WHO PHARMACEUTICALS NEWSLETTER prepared in collaboration with the WHO Collaborating Centre for International Drug Monitoring, Uppsala, Sweden The aim of this Newsletter is to disseminate information on the No. 6, 2004 safety and efficacy of pharmaceutical products, based on information received from our network of “drug information officers” and other sources such as specialized bulletins and journals, as well as partners in News & Issues WHO. The information is produced in the form of résumés in English, This is the final issue of the newsletter for the year 2004. We full texts of which may be obtained hope that the information covered has been useful in your work on request from: and in keeping abreast of recent developments in drug safety. As stated in the previous issues, we have now established a Quality Assurance and Safety: system for electronic mailing of the newsletter to accommodate Medicines, EDM–HTP those of you who cannot be included in our postal mailing list. World Health Organization, To join this list, please send an email to [email protected] 1211 Geneva 27, Switzerland with the message text: subscribe WHO-PHN. E-mail address: [email protected] Fax: +41 22 791 4730 This has been a busy year with many new priority areas emerging in drug safety. The World Alliance of Patient Safety Further information on adverse was launched in October and the WHO drug safety programme reactions may be obtained from the will work closely with the Alliance, particularly in reporting WHO Collaborating Centre for medication errors and conducting research on the impact of International Drug Monitoring, safety measures in promoting patient safety solutions. The Stora Torget 3, issue of safety of medicines in children, with emphasis on off- S-753 20 Uppsala, Sweden label use, is also recognized as an important and neglected area Tel: 46-18-65.60.60 that needs to be brought to the attention of WHO. Fax: 46-18-65.60.80 E-mail: [email protected] The Twenty-seventh Annual Meeting of National Centres Internet:http://www.who-umc.org participating in the WHO Programme for International Drug prepared in collaboration with the Monitoring was held from 4 to 6 October, in Dublin, Ireland. We WHO Collaborating Centre for include, in this issue, the observations on the questions International Drug Monitoring, discussed by the working groups at the meeting. We hope these Uppsala, Sweden observations will stimulate innovative and collaborative _________________________ approaches to pharmacovigilance. Last, but not least, we wish Contents all our readers good health and happiness in 2005. Regulatory matters Safety of medicines Feature TABLE OF CONTENTS REGULATORY MATTERS ACTRA-RX AND YILISHEN -- Presence of undeclared sildenafil ................................................................. 1 ADALIMUMAB -- Serious infections if used together with anakinra ............................................................ 1 ANTIDEPRESSANTS -- Label to warn of increased suicidality in children; Patient Medication Guide to advise on risks and precautions to be taken ................................................. 1 ATORVASTATIN -- Interaction with grapefruit juice ................................................................................ 2 BLACK COHOSH COMBINATION #2; YELLOW DOCK COMBINATION #3 -- Presence of aristolochic acid........ 2 CELECOXIB -- Withdrawn in Turkey...................................................................................................... 2 EPOETIN ALFA -- Label change to reflect thrombosis risk ........................................................................ 2 ETANERCEPT, INFLIXIMAB -- Reports of serious infections ..................................................................... 2 INFLIXIMAB -- Lymphoma warning added to label.................................................................................. 2 ISOTRETINOIN -- Enhancement to risk management programme ............................................................ 3 LEVOTHYROXINE SODIUM -- Dysphagia and risk of choking .................................................................... 3 MIFEPRISTONE -- Important labelling changes proposed......................................................................... 3 PERGOLIDE MESYLATE -- Label change: risk of cardiac valvulopathy ........................................................ 4 REMINYL AND AMARYL -- Reports of medication errors ........................................................................... 4 VALDECOXIB -- Label updated to warn about skin reactions .................................................................... 4 SAFETY OF MEDICINES CHOLINESTERASE INHIBITORS -- Reports of cardiac arrhythmias ............................................................ 