Nexavar

Unresectable hepatocellular carcinoma (HCC); Advanced renal cell carcinoma (RCC); Locally recurrent or metastatic, progressive, differentiated thyroid carcinoma (DTC) refractory to radioactive iodine treatment

All indications: 400 mg (two 200 mg tablets) orally twice daily without food (at least 1 hour before or 2 hours after eating)
Dose reductions: 400 mg once daily, then 400 mg every other day
Hepatic impairment (mild-moderate): No adjustment needed
Hepatic impairment (severe, Child-Pugh C): Not studied, use with caution

Tablets: 200 mg

Known severe hypersensitivity to sorafenib or any component. Co-administration with carboplatin and paclitaxel in patients with squamous cell lung cancer.

• Cardiac Ischemia/Infarction: Incidence of 2.9% vs 0.4% placebo. Consider temporary or permanent discontinuation.
• Hemorrhage: Increased risk of bleeding. Monitor INR in patients on warfarin.
• Hypertension: Monitor BP weekly during first 6 weeks and periodically thereafter.
• Dermatologic Toxicities: Hand-foot skin reaction (HFSR) in up to 30%, rash in 40%. May require dose modification.
• GI Perforation: Discontinue if GI perforation occurs.
• QT Prolongation: Monitor electrolytes and ECGs in patients at risk.
• Drug-Induced Hepatitis: Monitor LFTs regularly; increases in bilirubin and transaminases more common in HCC.
• Impaired TSH Suppression in DTC: Monitor TSH levels monthly.

Diarrhea (43%), fatigue (37%), hand-foot skin reaction (30%), rash/desquamation (40%), alopecia (27%), nausea (23%), hypertension (17%), pruritus (14%), anorexia (16%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Sorafenib is a kinase inhibitor that decreases tumor cell proliferation by inhibiting multiple intracellular (CRAF, BRAF, mutant BRAF) and cell surface kinases (KIT, FLT-3, RET, VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-β). It inhibits tumor angiogenesis via VEGFR and PDGFR inhibition and direct anti-tumor activity via RAF/MEK/ERK pathway inhibition.

Tmax: approximately 3 hours. Half-life: 25-48 hours. Bioavailability: 38-49% (reduced by high-fat meals). Protein binding: 99.5%. Metabolized by CYP3A4 and UGT1A9. Primarily excreted in feces (77%).

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• SHARP — Sorafenib vs. placebo in advanced HCC. Phase III, n=602.
  🔬 NCT00105443 ↗ 📄 Primary Publication ↗
• TARGET — Sorafenib vs. placebo in advanced clear-cell RCC after prior therapy. Phase III, n=903.
  🔬 NCT00073307 ↗ 📄 Primary Publication ↗

Nexavar has FDA-approved indications across the following cancer types covered on PipelineEvidence: