Sirolimus

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 a mechanism that is distinct from that of other immunosuppressants. Sirolimus also inhibits antibody production.

• Sirolimus is an mTOR inhibitor immunosuppressant indicated for the prophylaxis of organ rejection in patients aged ≥13 years receiving renal transplants: Patients at low- to moderate-immunologic risk: Use initially with cyclosporine (CsA) and corticosteroids. CsA withdrawal is recommended 2 months to 4 months after transplantation ( 1.1 ).

• Sirolimus is contraindicated in patients with a hypersensitivity to sirolimus [ see Warnings and Precautions ( 5.4 ) ]. Hypersensitivity to sirolimus ( 4 ).contraindicated

Sirolimus tablets are to be administered orally once daily, consistently with or without food [ see Dosage and Administration ( 2.5 ), Clinical Pharmacology ( 12.3 ) ]. Tablets should not be crushed, chewed or split. Patients unable to take the tablets should be prescribed the solution and instructed in its use. Renal Transplant Patients : Administer once daily by mouth, consistently with or without food ( 2 ). Administer the initial dose as soon as possible after transplantation and 4 hours after CsA ( 2.1 , 7.1 ). Adjust the sirolimus maintenance dose to achieve sirolimus trough concentrations within the target-range ( 2.5 ). Hepatic impairment: Reduce maintenance dose in patients with hepatic impairment ( 2.7 , 8.6 , 12.3 ). In renal transplant patients at low-to moderate-immunologic risk : Sirolimus and CsA Combination Therapy: One loading dose of 6 mg on day 1, followed by daily maintenance doses of 2 mg ( 2.2 ). Sirolimus Following CsA Withdrawal: 2 months to 4 months post-transplantation, withdraw CsA over 4 weeks to 8 weeks ( 2.2 ). In renal transplant patients at high-immunologic risk: Sirolimus and CsA Combination Therapy (for the first 12 months posttransplantation): One loading dose of up to 15 mg on day 1, followed by daily maintenance doses of 5 mg ( 2.3 ). Lymphangioleiomyomatosis Patients: Administer once daily by mouth, consistently with or without food ( 2 ). Recommended initial sirolimus dose is 2 mg/day ( 2.4 ). Adjust the sirolimus dose to achieve sirolimus trough concentrations between 5 to 15 ng/mL ( 2.4 ).

Hypersensitivity Reactions ( 5.4 ) Angioedema ( 5.5 ) Fluid Accumulation and Impairment of Wound Healing ( 5.6 ) Hyperlipidemia ( 5.7 ) Decline in Renal Function ( 5.8 ) Proteinuria ( 5.9 ) Latent Viral Infections ( 5.10 ) Interstitial Lung Disease/Non-Infectious Pneumonitis ( 5.11 ) De Novo Use Without Cyclosporine ( 5.12 ) Increased Risk of Calcineurin Inhibitor-Induced Hemolytic Uremic Syndrome/ Thrombotic Thrombocytopenic Purpura/ Thrombotic Microangiopathy ( 5.13 ) Embryo-Fetal Toxicity: Can cause fetal harm. Use of highly effective contraception is recommended for females of reproductive potential during treatment and for 12 weeks after final dose of sirolimus ( 5.15 , 8.1 ) Male Infertility: Azoospermia or oligospermia may occur ( 5.16 , 13.1 ) Immunizations: Avoid live vaccines ( 5.19 ) 5.1 Increased Susceptibility to Infection and the Possible Development of Lymphoma Increased susceptibility to infection and the possible development of lymphoma and other malignancies, particularly of the skin, may result from immunosuppression. The rates of lymphoma/lymphoproliferative disease observed in Studies 1 and 2 were 0.7 to 3.2% (for sirolimus-treated patients) versus 0.6 to 0.8% (azathioprine and placebo control) [ see Adverse Reactions ( 6.1 ) and ( 6.2 ) ]. Oversuppression of the immune system can also increase susceptibility to infection, including opportunistic infections such as tuberculosis, fatal infections, and sepsis.

