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Generic Afinitor ( Everolimus )
Afinitor (everolimus) is an oral mammalian target of rapamycin (mTOR) inhibitor indicated for the treatment of advanced renal cell carcinoma after failure of sunitinib or sorafenib, advanced pancreatic neuroendocrine tumours, advanced breast cancer in postmenopausal women with hormone receptor‑positive, HER2‑negative disease in combination with exemestane, subependymal giant cell astrocytoma associated with tuberous sclerosis, and renal angiomyolipoma associated with tuberous sclerosis complex. Everolimus binds to the intracellular protein FKBP‑12, forming a complex that inhibits mTOR, a serine‑threonine kinase that regulates cell growth, proliferation, and angiogenesis. By blocking mTOR signalling, Afinitor reduces tumour cell division, tumour angiogenesis, and glucose metabolism.
Usual adult dose: The recommended dose is 10 mg taken orally once daily at the same time each day, with or without food. The 5 mg tablet is used for dose reductions and for patients who require lower dosing due to toxicity or concurrent medications. Tablets should be swallowed whole with a glass of water; they must not be crushed, chewed, or broken. If a patient cannot swallow the tablets, a 5 mg or 10 mg dose can be prepared as an oral suspension by a pharmacist. Treatment continues as long as clinical benefit is observed or until unacceptable toxicity occurs. Dose modifications are based on adverse reactions; the dose may be reduced from 10 mg to 5 mg daily, or interrupted temporarily. In patients with moderate hepatic impairment, the recommended starting dose is 5 mg once daily; in severe hepatic impairment, 2.5 mg once daily is recommended but may not be available in tablet form; use of the 5 mg tablet may require alternate dosing under specialist guidance. If a dose is missed, the patient should take it as soon as remembered, but two doses must not be taken on the same day.
Dosage form: Tablets: 5 mg (white to slightly yellow, elongated, debossed with "NVR" and "5") and 10 mg (white to slightly yellow, elongated, debossed with "NVR" and "10"). Available in blister packs of 28 or 30 tablets.
Onset of action: Steady‑state plasma concentrations are reached within 2 weeks of once‑daily dosing. Antitumour response is typically assessed radiographically after 2 to 3 months of continuous therapy. For some indications, such as tuberous sclerosis‑associated lesions, reduction in tumour volume may be observed within the first months of treatment.
Duration of action: The elimination half‑life of everolimus is approximately 30 hours, supporting once‑daily dosing without a drug‑free interval. The therapeutic effect is maintained as long as therapy is continued. Upon discontinuation, mTOR pathway activity returns to baseline over several days.
Alcohol recommendation: Alcohol should be avoided or limited during treatment with Afinitor. Alcohol may increase the risk of hepatotoxicity and can exacerbate common side effects such as nausea, vomiting, and diarrhea. Patients with pre‑existing liver impairment or those taking other hepatotoxic medications should exercise particular caution.
Most common side effects: Stomatitis (mouth ulcers), rash, diarrhea, fatigue, nausea, decreased appetite, peripheral edema, and infections. Stomatitis is a frequent dose‑limiting toxicity; patients should be counselled on oral hygiene and early reporting of mouth pain. Non‑infectious pneumonitis is a serious adverse event and may require dose reduction or discontinuation; patients should report new or worsening cough, dyspnea, or chest pain. Metabolic abnormalities include hyperglycemia, hyperlipidemia, and hypercholesterolemia; fasting glucose and lipids should be monitored at baseline and periodically thereafter. Everolimus is immunosuppressive and increases the risk of opportunistic infections, including Pneumocystis jirovecii pneumonia and cytomegalovirus; prophylactic measures may be considered. Renal impairment may occur, and creatinine should be monitored. Wound healing complications have been reported; therapy should be interrupted before surgery. Live vaccines should be avoided. Women of childbearing potential must use effective contraception during treatment and for 8 weeks after the last dose, as everolimus may cause fetal harm. Afinitor is available only by prescription and must be prescribed and supervised by a healthcare professional experienced in oncology.
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