This Survey shows the situation is even worse than many suspected yet the Government has taken little or no action, apart from the publication of a Bill which has yet to be enacted," he added. Deputy Seán Crowe says: “It is outrageous that people in this State are paying up to 12 times more for generic drugs when compared to patients in the North's Health Service (NHS) . In a deal seemingly sanctioned by the Department of Health
two years ago, generic drug manufacturers are allowed to charge the State up to 98% of the price of the original branded medicine. This means Irish taxpayers are actually paying drug companies almost the same price for cheaper generic
drugs as it pays for well known branded medicines. "We know that there is crisis after crisis in the roll out of services in Health and cost of drugs is playing a significant part in cost overuns. What is equally
HPN will be addressing this issue as a Debate feature in our next issue. To voice your comments please email the Editor at: kjeastwood@hotmail. com
Improvement in clinical trial regulation Hospital pharmacists have given an early welcome to the recently published proposals of the European Commission to improve the regulation of clinical trials (published 17 July 2012). In 4 key areas the Commission’s proposals have met the aspirations of a recent EAHP statement on trial regulation including: 1) The introduction of new risk
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based approaches the clinical trial regulation with the concept of low-interventional clinical trials for products with existing marketing authorisation and whose use is considered as a standard treatment in the member state.
multinational trial applications to be submitted to a single electronic portal for delegated single assessment
2) New provisions to allow cosponsorship of trials.
Commenting on the Commission’s proposals, EAHP President Dr. Roberto Frontini said: "One area where we undoubtedly want to see
3) Centralised application procedures to enable
4) The maintenance of Ethics Committees and procedures at a national level
more action on is the access to clinical trial data available to health professionals such as hospital pharmacists. This is critical for many reasons, including independent review and ethical decision-making. We are certain that there is more that can be achieved and we will develop our suggestions further as we scrutinise in detail the Commission proposals in the coming months.”
A single step forward in BPH management
Combodart provides: Symptom relief as rapid as tamsulosin monotherapy1,2
Superior Symptom improvement Vs tamsulosin or dutasteride monotherapy1,2 66% Relative Risk Reduction in AUR or BPH related surgery Vs tamsulosin at 4 years1,2
COMBODART ABRIDGED PRESCRIBING INFORMATION (API). (Please refer to the full Summary of Product Characteristics before prescribing) PRESENTATIONS: Each hard capsule contains 0.5 mg dutasteride and 0.4 mg tamsulosin hydrochloride, (equivalent to 0.367 mg tamsulosin). INDICATION: Treatment of moderate to severe symptoms of benign prostatic hyperplasia (BPH). Reduction in the risk of acute urinary retention (AUR) and surgery in patients with moderate to severe symptoms of BPH. POSOLOGY & ADMINISTRATION: Adults (including elderly): The recommended dose is one capsule (0.5 mg/ 0.4 mg) taken orally approximately 30 minutes after the same meal each day. The capsules should be swallowed whole and not chewed or opened. Contact with the contents of the dutasteride capsule contained within the hard-shell capsule may result in irritation of the oropharyngeal mucosa. Where appropriate, Combodart may be used to substitute concomitant dutasteride and tamsulosin hydrochloride in existing dual therapy to simplify treatment. Where clinically appropriate, direct change from dutasteride or tamsulosin hydrochloride monotherapy to Combodart may be considered. Renal impairment: The effect of renal impairment on dutasteridetamsulosin pharmacokinetics has not been studied. No adjustment in dosage is anticipated for patients with renal impairment. Hepatic impairment: The effect of hepatic impairment on dutasteride-tamsulosin pharmacokinetics has not been studied so caution should be used in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, the use of Combodart is contraindicated. CONTRAINDICATIONS: Combodart is contraindicated in: women, children and adolescents; patients with hypersensitivity to dutasteride, other 5-alpha reductase inhibitors, tamsulosin (including tamsulosin-induced angio-edema), soya, peanut or any of the other excipients; patients with a history of orthostatic hypotension: patients with severe hepatic impairment. SPECIAL WARNINGS & PRECAUTIONS: Combodart should be prescribed after careful benefit risk assessment and after consideration of alternative treatment options including monotherapies. In two 4-year clinical study, the incidence of cardiac failure (a composite term of reported events, primarily cardiac failure and congestive cardiac failure) was higher among subjects taking the combination of dutasteride and an alpha blocker, primarily tamsulosin, than it was among subjects not taking the combination. Digital rectal examination, as well as other evaluations for prostate cancer or other conditions which can cause the same symptoms as BPH, must be performed on patients prior to initiating therapy with Combodart and periodically thereafter. Combodart causes a decrease in mean serum PSA levels by approximately 50%, after 6 months of treatment. Patients should have a new baseline established after 6 months of treatment with Combodart and PSA should be monitored regularly thereafter. Any confirmed increase from the lowest PSA levels while on Combodart may signal the presence of prostate cancer (particularly high grade cancer) or non-compliance to therapy with Combodart and should be carefully evaluated, even if those values are still within the normal range for men not taking α 5 reductase inhibitor (see SPC section 5.1). The relationship between dutasteride and high grade prostate cancer is not clear. Men taking Combodart should be regularly evaluated for prostate cancer risk including PSA testing (see SPC section 5.1). Results of one clinical study (the REDUCE study) in men at increase risk of prostate cancer revealed a higher incidence of Gleason 8 – 10 prostate
In moderate BPH patients
cancers in dutasteride treated men compared to placebo. The relationship between dutasteride and high grade prostate cancer is not clear. Men taking Combodart should be regularly evaluated for prostate cancer risk including PSA testing (see SPC section 5.1). As with other alpha-blockers, a reduction in blood pressure can occur during treatment with tamsulosin, as a result of which, rarely, syncope can occur. Intraoperative Floppy Iris Syndrome (IFIS, a variant of small pupil syndrome) has been observed during cataract surgery in some patients on or previously treated with tamsulosin and may lead to increased procedural complications during the operation. Breast cancer has been reported in men taking dutasteride. Physicians should instruct their patients to promptly report any changes in their breast tissue such as lumps or nipple discharge. Dutasteride is absorbed through the skin, therefore, women, children & adolescents must avoid contact with leaking capsules. Caution should be used in the administration of Combodart to patients with mild to moderate hepatic impairment. The treatment of severely renally impaired patients (creatinine clearance of less than 10 ml/min) should be approached with caution. This medicinal product contains the colouring agent Sunset Yellow (E110), which may cause allergic reactions. INTERACTIONS: There have been no drug interaction studies for Combodart. The following reflect information available on the individual components. Dutasteride: is mainly eliminated via metabolism and studies indicate that this metabolism is catalysed by CYP3A4 and CYP3A5. Longterm combination of dutasteride with drugs that are potent inhibitors of the enzyme CYP3A4 (e.g. ritonavir, indinavir, nefazodone, itraconazole, ketoconazole administered orally) may increase serum concentrations of dutasteride. Tamsulosin: Concomitant administration of tamsulosin hydrochloride with drugs which can reduce blood pressure, including anaesthetic agents and other alpha-1 adrenergic blockers could lead to enhanced hypotensive effects. Dutasteride-tamsulosin should not be used in combination with other alpha-1 adrenergic blockers. Caution should be used when dutasteride-tamsulosin is used in combination with cimetidine and with concomitant administration of warfarin and tamsulosin hydrochloride. Diclofenac may increase the elimination rate of tamsulosin. FERTILITY, PREGNANCY & LACTATION: Combodart is contraindicated for use by women. There have been no studies to investigate the effect of Combodart on pregnancy, lactation and fertility - the following statements reflect the information available from studies with the individual components; Fertility: Dutasteride has been reported to affect semen characteristics in healthy men. The possibility of reduced male fertility cannot be excluded. Effects of tamsulosin hydrochloride on sperm counts or sperm function have not been evaluated. Pregnancy: As with other 5 alpha reductase inhibitors, dutasteride inhibits the conversion of testosterone to dihydrotestosterone and may, if administered to a woman carrying a male foetus, inhibit the development of the external genitalia of the foetus. It is not known whether a male foetus will be adversely affected if his mother is exposed to the semen of a patient being treated with dutasteride (the risk of which is greatest during the first 16 weeks of pregnancy). As with all 5 alpha reductase inhibitors, when the patient's partner is or may potentially be pregnant it is recommended that the patient avoids exposure of his partner to semen by use of a condom. Lactation: It is not known whether dutasteride or tamsulosin are excreted in human milk. ABILITY TO DRIVE & USE MACHINES: No studies on the effects of Combodart on the ability to drive and use machines have
For more information on this and other GSK brands visit www.Health.gsk.ie
been performed. However, patients should be informed about the possible occurrence of symptoms related to orthostatic hypotension such as dizziness when taking Combodart. UNDESIRABLE EFFECTS: DUTASTERIDE AND TAMSULOSIN CO-ADMINISTRATION: The following adverse events have been reported with an incidence of ≥1% during the four years of treatment in the CombAT Study (Combination of Avodart and Tamsulosin-study, a comparison of dutasteride 0.5mg and tamsulosin 0.4mg once daily for four years as co-administration or as monotherapy): Cardiac failure, impotence, altered (decreased) libido, ejaculation disorders, breast disorders (includes breast enlargement and/or breast tenderness), dizziness. Adverse Events identified through post-marketing experience (therefore the true incidence is unknown) with dutasteride monotherapy include allergic reactions, including rash, pruritus, urticaria, localised oedema, and angioedema, skin and subcutaneous tissue disorders. Uncommon: Alopecia (primarily body hair loss), hypertrichosis. The following adverse events related to tamsulosin monotherapy have been reported from both clinical trials and post marketing data: Common (≥1/100 <1/10); dizziness. Uncommon (≥1/1000 <1/100); palpitations, constipation, diarrhoea, nausea, vomiting, asthenia, headache, abnormal ejaculation, rhinitis, rash, pruritis, urticaria, postural hypotension. MA Number PA1077/118/001. Marketing authorisation holder GlaxoSmithKline (Ireland) Limited, Stonemasons Way, Rathfarnham, Dublin 16, Ireland. Legal category POM; S1A. Date of preparation of API: April 2012. Copy Approval Code: IE/COM/0021/12. Further information available on request from GlaxoSmithKline, Stonemasons Way, Rathfarnham, Dublin 16 Ireland. Tel: 01-4955000. The recommended dose of Combodart is one capsule (0.5 mg/ 0.4 mg) taken orally approximately 30 minutes after the same meal each day. The capsules should be swallowed whole and not chewed or opened. * vs either tamsulosin or dutasteride monotherapy † No significant difference was seen between combination and dutasteride monotherapy (RRR 19.6%, p=0.18) References: 1. Combodart Summary of Product Characteristics, 2010. 2. Roehrborn CG et al. Eur Urol 2010; 57: 123-131.
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Bringing pharmacy into the healthcare spectrum Hospital Pharmacy of the Year - Sponsored by Roche Products (Ireland)
From left to right: Muireann Ni Shuilleabhain, Grace Daly, Margaret Mitchell, Niamh O’Connell, Marianne O’Callaghan
The pharmacy team at South Infirmary Victoria University Hospital (SIVUH), headed up by hospital pharmacist Muireann Ni Shuilleabhain, was crowned the 'Hospital Pharmacy Team' at the Irish Pharmacy Awards 2012. Muireann and her team fought off tough competition at the prestigious awards held in May of this year at the Burlington Hotel in Dublin. The glittering ceremony aims to recognise the positive innovation and dedication ongoing within the pharmacy profession in Ireland, both in the community and hospital sectors. Muireann picks up the story, "2012 has been the year where two of our patient safety and staff efficiency projects have
come together and been realised. Our focus has been to bring the Pharmacy team into the wider spectrum of the hospital organisation and the whole pharmacy team has worked tirelessly towards this goal, overcoming many obstacles (mainly logistical and cultural) along the way. "While both projects are diverse, we think that they show the flexibility and complexity of the Pharmacy Department’s services, all of which are rotational, in the delivery of patient centered pharmaceutical care." ACHIEVING THE IDEAL The team have been focusing on two novel projects in particular;
one looking at a pharmacist medicines reconciliation service and the other focusing on increased efficiencies achieved with restructuring an existing model of pharmaceutical care. The timelines for these projects were extremely close, both being implemented December 2011/ January 2012. "This was not ideal, but the pharmacy team realised that this was an opportunity that could not be missed," she says. The Pharmacy Department at St Vincent's provides a comprehensive range of pharmaceutical services to patients and staff in SVUH. Muireann adds, "Our principal objective is to provide patientfocused pharmaceutical care in order to achieve definite outcomes that improve patients’
quality of life. The department has a skill mix of pharmacists and pharmaceutical technicians. "Clinical pharmacists work closely with doctors, nurses and other members of the multidisciplinary team to ensure that patients receive optimal pharmaceutical care while attending the hospital. They have a key role in monitoring and reviewing patients and their medications, providing medication counselling where appropriate and liaising with community pharmacy colleagues and GPs to promote seamless pharmaceutical care after discharge." The first team project involved the introduction of a pharmacist in the medicines reconciliation
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10 Awards process in the pre assessment stage for elective orthopaedic patients. This involved lengthy proposals, discussions, piloting and planning with a wide team including Planning & Development, Reconfiguration, Anaesthetics, Medical & Surgical teams, Nursing and Hospital Management staff. "In the medication reconciliation process we focus on the concept of a single list to document patient’s current medications. This list is completed by the pharmacist at the pre assessment interview stage and then utilised as the “one source of truth” medication list by all medical, nursing, pharmacy and other HCP staff. The list is verified by the pre assessment pharmacist (rotational) with the community pharmacist/ GP or family member as appropriate. This list becomes the documented source of medication reconciliation from then on through to the admission process and beyond. A “Patient Own Drug” (POD) scheme is planned to follow on from the Pre Assessment stage, which will include technician involvement. This service is at the final stages and it is intended to have it in progress by mid 2012. The involvement of a pharmacist at pre assessment has been audited and has been shown to be very successful as a patient safety initiative." UTILISING PHARMACY AS KEY STAKEHOLDERS The second team project involves the Pharmacy as key stakeholders in the developments of the day infusion unit at SIVUH, thereby facilitating a more streamlined, efficient and multidisciplinary team based service. The multidisciplinary team included members from Pharmacy, Nursing, Medical, Surgical, Management, Admissions, Medical Records and Planning & Development. The positive changes seen from the key involvement in this multidisciplinary team collaboration shows improvement in overall scheduling of patients, documentation, more inclusive team environment, enhanced communication facilitated by an electronic shared folder,
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more easily accessible data and measurable costs savings/ efficiencies. The pharmacy team is now an integral part of the Day Infusion Unit service at SIVUH. "The commitment to both of these projects in consultation with the wider hospital team has shown very positive results in terms of patient safety, measurable cost savings and enhanced working relationships throughout the hospital team environment. The Pharmacy Department‘s team ethos facilitates a safer, cost efficient use of resources in delivering complex patient centered pharmaceutical care," she adds. The Medicines Information service (MI) provided at the hospital strives to optimise patient care through the provision of accurate, up-todate, unbiased information on medication use to health care professionals within the organisation, both in terms of individual patient care, and in the provision of general information on safe use of medicines and SVUH has a busy oncology and haematology service. The pharmacy has a Aseptic Services Unit (ASU) that operates under Good Clinical Practice, where all the chemotherapy for patients in the hospital is prepared under sterile conditions. The ASU is also involved in the preparation of products for ENT, Transplant patients, Ophthalmology, Interventional Radiology, Urology and other departments. "In addition, our team here is actively involved in supporting ongoing research projects, in particular clinical research in oncology. Pharmacists are also involved in teaching and tutoring undergraduate and postgraduate healthcare personnel and in clinical training of pharmacists in particular for the M.Sc. in Hospital Pharmacy in Trinity College Dublin and the National Pharmacy Internship Programme. The pharmacy department co-ordinates the production and publication of the Medicines Guide for the hospital," adds Muireann
2012 has been the year where two of our patient safety and staff efficiency projects have come together and been realised. Our focus has been to bring the Pharmacy team into the wider spectrum of the hospital organisation and the whole pharmacy team has worked tirelessly towards this goal, overcoming many obstacles (mainly logistical and cultural) along the way.
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Call for action on medication safety Dr Roberto Frontini
information-sharing with health professional colleagues about the problem; > use of quotas by wholesalers to ensure fair distribution when demand exceeds supply;
Problems caused by medicines shortages are serious, threaten patient care in hospitals and require urgent action. So said a statement issued this month by the European Association of Hospital Pharmacists (EAHP). EAHP’s recent General Assembly of 31 member countries prioritised the issue for discussion and resolved that the solutions to the shortage problem include: > greater prescriber awareness of shortage difficulties and willingness to discuss the matter with hospital pharmacist colleagues; > vigilance by hospital pharmacists and pro-active
> adequate notice and alerts by manufacturers, and the maintenance of buffer stocks; and, > rigorous action by regulatory agencies including monitoring of shortages and best practice sharing. EAHP’s statement also called for the European Commission to commence an investigation of the medicines shortage problem looking at: the issue of free movement of goods, and whether or not this is a factor in undermining national medicines supply chains, and if so, how can the conflict best be resolved at a European level; the extent to which European Guidelines on Good Distribution Practice of
Medicinal Products for Human Use (94/C 63/03) are being adhered to; and, the extent to which this Guideline may need to be updated in view of the shortage problem. Commenting on the statement, Dr. Roberto Frontini, President of the EAHP, said: “I have great fears for patient safety if the medicines shortage problem in Europe continues or worsens. Medicines are not simple items of commerce, they are an essential component of patient care and in the hospital sector they must be administered to the patient in a timely manner. Furthermore managing medicines shortages and ensuring continuity of supply can also divert significant amounts of a hospital pharmacist’s time and attention from other tasks important in the provision of high quality, safe and efficacious care.”
Prestigious conferring ceremony at TCD World renowned scientists were among those conferred with honorary doctorates at a special honorary degree ceremony at Trinity last month, marking the Dublin City of Science 2012 and the Euroscience Open Forum. They included: Professor William Campbell, former Director of Parasitology at Merck who was centrally involved in developing Ivermectin, the cure against river blindness was conferred with a Doctor in Science (Sc.D). In 1987 he spearheaded the decision by Merck to distribute Ivermectin free to millions of people in what became one of the first and foremost examples of a public/private partnership in international health. Originally from Donegal, he is a graduate of Trinity with first class honours in Zoology.
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Clinical Scientist, Dr John Climax and founder of ICON plc in Dublin in 1990 was conferred with a Doctor in Science (Sc.D). Today Icon is a global provider of development services to pharmaceutical and related health industries, employing some 9,000 people in 42 countries. Originally from Singapore, Dr Climax is Chairman Emeritus of ICON, a founding member of the Board of the Science Gallery at Trinity College and Adjunct Professor at the Royal College of Surgeons in Ireland. Immunologist and Nobel Prize Winner Professor Peter Doherty, the Michael F. Tamer Chair of Biomedical Research at St Jude Children’s Research Hospital, Memphis, Tennessee and Laureate Professor at the University of Melbourne was
conferred with a Doctor in Medicine (M.D). Theoretical physicist, mathematician and cosmologist Professor Sir Roger Penrose and Kiran Mazumdar-
Shaw, an Indian businesswoman and innovator in Bangalore were also conferrred.
