Everolimus

Everolimus is used for the prevention of organ rejection in transplant patients. It regulates the body's immune response, so the body can accept the new organ. It is also used in combination with other medicines to treat cancers of breast, pancreas, lungs and kidney.

Everolimus is a proliferation signal inhibitor. It exerts its immunosuppressive effect by inhibiting the proliferation of antigen-activated T cells. At the molecular level, everolimus forms a complex with the cytoplasmic protein FKBP-12 and interferes with the function of FRAP (also called m-TOR), which governs cell metabolism, growth and proliferation.

• Breast Cancer: Used in postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer.
• Neuroendocrine Tumors: Used in pancreatic and GI/lung NET.
• Renal Cell Carcinoma: Used after sunitinib or sorafenib failure.
• Tuberous Sclerosis Complex (TSC): Used for renal angiomyolipoma and SEGA.

Immunosuppressant

mTOR Inhibitor (Kinase Inhibitor)

Everolimus is an inhibitor of mammalian target of rapamycin (mTOR), a serine-threonine kinase, downstream of the PI3K/AKT pathway. It 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 inhibits the mTOR pathway, reducing cell proliferation, angiogenesis, and glucose uptake, which helps prevent cancer cell growth and organ rejection.

Adult Dose (Oral):

• Breast Cancer, RCC, NET, Renal Angiomyolipoma: 10 mg once daily (with or without food).
• TSC-Associated SEGA: 4.5 mg/m² once daily (pediatric and adult) or tablet form dosing as per guidelines.
• TSC-Associated Partial-Onset Seizures: 5 mg/m² once daily.

Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Everolimus may be taken with or without food, but it is better to take it at a fixed time.

If you miss a dose of Everolimus, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose.

Common Side Effects (>=30%):

• Stomatitis
• Infections
• Rash
• Fatigue
• Diarrhea
• Edema
• Abdominal pain
• Nausea
• Fever
• Asthenia
• Cough
• Headache
• Decreased appetite

Precautions:

• Everolimus may cause fatigue which may affect your ability to drive.
• Inform doctor if you have liver problems, diabetes, high cholesterol, recent surgery, or infection.
• Seek medical advice if you have increased thirst, increased urination, infection, shortness of breath, cough, or fever.
• Inform doctor before receiving any vaccination.
• Everolimus may affect male or female fertility; consult doctor if planning to have a child.
• Non-infectious pneumonitis: monitor symptoms.
• Infections: monitor symptoms; discontinue if severe.
• Angioedema: increased risk with ACE inhibitors.
• Wound healing: withhold 1 week before elective surgery; do not administer for 2 weeks after major surgery.

Contraindications:

• Hypersensitivity to everolimus or other rapamycin derivatives
• Pregnancy and lactation

Drug Interactions:

• Strong CYP3A4 inhibitors and P-gp inhibitors: Avoid concomitant use.
• Moderate CYP3A4 inhibitors: Reduce dose.
• Strong CYP3A4 inducers: Increase dose.
• Rifampicin: Decreases everolimus exposure.
• ACE inhibitors: May increase risk of angioedema.
• Live vaccines: Avoid.

Food Interactions: It is not known whether it is safe to consume alcohol with Everolimus. Consult your doctor.

Use in Pregnancy: Can cause fetal harm based on animal studies and mechanism of action; unsafe during pregnancy.

Use in Lactation: Everolimus is probably unsafe during breastfeeding; limited data suggests drug may pass into breastmilk and harm the baby.

Pediatric Use: Indicated for TSC-SEGA in patients 1 year and older; TSC-associated seizures in patients 2 years and older.

Geriatric Use: Monitor and adjust dose for adverse reactions in elderly patients.

Renal Impairment: Safe to use in patients with kidney disease; no dose adjustment recommended.

Hepatic Impairment: Use with caution; dose adjustment may be needed; not recommended in severe liver disease.

Overdose: Limited information on overdose; symptomatic treatment.

Storage: Keep below 30 degree C, away from light and moisture. Keep out of reach of children.

Everolimus