Association between Torisel (temsirolimus) concentrate for injection and hypersensitivity/infusion reactions- For Health Professionals

Starting date:

August 6, 2008

Posting date:

August 11, 2008

Type of communication:

Dear Healthcare Professional Letter

Subcategory:

Drugs

Source of recall:

Health Canada

Audience:

Healthcare Professionals

Identification number:

RA-170001915

This is duplicated text of a letter from Wyeth Canada.
Contact the company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

Health Canada Endorsed Important Safety Information on Torisel (temsirolimus) concentrate for injection

August 6, 2008

Subject: Association of Torisel™ (temsirolimus) concentrate for injection with Hypersensitivity/Infusion reactions

Dear Health Care Professional,

Wyeth Pharmaceuticals, a division of Wyeth Canada, in collaboration with Health Canada, would like to advise you regarding new safety information concerning the timing of and monitoring for hypersensitivity/infusion reactions associated with Torisel™ (temsirolimus) administration.

Torisel™ (temsirolimus) concentrate for injection is indicated for the treatment of metastatic renal cell carcinoma.

Forty-six (46) medically confirmed reports (30 spontaneous reports) of hypersensitivity/infusion reactions of variable severity including 6 life-threatening and 1 fatal reaction have been reported worldwide, as of April 03, 2008. Other related adverse events including but not limited to flushing, chest pain, dyspnea, hypotension, apnea, and loss of consciousness in association with the intravenous administration of 25 mg Torisel™ (temsirolimus) have been reported. There have been no serious Canadian post-marketing cases reported at this time.

• Of 39 reports in which dose-time was reported, the majority (25) occurred with the first dose, often within the first few minutes of the infusion, although hypersensitivity reactions have also been reported associated with subsequent infusions.
• Patients should be pre-medicated accordingly and monitored strictly during Torisel™ (temsirolimus) use and emergency supportive care should be readily available.
• Torisel™ (temsirolimus) infusion should be interrupted in all patients with severe infusion reaction and appropriate medical care administered. A benefit-risk assessment should be done prior to the continuation of Torisel™ (temsirolimus) therapy in patients with severe or life-threatening reactions.

It is recommended that patients be pre-medicated with a selective H₁-receptor antagonist before the start of the intravenous Torisel™ (temsirolimus) infusion. Torisel™ (temsirolimus) should be used with caution in patients with known hypersensitivity to an antihistamine, or who cannot receive an antihistamine for other medical reasons. If a patient develops a hypersensitivity/infusion reaction during the Torisel™ (temsirolimus) infusion despite the pre-medication, the infusion should be stopped immediately and appropriate medical care administered. A benefit-risk assessment should be done for each patient in order to decide whether treatment can resume with the administration of an appropriate medication such as an intravenous antihistamine with H₁-receptor antagonist activity (e.g. diphenhydramine, or equivalent) and/or an intravenous H₂-receptor antagonist (e.g. famotidine, ranitidine, or equivalent) prior to continuation of Torisel™ (temsirolimus) at a slower infusion rate (up to 60 minutes).

Torisel™ (temsirolimus) is contraindicated in patients who have a history of anaphylaxis after exposure to Torisel™ (temsirolimus), sirolimus or any other component of Torisel™ (temsirolimus).

The Warnings and Precautions section of the Torisel™ (temsirolimus) Product Monograph has been updated in consultation with Health Canada with respect to this safety information. Please contact Wyeth Canada Medical Information at 1-800-461-8844 with any questions or concerns, or to request a copy of the current Product Monograph.

A copy of this letter and the Public Communication are available on the Health Canada website. These documents can also be viewed on the Wyeth Canada website.

Managing marketed health product-related adverse reactions depends on the reporting of such events by health care professionals and consumers. Reporting rates determined on the basis of spontaneously reported post-marketing adverse reactions are generally presumed to underestimate the risks associated with health product treatments. Any case of serious hypersensitivity/infusion reactions or other serious or unexpected adverse reactions in patients receiving Torisel™ (temsirolimus) should be reported to Wyeth Canada or Health Canada at the following addresses:

Wyeth Canada
Medical Information & Pharmacovigilance
50 Minthorn Boulevard
Markham, Ontario L3T 7Y2
Tel.: 1-800-461-8844
Fax: 905-470-4385

Any suspected adverse reaction can also be reported to:

Canada Vigilance Program
Marketed Health Products Directorate
Health Canada
Address Locator: 0701C
Ottawa, Ontario, K1A 0K9
Tel.: 613-957-0337
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
CanadaVigilance@hc-sc.gc.ca

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.

For other inquiries related to this communication, please contact Health Canada at:

Marketed Health Products Directorate (MHPD)
E-mail: MHPD_DPSC@hc-sc.gc.ca
Tel.: 613-954-6522
Fax: 613-952-7738

Wyeth is committed to ensuring that Torisel™ (temsirolimus) is used safely and effectively and to providing you with the most current product information.

original signed by

Dr. Neil Maresky, M.B., B.Ch.
Vice-President
Scientific Affairs