Job code: XIA/2011/014
Date of preparation: August 2011
Dissolve the frustration of Dupuytren’s contracture
Introducing XIAPEX, an innovative injectable treatment for Dupuytren’s contracture XIAPEX is the first pharmaceutical treatment indicated for Dupuytren’s contracture.1,2 It is a minimally invasive, outpatient procedure, which improves joint contractures and helps restore hand function.1,2 To find out more about XIAPEX and how you can incorporate it into your treatment protocol for Dupuytren’s contracture, please visit www.xiapex.eu or contact your local Pfizer representative today.
Transforming treatment XIAPEX® Abbreviated Prescribing Information: (See Xiapex Summary of Product characteristics for full Prescribing Information) Presentation: Powder and solvent for solution for injection for intralesional use. The vial of powder contains 0.9mg collagenase clostridium histolyticum. The powder is a white lyophilised powder and the solvent is a clear colourless solution. Indications: Treatment of Dupuytren’s contracture in adult patients with a palpable cord. Dosage: Xiapex must be administered by a physician appropriately trained in the correct administration of the product and experienced in the diagnosis and management of Dupuytren’s disease. The recommended dose of Xiapex is 0.58mg per injection into a palpable Dupuytren’s cord. For an MP joint, each dose is administered in an injection volume of 0.25ml (requiring 0.39ml solvent for reconstitution). For a PIP joint, each dose is administered in an injection volume of 0.20ml (requiring 0.31ml solvent for reconstitution). Approximately 24 hours after injection, a finger extension procedure may be performed to facilitate cord disruption. If a satisfactory response has not been achieved, injections and finger extension procedures may be repeated up to 3 times per cord at approximately 4-week intervals. Only one cord must be treated at a time. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Warnings and Precautions: Allergic reactions - 17% of Xiapex-treated patients in phase 3 placebo-controlled clinical studies had mild allergic reactions (i.e. pruritus). Physicians must be prepared to address any severe local or systemic allergic reactions including the
potential for anaphylaxis following injection, including the potential for such reactions following repeated use. Whilst there is no evidence from the clinical data of an increased risk of serious allergic reactions upon repeated injections, the potential for such reactions following repeated use cannot be excluded. Tendon rupture or other serious injury to the injected extremity – Injection of Xiapex into collagen containing structures of the hand other than the Dupuytren’s cord may result in damage to those structures including possible tendon rupture or ligament damage. Injections into cords affecting the PIP joint of the 5th finger must not be more than 2 to 3 mm in depth and nor more than 4mm distal to the palmar digital crease. Patients should be instructed to contact their physician in case of symptoms of tendon rupture. Use in patients with coagulation disorders – Xiapex must be used in caution in patients with coagulation disorders or those taking anticoagulants. Use of Xiapex in patients who have received anticoagulants (with the exception of up to 150mg acetylsalicylic acid daily) within 7 days prior to receiving an injection of Xiapex is not recommended. Immunogenicity As with any non-human protein medicinal product, patients may develop antibodies to the therapeutic protein. Since the enzymes in Xiapex have some sequence homology with human matrix metalloproteinases (MMPs), anti-drug antibodies could theoretically interfere with human MMPs. No safety concerns related to the inhibition of endogenous MMPs have been observed, in particular no adverse events indicating the development or exacerbation of autoimmune diseases or the development of a musculoskeletal syndrome
but the potential for it to occur cannot be excluded. If this syndrome were to develop, it would occur progressively and is characterized by one or more of the following signs and symptoms: arthralgia, myalgia, joint stiffness, stiffness of the shoulders, hand oedema, palmar fibrosis and thickening or nodules forming in the tendons. Long-term safety - Longterm safety of Xiapex is not fully characterised. The impact of treatment with Xiapex on subsequent surgery, if needed, is not known. Drug Interactions: Use of Xiapex in patients who have received tetracycline antibiotics e.g. doxycycline, within 14 days prior to receiving an injection of Xiapex is not recommended. Pregnancy & Lactation: Not recommended in pregnancy. Xiapex can be used during breast feeding. Driving and operating machinery: Xiapex may have a major influence on the ability to drive and use machines due to swelling and pain in the treated hand. Other minor influences include dizziness, paraesthesia, hypoesthesia, and headache, see side effects. Patients must be instructed to avoid potentially hazardous tasks such as driving or using machines until it is safe to do so or as advised by the physician. Side Effects: In clinical trials, the most frequently reported adverse reactions during the Xiapex were local injection site reactions such as oedema peripheral (local to the injection site), contusion (including ecchymosis), injection site haemorrhage and injection site pain. Injection site reactions were very common, occurring in the vast majority of patients, were mostly mild to moderate in severity and generally subsided within 1-2 weeks post injection. Serious adverse reactions of tendon rupture, tendonitis, other ligament injury and
complex regional pain syndrome related to the medicinal product were reported. Very commonly reported adverse reactions include lymphadenopathy, pruritus, ecchymosis, pain in extremity, oedema peripheral (including injection site oedema and oedema), injection site haemorrhage, injection site pain, injection site swelling, tenderness, contusion. Commonly reported adverse reactions include lymph node pain, paresthesia, hypoesthesia, burning sensation, dizziness, headache, nausea, blood blister, blister, rash, erythema, hyperhidrosis, arthralgia, joint swelling, myalgia, axillary pain, inflammation, injection site inflammation, swelling, injection site erythema, injection site pruritus, injection site warmth, injection site vesicles, skin laceration. Overdose: Overdose is expected to be associated with increased local injection site reactions. Provide routine supportive care and treat symptomatically. Legal Category: S1C Marketing authorisation holder: Pfizer Ltd, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK. Package quantities, Marketing Authorisation numbers: XIAPEX 0.9mg powder and solvent for solution for injection, EU/1/11/671/001 Further information is available on request from: Pfizer Healthcare Ireland, Pfizer Building, 9, Riverwalk, National Digital Park, Citywest Business Campus, Dublin 24. Date of Preparation: August 2011. Company reference: XP2_0 References 1. XIAPEX Summary of Product Characteristics. February 2011. 2. Hurst LC, Badalamente MA, Hentz VR et al. N Engl J Med. 2009;361: 968-79.
The growing issue of Hepatitis C and the role of the hospital pharmacist National Governments, including Ireland, must urgently put in place comprehensive strategies to ensure patients with chronic infectious diseases are able to manage their condition and receive continuity of care. likely to further revolutionise the HCV treatment landscape in the near future.”
Dr Leila Thornton
Furthermore, VICTRELIS® (boceprevir) is one of a new class of treatments for chronic hepatitis C (CHC) genotype 1 infection. It was launched by healthcare company MSD. It will be used in combination with current treatments (peginterferon alfa and ribavirin), in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy.
The news comes from the European Association of Hospital Pharmacists coinciding with World Hepatitis Day at the end of July. Central to this, they say, is utilising the role of the hospital pharmacist in medicines reconciliation and ensuring systems encourage seamless care between sectors. The disease area looks certain to become a huge Irish concern. GROWING INCIDENCE As recently as April of this year, Dr Leila Thornton of the Health Protection Surveillance Centre told delegates at the Irish Society of Gastroenterology meeting in Kilkenny that Ireland will have to prepare for a significant surge in liver disease over the next 20 years due to the prevalence of the disease among hepatitis C sufferers. Dr Thornton found that the prevalence of hepatitis C in Ireland stands at 20,000- 50,000 people. It is estimated that 5-20% of these sufferers are likely to develop cirrhosis within 20 years of being infected. In terms of self-management,
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many patients with hepatitis have a chronic disease which means drug treatment will not cure their condition and they must continue taking medicines until the end of their life. During these long-term therapies a resistance to the medication can often develop, so the patient has to switch to another drug. Other medication management challenges include potential polypharmacy, adherence difficulties and the reconciliation of side effects. According to the EAHP, as the hospital’s resident expert in medicines numerous studies have illustrated the positive and cost-effective role hospital pharmacist play by empowering patients with relevant information, checking the appropriateness of prescribing, and screening for potential drugdrug interactions. THERAPY DEVELOPMENTS As the news of Ireland's growing problem was breaking, a new direct acting antiviral (DAA) protease inhibitor (PI), for the treatment of genotype-1 chronic
hepatitis C, in combination with peginterferon alfa and ribavirin treatment was launched into the Irish market. Incivo (telaprevir) is one of a new class of medicines which directly targets the hep C virus and offers patients infected with genotype-1 chronic hep C the chance of clearing the virus, compared to current standard treatment. Dr Raphael Merriman, consultant hepatologist, St Vincent's Hospital, Dublin commented on the launch: “This year marks the dawn of an exciting new era of antiviral therapy for patients with chronic hepatitis C virus (HCV) with the approval of new agents for the first time since 1998. “Two protease inhibitors boceprevir and telaprevir - will now be available for Irish patients. Though this new standard of care comes at the cost of increased sideeffects and greater complexity, many patients may qualify for substantially reduced treatment duration. Many other DAAs that are currently in clinical trials are
The addition of boceprevir to current treatment was investigated in two pivotal Phase III studies, RESPOND-2 and SPRINT-2, involving 403 treatment-failure and 1,097 untreated patients respectively. In RESPOND-2, the addition of boceprevir for patients who had failed previous treatment, almost tripled (x2.8) sustained virologic response (SVR) from 21% (17/80) to 59% (95/162). For prior relapsers specifically, triple therapy improved SVR by over 2-fold (x2.2) from 29% (15/51) to 69% (72/105). In SPRINT-2 for previously untreated patients, the addition of boceprevir nearly doubled (x1.7) SVR rates from 38% (137/363) to 63% (233/368) compared to standard therapy alone. Dr Stephen Stewart, Consultant in Gastroenterology and Hepatology, Mater Hospital, Dublin comments, "The launch of VICTRELIS for chronic hepatitis C genotype 1 is very exciting and meets a major public health need. Finally we have new options for patients with the hardest to treat form of the disease. Patients who have failed previous therapy or are new to treatment can significantly improve their chances of clearing the virus compared to current standard treatment.”
nEW Win With ViCtRELiS
VICTRELIS® (boceprevir) PRESCRIBING INFORMATION Refer to Summary of Product Characteristics before prescribing PRESENTATION 200mg hard capsule each containing 200 mg of boceprevir. USES Victrelis is indicated for the treatment of chronic hepatitis C (CHC) genotype 1 infection, in combination with peginterferon alfa and ribavirin (PR), in adult patients with compensated liver disease who are previously untreated or who have failed previous therapy. DOSAGE AND ADMINISTRATION Treatment with Victrelis should be initiated and monitored by a physician experienced in the management of CHC. Victrelis must be administered in combination with peginterferon alfa and ribavirin (PR). Consult the Summary of Product Characteristics (SmPC) of peginterferon alfa and ribavirin prior to initiation of therapy with Victrelis. Adults: 800 mg orally TID with food. Maximum daily dose: 2,400 mg. Administration without food could be associated with a net loss of efficacy due to sub-optimal exposure. Patients without cirrhosis who are previously untreated or who have failed previous therapy: These dosing recommendations differ for some subgroups from the dosing studied in the Phase 3 trials. ASSESSMENT* (HCV-RNA Results†) At Treatment Week 8
At Treatment Week 24
Previously Untreated Patients
Treatment duration = 28 weeks 1. Give PR for 4 weeks, and then 2. Continue with all 3 ( [PR] + Victrelis) and finish through Treatment Week 28 (TW 28).
Treatment duration = 48 weeks 1. Give PR for 4 weeks, and then 2. Continue with all 3 (PR + Victrelis) and finish through TW 36; and then 3. Give PR and finish through TW 48.
Patients Who have Failed Previous Therapy
Treatment duration = 48 weeks 1. Give PR for 4 weeks, and then 2. Continue with all 3 (PR + Victrelis) and finish through TW 36, and then 3. Give PR and finish through TW 48.
*Stopping rule If patient has HCV-RNA results > 100 IU/ml at TW 12; then discontinue 3-medicine regimen. If the patient has confirmed, detectable HCV-RNA at TW 24; discontinue 3-medicine regimen. PR – Peginterferon alfa and ribavirin All cirrhotic patients and null responders: Recommended treatment duration is 48 weeks: 4 weeks of dual therapy with peginterferon alfa and ribavirin + 44 weeks of triple therapy with peginterferon alfa, ribavirin +Victrelis. (Refer to the stopping rule in Table 1 for all patients.) Duration of the triple therapy after the first 4 weeks of dual therapy should not be less than 32 weeks. Given the incremental risk of adverse events with Victrelis (anaemia notably); if the patient cannot tolerate triple therapy consider dual therapy of peginterferon alfa + ribavirin for the final 12 weeks of treatment instead. Missed doses: If the missed dose is less than 2 hours before next dose is due, the missed dose should be skipped. If a dose is missed 2 or more hours before the next dose is due, take the missed dose with food and resume the normal dosing schedule. Dose reduction: Not recommended. In case of serious adverse reactions potentially related to peginterferon alfa and/or ribavirin, the peginterferon alfa and/or ribavirin, dose should be reduced. Refer to the individual SmPC for information about how to reduce and/or discontinue the peginterferon alfa and/or ribavirin dose. Do not give Victrelis monotherapy. Renal impairment: No dose adjustment needed with any degree of impairment. Hepatic impairment: No dose adjustment needed No data in patients with decompensated cirrhosis. Paediatric population: No data available. Elderly: Insufficient numbers in clinical studies to determine whether they respond differently to younger subjects. CONTRA-INDICATIONS Hypersensitivity to the active substance or any of the excipients; Autoimmune hepatitis; Co-administration with medicines highly dependent on CYP3A4/5 for clearance, and for which elevated plasma concentrations are associated with serious and/or lifethreatening events such as orally administered midazolam and triazolam, bepridil, pimozide, lumefantrine, halofantrine, tyrosine kinase inhibitors, and ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine); Pregnancy. PRECAUTIONS Anaemia: Onset of anaemia has been reported with peginterferon alfa + ribavirin therapy by TW 4. The addition of Victrelis to PR is associated with an additional decrease in haemoglobin concentrations of approx 1 g/dl by TW 8 compared to standard of care. Obtain full blood counts pretreatment, TW 4, TW 8, and thereafter, as appropriate. If Haemoglobin is < 10 g/dl consider anaemia management. Neutropenia: Addition of Victrelis to peginterferon alfa + ribavirin resulted in higher incidences of neutropenia and Grade 3-4 neutropenia compared with PR alone. Frequency of severe or life threatening infections tends to be higher in Victrelis-containing arms than the control arm. Evaluate neutrophils counts before and regularly after treatment starts. Evaluate and treat infections promptly.
Combined use with peginterferon alfa–2a as compared to alfa–2b: Compared to the combination of Victrelis with peginterferon alfa– 2b and ribavirin, the combination of Victrelis with peginterferon alfa–2a and ribavirin was associated with a higher rate of neutropenia (including grade 4 neutropenia) and a higher rate of infections. Use in prior null responders: Null responders might gain some benefit in adding Victrelis to peginterferon alfa and ribavirin. Optimal management of null responders remains to be established. Contains lactose: Not for use in rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. Proarrhythmic effects: Use caution in patients at risk of QT prolongation (long congenital QT, hypokalaemia). Use in patients with HIV co-infection: Safety and efficacy has not been established. A clinical study is ongoing. Use in patients with HBV co-infection/organ transplant: Has not been studied. Use in patients having HCV genotypes other than G1: Safety and efficacy have not been established. Use in patients who have previously failed treatment with an HCV protease inhibitor: Has not been studied. Drug Interactions Victrelis is a strong inhibitor of CYP3A4/5. Medicines metabolized primarily by CYP3A4/5 may have increased exposure when administered with Victrelis, which may increase or prolong therapeutic and adverse reactions. It does not inhibit or induce the other enzymes of the CYP450. Victrelis is partly metabolized by CYP3A4/5. Co-administration with medicines that induce or inhibit CYP3A4/5 could increase or decrease exposure to Victrelis. Use with rifampicin or anticonvulsants (e.g. phenytoin, phenobarbital or carbamazepine) may significantly reduce the plasma exposure of Victrelis and is not-recommended). Exercise caution with medicines known to prolong QT interval such as amiodarone, quinidine, methadone, pentamidine and some neuroleptics. Pharmacokinetic interactions Ketoconazole or azole antifungals: exercise caution; Ritonavir: No data are currently available with ritonavir as a booster in combination with protease inhibitors. Theoretically, the combination of boceprevir with PIs/ritonavir is not expected to result in clinically significant interactions; Efavirenz: plasma trough concentrations of Victrelis were decreased. The clinical outcome has not been directly assessed; Raltegravir: no data but pay attention; Drospirenone/Ethinyl estradiol: exercise caution in patients predisposed to hyperkalaemia or taking K+sparing diuretics; Use alternative OCs. Midazolam/triazolam (oral administration): contraindicated; IV benzodiazepines: monitor closely. Immunosuppressants: Therapeutic medicine monitoring is recommended when administering Victrelis with CYP3A4/5 substrates that have a narrow therapeutic window (e.g. tacrolimus, ciclosporin). Individual patients may require a change in their immunosuppressant dosage when Victrelis is started or stopped to ensure clinically effective blood levels; Statins: Individual patients may require a change in statin dosage when Victrelis is started or stopped to ensure clinically effective blood levels; Methadone: Individual patients may require a change in methadone dosage when Victrelis is started or stopped to ensure clinically effective blood levels. PREGNANCy Contraindicated. Patients and partners must use two effective forms of contraception during treatment. Breastfeeding: A risk to the newborns/infants cannot be excluded. Make decision considering the benefit of breastfeeding for the child and the benefit of therapy for the woman. SIDE EFFECTS Refer to Summary of Product Characteristics for complete information on side-effects Most frequently reported adverse reactions were fatigue, anaemia, nausea, headache, and dysgeusia. Most common reason for dose reduction was anaemia, which occurred more frequently in subjects receiving the combination of Victrelis with peginterferon alfa and ribavirin than in subjects receiving peginterferon alfa 2b and ribavirin alone. Adverse Reactions are listed under headings of frequency using the categories: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1,000 to < 1/100); rare (≥ 1/10,000 to < 1/1,000). Very common: Anaemia, neutropenia, decreased appetite, anxiety, depression, insomnia, irritability, dizziness, headache, cough, dyspnoea, diarrhoea, nausea, vomiting dry mouth, dysgeusia, alopecia, dry skin, pruritus, rash, arthralgia, myalgia, asthenia, chills, fatigue, pyrexia, influenza-like illness, weight decrease. Common: Bronchitis, cellulitis, herpes simplex, influenza, oral fungal infection, sinusitis, leukopenia, thrombocytopenia, goitre, hypothyroidism, dehydration, hyperglycaemia, hypertriglyceridaemia, hyperuricaemia, affect lability, agitation, libido disorder, mood altered, sleep disorder, hypoaesthesia, paraesthesia, syncope, amnesia, disturbance in attention, memory impairment, migraine, parosmia, tremour, vertigo, dry eye, retinal exudates, vision blurred, visual impairment, tinnitus, palpitations, hypotension, hypertension, epistaxis, nasal congestion, oropharyngeal pain, respiratory tract congestion, sinus congestion, wheezing, abdominal pain, abdominal pain upper, constipation, gastrooesophageal reflux disease, haemorrhoids, abdominal discomfort, abdominal distention, anorectal discomfort, aphthous stomatitis, cheilitis, dyspepsia, flatulence, glossodynia, mouth ulceration, oral pain, stomatitis, tooth disorder, dermatitis, eczema, erythema, hyperhidrosis, night sweats, oedema peripheral, psoriasis, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, skin lesion, back pain, pain in extremity, muscle spasms, muscular weakness, neck pain, pollakiuria, erectile dysfunction, chest discomfort, chest pain, malaise, feeling of body temperature change, mucosal dryness, pain. Uncommon serious: Pneumonia haemorrhagic diathesis, lymphopenia, hyperthyroidism, hypokalaemia¸ diabetes mellitus, suicidal ideation, confusional state, loss of consciousness, retinal ischaemia, retinopathy, deep vein thrombosis, pulmonary embolism, dry pancreatitis, rectal haemorrhage. Rare serious: Epiglottitis, thyroid neoplasm (nodules), sarcoidosis, porphyria non-acute, bipolar disorder, completed suicide, suicide attempt, cerebral ischaemia, encephalopathy, papilloedema, acute myocardial infarction, atrial fibrillation, coronary artery disease, pericarditis, pericardial effusion, venous thrombosis, pleural fibrosis, respiratory failure, pancreatic insufficiency, cholecystitis, aspermia. Other less serious uncommon and rarely reported side effects are listed in the Summary of Product Characteristics PACKAGE QUANTITIES Packs of 336 capsules ( 4 inner cartons each of 84 capsules). Marketing Authorisation Holder: Merck Sharp & Dohme Ltd Hertford Road, Hoddesdon, Hertfordshire EN11 9BU, United Kingdom Marketing Authorisation Number: EU/1/11/704/001 POM Date of review of Prescribing information: August 2011. Further information is available on request from: MSD Pelham House, South County Business Park, Leopardstown, Dublin 18 or from www.medicines.ie. © Merck Sharp & Dohme Ireland (Human Health) Limited, 2012. All rights reserved. Date of preparation: March 2012. References: 1. Bacon BR, Gordon SC, Lawitz E, et al; for HCV RESPOND-2 Investigators. Boceprevir for previously treated chronic HCV genotype 1 infection. N Engl J Med. 2011; 364(13): 1207–1217. 2. Poordad F, McCone J Jr, Bacon BR, et al; for SPRINT-2 Investigators. Boceprevir for untreated chronic HCV genotype 1 infection. N Engl J Med. 2011; 364(13): 1195–1206. G1* = genotype 1 Pelham House, South County Business Park, Leopardstown, Dublin 18.
