WHO DRUG INFORMATION VOLUME 2 1• NUMBER 2 • 2007 PROPOSED INN LIST 9 7 INTERNATIONAL NONPROPRIETARY NAMES FOR PHARMACEUTICAL SUBSTANCES WORLD HEALTH ORGANIZATION • GENEVA WHO Drug Information Vol 21, No. 2, 2007 World Health Organization WHO Drug Information Contents Safety and Efficacy Issues Eculizumab approved for paroxysmal Entecavir: not for use in HIV/HBV nocturnal haemoglobinuria 115 co-infection 87 Deferasirox: acute renal failure and Access to Medicines cytopenias 87 Neglected tropical diseases 116 Safety of oseltamivir 87 Open access database for neglected Fluticasone: reports of behavioural medicines development 116 changes 88 Quetiapine: pancreatitis and thrombo- cytopenia 88 Consultation Document Aprotinin: hypersensitivity reactions and renal dysfunction 89 International Pharmacopoeia Metoclopramide in children: extra- Artemether and lumefantrine capsules 118 pyramidal symptoms 90 Magnesium sulfate injection 123 Drug-eluting stents: to be used with Zinc sulfate 124 caution 90 Paediatric zinc sulfate tablets 125 Darbepoetin alfa and epoetin alfa: update Paediatric zinc sulfate oral solution 127 for non-myeloid malignancies 91 Ayurvedic and Chinese medicines: Recent Publications, heavy metals 91 ADHD drugs: cardiovascular and psychi- Information and Events atric events 92 Informed consent for research in resource- Clozapine can impair motility of the entire poor settings 129 GI tract 93 Lessons learned in home management of malaria 129 Developing drug information centres Essential Medicines in India 130 th 15 Model List of Essential Medicines 94 First-in-man clinical trials for high risk th Model List of Essential Medicines, 15 products 130 Edition, revised March 2007 95 Pakistan Pharmacists Society discussion forum 130 New quality assurance compendium 130 Regulatory Action and News Pharmacological management of human Tegaserod: marketing suspension 112 H5N1 infection 131 Pergolide: voluntary withdrawal of products 112 Aliskiren approved for hypertension 113 Proposed International Lapatinib approved for breast cancer 114 Adalimumab approved for Crohn disease114 Nonproprietary Names: Rapid test for meningitis cleared for List 97 133 marketing 114 85 World Health Organization WHO Drug Information Vol 21, No. 2, 2007 Announcement The 13th International Conference of Drug Regulatory Authorities (ICDRA) will be hosted by the Swiss Agency for Therapeutic Products (Swissmedic) in collaboration with the World Health Organization The ICDRA will take place in Berne, Switzerland from 16 to 19 September 2008 Updated information will be provided regularly at: http://www.icdra.ch or http://www.who.int/medicines/icdra/en/index/html 86 WHO Drug Information Vol 21, No. 2, 2007 Safety and Efficacy Issues Entecavir : not for use in Deferasirox is indicated in the manage- HIV/HBV co-infection ment of chronic iron overload in patients with transfusion-dependent anaemias European Union — The Committee for aged 6 years or older. It is also indicated Medicinal Products for Human Use in the management of chronic iron over- (CHMP) reminds healthcare professionals load in patients with transfusion-depend- that entecavir (Baraclude®) has not been ent anaemias aged two to five who evaluated for the treatment of patients cannot be adequately treated with with chronic hepatitis B virus (HBV) infec- deferoxamine. tion who are co-infected with the human immunodeficiency virus (HIV) and are not Therapy should be initiated and main- receiving highly active antiretroviral tained by physicians experienced in the therapy (HAART). treatment of chronic iron overload due to blood transfusions. Based on new data, the EMEA advises healthcare professionals that: Cases of acute renal failure (some with fatal outcome) have been reported • Baraclude® has not been evaluated in following the post-marketing use of HIV/HBV co-infected patients not deferasirox. For the fatal cases, it is simultaneously receiving effective HIV impossible to completely exclude a treatment. contributory role of deferasirox to the renal impairment The fact that there was • When considering therapy with ente- an improvement after stopping the cavir in an HIV/HBV co-infected patient treatment in most of the cases with non- not receiving HAART, there appears to fatal acute renal failure is suggestive of a be a risk of developing HIV resistance. contributory role. Deferasirox has not • Until reassuring data become available, been studied in patients with renal impair- Baraclude® should only be considered ment. in this setting under exceptional circum- stances. Reference: Communication from Novartis Pharmaceuticals Canada Inc. on Medeffect at http://www.hc-sc.gc.ca Reference: European Medicines Agency, Public Statement, EMEA/79902/20075. March 2007. Safety of oseltamivir Deferasirox: acute renal European Union — The European Medicines Agency (EMEA) has docu- failure and cytopenias mented new reports of neuropsychiatric Canada — The manufacturer of defera- adverse events occurring with the use of sirox (Exjade®) has updated the safety oseltamivir (Tamiflu®) originating from information regarding reports of acute Japan. These cases have been detected renal failure and peripheral blood cyto- through routine safety monitoring. penias. 