Nurses Compass
Drug Guide
Sirolimus
Classification
Therapeutic: Immunosuppressant, Antineoplastic
Pharmacological: mTOR inhibitor
FDA Approved Indications
- Prophylaxis of organ rejection in kidney transplant patients
- Treatment of certain cancers (e.g., relapsed or refractory Hodgkin lymphoma, systemic anaplastic large cell lymphoma)
Mechanism of Action
Sirolimus inhibits the mammalian target of rapamycin (mTOR), a kinase involved in cell proliferation, growth, and survival, thereby suppressing T-cell and B-cell proliferation that are dependent on IL-2.
Dosage and Administration
Adult: Dose varies based on indication; for kidney transplant, initial dose is typically 6 mg once daily, adjusted to target blood levels.
Pediatric: Use with caution; dosing is based on weight and clinical response.
Geriatric: Start at lower doses due to potential increased sensitivity.
Renal Impairment: Adjust dosage based on blood levels and renal function.
Hepatic Impairment: Adjustments may be necessary; monitor liver function closely.
Pharmacokinetics
Absorption: Excellent oral bioavailability (~14%).
Distribution: Extensively bound to erythrocytes and plasma proteins.
Metabolism: Primarily hepatic via CYP3A4 and P-glycoprotein.
Excretion: Metabolites excreted mainly via feces; minimal urinary excretion.
Half Life: Approximately 62 hours in adults, allowing once-daily dosing.
Contraindications
- Known hypersensitivity to sirolimus or sirolimus-containing products.
Precautions
- Monitor lipid levels; risk of hyperlipidemia.
- Assess for signs of infection; immunosuppression increases infection risk.
- Use with caution in patients with hepatic impairment.
Adverse Reactions - Common
- Infections (e.g., respiratory, urinary, skin infections) (Very common)
- Hyperlipidemia (hypertriglyceridemia, hypercholesterolemia) (Common)
- Myelosuppression (thrombocytopenia, leucopenia, anemia) (Common)
- Stomatitis/mucositis (Common)
Adverse Reactions - Serious
- Pneumonitis (interstitial lung disease) (Less common)
- Hepatotoxicity (Less common)
- Delayed wound healing (Less common)
- Lymphocele or seroma formation (Less common)
Drug-Drug Interactions
- CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) increase sirolimus levels.
- CYP3A4 inducers (e.g., rifampin, carbamazepine) decrease levels.
Drug-Food Interactions
- Grapefruit and grapefruit juice may increase sirolimus levels.
Drug-Herb Interactions
- St. John’s Wort may reduce effectiveness.
Nursing Implications
Assessment: Monitor for signs of infection, wound healing, lipid profile, renal and liver function, blood counts, and sirolimus blood levels.
Diagnoses:
- Risk for infection
- Impaired tissue integrity
- Imbalanced nutrition: less than body requirements (due to gastrointestinal symptoms)
Implementation: Administer as prescribed, monitor drug levels regularly, observe for adverse reactions, educate patient about infection control.
Evaluation: Assess effectiveness in preventing rejection or controlling cancer, monitor side effects, adjust dosage accordingly.
Patient/Family Teaching
- Take medication exactly as prescribed.
- Report signs of infection (fever, sore throat, cough).
- Avoid grapefruit juice.
- Keep appointments for blood tests.
- Notify provider for wound issues or unusual symptoms.
Special Considerations
Black Box Warnings:
- Risk of increased susceptibility to infection and lymphoma due to immunosuppression.
- Potential for hypersensitivity reactions.
Genetic Factors: Pharmacogenetic testing is not routinely performed but may influence metabolism.
Lab Test Interference: May affect lipid levels, liver enzymes, renal function, and blood counts.
Overdose Management
Signs/Symptoms: Severe immunosuppression, bleeding, toxicity signs.
Treatment: Supportive care; no specific antidote. Hemodialysis not effective due to extensive tissue binding.
Storage and Handling
Storage: Store at room temperature (20-25°C), away from moisture and light.
Stability: Stable through expiration date if stored properly.