plus peginterferon alfa and ribavirin (PR) in the treatment of chronic Hepatitis C Virus G1* compared to PR alone1,2
Challenging the HIV stigma Dr Jack Lambert
The stigma of HIV must be challenged to incur change. These are the words of Dr Jack Lambert, Infectious Disease Consultant at the Mater Hospital. “We have to continue challenging the stigma that still surrounds HIV in Ireland in order to effect change," he said on the heels of launching a new awareness campaign Don't Guess, Get Tested.' This campaign was launched by Open Heart House (Dublin),
the Sexual Health Centre (Cork), AIDS West (Galway) and Dublin AIDS Alliance (Dublin) and the Red Ribbon Project (Limerick) to raise awareness for the alarming number of late presenters of HIV in Ireland and to encourage early HIV testing, with the aim of reducing the number of late presenters of HIV in 2012. As part of the campaign, the local organisations are hosting events to educate members and/ or the public around Irish Aids Day. The campaignis supported by the global health care company Abbott. "The public needs to know that
by avoiding early HIV testing, you put yourself at risk of rapid disease progression, possibly leading to AIDS. Presenting late with HIV also causes problems from a socio economic point of view, as people tend to be more ill when they do present, leading to a greater burden of care. I would encourage those people who suspect they may be at risk to look at the long-term benefits of getting tested early and to contact your doctor or STI Clinic. Healthcare professionals also need to become more pro-active about referring patients for testing at an appropriate time," he added.
Joan elected to board Joan Peppard
President of the Hospital Pharmacists Association of Ireland, Joan Peppard, has been elected for the first time to the Board of the European Association of Hospital Pharmacists. Joan was elected at the 2012 EAHP General Assembly along with Dr Petr Horak from the Czech Republic. Joan Peppard is Chief Pharmacist at the Health Service Executive in the Republic of Ireland. The new Board Members will share the title of Director of Professional Development.
Joan has served as EAHP representative for a number of years and has considerable experience working at an international level. On two occasions, she has co-ordinated the large survey conducted by EAHP on hospital pharmacy. Last summer, she led the Irish team that hosted the EAHP General assembly in Dublin. Tajda Miharija Gala (Slovenia) was elected as the new VicePresident and Prof. Dr. Cees Neef as the new Director of Education, Science and Research.
Hospital spillage Two hospital pharmacy workers were treated after a chemical spillage at a Cork hospital. The incident occurred in the pharmacy department of St Finbarr’s Hospital when a small bottle of liquid ammonia fell from a shelf during cleaning. The fumes affected two staff members who suffered from streaming eyes and complained of difficulty breathing. Both were taken to Cork University Hospital for treatment but both staff members were discharged from the hospital within a matter of hours. As a safety measure, an administrative area next to the pharmacy department was evacuated. Normal service has since resumed in the pharmacy department and in the area which was evacuated.
Issue 5 • HPN
NEW oral anti-platelet treatment for a broad range of ACS patients
BRILIQUE saves more lives than clopidogrel as measured by CV deaths (PLATO study)1
BRILIQUETM 90MG FILM-COATED TABLETS (ticagrelor) Abridged Prescribing Information (For full details see Summary of Product Characteristics (SmPC)) Use: Adults aged 18 years and older, co-administered with acetylsalicylic acid (ASA) daily: for the prevention of atherothrombotic events in patients with acute coronary syndromes (unstable angina, non-ST-segment elevation myocardial infarction [NSTEMI] or ST-segment elevation myocardial infarction [STEMI]); including patients managed medically, and those who are managed with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Presentation: 90mg ticagrelor film-coated tablets. Dosage and administration: Treatment should be initiated with a single 180mg loading dose (two tablets of 90mg) and then continued at 90mg twice daily. Following an initial dose of ASA, patients should also take a daily maintenance dose of 75-150mg of ASA with Brilique, unless ASA is specifically contraindicated. Treatment is recommended for up to 12 months unless discontinuation is clinically indicated. Premature discontinuation of treatment or lapses in therapy should be avoided. Patients treated with clopidogrel can be directly switched to Brilique. For oral use. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Active pathological bleeding. History of intracranial haemorrhage. Moderate-to-severe hepatic impairment. Co-administration with strong CYP3A4 inhibitors (e.g. ketoconazole). Precautions: Due to the increased risk of non-fatal or non-life threatening bleeding, use with caution in patients at an increased risk for bleeding (e.g. recent trauma or surgery, bleeding disorders or recent gastrointestinal bleeding) or those on concomitant medication that may increase bleeding risk (e.g. NSAIDs, anticoagulants) within 24 hours of taking Brilique. Brilique should be stopped 7 days prior to elective surgery if the antiplatelet effect is not desired. Use with caution in patients with an increased risk of bradycardic events (e.g. patients on digoxin), as asymptomatic ventricular pauses have been observed with Brilique, a history of asthma and/or COPD, a history of hyperuricaemia or gouty arthritis. Creatinine levels may increase during treatment with Brilique. Renal function should be checked after one month and thereafter according to routine medical practice, paying special attention to patients ≥ 75 years, patients with moderate-to-severe renal impairment and those receiving concomitant treatment with an ARB. Co administration of Brilique is not recommended with a high maintenance dose of ASA (> 300mg) or with doses of simvastatin > 40mg. Co administration of ticagrelor with strong CYP3A4 inducers is discouraged, as this may lead to a decrease in exposure and efficacy of ticagrelor. Co-administration with CYP3A4 substrates with narrow therapeutic indices is not recommended. Concomitant use of ticagrelor with doses of simvastatin or lovastatin > 40mg not recommended. Caution with concomitant use of P-gp inhibitors or P-gp substrates with narrow therapeutic indices e.g. verapamil, quinidine and cyclosporin. Caution with concomitant administration of SSRIs. Brilique is not recommended during pregnancy and breastfeeding. Undesirable effects: Common: Dyspnoea, epistaxis, gastrointestinal haemorrhage, subcutaneous or dermal bleeding, bruising and procedural site haemorrhage. Other undesirable effects include intracranial bleeding, elevations of serum creatinine and uric acid levels. Consult SmPC for a full list of undesirable effects. Legal category: POM. Marketing Authorisation Number: EU/1/10/655/004. Market Authorisation Holder: AstraZeneca AB, S 151 85, Södertälje, Sweden. Further information on request from: Freephone 1800 800 899 or contact AstraZeneca UK Limited, Horizon Place, 600 Capability Green, Luton, Bedfordshire, LU1 3LU, United Kingdom. Abridged prescribing information prepared: 04/12. BRILIQUE is a trade mark of the AstraZeneca group of companies. Reference 1: Brilique Summary of Product Characteristics. URN: 12/0266. Date of preparation: May 2012
Antimicrobial Prophylaxis in reducing Urinary Tract Infections in the Hospital setting Urinary tract infections (UTIs) are among the most prevalent infectious diseases with a substantial financial burden on society. Unfortunately, in Europe, there are no good data concerning the prevalence of various types of UTIs and their impact on the quality of life of the affected population. Nor is there good data regarding the impact of UTIs on economics in general and that of the health care system especially. For a well-functioning public health system, such data are urgently needed. Data obtained from other countries and societies, e.g. the USA, can only be applied with caution to the European situation. PATHOGENESIS OF URINARY TRACT INFECTIONS Micro-organisms can reach the urinary tract by haematogenous or lymphatic spread, but there is abundant clinical and experimental evidence to show that the ascent of microorganisms from the urethra is the most common pathway leading to a UTI, especially organisms of enteric origin (i.e. Escherichia coli and other Enterobacteriaceae). This provides a logical explanation for the greater frequency of UTIs in women than in men and for
the increased risk of infection following bladder catheterization or instrumentation. A single insertion of a catheter into the urinary bladder in ambulatory patients results in urinary infection in 1-2% of cases. Indwelling catheters with opendrainage systems result in bacteriuria in almost 100% of cases within 3-4 days. The use of a closed-drainage system, including a valve preventing retrograde flow, delays the onset of infection, but ultimately does not prevent it. It is thought that bacteria migrate within the mucopurulent space between the urethra and catheter, and that this leads to the development of bacteriuria in almost all patients within about 4 weeks. Haematogenous infection of the urinary tract is restricted to a few relatively uncommon microbes, such as Staphylococcus aureus, Candida spp., Salmonella spp. and Mycobacterium tuberculosis, which cause primary infections elsewhere in the body. Candida albicans readily causes a clinical UTI via the haematogenous route, but is
Issue 5 • HPN
also an infrequent cause of an ascending infection if an indwelling catheter is present or following antibiotic therapy. The concept of bacterial virulence or pathogenicity in the urinary tract infers that not all bacterial species are equally capable of inducing infection. The more compromised the natural defence mechanisms (e.g. obstruction, bladder catheterization), the fewer the virulence requirements of any bacterial strain to induce infection. This is supported by the well-documented in-vitro observation that bacteria isolated from patients with a complicated UTI frequently fail to express virulence factors. The virulence concept also suggests that certain bacterial strains within a species are uniquely equipped with specialized virulence factors, e.g. different types of pili, which facilitate the ascent of bacteria from the faecal flora, introitus vaginae or periurethral area up the urethra into the bladder, or, less frequently, allow the organisms to reach the kidneys to induce systemic inflammation. CLASSIFICATION OF URINARY AND MALE GENITAL TRACT INFECTIONS Infections can be classified according to their location within the urogenital tract, e.g. pyelonephritis, cystitis, prostatitis, urethritis, epididymitis
or orchitis. The different parts of the urinary tract, however, communicate with each other to some degree. As a result, bacteria in one area are probably also present elsewhere. For practical clinical reasons, however, UTIs and infections of the male genital tract are classified according to the predominant clinical symptoms: • uncomplicated lower UTI (cystitis) • uncomplicated pyelonephritis • complicated UTI with or without pyelonephritis • urosepsis • urethritis • special forms: prostatitis, epididymitis and orchitis. The clinical presentation and management of different UTI categories may vary during life and may depend on the patient’s condition. Therefore, special patient groups (the elderly, those with underlying diseases and the immunocompromised) have also to be considered. Insertion of urethral catheters is a very common procedure, carried out in 11% of inpatients in one European study9 and has a variety of indications including: peri-operative urine collection, management of urinary incontinence/retention and to measure urine output in acutely unwell patients.
NEW in Ireland
Treats acute uncomplicated UTIs with just one dose
One Treatment. One Solution.
One-dose sachet dissolves in water
Fos fom ycin (a s Trom eta m ol)
Name of mediciNal al Product: monuril 3g granules for oral solution. Each single-dose sachet contains 5.631g fosfomycin â€“ trometamol (1:1) equivalent to 3g fosfomycin. It is a white granular powder for oral solution with a characteristic odour and flavour of mandarin. TheraPeutic iNdicatioNs: Treatment of acute uncomplicated urinary tract infections due to sensitive organisms in adults. Posology aNd admiNistratioN: Adults only: A single dose of 3g taken on an empty stomach, preferably before bedtime, after bladder emptying. The contents of the sachet should be dissolved in water and the solution swallowed immediately. Elderly patients: Not recommended due to diminished urinary excretion. Paediatric population: It is not for use in children coNtraiNdicatioNs: Hypersensitivity to the active substance or to any of the excipients. Monuril should not be used in patients with impaired renal function (creatine-clearance <80 ml/min). WarNiNgs aNd sPecial PrecautioNs for use: Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including fosfomycin trometamol, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C.difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated. this medicinal product contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine. Do not use more than one single dose of Monuril to treat a single episode of acute cystitis. Prolonged use of an anti-infective may result in the development of super infection due to organisms resistant to that anti-infective. iNteractioNs: When co-administered with fosfomycin, metoclopramide lowers the serum and urine concentrations of fosfomycin. Other drugs that increase gastrointestinal motility may produce similar effects. No information is available on the interaction between fosfomycin and oral contraceptives, nevertheless there is a potential for interaction between oral contraceptives and antibiotics. PregNaNcy aNd lactatioN: Pregnancy: Data on a limited number of exposed pregnancies indicate no adverse effects of fosfomycin on pregnancy or on the health of the foetus/new-born child. To date, no other relevant epidemiological data are available. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Caution should be exercised when prescribing to pregnant women. Lactation: Due to lack of safety information, the use of fosfomycin during human lactation cannot be recommended usiNg moNuril With food & driNk: Take Monuril on an empty stomach (2-3 hrs after a meal) as food delays and reduces the absorption of fosfomycin trometamol, resulting in reduced blood and urinary concentrations. driviNg aNd usiNg machiNery: Monuril oral solution has no influence on the ability to drive and use machines. uNdesirable effects: commoN (1/100 to <1/10): Headache, Dizziness, Diarrhoea, Nausea, Vulvo-vaginitis, Dyspepsia and Asthenia uNkNoWN Anaphylactic shock, Allergic reaction, Asthma, Vomiting, Abdominal pain, Angioedema, Rash, Urticaria and Pruritus overdose: Symptoms: The following events have been observed in patients who have taken MONURIL 3g granules for oral solution in overdose: vestibular loss, impaired hearing, metallic taste, and general decline in taste perception. Treatment in the event of overdose: In the event of over dosage, treatment should be symptomatic and supportive. PharmacodyNamic ProPerties: Fosfomycin trometamol [mono (2-ammonium-2-hydroxymethil-1,3propandiol) (2R-cis) (3- methiloxyranil) phosphonate] is a broad spectrum antibiotic, derived from phosphonic acid, for the treatment of urinary tract infections. The antibacterial activity of fosfomycin is due to an inhibition of bacterial cell wall synthesis. Its particular mechanism of action, specific inhibition of enol pyruviltransferase, results in lack of cross resistance with other classes of antibiotic, and the possibility of synergism with other antibiotics (in vitro synergic effect with amoxicillin, cephalexin, pipedimic acid and aztrenam). Pharmacokinetic properties: Fosfomycin trometamol which is an orally well absorbed salt of fosfomycin, in which the formulation is completely soluble in water. Fosfomycin, unbound to the plasma proteins, is eliminated mainly unchanged through the kidneys and this results in very high urinary concentrations (about 3000mcg/ml) within 24 hours. Therapeutic concentrations of the active moiety in the urine are usually maintained for at least 36-48 hours. In patients with moderately reduced renal function (including elderly patients) the serum half-life of fosfomycin is slightly prolonged but urinary concentration remains therapeutically adequate. legal category: POM Package Quantities: Sachets are supplied in cardboard outer containing 1 sachet. date of last Pi revision: Nov 11. marketiNg authorisatioN holder: Zambon S.p.A. via Lillo del duca, 10 20091-Bresso, Milano. marketiNg authorisatioN Number: PA1441/2/2 distributor: Sinclair IS Pharma Ireland Ltd. marketed iN irelaNd by: faNNiN ltd, faNNiN house, leoPardstoWN, dubliN 18. for a copy of the smPc or further medical information, please contact email@example.com adverse events should be reported to fannin ltd, Pharmacovigilance at 01 2907000 or firstname.lastname@example.org fN2012-07-003. date of Preparation: August 2012
Many factors have been associated with catheterassociated urinary tract infections and there are multiple approaches to reducing these infections such as systemic antimicrobial prophylaxis. There are relatively few studies of prophylaxis for routine catheter insertion. Most are not powered to detect any statistically significant difference in the rates of infection. There is considerable variation in the practise of prophylaxis for urethral catheter insertion thoughout Europe. Practise in the UK varies with patient group and between healthcare professionals. Gentamicin is commonly used for insertion, change and removal; without a clear evidence base. The European Association of Urology guidelines on urological infection have recently recommended against antimicrobial prophylaxis for urinary catheter insertions. Because urinary catheters are used in many different settings with different risks, a blanket approach to systemic antimicrobial prophylaxis would result in many patients receiving antimicrobials unnecessarily. Local antibiotic policy makers have the experience and information required to make recommendations about specific drug regimens based on an assessment of evidence and local information about microbiology and drug costs. Any planned antibiotic prophylaxis should take into consideration the clinical condition of the patient and the diagnostic and treatment options available. Hospital acquired infection with pseudomonas, staphylococcus (including MRSA) and multiresistant acinetobacters are increasingly a problem worldwide. Antimicrobial drug resistance is widespread and this can limit the number of effective anti-microbial agents. Always
Issue 5 â€˘ HPN
take local advice from your microbiologist about antibiotic resistance and which antibiotics to use in order to be both effective and to minimise the development of resistant strains. Benefits must be weighed against risks of toxic and allergic reactions, emergence of resistance, superinfections and cost. A past history of a serious adverse reaction to an antibiotic is a contra-indication to its use. Usually a single intravenous dose of an antibiotic given preoperatively within 30 minutes of induction of anaesthesia provides adequate tissue levels throughout the operation. Post operative doses of antibiotic for prophylaxis should not be given.