5 CYCLO-OXYGENASE-2 INHIBITORS -- Plans to review all medicines in this class ........................................ 5 ETHINYLESTRADIOL / CYPROTERONE -- Increased risk of thrombosis....................................................... 5 HERBAL MEDICINES -- Cardiovascular ADRs reported to Health Canada.................................................... 5 INFLUENZA VIRUS VACCINE -- Interactions with drugs........................................................................... 6 MEDROXYPROGESTERONE -- Effect on bone mineral density ................................................................... 6 PAMIDRONATE DISODIUM, ZOLEDRONIC ACID -- Spontaneous reports of osteonecrosis of the jaw ............. 6 SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) -- ADRAC reviews use in children and adolescents . 7 TERBINAFINE -- Reports of blood dyscrasias ......................................................................................... 7 TRICYCLIC ANTIDEPRESSANTS -- Overdose risk .................................................................................... 7 FEATURE Twenty-seventh Annual Meeting of Representatives of the National Centres participating in the WHO Programme for International Drug Monitoring: Observations from Working Groups .................. 8 REGULATORY MATTERS ACTRA-RX AND use of anakinra and other TNF antidepressant drugs, including blocking agents, and since the selective serotonin reuptake YILISHEN adalimumab is also a TNF inhibitors (SSRIs), in children Presence of undeclared blocking agent, Abbott and adolescents with major Laboratories warn that the depressive disorder (MDD), sildenafil combination of anakinra with obsessive compulsive disorder USA. The Food and Drug adalimumab is not (OCD) or other psychiatric Administration (FDA) has recommended. In addition, disorders. The analysis showed warned consumers not to Abbott is also warning that rare a greater risk of suicidality purchase or to consume Actra- but serious anaphylactic and during the first few months of Rx or Yilishen, two products hypersensitivity reactions as treatment in those receiving promoted and offered for sale well as haematologic reactions antidepressants. The average on websites as dietary including aplastic anaemia have risk of such events on drug was supplements for treating been reported in patients 4%, twice the placebo risk of erectile dysfunction and treated with adalimumab; 2 %. According to the FDA enhancing sexual performance treatment should be Public Health Advisory, the in men. The FDA has found that discontinued immediately when expanded warning statements these products contain such hypersensitivity reactions will highlight the following: undeclared prescription are observed and patients strength sildenafil. Sildenafil, should be advised to seek • Antidepressants increase the when taken together with medical attention if signs and risk of suicidal thinking and certain prescription drugs symptoms of haematologic behaviour (suicidality) in containing nitrates (such as events (e.g. persistent fever, children and adolescents nitroglycerin) may cause a pallor, bruising, bleeding) are with MDD and other significant lowering of blood noticed. psychiatric disorders. pressure to an unsafe level. Reference: • Anyone considering the use These drugs should therefore 'Dear Health-care Professional' of an antidepressant in a be taken only under medical letter from Abbott Laboratories, child or adolescent for any supervision. The FDA is 5 November 2004. Available on the clinical use must balance the advising consumers who use Internet at www.fda.gov risk of increased suicidality Actra-Rx or Yilishen to stop with the clinical need. taking these products and to ANTI- consult their health-care • Patients on therapy should providers regarding erectile DEPRESSANTS be observed closely for dysfunction treatment. clinical worsening, Label to warn of suicidality, or unusual Reference: increased suicidality in changes in behaviour. FDA Talk Paper, 2 November 2004. children; Patient Available on the Internet at • Families and caregivers www.fda.gov Medication Guide to should be advised to closely advise on risks and observe the patient and to ADALIMUMAB precautions to be communicate with the taken prescriber. Serious infections if used together with USA. The FDA has directed • A statement regarding whether the particular drug anakinra manufacturers of all antidepressant drugs to include is approved for any USA. Abbott Laboratories, in a boxed warning and expanded paediatric indication(s) and, consultation with FDA, has warning statements in the if so, which one(s). updated the prescribing labels of these products that The FDA has advised that a information for adalimumab alert health-care providers to Patient Medication