II. Indications

  1. Solid Organ Transplant immunosuppression (maintenance prevention of rejection)

III. Preparations

  1. Sirolimus
  2. Everolimus

IV. Adverse Effects

  1. Hyperlipidemia
  2. Hepatic artery thrombosis
  3. Myelosuppression
  4. Pulmonary fibrosis
  5. Rash
  6. Delayed Wound Healing

V. Drug Interactions

  1. See Cytochrome P-450 3A4
  2. Agents that increase Purine Synthesis Inhibitor concentrations
    1. Linezolid potentiates myelosuppression
    2. Erythromycin (and Clarithromycin to a lesser extent)
  3. Agents that decrease Purine Synthesis Inhibitor concentrations
    1. Rifampin

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Cost: Medications

sirolimus (on 8/17/2016 at Medicaid.Gov Survey of pharmacy drug pricing)
SIROLIMUS 0.5 MG TABLET Generic $6.15 each
SIROLIMUS 1 MG TABLET Generic $11.81 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

Ontology: everolimus (C0541315)

Definition (NCI_NCI-GLOSS) A drug used to treat advanced kidney cancer that did not respond to treatment with certain other anticancer drugs. It is also being studied in the treatment of other types of cancer. Afinitor stops cancer cells from dividing and may block the growth of new blood vessels that tumors need to grow. It also decreases the body's immune responses. It is a type of immunosuppressant and a type of antiangiogenesis agent.
Definition (NCI) A derivative of the natural macrocyclic lactone sirolimus with immunosuppressant and anti-angiogenic properties. In cells, everolimus 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. Inhibition of mTOR activation results in the inhibition of T lymphocyte activation and proliferation associated with antigen and cytokine (IL-2, IL-4, and IL-15) stimulation and the inhibition of antibody production. (NCI05)
Definition (PDQ) A derivative of the natural macrocyclic lactone sirolimus with immunosuppressant and anti-angiogenic properties. In cells, everolimus 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. Inhibition of mTOR activation results in the inhibition of T lymphocyte activation and proliferation associated with antigen and cytokine (IL-2, IL-4, and IL-15) stimulation and the inhibition of antibody production. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=372905&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=372905&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C48387" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C107135
SnomedCT 428127005, 428698007
LNC LP65523-0, MTHU026817
English 40-O-(2-hydroxyethyl)-rapamycin, (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-Dihydroxy-12-((1R)-2-((1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl)-1-methylethyl)-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo(30.3.1.04,9)hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentaone, 42-O-(2-Hydroxy)ethyl Rapamycin, Everolimus, Everolimus (product), Everolimus (substance), EVEROLIMUS, SDZ-RAD, SDZ RAD, everolimus
Spanish everolimus, everolimus (sustancia), everolimus (producto)

Ontology: mTOR Inhibitor (C2746052)

Definition (NCI) Any substance that inhibits mammalian target of rapamycin (mTOR or FK506 binding protein 12-rapamycin associated protein 1 (FRAP1)), a serine/threonine protein kinase that is active in the control of cell growth, cell proliferation, and cell motility. Inhibition of mTOR can inhibit cell proliferation.
Concepts Pharmacologic Substance (T121)
English mTOR Inhibitor