II. Indications

IV. Medications

  1. Sirolimus (Rapamune, Rapamycin)
    1. Tablets: 0.5 mg, 1 mg, 2 mg
    2. Solution: 1 mg/ml

V. Dosing

  1. See other references for specific dosing regimens per indication
  2. Prescribers are typically specialists knowledgeable about the risks and monitoring
  3. Decrease dose in renal dysfunction, and adjust doses based on serum levels

VI. Adverse Effects

  1. Nephrotoxicity including Proteinuria
  2. Myelosuppression
  3. Rash
    1. Includes Exfoliative Dermatitis
  4. Delayed Wound Healing
  5. New Diabetes Mellitus
  6. Secondary Malignancy
    1. Lymphoma
    2. Skin Cancer (use sun protection)
  7. Male Infertility
  8. Cardiopulmonary
    1. Interstitial Lung Disease or Pulmonary fibrosis
    2. Hyperlipidemia
    3. Edema
    4. Thrombosis
      1. Hepatic artery thrombosis
      2. Kidney graft thrombosis
  9. Thrombotic Thrombocytopenic Purpura (TTP) or Hemolytic Uremic Syndrome (HUS)
    1. More common in combination with Cyclosporine
  10. Angioedema (and other serious Allergic Reactions including Anaphylaxis)
    1. More common in combination with ACE Inhibitors
  11. Serious Infections (including Polyoma Virus Infections)
    1. Latent Viral Infection activation
    2. BK virus associated nephropathy

VII. Drug Interactions

  1. See Cytochrome P-450 3A4
  2. Agents that increase Purine Synthesis Inhibitor concentrations (strong CYP3A4 Inhibitors, and P-gp Inhibitors)
    1. Linezolid potentiates myelosuppression
    2. Erythromycin (and Clarithromycin to a lesser extent)
    3. Azole Antifungals (Ketoconazole, Voriconazole, Itraconazole)
  3. Agents that decrease Purine Synthesis Inhibitor concentrations (strong CYP3A4 Inducers, and P-gp Inducers)
    1. Rifampin
    2. Rifabutin
  4. Calcineurin Inhibitors (Cyclosporine, Tacrolimus)
    1. Increased risk of Hepatic Artery Thrombosis (HAT) when used with Sirolimus
    2. Increased risk of Bronchial anastomotic dehiscence in lung transplant
    3. Monitor Sirolimus drug levels closely after stopping Cyclosporine
  5. Cortocosteroids
    1. Increased risk of Bronchial anastomotic dehiscence in lung transplant

VIII. Safety

  1. Avoid in Lactation
  2. Avoid in Pregnancy (despite original Pregnancy Category C designation)
    1. Use reliable Contraception during treatment and for at least 12 weeks after completion
  3. Monitor Sirolimus serum trough levels
    1. Indications for more frequent monitoring (as often as every 1-2 weeks)
      1. Liver Impairment
      2. Altered Drug Metabolism
      3. Weight <40 kg in age >13 years
      4. Dose changes
      5. Drug Interactions (CYP3A4 or P-gp related)

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Related Studies

Cost: Medications

sirolimus (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
SIROLIMUS 0.5 MG TABLET Generic $5.11 each
SIROLIMUS 1 MG TABLET Generic $4.36 each
SIROLIMUS 1 MG/ML SOLUTION Generic $8.60 per ml
SIROLIMUS 2 MG TABLET Generic $3.81 each
rapamune (on 1/1/2023 at Medicaid.Gov Survey of pharmacy drug pricing)
RAPAMUNE 0.5 MG TABLET Generic $5.11 each
RAPAMUNE 1 MG TABLET Generic $4.36 each
RAPAMUNE 2 MG TABLET $66.73 each

Ontology: Sirolimus (C0072980)

Definition (NCI) A natural macrocyclic lactone produced by the bacterium Streptomyces hygroscopicus, with immunosuppressant properties. In cells, sirolimus binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate an immunosuppressive complex that binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase. This results in inhibition of T lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (IL-2, IL-4, and IL-15) stimulation and inhibition of antibody production. (NCI04)
Definition (NCI_NCI-GLOSS) A drug used to keep the body from rejecting organ and bone marrow transplants. Rapamune blocks certain white blood cells that can reject foreign tissues and organs. It also blocks a protein that is involved in cell division. It is a type of antibiotic, a type of immunosuppressant, and a type of serine/threonine kinase inhibitor. Rapamune was previously called rapamycin.
Definition (MSH) A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.
Definition (CSP) novel immunosuppressive drug used in transplantation; may inhibit receptor mediated activation of mast cells.
Definition (PDQ) A natural macrocyclic lactone produced by the bacterium Streptomyces hygroscopicus, with immunosuppressant properties. In cells, sirolimus binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate an immunosuppressive complex that binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase. This results in inhibition of T lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (IL-2, IL-4, and IL-15) stimulation and inhibition of antibody production. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42555&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=42555&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C1212" NCI Thesaurus)
Concepts Antibiotic (T195) , Organic Chemical (T109)
MSH D020123
SnomedCT 387014003, 116109004
LNC LP21368-3, MTHU013897
English 9,10,12,13,14,21,22,23,24,25,26,27,32,33,34,34a-Hexadecahydro-9,27-dihydroxy-3-((1R)-2-((1S,3R,4R)-4-hydroxy-3-methoxycyclohexyl)-1-methylethyl)-10,21-dimethoxy-6,8,12,14,20,26-hexamethyl-23,27-epoxy-3H-pyrido(2,1-c)(1,4)oxaazacyclohentriacontine-1,5,11,2, RAPA, sirolimus, Rapamycin, sirolimus (medication), SIROLIMUS, Sirolimus [Chemical/Ingredient], RAPAMYCIN, Sirolimus (product), Sirolimus (substance), rapamycin, SLM, Sirolimus
Swedish Sirolimus
Czech sirolimus, rapamycin
Spanish rapamicina, sirolimus, sirolimús (sustancia), sirolimús (producto), sirolimús, sirolimus (producto), Sirolimús, sirolimus (sustancia), Rapamicina, Sirolimus
Finnish Sirolimuusi
Italian Rapamicina, Sirolimus
Russian SIROLIM, RAPAMITSIN, РАПАМИЦИН, SIROLIMUS, СИРОЛИМУС, СИРОЛИМ
Japanese シロリムス, ラパマイシン
Polish Rapamycyna, Syrolimus
Croatian SIROLIMUS
Portuguese Sirolimus, Sirrólimo, Rapamicina, Sirolimo
French Rapamycine, Sirolimus
German Rapamycin, Sirolimus