II. Indications
-
Solid Organ Transplant
Immunosuppression (maintenance prevention of rejection)
- Renal Transplant
- Contraindicated in Liver Transplant and lung transplant (black box warning, see below)
- Lymphangioleiomyomatosis
- Ongoing research into mTOR Inhibitors as anti-aging drugs
- Resources
- Rapamycin (Peter Attia, Drive)
- References
- Resources
III. Mechanism
IV. Medications
- Sirolimus (Rapamune, Rapamycin)
- Tablets: 0.5 mg, 1 mg, 2 mg
- Solution: 1 mg/ml
V. Dosing
- See other references for specific dosing regimens per indication
- Prescribers are typically specialists knowledgeable about the risks and monitoring
- Decrease dose in renal dysfunction, and adjust doses based on serum levels
VI. Adverse Effects
- Nephrotoxicity including Proteinuria
- Myelosuppression
- Rash
- Includes Exfoliative Dermatitis
- Delayed Wound Healing
- New Diabetes Mellitus
- Secondary Malignancy
- Lymphoma
- Skin Cancer (use sun protection)
- Male Infertility
- Cardiopulmonary
- Interstitial Lung Disease or Pulmonary fibrosis
- Hyperlipidemia
- Edema
- Thrombosis
- Hepatic artery thrombosis
- Kidney graft thrombosis
-
Thrombotic Thrombocytopenic Purpura (TTP) or Hemolytic Uremic Syndrome (HUS)
- More common in combination with Cyclosporine
-
Angioedema (and other serious Allergic Reactions including Anaphylaxis)
- More common in combination with ACE Inhibitors
- Serious Infections (including Polyoma Virus Infections)
- Latent Viral Infection activation
- BK virus associated nephropathy
VII. Drug Interactions
- See Cytochrome P-450 3A4
- Agents that increase Purine Synthesis Inhibitor concentrations (strong CYP3A4 Inhibitors, and P-gp Inhibitors)
- Linezolid potentiates myelosuppression
- Erythromycin (and Clarithromycin to a lesser extent)
- Azole Antifungals (Ketoconazole, Voriconazole, Itraconazole)
- Agents that decrease Purine Synthesis Inhibitor concentrations (strong CYP3A4 Inducers, and P-gp Inducers)
-
Calcineurin Inhibitors (Cyclosporine, Tacrolimus)
- Increased risk of Hepatic Artery Thrombosis (HAT) when used with Sirolimus
- Increased risk of Bronchial anastomotic dehiscence in lung transplant
- Monitor Sirolimus drug levels closely after stopping Cyclosporine
- Cortocosteroids
- Increased risk of Bronchial anastomotic dehiscence in lung transplant
VIII. Safety
- Avoid in Lactation
- Avoid in Pregnancy (despite original Pregnancy Category C designation)
- Use reliable Contraception during treatment and for at least 12 weeks after completion
- Monitor Sirolimus serum trough levels
- Indications for more frequent monitoring (as often as every 1-2 weeks)
- Liver Impairment
- Altered Drug Metabolism
- Weight <40 kg in age >13 years
- Dose changes
- Drug Interactions (CYP3A4 or P-gp related)
- Indications for more frequent monitoring (as often as every 1-2 weeks)
IX. Resources
X. References
- Hamilton (2020) Tarascon Pocket Pharmacopoeia
- Cimino (2016) Am Fam Physician 93(3): 203-10 [PubMed]
- Costanzo (2010) J Heart Lung Transplant 29(8): 914-56 [PubMed]
Images: Related links to external sites (from Bing)
Related Studies
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 |