Consider repeat intraoperative doses if there is major blood loss or prolonged surgery. Antibiotic prophylaxis in caesarean section is delayed until clamping of the cord in order to prevent the drug reaching the neonate. The dose of prophylactic antibiotic is usually the same as the therapeutic dose. Prophylactic antibiotics should be administered at least 10 minutes before the application of a tourniquet to achieve appropriate tissue concentrations. PREVENTION OF ENDOCARDITIS This is a controversial area, there are many guidelines. The evidence base is unclear as
there is a lack of data in this area. Most recommendations are based on observational data. Some individuals who receive prophylaxis may still develop endocarditis. Prevention does not solely concern antibiotic prophylaxis. For example, adequate treatment of infection that could cause bacteraemia or fungaemia, the prompt removal of colonised intravascular devices and effective management of conditions that can lead to chronic or repeated infections are essential in reducing the risk of subsequent endocarditis.
22 Clinical Focus
An insight into one of the world’s largest pharmaceutical companies Written by Eamonn Brady (MPSI), a pharmacist who owns Whelehans Pharmacy in Mullingar. The tour of the Novartis facility took place on June 26th 2012. Eamonn Brady MPSI graduated from the Robert Gordon University in Aberdeen in 2000 with a Masters in Pharmacy. He worked for Boots in the UK before moving back to Ireland in 2002. He bought Whelehans Pharmacy in Mullingar in 2005. He undertakes clinical training for nurses in the midlands. In June, Novartis invited a group of pharmacists and journalists from around Europe to visit their facilities in their home city of Basel in northern Switzerland. I was one of two Irish representatives on the tour. I was accompanied by Irish Engineer Donal McGinnity who was assessing their manufacturing and logistical techniques and processes. The Novartis facilities in the Basel area are enormous so the two areas we focused on for the purpose of this visit was their ophthalmology manufacturing plant in Stein and their main research centre, Novartis Institute of Biomedical Research (NIBR), based in their headquarters in Basel. Before discussing the visit, I thought it appropriate to describe why Basel has become “Europe’s pharmaceutical hub” and how Novartis has become Europe’s largest pharmaceutical company. BASEL- “EUROPE’S PHARMACEUTICAL HUB” Basel is considered the hub of the European pharmaceutical and chemical industry. Amongst the hundreds of chemical and pharmaceutical companies based here, it is home to both Novartis and Roche, both in the top ten in terms of size in the global pharmaceutical industry. I asked a senior manager from Novartis how a city smaller than Cork has become a global player in the pharmaceutical industry? You probably will not find his response in many official history books; he explained it is all down to location and opportunity. He
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went on to explain how in the late 1800’s, Germany increased taxes on its chemical industry, therefore many chemical companies relocated over the border to Basel which had lower tax rates (which Switzerland still enjoys) and lower costs and wages (definitely not still the case today) than Germany. Its position on the Rhine also meant transportation of ingredients from Germany and transportation of completed goods to Germany was easy. The chemical industry then evolved in the 20th century into pharmaceuticals as the two industries are closely related.
In Ireland, we can ague that history repeated itself to a degree a century later with the success of Ireland in attracting so many major pharmaceutical companies to our shores for some of the same reasons. Switzerland has a population only slightly larger than Ireland, yet they punch above their weight and in some cases have achieved world domination in industries like pharmaceuticals, finance, watch making and confectionary. Switzerland is
Exterior of Stein Facility
an excellent example of how a small country can be successful by concentrating on quality and innovation and why Ireland shouldn’t be afraid to aim high. HISTORY OF NOVARTIS Novartis was created in 1996 through the merger of CibaGeigy and Sandoz, two Basel companies which were already leaders in the pharmaceutical sector. Over the last century, Novartis and its predecessors discovered and developed
many innovative products, a large number of which have changed the way conditions are treated and in some cases taken the lead in now common drug classes such as tri-cyclic antidepressants and NSAIDs. When Novartis was formed in 1996, it had “big shoes” to fill in relation to the discovery and development of the class leading drugs of its predecessors. Since 1996, Novartis has decided to focus on healthcare and has sold off its non-core sectors including its agricultural, food and chemical businesses. Novartis invested heavily in research in biotechnology, anti-viral and anti-infective therapies (including the goal of eradicating malaria) and more recently eye-care. It has partnered and acquired some niche and innovative pharmaceutical companies over the last decade worldwide. For example, its investment in eye care includes the acquisition in 2010 of Alcon, the world leader in eye-care whose portfolio includes pharmaceutical, surgical and consumer eye care products. Also in 2010, Novartis got approval for Gilenya®, the world’s first oral drug for relapsing-remitting multiple sclerosis. In the last few weeks (July 2012) Novartis gained FDA approval for everolimus (Afinitor®) which is considered by researchers to be the first major advance in the treatment of hormone receptor positive breast cancer since aromatase inhibitors were released 15 years ago. Novartis is truly a global firm employing 125,000 people, over 13,000 of which are in Switzerland. Despite their size, they have not forgotten their Basel base and are the biggest private employer in the Basel area. It is estimated that 40,000 Swiss jobs depend either directly or indirectly on Novartis.
Lucentis® Production Area
STEIN FACILITY On the morning of the visit, we went to Novartis’s Stein site which is the largest pharmaceutical production site within Novartis, with over 1500 employees. Around 4.3 billion tablets, capsules, ampoules, vials, syringes and transdermal patches are manufactured and distributed globally from the Stein site per annum. Novartis considers Stein as their centre of excellence for sterile production and transdermal therapeutic systems worldwide and their launch site worldwide for sterile and solid dosage forms. 99% of pharmaceuticals produced at the Stein site are exported. The Stein site accounts for 40% of Novartis’s total revenue, mainly due to the highly specialised and high value products manufactured there.
While at the Stein facility, we visited Sterile Facility 303, the main production facility and centre of excellence for injectables in the Novartis range. We were taken on a tour of the production line of Lucentis® (Ranibizumab), which is licensed for the treatment of wet Age Related Macular Degeneration. Production of injectables requires the highest level of cleanliness and sterility. As we were shown around the facility we were gowned and suited in a specially allocated area, in addition we used alcohol rubs to ensure sterility. We had to re-gown continually as we passed through different levels of sterility. Production areas are stringently controlled as an aseptic processing environment. The clean rooms use laminar flow air which has been filtered through microbial retentive
High Efficiency Particulate Air (H.E.P.A.) filters. The room is maintained under positive pressure and has specifications for room air changes per hour. Facility 303 uses different levels of sterility and staff must pass through a number a different sterilisation zones before reaching the most sterile production area. During our tour, we were brought through only two sterilisation zones but were able to view production through glass windows. The production of Lucentis® starts with the active substance and the excipients being dissolved in water to a precise concentration for injection. This completed, a two step sterile filtration process is then undertaken, any component coming into contact with the product at this stage is made of stainless steel. The glass vials
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24 Clinical Focus
which will ultimately store the product are washed three times with water and dried each time with sterile filtered air. Washed vials are then sterilised with dry heat at 300°c. 16000 vials per hour are then filled in an isolator under aseptic conditions. This process is fully automated to minimise operator input thereby increasing productivity and reducing the error rate. After filling, each vial is flushed with gas such as nitric oxide to prevent oxygen being trapped prior to sealing with a stopper. The next part of the process is the only part not done by machine; the vials are visually inspected by specially trained staff for signs of cloudiness or debris. Despite all the specialist technology, Novartis still find that visual inspection by a human is the most accurate way of ensuring product integrity. This is a tedious task which involves staff sitting at a bench looking at vials in-front of a bright light to check for imperfections. Due of the tedious nature of this task and risk of fatigue, staff shifts are short. Finally, in the packaging area, a
Lucentis® vials being labelled
product specific label containing information such as drug details and ingredients, batch numbers and expiry dates is attached to each vial. The labelling machine is a highly sophisticated device which labels at a rate of 95 vials per minute.
Packaging area for Lucentis®
There is some human input in this process as workers place “patient kits” into the boxes which contain the injection as the boxes pass
Visual inspection of Lucentis®
the semi-automatic packaging line. Each member of staff is responsible for placing one part of the patient kit into each box as it goes by them on the assembly line, for example, a BD Plastipak® syringe and needle. Some parts of the assembly line use robots, so whilst staff place the syringe and needles into the box manually, a robot places the vial and Patient Information Leaflet into the same box. The
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boxes are then sealed and sent to Stein’s logistic centre for delivery to customers. The site has over 10 inspections a year from governing bodies such as America’s Food and Drug Administration (FDA). Next month's second part features an exclusive look at Lucentis within Ireland, the logitics within Stein, further investment and research.
Lucentis® 10mg/ml solution for injection. ABBREVIATED PRESCRIBING INFORMATION. Please refer to the Summary of Product Characteristics (SmPC) before prescribing. Presentation: A glass single-use vial containing 0.23ml solution containing 2.3mg of ranibizumab (10mg/ml). Indications: The treatment of neovascular (wet) age-related macular degeneration (AMD). The treatment of visual impairment due to diabetic macular oedema (DME). The treatment of visual impairment due to macular oedema secondary to retinal vein occlusion (branch RVO or central RVO). Administration and Dosage: Single-use vial for intravitreal use only. Lucentis must be administered by a qualified ophthalmologist experienced in intravitreal injections under aseptic conditions. Patients should be monitored monthly for visual acuity. Treatment is given monthly and continued until maximum visual acuity is achieved i.e. the patient’s visual acuity is stable for three consecutive monthly assessments performed while on Lucentis treatment. If there is no improvement in visual acuity over the course of the first three injections, continued treatment is not recommended. Treatment is resumed when monitoring indicates loss of visual acuity due to wet AMD, DME or to macular oedema secondary to RVO. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments. The interval between two doses should not be shorter than 1 month. Lucentis and laser photocoagulation in DME or in BRVO. Lucentis has been used concomitantly with laser photocoagulation in clinical studies. When given on the same day, Lucentis should be administered at least 30 minutes after laser photocoagulation. Lucentis can be administered in patients who have received previous laser photocoagulation. Before treatment, evaluate the patients medical history for hypersensitivity. The patient should also be instructed to self-administer antimicrobial drops, four times daily for 3 days before and following each injection. Paediatric population: Not recommended for use in children and adolescents due to a lack of data. Elderly: No dose adjustment is required. Consult SmPC for full administration details before using Lucentis. There is limited experience in patients older than 75 years with DME. Contraindications: Hypersensitivity to the active substance or excipients. Patients with active or suspected ocular or periocular infections. Patients with active severe intraocular inflammation. Warnings and Precautions: Lucentis is for intravitreal injection only. Intravitreous injections have been associated with endophthalmitus, intraocular inflammation, rhegmatogenous retinal detachment, retinal tear and iatrogenic traumatic cataract. Monitor during week following injection for infections. Patients should be instructed to report symptoms suggestive of any of the above without delay. Transient increases in intraocular pressure (IOP) have been seen within 1 hour of injection. Sustained IOP increases have also been identified. Both intraocular pressure and perfusion of the optic nerve head should be monitored and managed appropriately. Concurrent use in both eyes has not been studied. Bilateral treatment at the same time could lead to an increased systemic exposure. There is a potential for immunogenicity and patients should report an increase in severity of intraocular inflammation. Since there is a potential for an increased systemic exposure in subjects with DME, an increased risk for developing hypersensitivity in this patient population cannot be excluded. Lucentis should not be administered concurrently with other anti-VEGF agents (systemic or ocular). Withhold dose and do not resume treatment earlier than the next scheduled treatment in the event of the following: a decrease in BCVA of ≥30 letters compared with the last assessment of visual acuity; an intraocular pressure of ≥30 mmHg; a retinal break; a subretinal haemorrhage involving the centre of the fovea, or if the size of the haemorrhage is ≥50% of the total lesion area; performed or planned intraocular surgery within the previous or next 28 days. Discontinue treatment in cases of rhegmatogenous retinal detachment or stage 3 or 4 macular holes. There is only limited experience in the treatment of subjects with DME due to type 1 diabetes. Lucentis has not been studied in patients who have previously received intravitreal injections, in patients with active systemic infections, proliferative diabetic retinopathy or in patients with concurrent eye conditions such as retinal detachment or macular hole. There is also no experience of treatment with Lucentis in diabetic patients with an HbA1c over 12% and uncontrolled hypertension. There are limited data on safety in the treatment of DME and macular oedema due to RVO patients with prior history of stroke or transient ischaemic attacks. Since there is a potential risk of arterial thromboembolic events following intravitreal use of VEGF inhibitors caution should be exercised when treating such patients. There is limited experience with treatment of patients with prior episodes of RVO and of patients with ischaemic branch RVO (BRVO) and central RVO (CRVO). In patients with RVO presenting with clinical signs of irreversible ischaemic visual function loss, treatment is not recommended. Ranibizumab should not be used during pregnancy unless the expected benefit outweighs the potential risk to the foetus. Women of child-bearing potential should use effective contraception during treatment. For women who wish to become pregnant and have been treated with ranibizumab, it is recommended to wait at least 3 months after the last dose of ranibizumab before conceiving a child. Breast-feeding is not recommended during treatment. The treatment procedure may induce temporary visual disturbances and patients who experience these signs must not drive or use machines until these disturbances subside. Interactions: No formal interaction studies have been performed. Adjunctive use of verteporfin photodynamic therapy (PDT) and Lucentis in an open study showed a low incidence of intraocular inflammation following initial combination treatment. Adverse Reactions: Serious adverse events related to the injection procedure included endophthalmitis, rhegmatogenous retinal detachment, retinal tear and iatrogenic traumatic cataract. Other serious ocular events included intraocular inflammation and increased intraocular pressure. Very Common: Intraocular pressure increased, headache, vitritis, vitreous detachment, retinal haemorrhage, visual disturbance, eye pain, vitreous floaters, conjunctival haemorrhage, eye irritation, foreign body sensation in eyes, lacrimation increased, blepharitis, dry eye, ocular hyperaemia, eye pruritus, arthralgia, nasopharyngitis. Common: Anaemia, retinal degeneration, retinal disorder, retinal detachment, retinal tear, detachment of the retinal pigment epithelium, retinal pigment epithelium tear, visual acuity reduced, vitreous haemorrhage, vitreous disorder, uveitis, iritis, iridocyclitis, cataract, cataract subcapsular, posterior capsule opacification, punctate keratitis, corneal abrasion, anterior chamber flare, vision blurred, injection site haemorrhage, eye haemorrhage, conjunctivitis, conjunctivitis allergic, eye discharge, photopsia, photophobia, ocular discomfort, eyelid oedema, eyelid pain, conjunctival hyperaemia, cough, nausea, allergic reactions (rash, urticaria, pruritus, erythema), hypersensitivity, anxiety, urinary tract infection (observed only in DME population). Uncommon: Blindness, endophthalmitis, hypopyon, hyphaema, keratopathy, iris adhesion, corneal deposits, corneal oedema, corneal striae, injection site pain, injection site irritation, abnormal sensation in eye, eyelid irritation. Please refer to SmPC for full listing of all undesirable effects. Pack Size: Lucentis is supplied in packs containing 1 vial. Legal Category: POM. Marketing Authorisation Number: EU/1/06/374/001. Marketing Authorisation Holder: Novartis Europharm Limited, Wimblehurst Road, Horsham, West Sussex, RH12 5AB, United Kingdom. Full prescribing information, including SmPC, is available upon request from Novartis Ireland Limited, Beech House, Beech Hill Office Campus, Clonskeagh, Dublin 4. Telephone: (01) 260 1255. Date of API Revision: September 2011. * Licensed for visual impairment due to macular edema secondary to retinal vein occlusion (RVO) ** Licensed for visual impairment due to diabetic macular edema (DME). References. 1. Lucentis Summary of Product Characteristics, September 2011. 2. Brown DM, et al., Sustained Benefits from Ranibizumab for Macular Edema Following Branch Retinal Vein Occlusion: 12-Month Outcomes of a Phase III Study. Ophthalmology 2011. Aug 118 (8) 1594-1602. Date of Preparation: January 2012. NO0112023
18 LETTER GAINS with LUCENTIS, the first anti-VEGF licensed to significantly improve vision in patients with Retinal Vein Occlusion (RVO)1,2*
BRING LIFE BACK INTO FOCUS
Now licensed in RVO*
Solutions to shortage problem identified - greater prescriber awareness of shortage difficulties and willingness to discuss the matter with hospital pharmacist colleagues; - vigilance by hospital pharmacists and pro-active information-sharing with health professional colleagues about the problem; - use of quotas by wholesalers to ensure fair distribution when demand exceeds supply; -adequate notice and alerts by manufacturers, and the maintenance of buffer stocks; and, Hospital pharmacists are growing increasingly concerned as to the shortage of certain key medicines and the risk posed to patients’ health. A
General Assembly of 31 member countries have prioritised the issue for discussion and resolved that the solutions to the shortage problem include:
- rigorous action by regulatory agencies including monitoring of shortages and best practice sharing. In a recent question session in
the Dail, Deputy Róisín Shortall commented that 'Shortages of essential medicines are a source of concern not only in Ireland but also throughout Europe and the rest of the world.' The HSE spends approximately 16% of the health budget on drugs, which amounts to almost €2 billion. The Minister added: "By any standard, that is a very high proportion and it is not sustainable into the future. That is why there is an onus on all of us to ensure we get better value for money in terms of drug costs. We all want to see new and effective drugs coming onto the market as quickly as possible. The HSE estimates that if we were to approve new drugs that are clinically effective, the cost of providing them could be up to €30 million."
First medicine approved under PUMA process A licensed buccal midazolam is now available for the emergency treatment of prolonged acute seizures in children and is the first medicine to be approved under the new Paediatric Use Marketing Authorisation (PUMA) procedure by the European Commission.
acute convulsive seizures in children aged from >3 months to <18 years. The aim of this PUMA process is to encourage the research and development of medicines for use in children and was introduced in an attempt to reduce the widespread off-label use of drugs in this age group.
administered into the buccal cavity ( i.e. the space between the gum and the cheek) for rapid buccal absorption. Buccolam is available in four colour coded, age-specific prefilled syringes, containing either 2.5 mg, 5 mg, 7.5 mg or 10 mg of midazolam hydrochloride.
