Reactions 927 - 9 Nov 2002 Lepirudin: important safety update from the EMEA The European Medicines Evaluation Agency (EMEA) has issued a public statement on ‘Refludan’ [lepirudin] and the risk of fatal anaphylactic reactions.1 The statement was made after the EMEA and its Committee for Proprietary Medicinal Products (CPMP) were made aware of 7 recent reports of severe anaphylactic reactions in patients receiving ‘Refludan’. In 6 cases, the anaphylactic reaction occurred in patients with previous exposure to ‘Refludan’, and 5 of these cases were fatal. In several of the reported cases, ‘Refludan’ was prescribed outside the approved therapeutic indication. The EMEA advises physicians considering treating patients with ‘Refludan’ of the following. • The approved indication for ‘Refludan’ is the anticoagulation of adult patients with heparinassociated thrombocytopenia type II with thromboembolic disease mandating parenteral antithrombotic treatment. • ‘Refludan’ may cause allergic reactions, including anaphylaxis. • Fatal anaphylactic reactions have been reported in patients upon re-exposure to ‘Refludan’, therefore alternative treatment plans must be considered before deciding to re-expose patients to ‘Refludan’. • Patients with recent exposure to ‘Refludan’, other hirudins, or hirudin analogues may be at increased risk of anaphylatic reactions, so prescribers should ascertain previous exposure to these drugs before prescribing ‘Refludan’. • Treatment with ‘Refludan’ should only be undertaken in a setting where medical assistance and access to treatment for anaphylaxis are readily available. • Patients should be informed they have received ‘Refludan’ and advised to inform future prescribers of this. As an urgent measure, the prescribing and patient information for ‘Refludan’ has been modified accordingly through a rapid procedure. The revised product information is available from the European Public Assessment Report of Refludan published on the EMEA website.

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1. EMEA European Agency for the Evaluation of Medicinal Products. EMEA public statement on Refludan (lepirudin) - fatal anaphylactic reactions. Internet Document : [2 pages], Oct 2002. Available from: URL: http://www.emea.eu.int. 2. Health Canada. Important safety information regarding Refludan (Rm). Internet Document : [2 pages], 30 Oct 2002. Available from: URL: http://www.hcsc.gc.ca. 800888337

. . . and from Berlex Canada Berlex Canada Inc. has issued a ‘Dear Healthcare Professional’ letter advising of recent post-marketing reports of anaphylaxis and intracranial bleeding associated with ‘Refludan’.2 In addition to reports of hypersensitivity and anaphylaxis following initial or subsequent exposure to ‘Refludan’, the company advises that rare cases of intracranial bleeding in the absence of thrombolytic therapy have been reported following the administration of ‘Refludan’. In Canada, ‘Refludan’ is indicated for anticoagulation (with aspirin) in adult patients with acute coronary syndromes (ACS), such as unstable angina or acute myocardial infarction without ST elevation, as well as for anticoagulation in patients with heparin-induced thrombocytopenia.

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Reactions 9 Nov 2002 No. 927