Treatment of advanced renal cell carcinoma (RCC) and unresectable liver carcinoma

Sorafenib is an inhibitor of multiple intracellular (CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT-3, VEGFR-2, VEGFR-3, and PDGFR-s), inhibiting tumor growth and angiogenesis of human hepatocellular carcinoma and renal cell carcinoma.

mean relative bioavailability: 38-49% when compared to oral solution; decreased bioavailabilty by 29% with high-fat meal (50% fat); Protein binding: 99.5%; Metabolism: primarily hepatic, oxidative metabolism (CYP3A4) and glucuronidation (UGT1A9). Excretion: Feces (77%, 51% as unchanged drug); urine (19%, as metabolites); Elimination half-life: 25-48 hrs.

patients with known severe hypersensitivity to sorafenib or any of its components

D

Excretion in breast milk unknown/not recommended

Hypertension (9-17%), hand-foot syndrome due to cytotoxic therapy(21-30%); alopecia (14% to 27% ); rash (19% to 40%); diarrhea (43-55%); increased amylase level; increased lipase level; loss of appetite; nausea; and fatigue.

The recommended daily dose is 400 mg taken twice daily, at least 1 hour before or 2 hours after eating; continue until no longer benefit or until unacceptable toxicity. Dosage adjustment: dosage reduction is required for the management of adverse reactions; concomitant strong CYP3A4 inducers: avoid use if possible; consider increasing the sorafenib dose if a strong CYP3A4 inducer must be used concurrently.