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Archived – Important Drug Safety Information on Rapamune® – Wyeth-Ayerst Canada Inc.
- Starting date:
- May 14, 2002
- Posting date:
- May 14, 2002
- Type of communication:
- Dear Healthcare Professional Letter
- Subcategory:
- Drugs
- Source of recall:
- Health Canada
- Issue:
- Important Safety Information
- Audience:
- Healthcare Professionals
- Identification number:
- RA-17000380
This is duplicated text of a letter from Wyeth-Ayerst Canada Inc.
Contact the company for a copy of any references, attachments or enclosures.
Notice about Health Canada advisories
Important Correction Drug Safety Information
May 14, 2002
Dear Health Care Provider:
Following discussion with Health Canada, Wyeth-Ayerst Canada Inc. would like to bring to your attention an important correction to drug information about Rapamune® (sirolimus). Recently, a publication was produced by Galen Press as a part of the Protocols Series. It had the title "Protocols Series - Guidelines from experts in transplantation: Sirolimus for liver transplantation: Primary and rescue immunosuppression." This publication was supported by an unrestricted educational grant from Wyeth.
This publication did not provide the following important information:
The safety and efficacy of Rapamune® (sirolimus) as immunosuppressive therapy have not been established in liver transplant patients, and therefore, such use is not recommended. Wyeth-Ayerst Canada Inc. will be working with Health Canada to update the Product Monograph to reflect the following:
Liver Transplantation - Excess Mortality, Graft Loss, and Hepatic Artery Thrombosis (HAT): The use of sirolimus in combination with tacrolimus was associated with excess mortality and graft loss in a study in de novo liver transplant recipients. Many of these patients had evidence of infection at or near the time of death.
In this and another study in de novo liver transplant recipients, the use of sirolimus in combination with cyclosporine or tacrolimus was associated with an increase in HAT; most cases of HAT occurred within 30 days post-transplantation and most led to graft loss or death. The safety and efficacy of Rapamune as immunosuppressive therapy have not been established in liver transplant patients, and therefore, such use is not recommended.
Wyeth Research has suspended enrollment in a Phase II clinical study comparing sirolimus in combination with tacrolimus/corticosteroids to tacrolimus/corticosteroids alone in de novo liver transplant patients. This action was prompted by an imbalance in the observed rates of hepatic artery thrombosis with a rate of 5.5% (6/110) in the sirolimus-tacrolimus treatment group, all of which occurred within 16 days post-liver transplantation, versus 0.9% (1/112) in the tacrolimus-treated control arm.
A previous clinical trial in de novo liver transplant patients in which Rapamune was used in combination with cyclosporine and corticosteroids revealed an excess of hepatic artery thrombosis in patients on the combination regimen (10/112, 8.9%) as compared to the tacrolimus/corticosteroid control arm (2/52, 3.8%).
Rapamune is indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal transplants. Rapamune should be used concomitantly with cyclosporine and corticosteroids.
Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of organ transplant patients should use Rapamune. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient.
The identification, characterization, and management of drug-related adverse events are dependent on the active participation of health care professionals in adverse drug reaction reporting programmes. Any occurrences of adverse events in patients receiving Rapamune should be reported to Wyeth-Ayerst Canada Inc. or the Marketed Health Products Directorate at the following addresses:
Pharmacovigilance Department
Wyeth-Ayerst Canada Inc.
88 McNabb Street
MARKHAM, Ontario, L3R 6E6
Tel: 1-800-461-8844
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.
Sincerely,
original signed by
Victoria Kusiak, M.D.
Vice President,
Global Medical Affairs
original signed by
Adriana Ziff, M.Sc.Pharm., R.Ph.
Assistant Director,
Medical Information and Pharmacovigilance
Any suspected adverse reactions can also be reported to:
Canadian Adverse Drug Reaction Monitoring Program (CADRMP)
Marketed Health Products Directorate
Health Canada
Address Locator: 0201C2
Ottawa, Ontario, K1A 1B9
Tel: (613) 957-0337 or Fax: (613) 957-0335
Toll free for consumers and health professionals:
Tel: 866 234-2345, Fax: 866 678-6789
cadrmp@hc-sc.gc.ca
The ADR Reporting Form can be found in The Canadian Compendium of Pharmaceuticals and Specialties, or on the TPD website, along with the ADR Guidelines.