Liver Transplant Drug Linked to Increased Risk of Death

Liver transplant patients who were treated with the drug sirolimus (also called Rapamune) following surgery appear to be at increased risk of death, the Food and Drug Administration is warning.

New clinical trial data suggests that stable liver transplant patients who were switched from a calcineurin inhibitor (CNI)-based immunosuppressive regimen to treatment with sirolimus were more likely to die or suffer severe adverse reactions, the FDA said.
The clinical trial was conducted by Wyeth, the maker of sirolimus. Wyeth submitted the results of the study to the FDA on March 25, 2009, officials said. The trial compared stable liver transplant patients who were switched from a CNI-based therapy to sirolimus to patients who remained on the CNI-based regimen.

The FDA is advising transplant physicians and patients about the clinical trial findings and continuing to examine the study data. The agency may decide to order changes to the labeling of the drug to further warn users and their doctors of the risk of mortality, officials said.

The FDA also issued the following recommendations on how physicians should handle sirolimus treatment:

• Sirolimus is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving kidney transplants.

• The safety and the efficacy of sirolimus as an immunosuppressant have not been established in liver or lung transplant patients. This information is in the Boxed Warning of the sirolimus label.

• The current Boxed Warning of sirolimus indicates that the use of sirolimus in combination with tacrolimus was associated with excess mortality and graft loss in a study in de novo liver transplant patients. Many of these patients had evidence of infection at or near the time of death.

• Therapeutic drug monitoring is recommended for all patients receiving sirolimus.

• Therapeutic drug monitoring should not be the sole basis for adjusting sirolimus therapy. Careful attention should be paid to clinical signs and symptoms, tissue biopsy findings, and laboratory parameters.

• Patients unable to take the tablets should be prescribed the sirolimus oral solution and instructed in its use.

• Patients should be counseled that sirolimus is to be taken by mouth, once a day, consistently and with or without food.

• Sirolimus tablets should not be crushed, chewed or split.

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