Buccolam® (midazolam oromucosal solution is approved for the treatment of prolonged
Buccolam the active substance midazolam. It is available as an ‘oromucosal solution’ to be
It is recommended that Buccolam be prescribed by brand name to reduce the risk
of confusion with other buccal midazolam products and of dosing errors (guidance issued by the All Wales Medicines Strategy Group (AWMSG). Buccal midazolam is now recommended by NICE as firstline treatment of in children and young people with prolonged or repeated seizures.
New viruses revealed New ways that viruses manipulate the human immune response have been revealed in a research paper just published by TCD scientists. Dr Orla Mulhern and Professor Andrew Bowie, School of Biochemistry and Immunology based in the Trinity Biomedical Sciences Institute were part of the multi-disciplinary, multi-centre study comprising immunologists, virologists, biochemists and bioinformaticians from across Europe. This research is the most comprehensive study to date analysing strategies used by over 30 viruses to target defence networks in human cells, and provides many new insights into how viruses seek to avoid and weaken the immune response.
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HELP PROTECT THE FRAGILE ELDERLY
• Costs 40% less than • •
N 60 T EW nearest competitor1* ABLE P ACK T No.1 in Ireland* Available in 100 tablet and 60 tablet packs
Their strength is our forte CALCICHEW-D3 FORTE CHEWABLE TABLETS PRESCRIBING INFORMATION. (Please refer to full Summary of Product Characteristics when prescribing). Presentation: Chewable tablet containing 1250mg calcium carbonate (equivalent to 500mg of elemental calcium) plus 400IU colecalciferol (equivalent to 10 micrograms vitamin D3). Uses: Prevention and treatment of vitamin D/calcium deficiency. Supplementation of vitamin D and calcium as an adjunct to specific therapy for osteoporosis, in pregnancy, in established vitamin D dependent osteomalacia and in other situations requiring therapeutic supplementation of malnutrition. Dosage and administration: Oral (suck or chew). Adults and elderly: Two tablets daily. Children: Not intended for use in children. Hepatic impairment: No dose adjustment required. Renal impairment: Should not be used in patients with severe renal impairment. Contraindications: Diseases and/or conditions resulting in hypercalcaemia and/or hypercalciuria, severe renal impairment, renal stones, hypervitaminosis D, hypersensitivity to ingredient(s) Precautions: Monitor serum calcium and creatinine levels, particularly in patients on cardiac glycosides or diuretics and in patients with high tendency to calculus formation. Use with caution in patients with impaired renal function. Take into account risk of soft tissue calcification. Avoid in patients with phenylketonuria or sugar intolerance.
Prescribe with caution in patients with sarcoidosis. Use with caution in immobilised patients. Additional doses of calcium or vitamin D should only be taken under close medical supervision. Interactions: Tetracyclines (take 2 hours before, or 4 to 6 hours after Calcichew-D3 Forte), bisphosphonates or sodium fluoride (take 3 hours before Calcichew-D3 Forte), Quinolone antibiotics (take two hours before or after), levothyroxine (take four hours before or after), thiazide diuretics, corticosteroids, cardiac glycosides, ion exchange resins (cholestyramine), laxatives (paraffin oil). Calcichew-D3 Forte should not be taken within 2 hours of eating foods high in oxalic acid (e.g. spinach and rhubarb) or phytic acid (e.g. whole cereals). Side effects: Hypercalcaemia, hypercalciuria, constipation, dyspepsia, flatulence, nausea, abdominal pain, diarrhoea, pruritus, rash, urticaria. Very rarely (usually only seen on overdose) milk-alkali syndrome. Use in pregnancy and lactation: Can be used in case of calcium and vitamin D deficiency. Daily intake in pregnancy should not exceed 1500mg calcium and 600IU colecalciferol (15 micrograms vitamin D3). Avoid overdose as permanent hypercalcaemia affects developing foetus. Calcium and vitamin D3 pass into breast milk so consider this when giving additional vitamin D to the child. Pharmaceutical precautions: Do not store above 30°C. Keep container tightly closed to protect from moisture. Legal category: Pharmacy
product. Product Authorisation No: 535/1/3. Product Authorisation holder: Shire Pharmaceuticals Ltd., Hampshire International Business Park, Chineham, Basingstoke, Hampshire RG24 8EP UK. Distributed in Republic of Ireland by: Cahill May Roberts, P.O. Box 1090, Chapelizod, Dublin 20, Republic of Ireland. Further information is available on request. Date of revision: May 2011. CALCICHEW is a registered trademark of Shire Pharmaceuticals Ltd in the Republic of Ireland.
Adverse events should be reported to the Pharmacovigilance Unit at the Irish Medicines Board (IMB) (email@example.com). Information about adverse event reporting can be found on the IMB website (www.imb.ie). Adverse events may also be reported to Shire Pharmaceuticals Ltd on +44 1256 894000. Reference: 1. MIMS May 2012. Date of preparation: June 2012. Item Code: IRE/BU/CDF/12/0007. *According to IMS unit sales data April 2012.
FINALIST Bestt use Technology of Tech hnology
Pharmasource – Your Sourcing Solution for all exempt medicinal products, manufactured specials and bespoke procurement requirements. Pharmasource has expertise in logistics, national and international regulatory affairs and quality control. A premium all in one service from orders to delivery is provided: Highly experienced professionals are ready to take your callpharmacist and pharmacy technicians on site High service level – in many cases product available for next scheduled delivery Multi ordering system – by fax, email, online and enquiries by phone Unique online ordering system – no need for manual order completion or faxing No minimum order charge Unparalleled competitive pricing, leveraging a global network of suppliers Traceability and counterfeit monitoring and observing of adverse effects Certificate of Analysis TSE Compliance – supplier verification Compliance with IMB regulations and HSE reimbursement scheme Order tracking providing further reliability Cold chain service Most orders despatched with your next scheduled delivery* Free phone number: 1800 440 440 Free fax number: 1800 441 441 Email: firstname.lastname@example.org Website: www.unipharlink.ie * in some cases unusual/hard to source items may take longer, please call 1800 440 440 for more information
Uniphar Group, 4045 Kingswood Road, Citywest Business Park, Dublin 24
Hospital Service Focus from Uniphar Group – Allphar Hospital Services, Pharmasource and Sundry Business
Mena Sheridan, Tony Toomey and Noilin O'Hara - the Allphar, Pharmasource and Sundry Team
Hospital pharmacy is an ever changing landscape and both pharmacists and technicians rely on pharmaceutical companies and wholesalers delivering efficient services to enhance the care offered to patients. Hospital pharmacists and technicians can rest easy knowing this service is being provided by the Uniphar Group from an excellent facility with dedicated staff and expertise within the hospital sector.
The Uniphar Group is headquartered in Dublin and consists of different operating divisions with 400 employees. Their business focuses on healthcare and the hospital and pharmacy sectors. Each of the different divisions concentrates on a specific business – from Allphar’s Pre-Wholesaling services for major international corporations, Allphar’s Hospital Services Division and Pharmacy distribution by Uniphar Wholesale.
With the main distribution centre based in Citywest, the team operates from a €65 million state-of-the art facility. The Group has three regional depots in Limerick, Cork and Sligo highlighting its commitment to servicing all hospital and retail pharmacies in these areas. The Company’s Board of Directors is comprised of pharmacists with direct experience of the market and Uniphar upholds the Co-Operative ethos for all community and hospital pharmacists.
Below Hospital Pharmacy News exclusively meets and chats with the team leaders for Allphar Hospital Services, Pharmasource and Uniphar Sundry business. FOSTERING EXCELLENT RELATIONSHIPS Mena Sheridan is a familiar face within the Allphar family, having been with the company since 1973, and has witnessed the company's growth in facing and overcoming obstacles and embracing new challenges. As
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manager of the Allphar Hospital Services division, she is ably assisted by Aoife Conroy and the rest of the team. Mena recalls the old Stillorgan and Belgard Road warehouses and reflecting on this notes how efficient the new warehouse in Citywest is. Mena and the team pride themselves on the service level they give to hospitals – no issue is too small for them – 100% focus is given to the needs of hospital pharmacists and technicians. Allphar is a major supplier to the hospital sector with a number of key pharma principals including Actavis, Boehringer Ingelheim, Chiesi, Fannin, Gerard Labs. Lundbeck, Novo Nordisk and Roche. Allphar also distributes for principals whose focus is on the surgical aspect of the hospital requirements. These principals include Promedicare,TPW surgical, John Bannon Ltd, Alcon, Covidien Ireland Commercial Ltd., and Slainte Solutions. Mena tells HPN: "Our hospital service chain runs smootly as we are able to deliver from Allphar directly to hospitals. We have full batch traceability to hospital level with excellent SOP in place to ensure compliance with GDP guidelines with a strong emphasis on continuous training. We can deliver overnight to anywhere in the country and pride ourselves on an excellent long-standing reputation." The Group is ISO accredited. Allphar Services as part of the Uniphar Group support and sponsor local pharmacist attendance at EAHP and are a major sponsor at the annual HPAI Conference, IACPT Conference and the NAHPT Conferences throughout the year. "At these conferences we meet and talk to as many hospital
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pharmacists and hospital technicians as possible so we can learn about their needs to give the best level of service possible," says Mena. "We are excited about our future growth and look forward to fostering lasting relationships with the hospital sector.” Allphar operate an emergency telephone number 01- 2916136, 24 hours/356 days a year. A recent development is the new track and trace ePOD system out of all our depots – all deliveries can now be electronically tracked from the time the order is placed until it is receipted by hospital staff. PROVIDING SPECIALIST SOURCING Pharmasource is a relatively new venture for Uniphar, established in 2011 and proving to be a tremendous success story. Headed by Noilin O'Hora, the Pharmasource manager, Pharmasource is a specialist sourcing service for all exempt medicinal products, manufactured specials and bespoke procurement requirements which is built on an award nominated Web platform allowing customers to order unlicensed medicines and unusual products in an efficient manner. Noilin comments: "The launch and development of Pharmasource has been the most successful launch I have ever been involved in and we continue to grow in strength on a daily basis." Pharmasource operates a multi-ordering system – email, fax, online and by telephone and has invested in a dedicated team of experienced pharmaceutical technicians to deliver the best service possible. Of the 6 qualified technicians, five have worked in hospital pharmacies and this experience and know-how helps to provide
support and knowledge. "Our ethos is to provide hospitals with the best service we can – we actively engage with our customers and take pride in knowing who are customers are and fulfilling their requirements," she adds. The online portal for Pharmasource was a finalist in the ‘best use of technology’ at the National Procurement Awards in 2011. "This online portal was only launched at the beginning of 2011 so we are delighted to have been viewed so positively by the judges. We aim to make everything as easy as possible for hospital pharmacists and technicians - our online documentation is very easy to use and there is no minimum order quantity." With a view to future progression Noilin adds: "We aim to broaden our customer base and continue to work with manufacturers whilst responding efficiently to the needs of our customers." Pharmasource contact details: Free telephone number: 1800 440 440, free fax: 1800 441 441. Email: email@example.com DEVELOPING THE SUNDRIES BUSINESS IN HOSPITALS Still relatively new within the company, Tony Toomey has made his stamp on the sundry business within Uniphar. Brought into the company for a specific task, Tony quickly became involved in other aspects of Uniphar, namely the sundry business within hospital accounts and as such he is in contact with hospitals all over the country. His aim is to ensure the best service and back up is given to hospitals as Uniphar offer a same day delivery service and that they carry all lines
currently available to the market. "My principle aim is to offer a complete service to our customers and the interdepartmental working within Uniphar is key to our success." Tony is very proud of the Citywest facility and as he comes from a sales and marketing background and finds the process of how the product is ordered right through to delivery very interesting. He is keen to invite hospital pharmacists and technicians to see the amazing facility. This open invitation is for any professionals, regardless of party size and at any time of the week. To arrange a visit or a chat, Tony can be contacted on: 087 243 7481. "Indeed our excellent office facilities are available for meetings – we are just off the N7 with excellent conference facilities, restaurant facilities and secure parking," he adds.
The Uniphar Group operates a onestop facility for all hospital pharmacists and technicians, the different departments within the Group continue to work with each other, and with manufacturers and key organisations to ensure their customers, and in turn the patient, benefit from excellent service and focus.
Irish Pharmacy Awards 2012 - The Guests Over 450 of the pharmacy industry's great and good turned up to The Burlington Hotel in Dublin for the inaugural Irish Pharmacy Awards on May 19th of this year. The night was hailed as the biggest success of the pharmacy calendar for 2012 with guests in their droves excited about booking their place at the 2013 extravanganza so watch this space for further details! 1) Gillian Marmion, Alan Hartnett, Brian Morgan, Jodie Morgan, Cahill May Roberts
2) Tadgh Scanlon, Tierneyâ€™s Pharmacy, Liz Matthews, Uniphar
3) Sean Dowling Roche Products Ireland Ltd and Muireann Ni Shuilleabhain South Infirmary, Victoria University Hospital
4) O'hAlmhain and Brighid Ui Almhain
5) Bryan Murphy, Sarah Corry, Jane Clements, Paul Moran, Teva Pharmaceuticals
HPN â€˘ Issue 5
32 Off Label
Cutting - A False Economy?
As we all know, the Government is under intense pressure to reduce public spending, none more so than in the area of health. Even prior to the publication of the Four Year Plan, the Government took steps in 2009 to unilaterally reduce payments to service providers, via mechanisms like the Financial Emergency Measures in the Public Interest Act 2009. Regulations adopted on foot of the 2009 Act operated to reduce payments to third parties providing services to the public health system. This included SI 246/20091 which effected controversial reductions in payments to community pharmacists, resulting in wellpublicised litigation with that service sector. This article examines the legality of one lesser-known aspect of current health cost-cutting strategy: the use of off-label medicines. This is an area of potentially high risk for the doctors who prescribe these medicines and for the hospitals, pharmacists and distributers who supply them and may therefore be ripe for future litigation. SOME BACKGROUND Like much of Ireland’s modern regulation, controls on the supply of medicines derive centrally from European Directives. The earliest Directives were enacted in and from 1965, in response to the thalidomide tragedy, and dealt diversely with matters such as medicines licensing, manufacturing, wholesale distribution, labelling, advertising and the monitoring of and reporting upon adverse drug reactions. The rules were consolidated and updated in 2001 by a Directive commonly referred to as the Human Medicines Directive2 (the HMD). The HMD is currently transposed into Irish law by a bundle of Regulations made in 2007, including - of most interest for the purposes of this article - the
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Medicinal Products (Control of Placing on the Market) Regulations 2007 – 20103 (the MPCPM Regulations). One of the main rules contained in the HMD (and so in the MPCPM Regulations) is that medicines (or “medicinal products”, as they are so-
called by the Directive) cannot be placed on the market in any member state without first being the subject of a licence (a “marketing authorisation”) issued by a relevant regulatory authority. This is a core principle of European medicines control. Attendant in this licensing system is
the need for the would-be marketing authorisation holder to demonstrate definitively to the regulatory authority, using the results of tests and clinical trials, that the medicine will be safe and effective for the patient in respect of the areas of treatment for which the authorisation is sought. The
licensing system is therefore predicated on close scrutiny by the regulatory authority concerned. Depending on whether the medicine is capable of being authorised nationally or centrally (in the latter case for all 27 member states together), the relevant regulatory authority for medicines to be marketed in Ireland is either the Irish Medicines Board or the European Medicines Agency. There are a number of limited exceptions permitted by the Directive to this fundamental rule of “licensing before marketing” One such exception recognises the right and freedom of the treating doctor/dentist to prescribe in the best interests of their individual patients, and so relaxes the strict controls which are otherwise placed on all elements of the medicines supply chain. Specifically, Article 5.1 of the Directive permits member states, in order “to fulfil special needs”, to exempt medicines which are supplied “in response to a bona fide unsolicited order, formulated in accordance with the specifications of an authorised healthcare professional and for use by an individual patient under his direct personal responsibility”. This exemption is taken up in the MPCPM Regulations4 and is commonly the exemption relied upon in member states to permit what is referred to as “named patient” supplies. Such supplies can also be categorised as “unlicensed” or “off label”. Without doubt, however, the focus of the exemption is very much upon treatments which are determined for individual patients, on a case-by-case basis. The supply chain for the medicine (be it the prescriber, pharmacist, hospital, distributor, laboratory or manufacturer) is dependent on the conditions of the exemption being correctly applied.
UNLICENSED AND NAMED PATIENT SUPPLY Medicines are licensed for specific treatments or indications. For example, paracetamol is generally authorised as an analgesic, i.e. for pain treatment. If an authorised medicine is prescribed for a treatment other than one specified in its marketing authorisation, and is supplied on that basis, such use and supply is generally referred to as “off label” or “unlicensed”. Unlicensed supply and use can also occur where an authorised medicine is reformulated (e.g. where a medicine which is authorised in tablet form is reformulated to unauthorised injectable form) or where a medicine is not the subject of a licence in Ireland at all and is formulated or procured and then administered to the patient. All such cases of supply and use are all potentially legal, as long as they meet the conditions laid down in Article 5.1 of the HMD. It is probably fair to say that named patient supply is common, for many reasons. For example, some medicines will be known in the healthcare community as providing an effective treatment for certain illnesses, but such indications may not yet be licensed in Europe; or the cost of obtaining licences for those indications may be prohibitively expensive for the pharmaceutical company involved. In such cases, prescribers will assess the information which is known to them (including, for example, from reported experiences with the medicine in the United States) and make prescribing decisions based on this. A more interesting and potentially problematic issue arises where the prescribing decision is based, not on availability of treatment, but on cost, i.e. there is a licensed treatment available to the prescriber, but
it is more expensive than the unlicensed treatment. Of course it is legitimate and proper for the prescriber to take into account the patient’s ability to pay for treatment. The issue becomes more difficult, however, where the cost of the licensed treatment can be reimbursed to the patient (e.g. through a State drugs scheme or under private health insurance), and where the ultimate payers (e.g. health authorities or hospitals, if the medicine is a hospital-only medicine) adopt purchasing policies which favour the unlicensed treatment over the licensed one. This can have the effect of removing the treatment decision from the prescriber, thus running the risk that the exemption conditions of Article 5.1 are not met. THE RISK In the case of the use of medicines which are prescribed for their licensed indications, the risk of an adverse reaction by the patient is generally shared between the prescribing doctor/ dentist and the pharmaceutical company. If the medicine has been prescribed and administered in accordance with its authorisation, and the medical team has done everything correctly, then the greater part of the risk inevitably falls upon the pharmaceutical company. However, in the case of named patient supply, a greater share of the risk undoubtedly falls upon the prescriber. The principle risk being that the prescriber would be found negligent in prescribing off label. The act of prescribing an off label medicine itself would not constitute a breach of the standard of care, however in order to avoid liability a prescriber would have to prove that a prescriber of equal status would have taken the same action if acting with reasonable care. Named patient supply also raises liability issues surrounding
patient consent discussed below. Case law suggests that the pharmaceutical company may not entirely escape the burden, especially in cases where the use of the unlicensed medicine and the attendant risk is reasonably foreseeable. The company will have a duty to warn of all risks (whether the use is licensed or unlicensed) of which they know or should know and may be liable if they fail to do so5. Of course, the prescriber’s risk (or that of the person who formulated the medicine at their direction) may not necessarily act as a dissuader to named patient use/supply, especially if they are covered by insurance or an enterprise liability scheme such as (in Ireland) the Clinical lndemnity Scheme. Again, however, such cover may be predicated upon the strict conditions of the Article 5.1 exemption being met. Fundamentally, this includes that the prescription and consequent supply of the medicine is on the basis of fulfilling special needs, for the individual patient, assessed by the prescriber on a case-by-case basis, and is not on the basis of blanket policies or purchasing decisions which have been taken by the hospital or clinic out of which the prescriber practices. THE EXPERIENCE ABROAD Other EU member states, including the UK, Italy, Demark, Belgium and The Netherlands, have adopted the named patient exemption. In addition, they are under similar pressures to reduce their health expenditure. Of interest, however, in relation to many of these countries is that the relevant national authorities (usually the medicines regulator) have specified in guidelines that the named patient exemption should not be availed of where a licensed alternative is available
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34 Off Label
to treat the particular illness. In those circumstances, it is not justifiable for the prescriber to make a decision to treat a patient with a “named patient” alternative where that decision is based on cost.
treatment, called Lucentis, involves injections into the eye over a course of months. There is a less expensive unlicensed alternative, called Avastin, which is a drug licensed to treat breast and colon cancer. Use of Avastin to treat the eye condition involves reformulating it into an injection. The UK equivalent of the Irish Medicines Board , the Medicines and Healthcare products Regulatory Agency , has warned against the off-label use of Avastin6 to treat wet AMD, noting that it has been associated with reports of severe eye inflammation, and advises doctors that before prescribing a medicine off-label, they should be satisfied that such use would better serve the patient’s needs than an appropriately licensed alternative. In Italy, in May 2007, the AFIA (the relevant regulatory agency) approved reimbursement of Avastin where it was used to treat wet AMD. However, Avastin was subsequently removed from the reimbursement list in relation to wet AMD in March 2009 when Lucentis was licensed in Italy and given reimbursement status.
