Everolimus is a kinase inhibitor used for the treatment of:

• Postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer, in combination with exemestane, after failure of treatment with letrozole or anastrozole.
• Adults with progressive pancreatic neuroendocrine tumors (PNET). Adults with progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal or lung origin that are unresectable, locally advanced, or metastatic.
• Adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib.
• Adults with renal angiomyolipoma associated with tuberous sclerosis complex (TSC), not requiring immediate surgery.

Adult and pediatric patients (aged ≥1 year) with TSC who have subependymal giant cell astrocytoma (SEGA) requiring treatment but not suitable for surgical removal. Adult and pediatric patients (aged ≥2 years) with TSC-associated partial-onset seizures as an adjunct therapy.

Everolimus is an inhibitor of the mammalian target of rapamycin (mTOR), a serine-threonine kinase involved in the PI3K/AKT signaling pathway. This pathway is often dysregulated in cancers and in tuberous sclerosis complex (TSC). Everolimus binds to the intracellular protein FKBP-12, forming a complex that inhibits mTOR complex 1 (mTORC1), thereby reducing mTOR activity. This leads to decreased activity of downstream proteins such as S6K1 and 4E-BP1, which are involved in protein synthesis. It also reduces: Hypoxia-inducible factors (e.g., HIF-1), Vascular endothelial growth factor (VEGF).

As a result, everolimus inhibits cell growth, angiogenesis, and glucose uptake. Activation of the PI3K/Akt/mTOR pathway contributes to resistance to hormonal therapy in breast cancer. Studies show that everolimus enhances anti-tumor effects, especially when combined with Akt inhibitors, HER2 inhibitors, or aromatase inhibitors.

Everolimus are two different dosage forms. Select the recommended dosage form based on the indication. Do not combine Everolimus to achieve the total dose. Modify the dosage for patients with hepatic impairment or for patients taking drugs that inhibit or induce P glycoprotein (P-gp) and CYP3A4.

Hormone Receptor-Positive, HER2-Negative Breast Cancer: The recommended dosage of Everolimus is 10 mg orally once daily until disease progression or unacceptable toxicity.

Neuroendocrine Tumors (NET): The recommended dosage of Everolimus is 10 mg orally once daily until disease progression or unacceptable toxicity.

Renal Cell Carcinoma (RCC): The recommended dosage of Everolimus is 10 mg orally once daily until disease progression or unacceptable toxicity.

Tuberous Sclerosis Complex (TSC): Associated Renal Angiomyolipoma: The recommended dosage of Everolimus is 10 mg orally once daily until disease progression or unacceptable toxicity.

Tuberous Sclerosis Complex (TSC)-Associated Subependymal Giant Cell Astrocytoma (SEGA): The recommended starting dosage of Everolimus is 4.5 mg/m² orally once daily until disease progression or unacceptable toxicity.

Tuberous Sclerosis Complex (TSC)-Associated Partial-Onset Seizures: The recommended starting dosage of Everolimus is 5 mg/m² orally once daily until disease progression or unacceptable toxicity.

• Avoid using Everolimus with strong P-gp and CYP3A4 inhibitors.
• If used with moderate P-gp and CYP3A4 inhibitors, reduce the dose as recommended.
• If used with strong P-gp and CYP3A4 inducers, increase the dose as recommended.

Everolimus is contraindicated in patients with clinically significant hypersensitivity to everolimus or other rapamycin derivatives.

Breast cancer, NET, RCC: Common adverse effects (≥30%) include stomatitis, infections, rash, fatigue, diarrhea, edema, abdominal pain, nausea, fever, weakness, cough, headache, and decreased appetite.

TSC-Associated Renal Angiomyolipoma: Most common side effect is stomatitis.

TSC-Associated SEGA: Common side effects include stomatitis and respiratory tract infections.

TSC-Associated Partial-Onset Seizures: Most common side effect is stomatitis.

Everolimus may cause harm to the fetus based on animal studies and its mechanism of action. Limited human data are available and insufficient to determine risks. It is unknown whether everolimus passes into human milk or affects breastfed infants or milk production.

Non-infectious pneumonitis: Monitor symptoms; stop or discontinue depending on severity.

Infections: Monitor closely; adjust or stop treatment if needed.

Severe hypersensitivity: Permanently discontinue.

Angioedema: Increased risk with ACE inhibitors; discontinue permanently.

Stomatitis: Use dexamethasone alcohol-free mouthwash at treatment start.

Renal failure: Monitor kidney function regularly.

Wound healing: Stop before surgery and delay restarting until healing is adequate.

Elderly patients: Monitor and adjust dose.

Metabolic disorders: Monitor glucose and lipid levels.

Myelosuppression: Monitor blood counts.

Vaccination: Avoid live vaccines and exposure to vaccinated individuals.

Radiation effects: Severe reactions may occur.

Embryo-fetal toxicity: Use effective contraception; risk to fetus exists.

Immunosuppressant

Store below 30°C, away from light and moisture. Keep out of reach of children.