Generic Name

Sirolimus

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Classification

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

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.