For example, in the UK and Italy, their regulators have recently looked at an example involving licensed and unlicensed alternatives for the treatment of an eye condition called “wet aged macular degeneration” (or wet AMD), which can lead to blindness. The licensed
These approaches are arguably consistent with a necessarily strict interpretation of the exemptions available under the HMD. To allow otherwise would be to weaken the licensing regime governed by the HMD whereby medicines must be tested for specific indications of
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treatment, which must then be corroborated by clinical trials, and should only be marketed and supplied to patients where they are licensed for those relevant indications. Some recent legal commentators have argued that reliance on the exception should be stricter still, and that prescribers must follow four rules of thumb in making decision to prescribe off-label: (1) that off-label use can only be justified in exceptional circumstances, which circumstances do not arise where there is a licensed alternative available to treat the patient; (2) that off-label prescription should have a strong scientific basis; (3) that prescribers maintain full and accurate records of off-label use to ensure proper follow-up and ongoing assessment of the extent and efficacy of such treatments; and (4) that patients are fully informed. PATIENT CONSENT The use of unlicensed or off-label medicines also raises interesting issues in relation to patient consent. Legal commentators argue that prescribers should inform their patients explicitly about the nature of the proposed off-label treatment, their reasons for proposing the treatment, the potential sideeffects (if known) and of the risks, benefits and available alternatives. Failure to obtain a patient’s consent to could give rise to an action against the prescriber for trespass to the person or claim in negligence. In Ireland, obtaining a patient’s informed consent to treatment is highlighted in the Medical Council’s ethical conduct guidelines, and is underscored in the patient’s Constitutional right to bodily integrity and in the human rights available to them as citizens of the EU.
CONCLUSION Although the use of off label medicines may have clinical advantages for the treatment of certain illnesses and conditions affecting individual patients, the use of off label medicines on budgetary grounds raises a number of legal and ethical risks, particularly if the practice is promoted by the Health Service Executive. There is a strong argument that hospitals and doctors using treatment outside their original licence in order to achieve costs savings (rather than on the basis of the best treatment which is available for the patient and which has been assessed based on the individual patient’s needs) do not in fact have such prescribing behaviour covered by the named patient exemption laid down in Article 5.1. and therefore are in direct violation of Ireland’s obligations under the HMD. Further, their suppliers also risk exposure on this basis. Indeed, Tomas Lonngren, Director of the European Medical Agency, the body with ultimate responsibility for pan-European medicine supply and to which the Irish Medicines Board is directly affiliated, recently expressed concerns in relation to the use of off license medicines for cost saving reasons by the UK. Mr. Lonngren specifically stated that the encouragement of such use by Member States could constitute a breach of EU legislation. The use of off label medicines also raises risks in negligence and trespass to the person, in particular in cases of adverse reaction, and arguably places a higher duty on prescribers to disclose information to patients. These issues could have significant consequences for prescribers, their institutions, the Irish Medicines Board, the Clinical Indemnity Scheme and – ultimately – the Minister for Health.
think smart medicine
Having faith in the anchor that is Tim Delaney - Hospital Pharmacist of the Year Sponsored by Roche Products (Ireland) The lynchpin of all issues pertinent to pharmacy. That is how Tim Delaney has been described by his peers. The executor of awareness and education in patient safety is another. However on a night of celebration and recognition held in the Burlington Hotel in May of this year, the title simply bestowed upon him was that of 'Hospital Pharmacist of the Year' at the prestigious Irish Pharmacy Awards 2012. Tim has been working within the hospital pharmacy sector in Ireland for over twenty years and in positions ranging from working within the dispensary to liaising with the profession on behalf of matters related to patient medication safety. Tim is currently employed as the Medication Safety Programme Lead for the Health Services Executive in Ireland. This is a programme established within the Quality & Patient Safety Directorate. Tim says, "In light of the findings and recommendations in the Report of the Commission on Patient Safety and Quality Assurance, the HSE established the Medication Safety Programme in 2010 and set a number of priority goals. TASKED WITH ACHIEVING GOALS "By achieving these goals, we will make practical improvements to the way we manage medicines, and these improvements will result in better treatment for patients and the avoidance of harm." The priorities for 2011-2012 are: • Standardise the Medication Prescription & Administration Record in acute hospitals to facilitate efficient care and minimise medication errors
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caused by documentation processes. • Implement medication reconciliation at transitions of care between hospitals, longstay facilities and the community to reduce errors at hand-over of care. • Develop a national Medication Safety Standard for Acute Hospitals and a Self-Assessment Tool. • Establish an audit to assure compliance with safe practice guidance on oral methotrexate for non-cancer treatment (arthritis and psoriasis) in the community. • Assist the National Cancer Control Programme in designing a system of safe management of Oral Anticancer Medicines for cancer patients. • Develop a practice research programme in collaboration with the universities to ensure that there is a robust collection of evidence to support changes to the way medications are managed. • Work towards introduction of technology to underpin safe, efficient work practices in medication management (electronic prescribing with decision support, automated dispensing systems, barcode technology in drug administration, seamless electronic communication of data throughout the patient journey). The Medication Safety Programme is charged with making practical improvements to the way medicines are managed, to deliver better, more efficient care for patients and avoid harm. As Programme Lead, Tim is responsible for a number of initiatives including the standardisation
of Medication Prescriptions & Administration Records to minimise medication errors caused by documentation processes as well as addressing the introduction of technology to underpin safe, efficient work practices in medication management. These technologies include electronic prescribing with decision support, automated dispensing systems, bar-code technology in drug administration and the seamless electronic communication of data throughout the patient journey. Prior to taking up this job Tim was Head of Pharmacy and Director of Process Improvement at Tallaght Hospital, Dublin and from there he was seconded to the HSE. As well as his pharmacy qualifications, Tim earned a Masters degree in
Organisational Behaviour from the IMI/Trinity College Dublin. He is a Six Sigma Green belt, which is a process improvement qualification. However he is ever humble about his award, and the high regards he is obviously held in by his colleagues within the profession. He says, "I am delighted to receive this Award and I see it as an affirmation of my work in medication safety, which is gratifying. I have been fortunate in my hospital pharmacy career to have worked with many excellent colleagues, both pharmacists and technicians whose enthusiasm, intelligence and hard work made so many developments possible. "However I would like to dedicate this award to the first pharmacis I recruited when I became a Chief Pharmacist.
He was a member of the Management Team in Tallaght Hospital, with responsibility for Pharmacy, Process Improve, Medical Physics and Clinical Engineering and Catering. Whilst in Tallaght Hospital, Tim established Ireland's first Medication Safety Programme in the acute healthcare setting, providing a national blueprint for the reporting of medication safety incidents for the purpose of organisational learning and systems improvements.
Denise Ward Molloy worked with me for twelve years in the Adelaide and Tallaght Hospital. She played a key role in the forging of one team from three as we moved from our three small city centre hospitals to one large one. Her untimely death, just one week before this ceremony, leaving her husband David and two boys bereft, reminds us of how precious and unpredictable life is. I dedicate this award to her." A WEALTH OF KNOWLEDGE AND EXPERTISE Tim has extensive experience in pharmacy and healthcare management having held positions as the Head of Pharmacy in Adelaide Hospital (1989-1994), Chief executive Officer, Adelaide Hospital (19941998) and Chief Pharmacist, Tallaght Hospital (1998-2010).
Tim was a Member of the Commission on Patient Safety and Quality Assurance, convened by the Minister for Health and Children in Ireland to develop recommendations to improvement patient safety. He adds, "The report from the Commission, Building a Culture of Patient Safety, 2008, has since been accepted as Irish government policy. I came to work as National Lead in Medication Safety for the HSE because I was excited about being able to help make coordinated improvements in the way we use medication at national level. "In my most recent post, amongst other projects, I leads the development of a national medication prescription and administration record (MPAR) for use in acute hospital settings across Ireland." This project involves extensive consultation, collaboration, feedback and consensus of healthcare professionals at a national level. The project benefits from Tim's considerable experience in continuous improvement and organisational management. This is an extremely complex endeavour, charged with optimising safe use of medication for the management of acute on chronic episodes in multimorbid, polypharmacy patients, with
consideration of anticoagulation, blood glucose monitoring and nutritional management. The undertaking of this project will not only result in a national standardised approach for medication management in the acute hospital setting in Ireland but also provides an opportunity to disseminate and share key learnings in organisational change with national and international colleagues.
The undertaking of this project will not only result in a national standardised approach for medication management in the acute hospital setting in Ireland but also provides an opportunity to disseminate and share key learnings in organisational change with national and international colleagues.
CAREER PATHWAY Tim Delaney graduated from Trinity College Dublin with a B.Sc. (Pharm.) degree in 1983 and completed his hospital pharmacy pre-registration training at St Vincent's Hospital, Dublin in November 1984.He worked in various pharmacy posts at the Meath Hospital, the Charitable Infirmary and Beaumont Hospital in Dublin, before becoming Chief Pharmacist at the Adelaide Hospital, Dublin in 1989.In January 1994 he became Chief Executive Officer of the Adelaide Hospital, which was one of three hospitals about to merge to form The Adelaide & Meath Hospital, Dublin Incorporating the National Children's Hospital, When the new hospital opened in June 1998, Mr Delaney became a member of the management executive with portfolio responsibilities for Research, Accreditation & Quality, Medical Physics & Clinical Engineering & Catering, in addition to his role as Head of Pharmacy. Mr Delaney is a former Secretary and President of the Hospital Pharmacists' Association of Ireland and a former Secretary of the European Association of Hospital Pharmacists (EAHP). He was Executive Vice-Chairman of EAHP Congresses from 1997 to 2000.At Madrid in 2000, he received an EAHP award for outstanding service to European Pharmacy. Mr Delaney is a Governor and member of the Board of the Adelaide Hospital Society and sits on their Health Policy Sub-committee.He is a member of the External Drug Policy Validating Group for St Anne's Service, Roscrea, Ireland - a health system with a mission to care for people with intellectual disabilities. He is an honorary life member of the British Guild of Hospital Pharmacists. Mr Delaney is a founding member of the Course Co-ordinating and Advisory Committee of the TCD Masters' Degree in Hospital Pharmacy.He lectures on health service structure and funding, and quality management, in that course.
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Working hand in hand to optimise patient care - Palliative Care Meds Info Service Hospital & Community Pharmacy Alliance Award sponsored by Hospital Pharmacy News THE INDEPENDENT VOICE OF HOSPITAL PHARMACY
The importance of crossdiscipline working can never be underestimated and the benefits to be derived from working in tandem can be immense. Whether pharmacists are working within the hospital setting or in a retail business unit in the community, the ultimate goal is the enhancement of patient care and ensuring patients and customers receive the highest possible level of service and the greatest access to necessary medications. To this end the pharmacy team at Our Lady's Hospice in Dublin established an initiative to work closer together with those healthcare professionals caring for patients with life-limiting illnesses throughout Ireland. Their display of excellence scooped them the Hospital and Community Pharmacy Alliance Award at the Irish Pharmacy Awards 2012 in the Burlington Dublin. PROVIDING PRACTICE-BASED MEDICINES Senior Pharmacist within the Palliative Meds Info Service, Cliona Hayden picks up the story: "The team here at Our Lady's Hospice were receiving numerous phone calls from community pharmacists, home care teams and allied professionals asking questions about palliative care medicines. "We are a small department and found it difficult to respond to these queries within an adequate timeframe. It was unsatisfactory from a safety point of view in terms of changing guidelines and the advice we gave." With no established mechanism for feedback, the team identified a need within the community for a service catering to healthcare professionals needs within the palliative care sector and the idea for the Palliative Meds Info Service was borne.
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The ‘Palliative Meds Info Service’ responds to telephone and email enquiries from healthcare professionals caring for patients with life-limiting illnesses. Team member and Chief II Pharmacist at Our Lady's, Eimear O'Dwyer states: "There are several specialist medicines information centres throughout the UK. However, the Palliative Meds Info service is the first specialist medicines information service in the Republic of Ireland and the first specialist palliative care service in both the UK and Ireland. "The necessary use of drugs beyond licence in palliative care presents a challenge in that readily available, relevant medicines information may not be easily available to all professionals involved in caring for patients with palliative care needs. This service supports the safe, effective and efficient use of medicines by the provision of evidence-based information and advice on their therapeutic use." The service provides medicines information to both specialist and non-specialist practitioners (including GP’s, community pharmacists) to ensure that accurate and up-to-date information is continuously available. The service provides hospice based expertise to practitioners in the community, who infrequently care for palliative care patients and help to overcome regional inequalities in the availability of hospice services throughout Ireland. The Palliative Meds Info service has developed an enquiry answering service that follows a standardised search pattern of the literature incorporating specialised palliative care information sources. The standardised search pattern covers a wide range of reliable literature sources to ensure a comprehensive and up-to-
date review of all available information. The information available is linked with clinical interpretation to provide the advice to the enquirer. Since the service has been launched in 2009, there has been a steady stream of enquiries received from a range of health care professionals working with patients care needs in different settings, including hospitals, hospices, palliative care home care teams, palliative care specialists, GPs and community pharmacists throughout the country. The Palliative Meds Info service is sharing the expertise of
a specialist palliative care setting in a safe and convenient way for healthcare professionals. ESTABLISHING EASE OF ACCESS The support the service provides to healthcare professionals will hopefully improve the patients’ experience with medicines, reduce the risk of side effects and produce quicker or more effective relief of symptoms and improve the quality of life of patients and their families facing the problems associated with life-threatening illness. Once the idea was initiatiated, a
Cliona Hayden and Eimear O'Dwyer
even better informed about developments. "The provision of medicines information and support to healthcare professionals in making informed treatment decisions when caring for patients with life-limiting illnesses will contribute to the quality of life for both the patient and their family at the end-of-life. Palliative Meds Info is committed to upholding the core values of Our Lady’s Hospice and Care Services and to the delivery of integrated palliative care services in the community and other healthcare settings," says Cliona. Eimear adds: "The service is building up an extensive database of enquiries. It is allowing us to identify areas and issues where proactive and readily available information is needed. The service is developing information sheets to address these issues. The accessibility of this information will support healthcare professionals in caring for palliative care patients and help the transition of patients from hospice/hospital setting to their homes, which is often done with very short notice and out-of hours."
steering group was gathered and Liz Hoctor was nominated by the Irish Pharmaceutical Union to serve on the board representing community pharmacists. The steering committee contributes expert input and knowledge on the provision of the service and to advise on the continuing improvement of the service. It is also composed of the Chief Pharmacist at OLH, the Director of Pharmacy at St James’s Hospital, the Director of Clinical Services at OLH, the Medical Director of palliative care at OLH or a medical representative of his choice,
the director of the National Medicines Information Centre, a representative from the Irish Hospice Foundation (IHF), a palliative care clinical nurse specialist, a GP representative and an IAPC pharmacists group representative. One of the first services launched was the introduction of a methadone supply protocol which community pharmacists found invaluable and the team have recently launched their own webpage at www.olh.ie. This site publishes all new materials and a quarterly newsletter keeping healthcare professionals
Turning to the future Eimear adds: "We hope to continue to grow the service. This year has been incredibly proactive and we envisage developing the service to include educational resources and we would like to audit it to see how we can improve to include this as part of a wider service. "Winning the Hospital and Community Pharmacy Alliance award was such a tremendous boost in recognising the vital need this service provides and highlights how important it is for us, as pharmacy professionals, to continue to grow and develop as a team"
Winning the Hospital and Community Pharmacy Alliance award was such a tremendous boost in recognising the vital need this service provides and highlights how important it is for us, as pharmacy professionals, to continue to grow and develop as a team.
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Inappropriate prescribing too evident found in older patients residing in long term care facilities, which often results in more medicines being prescribed.” “We found that medicines for the blood and blood forming organs accounted for almost ten per cent (9.2%) of the medicines prescribed in this study. We feel that this is an underestimation of the true requirements for these medicines, as anti-platelet agents and anticoagulants accounted for a third of the omissions identified.” The research also identified 199 potential prescribing omissions in 132 patients. The cardiovascular system accounted for most of the potential prescribing omissions identified and of these, the most common was the omission of a low-dose aspirin.
Dr. Stephen Byrne, School of Pharmacy, UCC main investigator in CARDI study.
Significant numbers of nursing home patients in the Munster area are being prescribing potentially inappropriate medicine, or not given a beneficial one, a study by UCC School of Pharmacy has found. The research identified 329 instances of potentially inappropriate prescribing (PIP) in 187 (59.8%) patients. Of these patients, 98 (31.3%) were prescribed one medicine that
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was potentially inappropriate, 47 (15.0%) were prescribed two, and 32 (10.2%) were prescribed three.
accounted for the highest proportion of potentially inappropriate medicines prescribed.