The following adverse reactions are discussed in greater detail in other sections of the label. Increased susceptibility to infection, lymphoma, and malignancy [ see Boxed Warning, Warnings and Precautions ( 5.1 ) ] Excess mortality, graft loss, and hepatic artery thrombosis in liver transplant patients [ see Boxed Warning, Warnings and Precautions ( 5.2 ) ] Bronchial anastomotic dehiscence in lung transplant patients [ see Boxed Warning, Warnings and Precautions ( 5.3 ) ] Hypersensitivity reactions [ see Warnings and Precautions ( 5.4 ) ] Exfoliative dermatitis [ see Warnings and Precautions ( 5.4 ) ] Angioedema [ see Warnings and Precautions ( 5.5 ) ] Fluid accumulation and impairment of wound healing [ see Warnings and Precautions ( 5.6 ) ] Hypertriglyceridemia, hypercholesterolemia [ see Warnings and Precautions ( 5.7 ) ] Decline in renal function in long-term combination of cyclosporine with sirolimus [ see Warnings and Precautions ( 5.8 ) ] Proteinuria [ see Warnings and Precautions ( 5.9 ) ] Interstitial lung disease [ see Warnings and Precautions ( 5.11 ) ] Increased risk of calcineurin inhibitor-induced HUS/TTP/TMA [ see Warnings and Precautions ( 5.13 ) ] Embryo-fetal toxicity [see Warnings and Precautions ( 5.15 )] Male infertility [see Warnings and Precautions ( 5.16 )] The most common (≥ 30%) adverse reactions observed with sirolimus in clinical studies for organ rejection prophylaxis in recipients of renal transplantation are: peripheral edema, hypertriglyceridemia, hypertension, hypercholesterolemia, creatinine increased, constipation, abdominal pain, diarrhe…

Pregnancy: Based on animal data can cause fetal harm ( 5.15 , 8.1 ). Lactation: Potential for serious adverse effects in breastfed infants based on mechanism of action ( 8.2 ). Females and Males of Reproductive Potential: May impair fertility ( 8.1 , 8.3 , 13.1 ). 8.1 Pregnancy Risk Summary Based on animal studies and the mechanism of action, sirolimus can cause fetal harm when administered to a pregnant woman [see Data, Clinical Pharmacology ( 12.1 )] . There are limited data on the use of sirolimus during pregnancy; however, these data are insufficient to inform a drug-associated risk of adverse developmental outcomes. In animal studies, sirolimus was embryo/fetotoxic in rats at sub-therapeutic doses [ see Data ]. Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Sirolimus crossed the placenta and was toxic to the conceptus. In rat embryo-fetal development studies, pregnant rats were administered sirolimus orally during the period of organogenesis (Gestational Day 6 to 15).

Metabolism

Sirolimus pharmacokinetics activity have been determined following oral administration in healthy subjects, pediatric patients, hepatically impaired patients, and renal transplant patients. The pharmacokinetic parameters of sirolimus in low- to moderate-immunologic risk adult renal transplant patients following multiple dosing with sirolimus 2 mg daily, in combination with cyclosporine and corticosteroids, is summarized in Table 4.

Reports of overdose with sirolimus have been received; however, experience has been limited. In general, the adverse effects of overdose are consistent with those listed in the adverse reactions section [ see Adverse Reactions ( 6 ) ]. General supportive measures should be followed in all cases of overdose. Based on the low aqueous solubility and high erythrocyte and plasma protein binding of sirolimus, it is anticipated that sirolimus is not dialyzable to any significant extent. In mice and rats, the acute oral LD 50 was greater than 800 mg/kg.

