Sorafenib Tosylate (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- NEXAVAR
- SORAFENIB TOSYLATE
Contraindications
•Sorafenib tablets are contraindicated in patients with known severe hypersensitivity to sorafenib or any other component of sorafenib tablets. •Sorafenib tablets in combination with carboplatin and paclitaxel are contraindicated in patients with squamous cell lung cancer [see Warnings and Precautions (5.8)].
Adverse Reactions
The following clinically significant adverse reactions are discussed elsewhere in the labeling: •Cardiovascular events [see Warnings and Precautions (5.1)] •Hemorrhage [see Warnings and Precautions (5.2)] •Hypertension [see Warnings and Precautions (5.3)] •Dermatologic toxicities [see Warnings and Precautions (5.4)] •Gastrointestinal perforation [see Warnings and Precautions (5.5)] •QT interval prolongation [see Warnings and Precautions (5.9) and Clinical Pharmacology (12.2)] •Drug-induced liver injury [see Warnings and Precautions (5.10)] •Impairment of TSH suppression in DTC [see Warnings and Precautions (5.12)]
Mechanism of Action
Sorafenib is a kinase inhibitor that decreases tumor cell proliferation in vitro. Sorafenib was shown to inhibit multiple intracellular (c-CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT-3, RET, RET/PTC, VEGFR-1, VEGFR-2, VEGFR-3, and PDGFR-ß). Several of these kinases are thought to be involved in tumor cell signaling, angiogenesis and apoptosis. Sorafenib inhibited tumor growth of HCC, RCC, and DTC human tumor xenografts in immunocompromised mice. Reductions in tumor angiogenesis were seen in models of HCC and RCC upon sorafenib treatment, and increases in tumor apoptosis were observed in models of HCC, RCC, and DTC.
Overdosage
The adverse reactions observed at a dose of 800 mg twice daily (2 times the recommended dose) were primarily diarrhea and dermatologic. No information is available on symptoms of acute overdose in animals because of the saturation of absorption in oral acute toxicity studies conducted in animals. In cases of suspected overdose, withhold sorafenib and institute supportive care.