On June 11, 2009, the FDA altered healthcare professionals a clinical trial suggests sirolimus may be associated with an increased morality rate. The study compared the mortality rate of stable liver transplant patients who converted from a calcineurin inhibitor (CNI)-based immunosuppressive regimen to sirolimus (Rapamune) to those who remained on a CNI regimen.

The trial was conducted by sirolimus’ manufacturer, Wyeth. After one year, the overall treatment failure rates were significantly higher for the patients converted to sirolimus compared to those that continued on CNIs. Treatment failure is measured by the occurrence of acute rejection or premature discontinuation for any reason. Patients on sirolimus discontinued its use due to an adverse event more often than CNI patients. Sirolimus’s most frequent adverse events were peripheral edema, stomatitis, rash, and mouth ulceration.

Currently, Sirolimus is approved for treating prophylaxis of organ rejection in patients aged 13 years or older receiving kidney transplants. The safety and efficacy of this drug in liver or lung transplant patients have not been established by the FDA.

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.

The FDA is examining this information and will make the appropriate recommendations. The FDA is determining whether a labeling change for sirolimus is needed. In the interim, physicians should continue to use the drug’s professional labeling as a guide to therapy.

At this time, FDA has not made any changes to the professional label for sirolimus.
Any adverse events associated with Sirolimus should be reported to the FDA.

The FDA can be contacted via:
Online at www.fda.gov/medwatch/report.htm
Phone at 1-800-FDA-1088
Fax at 1-800-FDA-0178, using the MedWatch Form 3500
(available at www.fda.gov/medwatch/ getforms.htm)
Mail, using the postage-paid MedWatch Form 3500 (see above), to MedWatch, 5600
Fishers Lane, Rockville, MD 20852-9787
For information please see: http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm165015.htm

Labels: CNI, death, kidney failure, Liver, Rapamune, sirolimus, transplant, Wyeth