Last reviewed 2026-04-20 · How we verify

Rapamune (sirolimus)

Rapamune works by binding to the mTOR protein, inhibiting its activity and preventing the growth and proliferation of certain cells.

Rapamune (sirolimus) is a kinase inhibitor small molecule that targets the serine/threonine-protein kinase mTOR. It was originally developed by PF PRISM CV and is currently owned by the same company. Rapamune is FDA-approved for various indications, including prevention of kidney transplant rejection, pulmonary lymphangioleiomyomatosis, and tuberous sclerosis syndrome. The drug has a bioavailability of 15% and is available as a generic medication from multiple manufacturers. Rapamune is off-patent, with no active Orange Book patents.

At a glance

Mechanism of action

Sirolimus inhibits T-lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (Interleukin [IL]-2, IL-4, and IL-15) stimulation by mechanism that 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), key regulatory kinase. This inhibition suppresses cytokine-driven T-cell proliferation, inhibiting the progression from the G1 to the phase of the cell cycle.Mammalian target of sirolimus (mTOR) inhibitors such as sirolimus have been shown in vitro to inhibit production of certain growth factors that may affect angiogenesis, fibroblast proliferation, and vascular permeabilityStudies in experimental models show

Approved indications

• Gorham's disease
• Lymphangiectasis
• Lymphangioma
• Lymphangiomatosis
• Prevention of Kidney Transplant Rejection
• Pulmonary lymphangioleiomyomatosis
• Renal cell carcinoma
• Tuberous sclerosis syndrome

Boxed warnings

• WARNING: IMMUNOSUPPRESSION, USE IS NOT RECOMMENDED IN LIVER OR LUNG TRANSPLANT PATIENTS Increased susceptibility to infection and the possible development of lymphoma and other malignancies may result from immunosuppression Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of renal transplant patients should use sirolimus for prophylaxis of organ rejection in patients receiving renal transplants. Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient [ see Warnings and Precautions ( 5.1 ) ]. The safety and efficacy of sirolimus as immunosuppressive therapy have not been established in liver or lung transplant patients, and therefore, such use is not recommended [ see Warnings and Precautions ( 5.2 , 5.3 ) ]. Liver Transplantation – Excess Mortality, Graft Loss, and Hepatic Artery Thrombosis (HAT) 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. In this and another study in de novo liver transplant patients, the use of sirolimus in combination with cyclosporine or tacrolimus was associated with an increase in HAT; most cases of HAT occurred within 30 days post-transplantation and most led to graft loss or death [ see Warnings and Precautions ( 5.2 ) ]. Lung Transplantation – Bronchial Anastomotic Dehiscence Cases of bronchial anastomotic dehiscence, most fatal, have been reported in de novo lung transplant patients when sirolimus has been used as part of an immunosuppressive regimen [ see Warnings and Precautions ( 5.3 ) ]. WARNING: IMMUNOSUPPRESSION, USE IS NOT RECOMMENDED IN LIVER OR LUNG TRANSPLANT PATIENTS See Full Prescribing Information for Complete Boxed Warning . Increased susceptibility to infection and the possible development of lymphoma and other malignancies may result from immunosuppression ( 5.1 ). Only physicians experienced in immunosuppressive therapy and management of renal transplant patients should use sirolimus for prophylaxis of organ rejection in patients receiving renal transplants. The safety and efficacy of sirolimus as immunosuppressive therapy have not been established in liver or lung transplant patients, and therefore, such use is not recommended ( 5.2 , 5.3 ). − Liver Transplantation – Excess mortality, graft loss, and hepatic artery thrombosis ( 5.2 ). − Lung Transplantation – Bronchial anastomotic dehiscence ( 5.3 ).

Common side effects

• Peripheral edema
• Hypertriglyceridemia
• Hypertension
• Hypercholesterolemia
• Creatinine increased
• Constipation
• Abdominal pain
• Diarrhea
• Headache
• Fever
• Urinary tract infection
• Anemia

Drug interactions

• amobarbital
• aprobarbital
• barbital
• butalbital
• ethotoin
• fosphenytoin
• hexobarbital
• mephenytoin
• metharbital
• methylphenobarbital
• pentobarbital
• primidone

Key clinical trials

• A Phase 2, Baseline-Controlled Study Evaluating the Safety and Efficacy of PTX-022 (Sirolimus) Topical Gel 3.9% in the Treatment of Cutaneous Venous Malformations (PHASE2)
• Pilot Trial of Allogeneic Blood or Marrow Transplantation for Primary Immunodeficiencies (PHASE2)
• Testing Lutetium Lu 177 Dotatate in Patients With Somatostatin Receptor Positive Advanced Bronchial Neuroendocrine Tumors (PHASE2)
• Comparing Retreatment of 177Lu-DOTATATE PRRT Versus the Usual Treatment in Patients With Metastatic Unresectable Gastroenteropancreatic Neuroendocrine Tumors, NET RETREAT Trial (PHASE2)
• Virotherapy and Natural History Study of KHSV-Associated Multricentric Castleman s Disease With Correlates of Disease Activity (PHASE2)
• Part B- G1X-CGD (Lentiviral Vector Transduced CD34+ Cells) in Patients With X-Linked Chronic Granulomatous Disease (PHASE1,PHASE2)
• Combination Chemotherapy With or Without Temsirolimus in Treating Patients With Intermediate Risk Rhabdomyosarcoma (PHASE3)
• SELVA: A Phase 3 Study Evaluating QTORIN 3.9% Rapamycin Anhydrous Gel in the Treatment of Microcystic Lymphatic Malformations (PHASE3)

Patents

Primary sources

Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.

Competitive intelligence

For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:

• Rapamune CI brief — competitive landscape report
• Rapamune updates RSS · CI watch RSS
• Pfizer portfolio CI