87 Safety and Efficacy Issues WHO Drug Information Vol 21, No. 2, 2007 The Agency’s Committee for Medicinal the reporter did not see a causal relation- Products for Human Use (CHMP) has ship between the adverse drug reaction monitored closely all adverse drug and salbutamol. Psychiatric effects have reactions reported in connection with the also been reported in association with the use of oseltamivir since it was introduced use of oral corticosteroids and inhaled in the European Union in 2003. budesonide, which raises the possibility of a group effect. The CHMP recommended an update of the product information on neuropsychi- Reference: Fluticasone inhalation and behavioural changes in children. Lareb, atric side effects: “Convulsion, depressed Netherlands Pharmacovigilance Centre, level of consciousness, abnormal behav- January 2007 (www.lareb.nl). iour, hallucinations and delirium have been reported during Tamiflu® adminis- tration, leading in rare cases to accidental Quetiapine: pancreatitis injury. Patients, especially children and and thrombocytopenia adolescents should be closely monitored Canada — Quetiapine (Seroquel®) is an and their healthcare professional should atypical antipsychotic drug indicated for be contacted immediately if the patient the management of symptoms of schizo- shows any signs of unusual behaviour.” phrenia and the acute management of manic episodes associated with bipolar The EMEA and CHMP will continue to disorder (1). In Canada, quetiapine has closely monitor any emerging safety been marketed since December 1997. information on Tamiflu®, including neuro- psychiatric disorders. If any concerns From 1997 to 2006, Health Canada has emerge, further action will be taken. With received 615 domestic reports of adverse these measures in place, the CHMP reactions suspected of being associated maintains its opinion that the benefits of with the use of quetiapine. Nine reports Tamiflu® outweigh its risks when the involved cases of pancreatitis and 11 product is used according to the adopted involved cases of thrombocytopenia. recommendations. Neither of these ARs is mentioned in the Canadian product monograph (1). Reference: EMEA Press Release, 23 March 2007. Doc. Ref. EMEA/134566/2007. http:// www.emea.europa.eu Pancreatitis The 9 reported cases of pancreatitis involved patients aged 24–71 years. In 5 Fluticasone: reports of cases, quetiapine was the only suspect behavioural changes drug; in the other cases, reported co- Netherlands — The Netherlands Phar- suspect drugs included medications that have been associated with pancreatitis: macovigilance Centre, Lareb, has re- ceived 17 reports of behavioural changes clozapine, divalproex sodium, fenofibrate in children associated with the use of and minocycline (2, 3). inhaled fluticasone propionate or salmeterol/fluticasone propionate (4). In Acute pancreatitis typically presents as 11 cases, symptoms disappeared when an acute inflammation of the pancreas that may or may not involve the surround- fluticasone propionate was withdrawn. A positive rechallenge was observed in one ing tissues (2). Gallstones and heavy case. Six patients who had received alcohol use are the most common causes (2). The severity of drug-induced pan- fluticasone propionate also received salbutamol. However, in all but one case, creatitis is variable; the majority of pa- 88 WHO Drug Information Vol 21, No. 2, 2007 Safety and Efficacy Issues tients recover without any long-term 4. Kale-Pradhan PB, Conroy JL. Pancreatitis. morbidity, but 5% –15% of patients In: Drug-induced diseases: prevention, experience life-threatening complications detection, and management. Bethesda (MD): (4). People at risk of drug-induced pan- American Society of Health-System Pharma- creatitis include elderly patients taking cists, Inc.; 2005. p. 537–47. multiple medications, patients who are 5. Adverse Drug Reactions Advisory Commit- HIV positive, patients who have cancer tee (ADRAC). Drug induced pancreatitis. Aust and patients receiving immunomodulatory Adv Drug Reactions Bull, 2006;25(6):22. agents (5). 6. Skirvin JA. Thrombocytopenia. In: Tisdale Thrombocytopenia JE, Miller DA, editors. Drug-induced diseases: The 11 reported cases of thrombocytope- prevention, detection, and management. nia involved patients aged 28–84 years. Bethesda