Rapamune (sirolimus) Tablets

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.


Approval Status:

Approved August 2000

Specific Treatments:

Prevention of organ rejection in patients receiving kidney transplants

Therapeutic Areas

General Information

Rapamune (sirolimus) is an immunosuppressant agent developed to reduce organ rejection in patients receiving kidney transplants. It is to be used in combination with cyclosporine and corticosteroids, and has been shown to significantly reduce rejection rates when compared to control regimens.

Kidney transplantation is one of the most common transplant procedures performed in the United States. Patients receive immunosuppressant agents in order to lower the body's normal immune response, which in turn decreases the risk of organ rejection by the immune system.

Clinical Results

Previous trials for the oral solution of Rapamune indicated that sirolimus is more effective than placebo treatment in reducing the rate of transplant rejection. Two randomized, double-blind, multicenter, controlled trials were conducted to investigate the possible benefits of Rapamune. The studies compared two dose levels of Rapamune oral solution to placebo and azathioprine treatment, all of which were administered in combination with cyclosporine and corticosteroids.

The two phase III trials evaluating the efficacy of sirolimus have indicated that sirolimus is safe and effective. The Rapamune U.S. Multicenter Study included 719 renal transplant recipients who received either sirolimus or azathioprine treatments. Both sirolimus doses were found to be significantly more effective than azathioprine in reducing rejection. In the Rapamune Global Study, conducted in Australia, Canada, Europe, and the United States, 576 renal transplant recipients received either sirolimus or placebo treatment. Both studies demonstrated that sirolimus was more effective in reducing organ rejection within the first 6 months following a transplant. (from the Drug Monitor)

Side Effects

The following side effects have been associated with the oral solution of Rapamune:

  • High cholesterol
  • High blood pressure
  • Acne
  • Anemia
  • Fever
  • Diarrhea
  • Rash

Additionally, there is an increased risk of infection and malignancies, which is common with immunosuppression treatment.

Mechanism of Action

Sirolimus inhibits T lymphocyte activation and proliferation, which occurs in response to antigenic and cytokine stimulation; however, its mechanism is distinct from that of other immunosuppressants. Sirolimus also inhibits antibody production. In cells, sirolimus binds to the immunophilin, FK Binding Protein-12 (FKBP-12), to generate an immunosuppressive complex. The sirolimus: FKBP-12 complex has no effect on calcineurin activity. This complex binds to and inhibits the activation of the mammalian Target of Rapamycin (mTOR), a key regulatory kinase. This inhibition suppresses cytokine-driven T-cell proliferation, inhibiting the phase progression of the cell cycle. (from FDA label)

Additional Information

For more information on Rapamune, please visit the web site of Wyeth-Ayerst. The Products section of this web site offers prescribing and general information for many of their products.