• Sep 15, 1999NDANDA021083Pf Prism Cv
• Aug 25, 2000NDANDA021110Pf Prism Cv
• Jan 8, 2014ANDAANDA201676Zydus Pharms
• Oct 27, 2014ANDAANDA201578Dr Reddys
• Jan 28, 2019ANDAANDA211040Novitium Pharma
• Oct 18, 2019ANDAANDA211212Amneal
• Nov 22, 2021NDANDA213312Aadi
• Mar 22, 2022NDANDA213478Nobelpharma

1. 1Off Label Use1,96415%
2. 2Drug Ineffective1,0768.3%
3. 3Product Use In Unapproved Indication7746.0%
4. 4Pyrexia5174.0%
5. 5Diarrhoea5083.9%
6. 6Pneumonia4713.6%
7. 7Acute Kidney Injury4293.3%
8. 8Drug Interaction4233.3%
9. 9Thrombotic Microangiopathy3672.8%
10. 10Transplant Rejection3622.8%
11. 11Cytomegalovirus Infection3402.6%
12. 12Toxicity To Various Agents3092.4%
13. 13Death3012.3%
14. 14Condition Aggravated3002.3%
15. 15Infection2982.3%

Recent PubMed references pinned to Sirolimus as a MeSH major topic. Citations link to pubmed.ncbi.nlm.nih.gov.

• Exosomal immune decoy integrates cfDNA scavenging and mTOR inhibition for synergistic lupus nephritis therapy.
  Theranostics · 2026 · Zhu M, Xu Q, Tang Z, et al.
  PMID 42244981DOI 10.7150/thno.130906
• Distribution of CYP3A4*1/*1B (rs2740574) and CYP3A5*1/*3 (rs776746) Genetic Variants in Renal Transplant Recipients Treated with Sirolimus in Urmia (Iran).
  Iranian journal of kidney diseases · 2026 · Makhdoomi K, Mivefroshan A, Jafari L, et al.
  PMID 42234923DOI 10.61882/ijkd.3.03.9130
• Efficacy and Safety of Everolimus in Advanced Unresectable and Progressive Epithelioid Hemangioendothelioma: A Single-Center Case Series.
  Drug design, development and therapy · 2026 · Tan H, Wang H, Sun Y, et al.
  PMID 42221353DOI 10.2147/DDDT.S553262
• Long-term rapamycin treatment suppresses IL-17-producing gamma delta T cells and blunts neuroinflammation in aging.
  PloS one · 2026 · Torrent C, Gagliardi C, Fülle N, et al.
  PMID 42207784DOI 10.1371/journal.pone.0343183
• Sirolimus-based treatment regimens for antinuclear antibody (ANA)-positive immune thrombocytopenia: a retrospective single-center cohort study.
  Hematology (Amsterdam, Netherlands) · 2026 · Tan A, Liu J, Chen X, et al.
  PMID 42179326DOI 10.1080/16078454.2026.2678626
• Genotype and subependymal lesion burden influence volumetric response to everolimus in tuberous sclerosis complex-associated subependymal giant cell astrocytoma: A 10-year real-world study.
  Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026 · Su TH, Peng SS, Chen PL, et al.
  PMID 42155246DOI 10.1016/j.neurot.2026.e00926
• Treatment of Vascular Anomalies With Sirolimus: An Updated Comprehensive Review.
  Portuguese journal of cardiac thoracic and vascular surgery · 2026 · Santos PM, Loureiro L, Pinelo A, et al.
  PMID 42155131DOI 10.48729/pjctvs.614
• Antibody levels and immune memory in children with kaposiform hemangioendothelioma treated with sirolimus after catch up vaccination.
  Human vaccines & immunotherapeutics · 2026 · Yuan J, Ding Y, Wang Z, et al.
  PMID 42154819DOI 10.1080/21645515.2026.2653585

