Generic Name

Everolimus

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Classification

FDA Approved Indications

• Renal cell carcinoma, advanced
• Neuroendocrine tumors of gastrointestinal or lung origin, progressive, metastatic
• Breast cancer, hormone receptor-positive, HER2-negative, advanced ( Afinitor)
• Renal transplantation as prophylaxis against rejection (Zortress)
• Subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (Afinitor Disperz)

Mechanism of Action

Everolimus inhibits mTOR (mammalian target of rapamycin), a key regulatory kinase involved in cell proliferation, growth, and angiogenesis. It binds to FKBP-12, and the complex inhibits mTORC1, leading to cell cycle arrest and decreased angiogenesis.

Dosage and Administration

Adult: Dosing varies based on indication; typically, 5-10 mg orally once daily for cancer. In transplant patients, 0.75 mg twice daily, adjusted as needed.

Pediatric: Dosing depends on the condition; for SEGA, 0.75 mg/m² twice daily, with adjustments based on blood levels.

Geriatric: Start at lower doses due to increased sensitivity and comorbidities, monitor closely.

Renal Impairment: Adjust dose based on response; no specific guidelines, but careful monitoring recommended.

Hepatic Impairment: Use with caution; no specific dose adjustments established.

Pharmacokinetics

Absorption: Well-absorbed orally, with a bioavailability of approximately 30%.

Distribution: Widely distributed; high protein binding (~74%).

Metabolism: Primarily metabolized by CYP3A4 and CYP2C8 enzymes.

Excretion: Excreted mainly via feces (80%), with some urinary excretion.

Half Life: Approximately 30 hours.

Contraindications

• Hypersensitivity to everolimus, sirolimus, or any component of the formulation.

Precautions

• Use caution in patients with impaired liver function, infections, or bleeding disorders. Monitor blood counts and liver function regularly. Pregnancy category D; effective contraception required during treatment and for some time after discontinuation. Risk of serious infections and non-infectious pneumonitis.

Adverse Reactions - Common

• Stomatitis (Very common)
• Infections (viral, bacterial, fungal) (Common)
• Fatigue (Common)
• Peripheral edema (Common)

Adverse Reactions - Serious

• Non-infectious pneumonitis (Less common but serious)
• Hepatotoxicity (Less common)
• Thrombocytopenia, leukopenia (Less common)
• Gastrointestinal perforation (Rare)

Drug-Drug Interactions

• CYP3A4 inhibitors (ketoconazole, clarithromycin), CYP3A4 inducers (rifampin, carbamazepine), live vaccines.

Drug-Food Interactions

• Grapefruit juice may increase blood levels.

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Report signs of infection, bleeding, or lung problems.
• Avoid grapefruit and grapefruit juice.
• Keep regular follow-up appointments for blood tests and monitoring.
• Do not stop medication abruptly.

Special Considerations

Black Box Warnings:

• Increased risk of infections leading to serious or fatal infections.
• Liver failure, renal failure, or non-infectious pneumonitis.

Genetic Factors: Pharmacogenetic variations in CYP3A4 may affect drug levels.

Lab Test Interference: May affect blood glucose, lipid levels, and liver function tests.

Overdose Management

Signs/Symptoms: Severe mucositis, infections, hepatotoxicity, hematologic abnormalities.

Treatment: Supportive care, monitor vital signs, and laboratory parameters; specific antidote not available.

Storage and Handling

Storage: Store at 20°C to 25°C (68°F to 77°F). Keep in original container.

Stability: Stable for the duration of the labeled shelf life when stored properly.