Archived – Important New Safety Information Regarding ZENAPAX (Daclizumab)

Starting date:

November 6, 2003

Posting date:

November 11, 2003

Type of communication:

Notice to Hospitals

Subcategory:

Biologic/vaccine

Source of recall:

Health Canada

Issue:

New safety information

Audience:

Hospitals

Identification number:

RA-17000620

This is duplicated text of a letter from Hoffmann-La Roche Limited

Contact the company for a copy of any references, attachments or enclosures.

Notice about Health Canada advisories

NOTICE TO HOSPITALS Important New Safety Information Regarding ZENAPAX (daclizumab)

November 6, 2003

To: Hospital Chief of Medical Staff

Please distribute to the relevant Departments of Surgery, Medicine, Pediatrics, Geriatrics, Intensive Care, Anesthesiology, Emergency, Nursing, Pharmacy, Laboratory Services, and other involved professional staff and post this NOTICE in your institution.

Subject:

Possible increase in mortality associated with Zenapax (daclizumab) in cardiac transplant patients

The purpose of this notice is to inform you of important safety information regarding ZENAPAX® (daclizumab). Due to the significance of this information the Product Monograph will be revised to include statements describing the increased mortality observed in a cardiac transplant study and updated information regarding hypersensitivity reactions.

Please note that Zenapax is not indicated for the prophylaxis of acute organ rejection in patients receiving cardiac transplants.

• Zenapax in combination with cyclosporin, mycophenolate mofetil and corticosteroids may be associated with an increase in mortality due to fatal infections from pronounced immunosuppression in cardiac transplant patients.
  
   
• Concomitant use of anti-lymphocyte antibody therapy may be a factor in some of these fatal infections.
  
   
• As seen with similar IL-2 receptor antagonists, severe, acute hypersensitivity reactions, including anaphylaxis, have been observed both on initial exposure to Zenapax and following re-exposure.

Cardiac Transplant Study

A cardiac transplant study was conducted to determine if the incidence of acute rejection was reduced with daclizumab compared to placebo when used in combination with cyclosporin, mycophenolate mofetil, and corticosteroids. The study was double blinded with 434 patients randomized to receive either daclizumab (n=216) or placebo (n=218). It was observed that mortality at 6 and 12 months was increased in those patients receiving daclizumab compared to those receiving placebo (7% vs 5%, respectively at 6 months; 10% vs 6% respectively at 12 months).

Due to the blind nature of the study, there were cases where investigators prescribed concomitant polyclonal antilymphocyte therapy to protect patients who might be in the placebo arm. Because of the blinding, patients treated with daclizumab also got such therapy. Most of the differences in mortality can be explained by this over immunosuppression and the incidence of infection in the daclizumab treated patients who received this double antibody therapy. Concomitant use of anti-lymphocyte antibody therapy may also be a factor in some of the fatal infections.

Hypersensitivity Reactions

Severe, acute (onset within 24 hours) hypersensitivity reactions including anaphylaxis have been observed both on initial exposure to ZENAPAX and following re-exposure. These reactions may include hypotension, bronchospasm, wheezing, laryngeal edema, pulmonary edema, cyanosis, hypoxia, respiratory arrest, cardiac arrhythmia, cardiac arrest, peripheral edema, loss of consciousness, fever, rash, urticaria, diaphoresis, pruritus, and/or injection site reactions. If a severe hypersensitivity reaction occurs, therapy with ZENAPAX should be permanently discontinued. Medications for the treatment of severe hypersensitivity reactions including anaphylaxis should be available for immediate use. Patients previously administered ZENAPAX should only be re-exposed to a subsequent course of therapy with caution. The potential risks of such re-administration, specifically those associated with immunosuppression, are not known.

Reporting rates determined on the basis of spontaneous reported post-marketing adverse events are generally presumed to underestimate the risks associated with drug treatments.

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 occurrences of serious and/or unexpected adverse reactions in patients receiving ZENAPAX should be reported to Hoffmann-La Roche Limited:

Hoffmann-La Roche Limited

2455 Meadowpine Boulevard

Mississauga, Ontario, L5N 6L7

Drug Safety Tel: 1-888-762-4388 Fax: 905-542-5610

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.

Sincerely,

Hoffmann-La Roche Limited

original signed by

Lorenzo Biondi

Vice President, Medical and Regulatory Affairs

Any suspected adverse incident 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 AR Reporting Form and the AR Guidelines can be found on the TPD web site or in The Canadian Compendium of Pharmaceuticals and Specialties.