The 10 most recently updated of 2,361 ClinicalTrials.gov registrations naming Sirolimus as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Immunotherapy in Combination With Prednisone and Sirolimus for Kidney Transplant Recipients With Unresectable or Metastatic Skin Cancer
  Recruiting · Phase 1 · Phase 2 · Interventional · 16 enrolled · National Cancer Institute (NCI)
  NCT05896839updated 2026-06-12
• Open-Label Umbrella Study To Evaluate Safety And Efficacy Of Elacestrant In Various Combination In Participants With Metastatic Breast Cancer
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 435 enrolled · Stemline Therapeutics, Inc.
  NCT05563220updated 2026-06-12
• Nab-Sirolimus and Endocrine Therapy in Recurrent Low Grade Serous Ovarian Cancer (NARETO)
  Active not recruiting · Phase 2 · Interventional · 37 enrolled · University of Oklahoma
  NCT06494150updated 2026-06-12
• Extension Study for Participants in Studies That Include Belzutifan (MK-6482-043/LITESPARK-043)
  Recruiting · Phase 3 · Interventional · 450 enrolled · Merck Sharp & Dohme LLC
  NCT07405164updated 2026-06-12
• Comparison of Efficacy and Safety of Treatment With a Calcineurin Inhibitor (CNI)Versus a CNI-free Treatment in Renal Transplantation (CIME)
  Completed · Phase 3 · Interventional · 88 enrolled · Centre Hospitalier Universitaire, Amiens
  NCT01595984updated 2026-06-12
• EVERST- Everolimus After Alpelisib in Women With Hormone Receptor-positive (HR+) Metastatic Breast Cancer (MBC)
  Recruiting · Observational · 19 enrolled · Tel-Aviv Sourasky Medical Center
  NCT07646171updated 2026-06-12
• Low-Dose Sirolimus to Increase Hematopoietic Function in Patients With RUNX1 Familial Platelet Disorder
  Active not recruiting · Phase 2 · Interventional · 6 enrolled · M.D. Anderson Cancer Center
  NCT06261060updated 2026-06-12
• Combination Therapy (Mirdametinib and Sirolimus) for RAS Mutated Relapsed Refractory Multiple Myeloma
  Suspended · Phase 1 · Phase 2 · Interventional · 54 enrolled · National Cancer Institute (NCI)
  NCT06876142updated 2026-06-12
• Base Editing for Mutation Repair in Hematopoietic Stem & Progenitor Cells for X-Linked Chronic Granulomatous Disease
  Recruiting · Phase 1 · Phase 2 · Interventional · 10 enrolled · National Institute of Allergy and Infectious Diseases (NIAID)
  NCT06325709updated 2026-06-11
• Everolimus Aging Study
  Active not recruiting · Phase 2 · Interventional · 106 enrolled · University of Wisconsin, Madison
  NCT05835999updated 2026-06-11

CPIC-curated drug–gene pairs for Sirolimus. Levels describe the strength of curated evidence and guideline status — never a recommendation to test or to adjust therapy.

• CYP3A5CPIC C (provisional)ClinPGx 3

Frequently asked questions

How does Sirolimus work?

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 a mechanism that is distinct from that of other immunosuppressants. Sirolimus also inhibits antibody production.

What is Sirolimus used for?

According to FDA labeling, Sirolimus carries indications including: Sirolimus is an mTOR inhibitor immunosuppressant indicated for the prophylaxis of organ rejection in patients aged ≥13 years receiving renal transplants: Patients at low- to moderate-immunologic risk: Use initially with cyclosporine (CsA) and corticosteroids. CsA withdrawal is recommended 2 months to 4 months after transplantation ( 1.1 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Sirolimus?

Sirolimus is classified as Mammalian target of rapamycin (mTOR) kinase inhibitors, Other ophthalmologicals, Kinase Inhibitor, mTOR Inhibitor Immunosuppressant, mTOR Inhibitors, Protein Kinase Inhibitors, Cellular Growth Phase Arrest, Cellular Synthetic Phase Arrest, Decreased Immunologic Activity, Decreased T Lymphocyte Production.

What are the brand names for Sirolimus?

Sirolimus is marketed under brand names including Felycin, Fyarro, Hyftor, Rapamune.

What are the contraindications for Sirolimus?

Sirolimus labeling lists contraindications including: Sirolimus is contraindicated in patients with a hypersensitivity to sirolimus [ see Warnings and Precautions ( 5.4 ) ]. Hypersensitivity to sirolimus ( 4 ).. Always consult the full prescribing information and a clinician.