Nexavar Sorafenib Tosylate Tablets

1. Indications and Usage
Advanced Hepatocellular Carcinoma (HCC):
Indicated for the treatment of patients with unresectable hepatocellular carcinoma .
Advanced Renal Cell Carcinoma (RCC):
Indicated for the treatment of advanced renal cell carcinoma .
Differentiated Thyroid Carcinoma (DTC):
Indicated for the treatment of locally recurrent or metastatic, progressive, radioactive iodine-refractory differentiated thyroid carcinoma .
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY.
Recommended Dosage:
Standard Dose: 400 mg twice daily (approximately every 12 hours).
Schedule: Continuous daily dosing (no scheduled rest period) .
Administration Instructions:
Take on an empty stomach: at least 1 hour before or 2 hours after a meal.
High-fat meals may decrease bioavailability; therefore, low-fat or moderate-fat meals are recommended if taking with food .
Missed Dose:
If a dose is missed, do not take it. Resume at the next scheduled time.
3. Mechanism of Action
Dual Mechanism Inhibitor:
Sorafenib is a multikinase inhibitor that blocks intracellular kinases (B-Raf, K-Raf, mutant B-Raf) to inhibit tumor cell proliferation.
Anti-Angiogenesis:
It also blocks cell-surface receptor tyrosine kinases (VEGFR-1, VEGFR-2, VEGFR-3, PDGFR-β, c-Kit, FLT-3, RET) to inhibit tumor angiogenesis .
4. Safety and Warnings
Cardiovascular Events:
Can cause myocardial ischemia and myocardial infarction. Monitor for signs of cardiac ischemia .
Hemorrhage:
Can cause severe and fatal hemorrhagic events.
Dermatologic Toxicity:
Severe skin toxicity, including Hand-Foot Skin Reaction (HFSR) and Stevens-Johnson Syndrome (SJS) .
QT Prolongation:
Can cause QT interval prolongation. Monitor ECG and electrolytes in patients at risk.
Wound Healing Complications:
Can affect wound healing. Discontinue at least 24 hours prior to scheduled surgery.
5. Adverse Reactions
Most Common:
General: Fatigue, fever, diarrhea.
Dermatologic: Hand-Foot Skin Reaction (HFSR), rash, alopecia, pruritus.
Gastrointestinal: Diarrhea, nausea, vomiting, dyspepsia.
Metabolic: Hypertension .
6. Drug Interactions
Metabolic Pathway:
Primarily metabolized by CYP3A4 and UGT1A9.
CYP3A4 Inhibitors/Antacids: Antacids containing aluminum/magnesium may reduce exposure; separate administration by at least 4 hours .
CYP2C9 Substrates: Sorafenib inhibits CYP2C9. Caution is advised when co-administering with CYP2C9 substrates (e.g., Warfarin) due to increased INR risk .
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Sorafenib Tosylate.
Appearance: Orange, film-coated, biconvex, oval-shaped tablets.
Storage: Store at 25°C (77°F); excursions permitted to 15°C–30°C (59°F–86°F) .