Medicine for the central nervous system accounted for the highest proportion of PIP identified, followed by high proportions of medication for the gastrointestinal system, the cardiovascular system, and for patients who frequently fall. In this group, benzodiazepines
The study was led by Dr Stephen Byrne and co-authors. He says: “The figures found in this study are higher when compared with figures reported in studies conducted in primary and in secondary care. This may reflect the higher levels of multiple chronic conditions
“Our study shows that there is a need to consider measures of ensuring patients are not at risk of medication related adverse events," added Dr Byrne. The screening tools STOPP and START could form the basis of a pharmaceutical care review for these patients. The feasibility of establishing such a service needs to be further explored.” The study, entitled ‘Potentially inappropriate prescribing in older residents in Irish nursing homes’, collected data from seven publicly funded nursing homes in Muster over a period of three weeks. In total, 313 patients were recruited for the study and over the three week period in 2008, the author’s collected data about current medication and medical conditions, allergy status, biochemistry result and also other relevant previous conditions. The authors used the STOPP (Screening Tool of Older Person’s Prescriptions) and START (Screening Tool to Alert doctors to Right Treatment) screening tool and looked for instances of PIP and PPO in these prescriptions.
The Triple Threat in breast cancer
Sean Owens is a pharmacist studying medicine at UCD, and is currently on a research scholarship at the Winship Cancer Institute, Emory University, Atlanta. Here he speaks exclusively to Hospital Pharmacy News about novel breast cancer therapies and what's in the pipeline as he researches this disease area from Atlanta. LIMITED TREATMENT OPTIONS With over one million new cases each year, breast cancer is the leading cause of cancer death among women worldwide. Despite revolutionary novel endocrine and adjuvant therapy, there remains a subset of breast cancer that retains both poor prognoses along with limited treatment options. The negative connotations that accompany a diagnosis of “Triple Negative” Breast Cancer (TNBC) are not unfounded. Lacking estrogen and progestogen receptors, and HER2/neu overexpression, the traditional endocrine therapies and the highly successful trastuzumab are of no value and treatment is limited to appropriate combinations of surgery, existing adjuvant chemotherapy and radiotherapy. These therapies have well documented deleterious side effects and when they fail there is no known recourse. Furthermore TNBCs display a highly aggressive metastatic
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progression, are associated with extremely poor prognosis and favour both African American and minority females, especially those at a younger age. Accounting for around 20% of all breast cancer subtypes, there is a severe lack of targeted therapies in this field. In addition, there is an alarming increase in resistance to established therapies such as trastazumab and lapatinib(1).It is hoped that targeted therapies to TNBCs could perhaps offer treatment options to those resistant to traditional adjuvant therapy. Whilst the Human Epidermal Growth Factor (EGFR) family of receptors has attracted the most attention in recent years for targeted therapy, current research is now focusing on similar transmembrane signalling receptors such as the Insulin-like Growth Factor-1 Receptor (IGF1R), as well as their interactions with both themselves and other receptors via formation of homo and heterodimers respectively. Blockade of dimerization is an attractive potential therapeutic target, especially as there is evidence of “crosstalk” between heterodimers. For example, silencing one EGFR may upregulate a neighbouring growth factor or its heterodimer and hence compensate by increasing downstream intracellular signalling(2). These dimers are proposed to promote endocrine therapy resistance;
the intracellular tyrosine kinase (TK) cascade therefore offers cogent rationale for downstream targeting of cellular signalling. An example of one such target is that of mTOR protein; indeed the FDA has recently approved the first mTOR inhibitor (everolimus) for postmenopausal hormone positive HER2 negative breast cancer in conjunction with exemestane. It is hoped that dual targeted therapies via antibodies, small molecules, etc. may have synergistic actions and hamper the evasion of apoptosis. Blockade of mTOR, or other small molecules such as Akt, may also upregulate important tumour suppressor proteins such as PTEN (3). Combination therapy here may lessen the need for, or at the very best, negate the need for traditional cytotoxic chemotherapy. ADMINISTERING HIGHLY TOXIC CHEMOTHERAPY The use of targeted therapies is now being employed to selectively deliver highly toxic chemotherapy that is currently administered systemically, directly to the tumour cells. For example, trastuzumab has been trialled in combination with the cytotoxic emtansine attached via a thiol linker and is awaiting FDA approval later this year(4) . The role of IGF-1R with respect to the phenotype of TNBC cells has now garnered attention,
as the progression of epithelial cells to a mesenchymal phenotype is associated with cellular proliferation, migration and metastasis. Blockade of this receptor could prevent such transformation, curb the aggressive nature of the cancer and reduce the recurrence of metastasis(5). Of interest to pharmacists, a known inhibitor of IGF1R phosphorylation is picropodophyllin (PPP), sister to the toxic podophyllotoxin, traditionally used for burning off genital warts. There is therefore great interest in the effect of blocking IGF-1R, although its close resemblance to the Insulin Receptor retains the theoretical problem of inducing a hyperglycaemic response. TNBC seems to have received least attention in the literature, however as the pathways now under investigation are mirrored in lung, prostate and ovarian cancer amongst others, the continuing and blossoming research in this field may yet bear unsought rewards in the greater oncology field. REFERENCES: • Nahta R, O’ Regan R. Evolving strategies for overcoming resistance to HER2-directed therapy: targeting the PI3K/Akt/ mTOR pathway. Clinical Breast Cancer 2010;10:s72-s78 • Holboro T, Civenni et al. The ErbB receptors and their role in cancer progression. Experimental Cell Research 2003;284:99-110 • Nagata Y, Lan K et al. PTEN activation contributes to tumour inhibition by trastuzumab, and loss of PTEN predicts trastuzumab resistance in patients. Cancer Cell 2004;6:117-127 • Shawver L, Slamon D et al. Smart drugs: Tyrosine kinase inhibitors in cancer therapy. Cancer Cell 2002;1:117-123 • Vasilcanu, Girnita et al. The cyclolignan PPP induces activation loop-specific inhibition of tyrosine phosphorylation of the insulin-like growth factor-1 receptor. Link to the phosphatidyl inositol-3 kinase/ Akt apoptotic pathway. Oncogene 2004;23:7854-786
INCIVO® (telaprevir), a new treatment for genotype-1 chronic hepatitis C launched today, offers patients a higher chance of clearing the virus versus current standard treatment - Shortens the course of treatment for many patients who are either treatment naive or those who have previously relapsed after treatment with current standard treatment1
Dublin, Ireland, 20 June 2012: INCIVO® (telaprevir)*, a new direct acting antiviral (DAA) protease inhibitor (PI), for the treatment of genotype-1 chronic hepatitis C (hep C), in combination with peginterferon alfa and ribavirin (i.e. current standard treatment), in adults has been launched today in Ireland. Telaprevir, one of a new class of medicines which directly targets the hep C virus, now offers more patients infected with genotype 1 chronic hep C the chance of clearing the virus (achieving sustained virologic response, SVR) compared to current standard treatment2,3,4.
the chances of cure for patients who have never been treated previously and also substantially improves response rates for those who have undergone unsuccessful treatment in the past. Two protease inhibitors - boceprevir and telaprevir - will now be available for Irish patients. Though this new standard of care comes at the cost of increased sideeffects and greater complexity, many patients may qualify for substantially reduced treatment duration. Many other DAAs that are currently in clinical trials are likely to further revolutionise the HCV treatment landscape in the near future.”
Incivo underwent full pharmacoeconomic assessment by the National Centre for Pharmacoeconomics (NCPE) and was considered to be “highly cost effective” when added to peginterferon and ribaviron for the treatment of patients infected with genotype 1 hepatitis C in the Irish healthcare setting.
The marketing authorisation for telaprevir is based on results from three phase III clinical trials, ADVANCE, REALIZE and ILLUMINATE2,3,4 which evaluated the efficacy and safety of telaprevir in combination with peginterferon alfa and ribavirin in more than 2,290 treatment-naïve and previouslytreated chronic genotype 1 hep C patients. Data from ADVANCE and REALIZE were published in the 23rd June edition of the New England Journal of Medicine (NEJM). Data from the ILLUMINATE study were published in the 15th September edition of the NEJM. This marked the sixth paper to be published on telaprevir in the NEJM5,6,7.
Clinical trials have shown that a telaprevir based regimen is more effective than standard treatment in all genotype-1 patient types, including those with advanced liver disease such as cirrhosis. The addition of telaprevir cleared the virus in almost twice as many previously untreated patients (79% vs. 46%, p<0.0001) 1,2 and almost four times as many who had previously relapsed following treatment (84% vs. 22%, p<0.0001)1,3,. In addition, treatment naive patients and prior treatment relapsers who achieve undetectable levels of hep C virus RNA on testing at weeks 4 and 12 can have their total treatment duration reduced to 24 weeks from the current 48 weeks with standard treatment1. Dr Orla Crosbie, consultant hepatologist and gastroenterologist from Cork University Hospital said “The availability of direct acting antivirals in Ireland means success rates for treatment will now be significantly higher. In addition treatment duration will be far shorter for many groups of patients. We are seeing significant advances in the treatment of hepatitis C and given the current rate of development the future looks bright.” Dr Raphael Merriman, consultant hepatologist, St Vincent’s Hospital, Dublin commented on the launch: “This year marks the dawn of an exciting new era of antiviral therapy for patients with chronic hepatitis C virus (HCV) with the approval of new agents for the first time since 1998. “The new treatment paradigm for patients infected with the most common genotype (I) includes one direct-acting antiviral (DAA) - a protease inhibitor - in combination with conventional pegylated interferon and ribavirin. The addition of a protease inhibitor nearly doubles
In Ireland, it is estimated that 20,000 to 50,000 individuals are chronically infected with hep C.⁸ Chronic hep C poses a public health burden. It is an infectious disease, but patients are often asymptomatic for long periods. If it remains untreated, it can lead to severe liver conditions. Of those who develop chronic hep C an estimated 30% will develop cirrhosis, others will develop liver cancer, some of whom may require liver transplantation9. Chronic hep C is the most common reason for liver transplants in Europe9. The standard treatment for hep C, peginterferon alfa and ribavirin, is successful in only about 50% of patients with genotype 1, leaving the other 50% without a successful treatment outcome 10. In addition to the launch of telaprevir, Janssen, as part of its ongoing commitment to support the hep C community in Ireland, has launched MYINCIVO, a nurse-led support programme. This programme includes home visits, in-bound telephone support with scheduled out-bound telephone calls and optional educational clinics. This programme will be provided by qualified nursing staff and offered to patients who are receiving telaprevir for Genotype I Hepatitis C. The service will also monitor for non-adherence, help identify any possible side effects and provide further information and advice where applicable. The objective of the programme is to educate, support, motivate and monitor
for the total duration of treatment with Peginterferon, Ribavirin and telaprevir. The overall safety and tolerability profile of telaprevir is based on the phase II and III clinical development programme. The most frequently reported moderate adverse reactions (incidence ≥ 5.0%) were anaemia, rash, pruritus, nausea, and diarrhoea, and the most frequently reported severe adverse reactions (incidence ≥ 1.0%) were anaemia, rash, thrombocytopenia, lymphopenia, pruritus, and nausea1. Rash events were reported in 55% of patients with telaprevir based treatment compared with 33% in the control arm (peginterferon alfa and ribavirin only). More than 90% of rashes were of mild or moderate severity. Severe rashes were reported with telaprevir based treatment in 4.8% of patients. Rash led to discontinuation in 5.8% of patients. Anaemia was reported in 32.1% of patients compared with 15% in the control arm (peginterferon alfa and ribavirin only). It led to discontinuation in approximately 3% of patients1. * INCIVO® (telaprevir), a direct acting antiviral (DAA) protease inhibitor (PI), was co-developed by Vertex Pharmaceuticals and Tibotec, an affiliate of Janssen Pharmaceutical Companies of Johnson & Johnson, and the company responsible for marketing telaprevir in Europe. 1. Telaprevir Summary of Product Characteristics 2011. 2. Jacobson, Ira M. Telaprevir for Previously Untreated Hepatitis C Virus Infection. N Engl J Med. 2011; 364; 2405-16. 3. Zeuzem, Stefan MD. Telaprevir for Retreatment of HCV Infection. N Engl J Med. 2011; 364; 2417-28. 4. Sherman et al. Response Guided Telaprevir Combination Treatment for Hepatitis C Virus Infection N Engl J Med. 2011: 365; 1014-24. 5. McHutchinson et al. Telaprevir for Previously Treated Chronic HCV Infection. Engl J Med. 2010; 362; 1292-1303. 6. Hezode et al. Telaprevir and Peginterferon Alfa with or without Ribavirin for Chronic HCV. Engl J Med 2009; 360; 1839-50. 7. McHutchinson et al. Telaprevir with Peginterferon Alfa and Ribavirin for Chronic HCV Genotype 1 Infection 2009 N Engl J Med 2009; 360: 1827-38. 8. Thornton et al. Determination of the burden of hepatitis C virus infection in Ireland 2011 Epidemiol. Infect. 2011: doi: 10.1017/S0950268811001920 9. Mühlberger, N et al. HCV-related burden of disease in Europe: a systematic assessment of incidence, prevalence, morbidity, and mortality. BMC Public Health. 2009; 9(34):1-14. 10. McHutchison, J et al. Peginterferon Alfa-2b or Alfa-2a with Ribavirin for Treatment of Hepatitis C Infection. N Engl J Med. 2009; 361:580–93.
HPN • Issue 5
44 Clinical Profiles
Astra Zeneca has announced the launch of a new oral anti-platelet, BRILIQUE (ticagrelor), in Ireland. Brilique, in combination with low-dose aspirin (75-150mg) is indicated for the prevention of atherothrombotic events in adult patients with Acute Coronary Syndromes (ACS), including those managed medically or with invasive techniques (e.g. percutaneous coronary intervention (PCI). Specifically, Brilique is indicated to be taken
for up to 12 months in patients who are diagnosed with unstable angina (UA) or who experience a heart attack [either non-STelevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI)]. The approval of BRILIQUE is supported by data from the PLATO3 (A Study of PLATelet Inhibition and Patient Outcomes) study.
The study demonstrated that treatment with BRILIQUE with aspirin led to a significantly greater reduction in the primary endpoint [a composite of death from vascular causes, heart attack (myocardial infarction or MI), or stroke] compared to patients who received clopidogrel with aspirin (9.8% vs. 11.7% at 12 months; 16% relative risk reduction (RRR); 95% CI, 0.77 to 0.92; p<0.001)3,4.
Buccolam is approved for the treatment of prolonged, acute, convulsive seizures in infants, toddlers, children and adolescents (from 3 months to < 18 years) BUCCOLAM must only be used by parents/carers where the patient has been diagnosed to have epilepsy For infants between 3-6 months of age treatment should be in a hospital setting where monitoring is possible and resuscitation equipment is available. BUCCOLAM is for oromucosal use. The full amount of solution should be inserted slowly into the space between the gum and the cheek. Laryngo-tracheal insertion should be avoided to prevent accidental aspiration of the solution. If necessary (for larger volumes and/or smaller patients),
Procoralan now recognised in new Esc Guidelines for the treatment of heart failure
Issue 5 â€˘ HPN
Less than 2 years after the publication in The Lancet of the SHIFT study results demonstrating its benefits in heart failure, ProcoralanÂŽ is now integrated in the new ESC guidelines for the management of heart failure. The guidelines have been updated for the first time since 2008. They make recommendations for treatment based upon evidence for established and new diagnostic tests, and therapies for heart failure.
approximately half the dose should be given slowly into one side of the mouth, then the other half given slowly into the other side.
Precautions to be taken before manipulating or administering the product. BUCCOLAM is not for intravenous use.
In addition, a new indication for ivabradine in chronic heart failure was granted by the European Medicines Agency in February 2012. This was based on new data from the SHIFT study in which patients with an elevated heart rate of greater than or equal to 75 beats per minute (bpm) showed a significant reduction in the primary composite endpoint (CV death and hospitalisation for worsening heart failure) of 24% (p<0.0001), reduction in risk of cardiovascular
death by 17% (p=0.0166), allcause death by 17% (p=0.0109) and heart failure hospitalisation by 30% (p<0.0001). The new indication and the new ESC guidelines for the treatment of heart failure are the two major advances which will allow heart failure patients to benefit from ivabradine.
Eliquis proved cost effective
APO-go (apomorphine), from Clonmel Healthcare, is a dopamine agonist used in the treatment of Parkinson’s disease.
BMS & Pfizer have welcomed the results of the Health Technology Assessment (HTA) conducted by the National Centre for Pharmacoeconomics (NCPE) which has found that apixaban (Eliquis®) is a cost effective treatment for the prevention of venous thrombo-embolic events (VTE) following total hip and knee replacement. Additionally, it was reported that apixaban has the potential to generate significant savings for the HSE over a 5 year period.
The HTA is in relation to the prevention of VTE in adult patients who have undergone elective total hip replacement or total knee replacement surgery. From a net cost to the HSE perspective, apixaban was shown to be a cost saving treatment relative to comparators (enoxaparin and dabigatran) evaluated in VTEpO. Budget impact is based on expected utilisation and it was reported that apixaban has the potential to yield 5 year cumulative savings of about €301,408. The
NCPE noted that this budget impact may be an underestimate, and reported that if the end of Year-5 uptake is increased to 30%, the estimated net budget impact indicates a potential 5-year cumulative saving of about €959,376. Conclusion: ‘The NCPE believe that apixaban is cost effective for the prevention of VTE following total hip replacement and total knee replacement’.
The APO-go Pen is a quick, simple treatment to control unpredictable “off” periods and give patients control over their symptoms. Brian Magennis, Parkinson’s disease Nurse Specialist, at The Mater hospital is presenting an audit of apomorphine at The MDS 16th International Congress of Parkinson’s Disease and Movement Disorders. “Idiopathic Parkinson’s disease (IPD) is the second most common neurodegenerative disorder. Apomorphine, a dopamine agonist, is useful for treating ‘Off’ periods and motor fluctuations, which are a common disabling complication of IPD resulting in increased dependence”. If you are considering the APO-go Pen for your patient please contact our nurse specialist team on 01 – 620 4000.
Brian Magennis, Parkinson’s disease Nurse Specialist, The Mater hospital and Mary Twohill, Nurse Product Specialist, Clonmel Healthcare
Full prescribing information for APO-go is available on request or go to www.clonmel-health.ie.
Pfizer’s Xiapex® Proves Efficacious in Treatment of Dupuytren’s Contracture Recurrence
Data published recently in the Journal of Plastic Surgery and Hand Surgery suggest that Xiapex® (collagenase clostridium histolyticum) is efficacious and well-tolerated in patients whose Dupuytren’s contracture has returned (or recurred) following previous surgical treatment for the condition.
The data from 12 clinical trials (n=1082), confirm that previous surgery for Dupuytren’s contracture does not affect the efficacy or safety profile of collagenase clostridium histolyticum (CCH). After treatment with CCH, fixed-flexion contracture (FFC) at metacarpophalangeal (MP) joints was reduced by 75% in previously-operated hands and by
80% for non-operated hands (p = 0.6). For proximal interphalangeal (PIP) joints, the reductions in FFC for the operated and non-operated hands were 52% and 50%, respectively (p=0.6); improvements in range of motion (ROM) were 24 degrees and 26 degrees, respectively (p=0.3).
