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Important Safety Information on the Dosage and Administration of Refludan (lepirudin) - Berlex Canada Inc.
Date: 2005-06-09
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MHPD-DPSC
This is duplicated text of a letter from Berlex Canada Inc.
Contact the company for a copy of any references, attachments or enclosures.
NOTICE TO HOSPITALS
Health Canada Endorsed Important Safety Information on the Dosage and Administration of REFLUDAN® (lepirudin)
June 9, 2005
To: Hospital Chief of Medical Staff
Please distribute to the departments of Internal Medicine, Cardiology, Hematology, Surgery, and Pharmacy, to the Intensive and Coronary Care Units, and to other involved professional staff. Post this NOTICE in your institution.
Subject: Important dosage and administration information for the transition from REFLUDAN (lepirudin) to oral anticoagulation when REFLUDAN has been used to treat HIT (heparin induced thrombocytopenia).
Berlex Canada Inc., in consultation with Health Canada, has revised the Product Monograph for REFLUDAN® (lepirudin). REFLUDAN® is indicated for anticoagulation in patients with heparin induced thrombocytopenia (HIT) and associated thromboembolic disease in order to prevent further thromboembolic complications. REFLUDAN® is also indicated for anticoagulation in adult patients with acute coronary syndromes (ACS); i.e. unstable angina/acute myocardial infarction without ST elevation. In patients with ACS, REFLUDAN® is intended for use with ASA.
The following information is relevant to patients with HIT:
- Serious thrombotic events can occur in HIT patients. Caution should be exercised in the timing of drug administration during the transition period between discontinuing parenteral anticoagulation therapy, such as REFLUDAN , and starting oral anticoagulation.
- Coumarin derivatives should only be initiated when platelet counts are normalizing. The intended maintenance dose should be started with no loading dose. To avoid prothrombotic effects when initiating coumarin, REFLUDAN® should be continued for 4 to 5 days and discontinued when the INR stabilizes within the desired target range.
It is recommended that coumarin therapy be avoided during acute HIT and only be initiated after a substantial recovery of the platelet count has occurred. This is based on current scientific knowledge of coumarin-induced hypercoagulability during initiation of vitamin K antagonists, as presented in the literature.1 There is one published case report of venous limb gangrene involving a lepirudin-treated patient in the US.2 Reporting rates determined on the basis of spontaneously reported post-marketing events are generally presumed to underestimate the risks associated with the drug treatments.
The Product Monograph for REFLUDAN® has been updated as of April 25, 2005, to include this information under DOSAGE AND ADMINISTRATION, Monitoring and Adjustment of Therapy, Use in Patients Scheduled for a Switch to Oral Anticoagulation. It reads as follows:
"REFLUDAN® monotherapy influences the INR/prothrombin time in a dose dependent, gradual and linear fashion (mean INR increase +0.14 with a PTT in the recommended therapeutic range in the absence of other anticoagulants).
In REFLUDAN® -treated patients with a PTT values within the recommended target range receiving overlapping therapy with oral anticoagulants and who had stable therapeutic INR values, a cumulative analysis of two prospective trials did not find evidence of a relevant decrease in INR values upon cessation of REFLUDAN® treatment.
If a patient is scheduled to receive coumarin derivatives (vitamin K antagonists) for oral anticoagulation after REFLUDAN® therapy, the following should apply: Coumarin derivatives should be initiated only when platelet counts are normalizing. The intended maintenance dose should be started with no loading dose. To avoid prothrombotic effects when initiating coumarin, continue parenteral anticoagulation for 4 to 5 days. The parenteral agent can be discontinued when INR stabilizes within the desired target range."
The identification, characterization, and management of marketed health product-related adverse reactions are dependent on the active participation of health care professionals in adverse drug reaction reporting programmes. Any occurrence of serious and/or unexpected adverse reactions in patients receiving REFLUDAN® (lepirudin) should be reported to Berlex Canada Inc. or the Marketed Health Products Directorate at the following addresses:
334 Avro Avenue
Pointe-Claire, Quebec
H9R 5W5
Tel: (800) 361-0240 or by fax at (514) 631-4721
Any suspected adverse reaction can also be reported to:
Canadian Adverse Drug Reaction Monitoring Program (CADRMP)
Marketed Health Products Directorate
HEALTH CANADA
Address Locator: 0701C
OTTAWA, Ontario, K1A 0K9
Tel: (613) 957-0337 or Fax: (613) 957-0335
To report an Adverse Reaction, consumers and health professionals may call toll free:
Tel: 866 234-2345
Fax: 866 678-6789
cadrmp@hc-sc.gc.ca
For other inquiries, please refer to contact information:
Marketed Health Products Directorate
Email: mhpd_dpsc@hc-sc.gc.ca
Telephone: (613) 954-6522
Fax: (613) 952-7738
The AR Reporting Form and the AR Guidelines can be found on the Health Canada web site or in The Canadian Compendium of Pharmaceuticals and Specialties.
Your professional commitment in this regard has an important role in protecting the well-being of your patients by contributing to early signal detection and informed drug use. Health Canada asks that you share these recommendations with your staff or membership and encourage their implementation in the interest of patient safety.
Should you have any questions or require additional information, please contact Berlex Canada Inc. (telephone 800-361-0240 or by fax at 514-631-4721).
Sincerely,
original signed by
Jean-Louis Stril, M.D.
Manager, Disease Management and Drug Safety
Berlex Canada Inc.
1 Warkentin et al. : Heparin-induced thrombocytopenia : recognition, treatment and prevention. The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126 (Suppl):311S-337S.
2 Smythe et al.: Venous Limb Gangrene During Overlapping Therapy With Warfarin and a Direct Thrombin Inhibitor for Immune Heparin-Induced Thrombocytopenia. Am J Hematol 2002;71:50-52
334, avenue Avro, Pointe-Claire (Québéc) H9R 5W5
Tél. : (514) 631-7400 Fax : (514) 636-9177 
www.berlex.com
