prepared in collaboration with the WHO Collaborating Centre for International Drug Monitoring, Uppsala, Sweden TheThe aim aim of of the the Newsletter Newsletter is is to to No.No. 5, 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 documents. 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 be obtained on request from: Quality Assurance and Safety: The feature article in this issue gives you… Medicines, EMP-HSS, 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 Acetaminophen ............................................................................................ 4 Caffeine for apnoea of prematurity ................................................................. 4 Calcitonin medicines ..................................................................................... 4 Codeine ...................................................................................................... 5 Diclofenac ................................................................................................... 6 Ergot derivatives .......................................................................................... 6 Filgrastim and pegfilgrastim ........................................................................... 7 Flupirtine-containing medicines ...................................................................... 7 Intravenous iron-containing medicines ............................................................ 8 Ketoconazole, oral ........................................................................................ 8 Mefloquine Hydrochloride .............................................................................. 9 Meprobamate ............................................................................................. 10 Metoclopramide .......................................................................................... 10 Ondansetron for intravenous use ................................................................... 11 Retigabine .................................................................................................. 11 Sunitinib malate .......................................................................................... 11 Safety of medicines Nitrofurantoin ............................................................................................. 13 Panitumumab ............................................................................................. 13 Pazopanib hydrochloride............................................................................... 13 Rituximab .................................................................................................. 14 Vemurafenib ............................................................................................... 14 Signal Mirtazapine and Rhabdomyolysis ................................................................... 15 Roflumilast and Melaena .............................................................................. 18 Tapentadol and Delusion .............................................................................. 23 WHO Pharmaceuticals Newsletter No. 5, 2013 • 3 REGULATORY MATTERS with other drugs already citrate). All product doses Acetaminophen known to have such an should be prescribed as association, when assessing caffeine citrate, taking into patients with potentially drug- account the different strengths Association with risk of induced skin reactions. Any of the marketed products. serious skin reactions patient who develops a skin Caffeine (citrate) is authorised USA. The U.S. Food and Drug rash or reaction while using for treatment of apnoea of Administration (FDA) notified acetaminophen or any other premature newborns and may health-care professionals and pain reliever/fever reducer be given orally or patients that acetaminophen should stop the drug and seek intravenously. has been associated with a risk medical attention right away. of rare but serious skin Anyone who has experienced a There is no change to the reactions. Acetaminophen is a serious skin reaction with formulation of these products. common active ingredient to acetaminophen should not take The new packaging of Viridian treat pain and reduce fever; it the drug again and should Pharma products displaying is included in many contact their health-care the new name may not be prescription and over-the- professional to discuss immediately available. counter products. These skin alternative pain relievers/fever However, all packaging reactions, known as Stevens- reducers. (current and new) has dual Johnson Syndrome (SJS), toxic labelling, which clearly states The US FDA will require that a epidermal necrolysis (TEN), the strengths of both caffeine warning be added to the labels and acute generalized and caffeine citrate. of prescription drug products exanthematous pustulosis containing acetaminophen to (AGEP), can be fatal. These Doses specified when address the risk of serious skin reactions can occur with first- prescribing should always be reactions. The US FDA will also time use of acetaminophen or expressed as caffeine citrate request that manufacturers at any time while it is being because of a risk of confusion add a warning about serious taken. Other drugs used to and potential for dosing errors skin reactions to the product treat fever and pain/body (2 mg caffeine citrate is labels of OTC acetaminophen aches (e.g., non-steroidal anti- equivalent to 1 mg caffeine). drug products marketed under inflammatory drugs, or a new drug application and will Health-care professionals are NSAIDS, such as ibuprofen and encourage manufacturers of also advised that caffeine naproxen) also carry the risk drug products marketed under citrate is for use in neonatal of causing serious skin the OTC monograph do the intensive care units only, and reactions, which is already