Everolimus

What it is and how it works

Mechanism of Action Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), a serine-threonine kinase, downstream of the PI3K/AKT pathway. The mTOR pathway is dysregulated in several human cancers and in tuberous sclerosis complex (TSC). Everolimus binds to an intracellular protein, FKBP-12, resulting in an inhibitory complex formation with mTOR complex 1 (mTORC1) and thus inhibition of mTOR kinase activity. Everolimus reduced the activity of S6 ribosomal protein kinase (S6K1) and eukaryotic initiation factor 4E-binding protein (4E-BP1), downstream effectors of mTOR, involved in protein synthesis.

Mechanism class: Protein Kinase Inhibitors · Cytochrome P450 3A4 Inhibitors · Cytochrome P450 2D6 Inhibitors

Indications

1. INDICATIONS AND USAGE Everolimus tablets are a kinase inhibitor indicated 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 neuroendocrine tumors of pancreatic origin (PNET) and adults with progressive, well-differentiated, non-functional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic. Limitations of Use: Everolimus tablets are not indicated for the treatment of patients with functional carcinoid tumors. Adults with advanced renal cell carcinoma (RCC) after failure of treatment with sunitinib or sorafenib. Adults with renal angiomyolipoma and tuberous sclerosis complex (TSC), not requiring immediate surgery.

Dosage and administration (summary)

2. DOSAGE AND ADMINISTRATION Do not combine everolimus tablets and everolimus tablets for oral suspension to achieve the total daily dose. Modify the dose for patients with hepatic impairment or for patients taking drugs that inhibit or induce P-glycoprotein (P-gp) and CYP3A4. Breast Cancer: 10 mg orally once daily. NET: 10 mg orally once daily. RCC: 10 mg orally once daily. TSC-Associated Renal Angiomyolipoma: 10 mg orally once daily. TSC-Associated SEGA: 4.5 mg/m 2 orally once daily; adjust dose to attain trough concentrations of 5-15 ng/mL. ( 2.6 , 2.8 ) TSC-Associated Partial-Onset Seizures: 5 mg/ m 2 orally once daily; adjust dose to attain trough concentrations of 5-­15 ng/mL.

Contraindications

4. CONTRAINDICATIONS Everolimus tablets/everolimus tablets for oral suspension are contraindicated in patients with clinically significant hypersensitivity to everolimus or to other rapamycin derivatives . Clinically significant hypersensitivity to everolimus or to other rapamycin derivatives.

Warnings and precautions

5. WARNINGS AND PRECAUTIONS Non-Infectious Pneumonitis: Monitor for clinical symptoms or radiological changes. Withhold or permanently discontinue based on severity. ( 2.9 , 5.1 ) Infections: Monitor for signs and symptoms of infection. Withhold or permanently discontinue based on severity. ( 2.9 , 5.2 ) Severe Hypersensitivity Reactions: Permanently discontinue for clinically significant hypersensitivity. Angioedema: Patients taking concomitant angiotensin-converting-enzyme (ACE) inhibitors may be at increased risk for angioedema. Permanently discontinue for angioedema.

Pregnancy

Pregnancy Risk Summary Based on animal studies and the mechanism of action , everolimus tablets/everolimus tablets for oral suspension can cause fetal harm when administered to a pregnant woman. There are limited case reports of everolimus tablets use in pregnant women.

Storage and supply

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F). See USP Controlled Room Temperature. Store in the original container, protect from light and moisture. Follow special handling and disposal procedures for anti-cancer pharmaceuticals. 1

Source: Everolimus (Everolimus) — US FDA prescribing information, 2025-09-05, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.