North America - Two new warning statements have been added to the prescribing information for daclizumab (Zenapax®) indicated for the prevention of graft rejection. These include increased mortality in a cardiac transplant study and updated information regarding hypersensitivity reactions.

The use of daclizumab as part of an immunosuppressive regimen including cyclosporine, mycophenolate mofetil, and corticosteroids may be associated with an increase in mortality. In a randomized, double-blind, placebo-controlled trial of daclizumab for the prevention of allograft rejection in 434 cardiac transplant recipients receiving concomitant cyclosporine, mycophenolate mofetil and corticosteroids, mortality at 6 and 12 months was increased in those patients receiving daclizumab compared to those receiving placebo, sometimes through a higher incidence of severe infections. Concomitant use of anti-lymphocyte antibody therapy may also be a factor.

Severe, acute (onset within 24 hours) hypersensitivity reactions including anaphylaxis have been observed both on initial exposure to daclizumab and following re-exposure. These include hypotension, bronchospasms, wheezing, laryngeal oedema, pulmonary oedema, cyanosis, hypoxia, respiratory arrest, cardiac arrhythmia, cardiac arrest, peripheral oedema, loss of consciousness, fever, rash, urticaria, diaphoresis, pruritus, and/or injection site reactions. If a severe hypersensitivity reaction occurs, therapy with daclizumab should be permanently discontinued. Medications for the treatment of severe hypersensitivity reactions including anaphylaxis should be available for immediate use. Patients previously administered daclizumab 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.

Additionally, the following adverse reactions occurred more frequently in paediatric transplant patients than adult transplant patients: diarrhoea, postoperative pain, fever, vomiting, aggravated hypertension, pruritus and infections of the upper respiratory and urinary tracts.

Reference: Communication from Roche Pharmaceuticals available on http://www.fda.gov/medwatch and www.hc-sc.gc.ca dated 6 November 2003.