HPN • Issue 5
46 Clinical Profiles
Shire Pharmaceuticals Ireland Limited wishes to announce that Calcichew-D3 Forte will now be available in a new 60 pack and the current
100 pack as of 1st September 2012.Calcichew-D3 Forte is indicated for vitamin D / calcium deficiency in the elderly, adjunct in osteoporosis, pregnancy, vitamin 1* D dependent osteomalacia.
• Costs 40% less than
N 60 T EW nearest competitor ABLE P * ACK T • No.1 in Ireland • Available in 100 tablet and 60 tablet packs
Their strength is our forte Fingolimod for multiple sclerosis patients
Gilenya (Fingolimod (HCl) 0.5mg) is
CALCICHEW-D3 FORTE CHEWABLE TABLETS PRESCRIBING INFORMATIO a single disease therapy N. Prescribe with modifying caution in patients with sarcoidosis. Use with caution in product. Product Authorisation No: 535/1/3. (Please refer to full Summary of Product Characteristics when Product Authorisation holder: in highly active patients. relapsing remitting immobilised Additional doses of calcium or vitamin D should only be Shire Pharmaceuticals Ltd., Hampshire International prescribing). Presentation: Chewable tablet containing 1250mg calcium taken under Business Park, Chineham, close(MS) medical supervision. multiple sclerosis in patients Interactions : Tetracyclines (take 2 Basingstoke, Hampshire RG24 8EP UK. Distributed in Republic of Ireland by: carbonate (equivalent to 500mg of elemental calcium) plus 400IU colecalciferol hours before, or 4activity to 6 hoursdespite after Calcichew-D3 Forte), bisphosphonates or Cahill May Roberts, P.O. Box 1090, Chapelizod, with high disease (equivalent to 10 micrograms vitamin D ). Uses: Prevention and treatment of sodium fluoride Dublin 20, Republic of Ireland. 3 3 hours beforeand Calcichew-D3 Forte), Quinolone antibiotics Further information is available on request. with a (take β-interferon vitamin D/calcium deficiency. Supplementation of vitamin D and calcium treatment Date of revision: May 2011. as an (take two hours before or after), levothyroxine (take four hours before or after), CALCICHEW is a registered trademark of Shire Pharmaceuticals Ltd in the adjunct to specific therapy for osteoporosis, in pregnancy, in established vitamin patients withdiuretics, rapidly evolving thiazide corticosteroid s, cardiac glycosides, ion exchange resins Republic of Ireland. D dependent osteomalacia and in other situations requiring therapeutic severe(cholestyram relapsing MS. oil). Calcichew-D Forte should not be ine),remitting laxatives (paraffin 3 supplementation of malnutrition. Dosage and administration: Oral (suck or taken within 2 hours of eating foods high in oxalic acid (e.g. spinach and Adverse events should be reported to the Pharmacovigilance Unit at chew). Adults and elderly: Two tablets daily. Children: Not intended for use Fingolimod sphingosine in rhubarb)isor aphytic acid (e.g. whole cereals). Side effects: Hypercalcaemia, the Irish Medicines Board (IMB) (firstname.lastname@example.org). children. Hepatic impairment: No dose adjustment required. Renal impairment: 1-phosphate (S1P) receptor hypercalciuri a, constipation, dyspepsia, flatulence, nausea, abdominal pain, Should not be used in patients with severe renal impairment. diarrhoea, Information about adverse event reporting can be found on the IMB rash,as urticaria. modulator. Bypruritus, acting a Very rarely (usually only seen on overdose) Contraindications: Diseases and/or conditions resulting in hypercalcaemia milk-alkali syndrome. Use inS1P pregnancy and lactation: Can be used in case of website (www.imb.ie). Adverse events may also be reported to Shire functional antagonist of and/or hypercalciuria, severe renal impairment, renal stones, hypervitaminosis calcium and vitamin D deficiency. Daily intake in pregnancy should not exceed Pharmaceuticals Ltd on +44 1256 894000. on lymphocytes, D, hypersensitivity to ingredient(s) Precautions: Monitor serum calciumreceptors and 1500mg calcium and 600IU colecalciferol (15 micrograms vitamin D ). Avoid creatinine levels, particularly in patients on cardiac glycosides or diureticsfiand 3 Reference: 1. MIMS May 2012. ngolimod thehypercalcaem capacityiaof overdoseblocks as permanent the central nervous references available from Novartis affects developing foetus. Calcium and system, where n patients with high tendency to calculus formation. Use with caution lymphocytes to egress in vitamin D3 pass into breastfrom milk so lymph consider this when giving additional they would be involved nerve June 2012. vitamin Datein of preparation: Ireland Ltd, Beech House, Beech patients with impaired renal function. Take into account risk of soft tissue D to the child. Pharmaceut nodes, causing a redistribution of : Do not ical precautions above 30°C.and Keep nervous Item Code: IRE/BU/CDF/12/0007. inflstore ammation tissue calcification. Avoid in patients with phenylketonuria or sugar intolerance. container Hill Office Campus, Clonskeagh, tightly closed to protect from moisture. Legal category: lymphocytes. This redistribution damage. Pharmacy *According to IMS unit sales data April 2012.
reduces the infiltration of pathogenic lymphocyte cells into
Full prescribing information and
Dublin 4. Telephone: (01) 260 1255 . Fax: (01) 260 1263.
One Fosfomycin for urinary tract infections
Fosfomycin, a product of Fannin Ltd, is available for the treatment of urinary tract infections. Fosfomycin is a broad spectrum antibiotic derived from phosphonic acid and its antibacterial activity is due to inhibition of bacterial cell wall synthesis. Its particular mechanism of action, inhibition of enol pyruviltransferase, results in lack of cross resistance with other classes of antibiotic, and the possibility of synergism with other antibiotics. Fosfomycin Granules for oral solution is indicated for adults in a single dose of 3g on an empty stomach, before bedtime, after bladder emptying. It is not recommended for children or
Issue 5 • HPN
the elderly. Contraindications include hypersensitivity to the active substance or to any of the excipients; Impaired renal function (cc<80ml/min) and Lactation. It is to be discontinued if Clostridium difficile associated diarrhoea is suspected or in pregnancy. Full prescribing information and references available from Fannin Ltd. Email: email@example.com
Name of me diciNa uncom l Pr plic patients ated urinary tr oduct: mon u a : Not re sPecia comme ct infections d ril 3g granule ue nd s l of C. dif PrecautioN ed due to dim to sensitive o for oral soluti rga s fic in o diarrhe ile. C. difficile for use: Clo ished urinary nisms in adult n. Each single a follow e s -dose s s ing anti produces toxin tridium difficile xcretion. Paed . Posology achet c manag b aN s iatr em ioti as A take this ent, protein s c use. Carefu and B which sociated diarr ic populatio d admiNistr n h u c l o p : o m m the seru edicine. Do n plementation, edical history ntribute to the ea (CDAD) has It is not for us e an o m d b is lactat and urine co t use more th tibiotic treatm necessary sin evelopment of een reported w nc an en io C i c embryo N: Pregnanc entrations of fo one single d t of C. difficile e CDAD has b DAD. Hyperto xin y: na os ee ,a sfo (2-3 hrs l/foetal develo Data on a limit mycin. Other e of Monuril nd surgical e n reported to va to o pment, e d a parturiti d number of e rugs that incre treat a sing luation should c Dizzine fter a meal) a le e on s fo ss, xp as be solution Diarrhoea, N od delays an or postnatal d osed pregnan e gastrointesti pisode of ac d c a u e n ie u in te ve re al motilit propan overdose: ve sea, Vulvo-vag duces the ab lopment. Cau s indicate no y may p c dio sti ad so in ti ro results l) (2R-cis) (3- bular loss, imp itis, Dyspepsia rption of fosfo on should be e verse effects o d in lack m m a xe f ir a fo yc e rc n e th s d hearin d in trom iloxyran of cross is comp etamol, ised when pre fo g, meta Asthenia uN il) pho res le patients tely soluble in istance with o sphonate] is a llic taste, and kNoWN Ana resulting in re scrib the ph wa du g w b
ch to op a io o r id p p
Targin® tablets contain an opioid analgesic
Targin® (oxycodone hydrochloride/naloxone hydrochloride) 5mg/2.5mg, 10mg/5mg, 20mg/10mg and 40mg/20mg prolonged release tablets Prescribing Information Republic of Ireland Please read the Summary of Product Characteristics (SmPC) before prescribing. Indications: Severe pain, which can be adequately managed only with opioid analgesics. Naloxone is added to counteract opioidinduced constipation by blocking the action of oxycodone at opioid receptors locally in the gut. Dosage and administration: Adults over 18 years: Usual starting dose for opioid naïve patients: 10 mg/5 mg taken orally at 12hourly intervals. Patients already receiving opioids may be started on higher doses depending on their previous opioid experience. Targin® 5 mg/2.5 mg is intended for dose titration when initiating opioid therapy & individual dose adjustment. The dosage is dependent on the severity of the pain and the patient’s previous history of analgesic requirements. Maximum daily dose of Targin is 80 mg oxycodone hydrochloride & 40 mg naloxone hydrochloride. Targin is not intended for the treatment of breakthrough pain. Please refer to SmPC for further details. Targin must be swallowed whole & not be broken, chewed or crushed. Children under 18 years: Not recommended. Contra-indications: Hypersensitivity to active substances or excipients, any situation where opioids are contra-indicated, severe respiratory depression with hypoxia and/or hypercapnoea; severe COPD, cor pulmonale, severe bronchial asthma, non-opioid induced paralytic ileus, moderate to severe hepatic impairment. Precautions and warnings: Respiratory depression, elderly or infirm, opioid-induced paralytic ileus, severely impaired pulmonary function, myxoedema, hypothyroidism, adrenocortical insufficiency, toxic psychosis, cholelithiasis, prostate hypertrophy, alcoholism, delirium tremens, pancreatitis, hypo- or hyper-tension, pre-existing cardiovascular diseases, head injury, epileptic disorder, predisposition to convulsions, patients taking MAO inhibitors, history of alcohol/drug abuse, galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption, renal impairment, mild hepatic impairment, pre-operative use or within the first 12 - 24 hours post-operatively. Not suitable for treatment of withdrawal symptoms. Not recommended in cancer associated with peritoneal carcinomatosis or sub-occlusive syndrome in advanced stages of digestive & pelvic cancers. Concomitant use of alcohol and Targin may increase the undesirable effects of Targin and should be avoided. Tolerance and dependence may occur. It may be advisable to taper dose when stopping treatment to prevent withdrawal symptoms. Interactions: Substances having a CNS-depressant effect (e.g. other opioids, sedatives, hypnotics, anti-depressants, sleeping aids, phenothiazines, neuroleptics, anti-histamines and antiemetics) may enhance CNS-depressant effect of Targin (e.g. respiratory depression). Alcohol may enhance the pharmacodynamic effects of Targin; concomitant use should be avoided. Interaction with coumarin
anticoagulants may increase/decrease INR. Pregnancy and lactation: Not recommended. Side-effects: Common: decreased/loss of appetite, restlessness, dizziness, headache, vertigo, decrease in blood pressure, abdominal pain, diarrhoea, dry mouth, constipation, flatulence, vomiting, nausea, dyspepsia, increased hepatic enzymes, hiccups, altered mood, personality change, decreased activity, psychomotor hyperactivity, agitation, dysuria, pruritus, skin reactions, hyperhidrosis, drug withdrawal syndrome, feeling hot & cold, chills, asthenic conditions. Uncommon but potentially serious: hypersensitivity, confusion, depression, euphoric mood, hallucinations, paraesthesia, speech disorder, convulsions, sedation, syncope, visual disturbances, palpitations, angina pectoris, tachycardia, increase in blood pressure, dyspnoea, respiratory depression, biliary colic, erectile dysfunction, urinary retention, peripheral oedema, tooth disorder, chest pain and injuries from accidents. Refer to SmPC for further details of other uncommon side-effects and oxycodone class-effects. Legal category: CD (Sch2) POM. Package quantities: Blisters of 56 tablets. Marketing Authorisation numbers: PA913/025/001-4. Marketing Authorisation holder: Napp Pharmaceuticals Limited, Cambridge Science Park, Milton Road, Cambridge CB4 0GW, UK. Member of the Napp Pharmaceutical Group. Further information is available from: Mundipharma Pharmaceuticals Limited, Millbank House, Arkle Road, Sandyford, Dublin 18, Tel: +353 (0)1 2063800. Date of preparation: August 2011. References: 1. Nadstawek J, et al. Int J Clin Pract, August 2008; 62 (8): 1159–1167. 2. Simpson K, Leyendecker P, Hopp M, et al. Fixed-ratio combination oxycodone/naloxone compared with oxycodone alone for the relief of opioid-induced constipation in moderate-tosevere noncancer pain. Curr Med Res Opin 2008;24(12):3503-3512. 11144TRG
Adverse events should be reported to Mundipharma Pharmaceuticals Limited on 1800 991830
® The Napp device (logo) is a Registered Trade Mark. ® Targin is a Registered Trade Mark. © 2011-2012 Napp Pharmaceuticals Limited.
educedriskof r opioid-induced constipation
Targin® provides pain relief that is as effective as oxycodone alone2 Targin® reduces the risk of opioid-induced constipation when compared to oxycodone alone2 Targin® is indicated for severe pain, which can be adequately managed only with opioid analgesics. The opioid antagonist naloxone is added to counteract opioid-induced constipation by blocking the action of oxycodone at opioid receptors locally in the gut.
The power to reduce cardiovascular events1
ABBREVIATED PRESCRIBING INFORMATION. Product Name: Atorvas 10mg, 20mg, 40mg and 80mg Film-coated Tablets. Composition: Each film-coated tablet contains 10mg, 20mg, 40mg or 80mg atorvastatin respectively. Description: 10mg, 20mg and 40mg tablets: Light yellow, dappled, glossy, round biconvex film-coated tablets, debossed with ‘HLA 10’, ‘HLA 20’ and ‘HLA 40’ on one side respectively. 80mg tablets: Light yellow, dappled, glossy, oval biconvex film-coated tablets, debossed with ‘HLA 80’ on one side. Indication(s): Hypercholesterolaemia and prevention of cardiovascular disease. Dosage: Adults and elderly: Usual starting dose is 10mg daily with or without food. Primary hypercholesterolaemia and mixed hyperlipidaemia: 10mg daily, maintained for chronic therapy. Maximum therapeutic response seen after 4 weeks. Heterozygous familial hypercholesterolaemia: Initially 10mg daily. Adjust every 4 weeks to 40mg daily. Dose may still be increased to 80mg daily, or add a bile acid sequestrant with 40mg Atorvas as daily dose. Homozygous familial hypercholesterolaemia: Limited data available. Dose is 10mg to 80mg daily or as an adjunct to other lipid lowering treatments (i.e. LDL apheresis). Prevention of cardiovascular disease: Dose of 10mg daily may be increased to attain (LDL-) cholesterol levels in line with guidelines. Renal impairment: No adjustment of dose. Hepatic impairment: Caution. Paediatric use: Only by a specialist. Experience is limited to age group 4-17 years with severe dyslipidaemias at a starting dose of 10mg increased to 80mg daily. Contraindications: Hypersensitivity to the active or excipients. Active liver disease or unexplained persistent elevations of serum transaminases exceeding 3 times the upper limit. Pregnancy, breast-feeding and women of childbearing potential not using adequate contraception. Warnings and Precautions for Use: Liver effects: Monitor liver
function tests regularly. Caution in patients with liver disease or high alcohol intake. Stroke prevention by aggressive reduction in cholesterol levels: Increase in incidence of stroke with 80mg dose in prior haemorrhagic stroke or lacunar infarct. Caution as risks and benefits of 80mg dose is uncertain. Skeletal muscle effects: In rare occasions: myalgia, myositis, myopathy that may lead to rhabdomyolysis characterised by elevated creatine kinase (CK) levels, myoglobinaemia and myoglobinuria. Caution in predisposing factors for rhabdomyolysis; measure CK levels before treatment in the following situations: renal impairment, hypothyroidism, personal or familial history of muscular disorders, previous history of muscular toxicity with a statin or fibrate, previous history of liver disease or high alcohol intake, where an increase in plasma levels may occur, such as possible interactions, special populations. Increased CK levels 5 times higher than normal and if confirmed after 5 to 7 days; unsuitable for treatment. If patients complain about muscle pain, cramps, weakness with malaise, measure CK levels and act accordingly. Caution when taking drugs that may increase plasma concentration of atorvastatin (potent inhibitors of CYP3A4 or transport proteins, e.g. ciclosporin, telithromycin, clarithromycin, delavirdine, stiripentol, ketoconazole, voriconazole, itraconazole, posaconazole and HIV protease inhibitors). Higher risk of myopathy with gemfibrozil, other fibric acid derivatives, erythromycin, niacin, ezetimbe. Adjust dose of atorvastatin if use is necessary. Interstitial lung disease: Have been reported with long term therapy, discontinue atorvastatin. Interactions: Caution: CYP3A4 inhibitors: See above if given with potent inhibitors of CYP3A4. Moderate CYP3A4 inhibitors, e.g. erythromycin, verapamil, fluconazole: Monitor patients and give lower dose of atorvastatin. CYP3A4
inducers: Lower plasma levels of atorvastatin with efavirenz, rifampicin, St John’s Wort. Transport protein inhibitors: Ciclosporin can increase systemic exposure of atorvastatin. Gemfibrocil/fibric acid derivatives, Ezetimbe: Higher risk of muscle related events. Colestipol: Lower atorvastatin plasma levels, but lipid effects were greater when given in combination. Fusidic acid: Avoid. Digoxin: Monitor as digoxin levels may increase. Oral contraceptives: Increased plasma levels of norethindrone and ethinyl estradiol. Warfarin: Monitor prothrombin time. First 4 days of an 80mg dose gave a slight decrease in prothrombin time that normalised after 15 days of atorvastatin treatment. See SPC for recommended dosage schedules in combination with other drugs. Pregnancy and Lactation: Contraindicated. Ability to Drive and Use Machinery: Negligible influence. Undesirable Effects: Nasopharyngitis, allergic reactions, hyperglycaemia, headache, constipation, pharyngolaryngeal pain, epistaxis, flatulence, dyspepsia, nausea, diarrhoea, myalgia, arthralgia, pain in extremity, muscle spasms, joint swelling, back pain, liver function tests abnormal, and blood creatine kinase increased. Marketing Authorisation Holder: Rowex Ltd, Bantry, Co. Cork. Marketing Authorisation Numbers: PA 711/180/1-4. Further information and SPC are available from: Rowex Ltd, Bantry, Co. Cork. Freephone: 1800 304 400 Fax: 027 50417 E-mail firstname.lastname@example.org Legal Category: Subject to medical prescription. Date of Preparation: April 2012. Ref 1: PMID:21873710. Edition 1 05/12
Manufacturing in Ireland from our Bantry base, we believe in investing in the best medicines for your patients Medicinal products subject to prescription. Further information and SPC available from Rowex Ltd., Bantry, Co. Cork.
CCF No: 14111