SORAFENIB TOSYLATE

Multiple doses of sorafenib for 7 days resulted in a 2.5- to 7-fold accumulation compared to a single dose. Steady-state plasma sorafenib concentrations were achieved within 7 days, with a peak-to-trough ratio of mean concentrations of less than 2. The steady-state concentrations of sorafenib following administration of sorafenib 400 mg twice daily were evaluated in DTC, RCC and HCC patients. Patients with DTC have mean steady-state concentrations that are 1.8-fold higher than patients with HCC ...

14.1 Hepatocellular Carcinoma The SHARP (HCC) study (NCT00105443) was an international, multicenter, randomized, double blind, placebo-controlled trial in patients with unresectable hepatocellular carcinoma. Overall survival was the primary endpoint. A total of 602 patients were randomized; 299 to sorafenib 400 mg twice daily and 303 to matching placebo. All 602 randomized subjects were included in the ITT population for the efficacy analyses. Demographics and baseline disease characteristics were similar between the sorafenib and placebo arms with regard to age, gender, race, performance stat...

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-...

• 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) ] .
• Sorafenib tablets are contraindicated in patients with known severe hypersensitivit...

• Cardiovascular Events: Consider temporary or permanent discontinuation of sorafenib tablets. ( 2.2 , 5.1 )
• Hemorrhage: Discontinue sorafenib tablets if needed. ( 5.2 )
• Hypertension: Monitor blood pressure weekly during the first 6 weeks and periodically thereafter. Consider temporary or permanent discontinuation for severe or persistent hypertension despite antihypertensive therapy. ( 5.3 )
• Dermatologic Toxicities: Interrupt and/or decrease dose. Discontinue for severe or persistent reac...

7 DRUG INTERACTIONS

• Strong CYP3A Inducers: Avoid strong CYP3A4 inducers. ( 7.1 ) 7.1 Effect of Other Drugs on Sorafenib Strong CYP3A4 Inducers The concomitant use of sorafenib with rifampin, a strong CYP3A4 inducer decreased the mean AUC of sorafenib, which may decrease the antitumor activity [see Clinical Pharmacology (12.3) ] . Avoid concomitant use of sorafenib with strong CYP3A4 inducers, wh...