Mechanism of Action
Sorafenib is a kinase inhibitor that decreases tumor cell proliferation in vitro. It has been shown to inhibit multiple intracellular kinases (CRAF, BRAF, and mutant BRAF) and cell surface kinases (KIT, FLT-3, RET, VEGFR-1, VEGFR-2, VEGFR-3, and PDGFR-ß). Several of these kinases are believed to be involved in tumor cell signaling, angiogenesis, and apoptosis. Sorafenib has demonstrated the ability to inhibit tumor growth and angiogenesis in human hepatocellular carcinoma, renal cell carcinoma, and several other human tumor xenografts in immunocompromised mice.
Sorafenib is a kinase inhibitor indicated for the treatment of:
Unresectable hepatocellular carcinoma
Advanced renal cell carcinoma
The recommended dose is 400 mg (2 tablets) orally, twice daily without food.
Treatment interruption and/or dose reduction may be necessary to manage suspected adverse drug reactions. The dose may be reduced to 400 mg once daily or 400 mg every other day as needed.
Sorafenib is contraindicated in patients with a known severe hypersensitivity to Sorafenib or any of its components.
Sorafenib, when combined with carboplatin and paclitaxel, is contraindicated in patients with squamous cell lung cancer.
Cardiac Ischemia or Infarction: May occur. Consider temporary or permanent discontinuation of Sorafenib.
Bleeding: If bleeding requires medical intervention, discontinuation of Sorafenib should be considered.
Hypertension: Usually occurs early in the treatment course and can be managed with antihypertensive therapy. Blood pressure should be monitored weekly during the first six weeks and periodically thereafter.
Hand-Foot Skin Reaction and Rash: Common side effects. Management may include topical therapies for symptomatic relief, temporary treatment interruption, dose modification, or, in severe cases, permanent discontinuation.
Gastrointestinal Perforation: An uncommon but serious adverse reaction. If it occurs, Sorafenib therapy should be discontinued.
Surgical Procedures: Temporary interruption of Sorafenib is recommended in patients undergoing major surgery.
Drug Interactions: Caution is advised when co-administering substances metabolized or eliminated predominantly via the UGT1A1 pathway (e.g., irinotecan), docetaxel, or doxorubicin.
Pregnancy: Sorafenib may cause fetal harm. Women of childbearing potential should be advised to avoid pregnancy while on Sorafenib.
Common side effects include: Fatigue, weight loss, rash/desquamation, hand-foot skin reaction, alopecia, diarrhea, anorexia, nausea, and abdominal pain.
Pregnancy Category D: Sorafenib may cause fetal harm if administered during pregnancy.
Nursing Mothers: It is not known whether Sorafenib is excreted in human milk; therefore, caution is advised.
Pediatric Use
The safety and effectiveness of Sorafenib in pediatric patients have not been established.
Carboplatin and Paclitaxel: Caution is advised, as co-administration increases paclitaxel AUC.
UGT1A1 (e.g., irinotecan) and UGT1A9 substrates: Drug AUC increases when co-administered with Sorafenib.
Docetaxel: Co-administration increases docetaxel AUC.
Doxorubicin: Co-administration increases doxorubicin AUC.
Fluorouracil: Co-administration affects fluorouracil AUC.
CYP2B6 and CYP2C8 substrates: Systemic exposure is expected to increase with Sorafenib co-administration.
CYP3A4 inducers: Increase Sorafenib metabolism, reducing its concentration.
Neomycin: Co-administration decreases Sorafenib AUC.
There is no specific treatment for Sorafenib overdose. The highest clinically studied dose is 800 mg twice daily. Overdose symptoms primarily include diarrhea and dermatologic reactions.
Store at a temperature not exceeding 30°C in a dry place
Medicine: Keep out of reach of children.
