Afinitor

Company: Novartis Ireland Ltd.
Legal category: Prescription. High Tech. Sport permitted.
Active ingredient: Everolimus 5mg, 10mg.
Description: White to slightly yellow, elongated tablets with a bevelled edge and no score. Engraved with NVR on one side and, respectively, 5 or UHE on the other.
Presentations: 5mg-30, €2829.13; 10mg-30, €4041.62.
Indication: Treatment of patients with advanced renal cell carcinoma, whose disease has progressed on or after treatment with VEGF-targeted therapy.

Pharmacology: Everolimus is a selective mTOR (mammalian target of rapamycin) inhibitor. mTOR is a key serine-threonine kinase, the activity of which is known to be upregulated in a number of human cancers. Everolimus binds to the intracellular protein FKBP-12, forming a complex that inhibits mTOR complex-1 (mTORC1) activity. Inhibition of the mTORC1 signalling pathway interferes with the translation and synthesis of proteins by reducing the activity of S6 ribosomal protein kinase (S6K1) and eukaryotic elongation factor 4E-binding protein (4EBP-1) that regulate proteins involved in the cell cycle, angiogenesis and glycolysis. Everolimus reduces levels of vascular endothelial growth factor (VEGF), which potentiates tumour angiogenic processes. Everolimus is a potent inhibitor of the growth and proliferation of tumour cells, endothelial cells, fibroblasts and blood-vessel-associated smooth muscle cells and has been shown to reduce glycolysis in solid tumours in vitro and in vivo.
Dosage: Adult: Recommended dose: 10mg once daily. Continue treatment as long as clinical benefit is observed or until unacceptable toxicity occurs. Management of severe and/or intolerable suspected adverse reactions may require dose reduction to 5mg daily or temporarily withholding (e.g. for 1 week) followed by reintroduction at 5mg daily. Moderate hepatic impairment: 5mg daily. Elderly: As per adults. Children: Under 18 years, not recommended.
Contraindications: Hypersensitivity to the active substance, to other rapamycin derivatives or to any of the excipients. Pregnancy, lactation.
Special precautions: May occur: Non-infectious pneumonitis (advise patients to promptly report any new or worsening respiratory symptoms; discontinue if severe), infections (esp. opportunistic pathogens), hypersensitivity reactions, mouth ulcerations (ulcers, stomatitis, oral mucositis), impaired wound healing (caution in the peri-surgical period). Monitor renal function (blood urea nitrogen, serum creatinine), fasting serum glucose and complete blood count prior to starting therapy and periodically thereafter. Severe hepatic impairment, not recommended. Contains lactose.
Drug interactions: Avoid live vaccines, grapefruit juice. Not recommended: Potent inhibitors/inducers of CYP3A4 or PgP. Caution: Moderate inhibitors and substrates of CYP3A4 or PgP.
Adverse drug reactions: Infections, decreased lymphocytes / Hb / platelets / neutrophils, increased glucose / cholesterol / triglycerides, decreased phosphate, anorexia, dehydration, insomnia, abnormal taste, headache, conjunctivitis, eyelid oedema, hypertension, pneumonitis, dyspnoea, epistaxis, cough, haemoptysis, GI disorders, increased alanine aminotransferase /aspartate aminotransferase / bilirubin, rash, dry skin, pruritus, palmar-plantar erythrodysaesthesia syndrome, erythema, skin exfoliation, nail disorder, acneiform dermatitis, onychoclasis, increased creatinine, fatigue, asthenia, peripheral oedema, chest pain, pyrexia, weight decreased.
Full prescribing information and references available from Novartis Ireland Ltd. Telephone: (01) 2601255. Fax: (01) 2601263. E-mail: medinfo.dublin@novartis.com