prepared in collaboration with the WHO Collaborating Centre for International Drug Monitoring, Uppsala, Sweden TheThe aim aim of of the the N Newsletterewsletter is is to to No.No. 4, 3, 2013 2012 disseminatedisseminate information information on on the the safetysafety and and efficacy efficacy of of pharmaceuticalpharmaceutical products, products, based on communications received based onfrom communications our network of received "drug from our network of "drug information officers" and other TheThe WHO WHO Pharmaceuticals Pharmaceuticals Newsletter Newsletter provides provides you you wit withh informationsources such officers" as specialized and other sources such as specialized thethe latest latest information information on on the the safety safety of of medicines medicines a andnd bulletins and journals, as well as legallegal actions actions taken taken by by regulatory regulatory authorities authorities acros acrosss the the partnersbulletins in WHO. and journals, The information as well as partners in WHO. The information world.world. It It also also provides provides signals signals from from the the Uppsala Uppsala is produced in the form of résumés MonitoringMonitoring Centre's Centre's SIGNAL SIGNAL document. document inis English,produced full in thetexts form of which of résumés may in English,be obtained full texts on request of which from: may In addition to the usual features, this issue includes the be obtained on request from: summary of discussions from the tenth meeting of the Quality Assurance and Safety: The feature article in this issue gives you… WHO Advisory Committee on Safety of Medicinal Medicines, EMP-HSS, Products (ACSoMP). QualityWorld HealthAssurance Organization, and Safety: 1211 GenevaMedicines, 27, Switzerland, EMP-HSS, E-mail address: [email protected] World Health Organization, This Newsletter is also available on 1211 Genevaour Internet 27, Switzerland, website: http://www.who.int/medicineE-mail address: [email protected] Further information on adverse reactions may be obtained from the This Newsletter is also available on WHO Collaborating Centre for Internationalour Drug Internet Monitoring website: http://www.who.int/medicineBox 1051 s 751 40 Uppsala Tel: +46-18-65.60.60 Further Fax:information +46-18-65.60.80 on adverse reactionsE-mail: may [email protected] obtained from the Internet:WHO http://www.who-umc.org Collaborating Centre for International Drug Monitoring Box 1051 Contents Contents Regulatory matters Regulatory matters Safety of medicines Safety of medicines Signal Feature Feature © World Health Organization 2013 All rights reserved. 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Printed by the WHO Document Production Services, Geneva, Switzerland TAB LE OF CONTENTS Regulatory Matters Almitrine-containing medicines ....................................................................... 4 Codeine ...................................................................................................... 4 Cyproterone and ethinylestradiol containing medicinal products .......................... 5 Diclofenac ................................................................................................... 5 Hydroxyethyl starch intravenous infusion ......................................................... 6 Ketoconazole ............................................................................................... 7 Olmesartan medoxomil ................................................................................. 7 Strontium ranelate ....................................................................................... 7 Retigabine ................................................................................................... 8 Varenicline tartrate and bupropion hydrochloride .............................................. 8 Zolpidem containing products ........................................................................ 9 Safety of medicines Insulin glargine ........................................................................................... 10 Olanzapine Pamoate .................................................................................... 10 Renin-angiotensin-system (RAS)-acting agents ............................................... 10 Signal Agomelatine and QT prolonged ..................................................................... 12 Response from Servier ................................................................................. 18 Tapentadol and Aggressive reaction ............................................................... 19 Response from Grünenthal GmbH and Janssen Pharmaceuticals, inc. .................. 22 Feature Tenth Meeting of the WHO Advisory Committee on Safety of Medicinal Products (ACSoMP) ...................................................................................... 24 WHO Pharmaceuticals Newsletter No. 4, 2013 • 3 REGULATORY MATTERS The PRAC concluded that there European safety review. The Almitrine-containing is a clear association between review was triggered by case oral almitrine treatment and reports of children who medicines potentially serious and long- received codeine for pain lasting peripheral neuropathy control after tonsillectomy or Oral almitrine to be (damage to the nerves in the adenoidectomy (or both) for withdrawn by EU hands and feet) and significant obstructive sleep apnoea and Europe. The Coordination weight loss that further who developed rare, but life- Group for Mutual Recognition weakens patients. The PRAC threatening adverse events, and Decentralised Procedures noted that cases continue to including death. be reported even after – Human (CMDh), a medicines Codeine is converted to additional precautions on the regulatory body representing morphine in the liver by the use of the medicines were put the European Union (EU) CYP2D6 enzyme. There are in place. Furthermore, oral Member States, has endorsed many genetic variations of almitrine is no longer included the recommendation by the CYP2D6, which affect the as a recommended therapy in European Medicines Agency's extent of this conversion in international treatment (EMA's) Pharmacovigilance individuals. Different plasma guidelines for the management Risk Assessment Committee morphine concentrations in of COPD. The CMDh agreed (PRAC), that permission to patients’ blood leads not only with the PRAC conclusion that market oral medicines to different levels of pain relief, the benefits of these medicines containing almitrine should be but also to a variable and do not outweigh their risks, withdrawn across the EU. As unpredictable risk of side and adopted a final position the PRAC recommendation was effects due to morphine’s that the marketing endorsed by consensus by the action on the brain and authorisations should be CMDh, it will now be respiratory centre. implemented directly by the withdrawn throughout the EU. The MHRA advised Health-care Member States where oral Health-care professionals are professionals that: almitrine is authorised, advised the following: according to an agreed • Patients being treated • Codeine should only be timetable. with oral almitrine should have used to relieve acute Almitrine is a stimulant of the their treatment reviewed at the moderate pain in children next scheduled appointment, part of the brain responsible older than 12 years and and appropriate alternative for the breathing reflex. In the only if it cannot be relieved EU, it is authorised in France, treatments should be by other painkillers such as Poland and Portugal to be considered. taken orally for the treatment • Pharmacists should refer paracetamol or ibuprofen of chronic respiratory failure patients presenting a new or alone (inability of the lungs to take in repeat prescription to their • Codeine is now treating physician. oxygen and get rid of carbon contraindicated in: • Prescribers and dioxide properly), which is o all children age 0–18 pharmacists will be sent