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 | |