Indications

Hepatocellular Carcinoma : Sorafenib is indicated for the treatment of patients with unresectable hepatocellular carcinoma (HCC). Renal Cell Carcinoma : Sorafenib is indicated for the treatment of patients with advanced renal cell carcinoma (RCC).

Composition

Pharmacology

Sorafenib is a kinase inhibitor that decreases tumor cell proliferation. Sorafenib was shown to inhibit multiple intracellular (CRAF, BRAF and mutant BRAF) and cell surface kinases (KIT, FLT-3, RET, VEGFR-1, VEGFR-2, VEGFR-3, and PDGFR-β). Several of these kinases are thought to be involved in tumor cell signaling, angiogenesis, and apoptosis. Sorafenib inhibited tumor growth and angiogenesis of human hepatocellular carcinoma and renal cell carcinoma, and several other human tumor xenografts in immunocompromised mice.

Dosage & Administration

The recommended daily dose of Sorafenib is 400 mg tablets taken twice daily without food (at least 1 hour before or 2 hours after a meal). Treatment should continue until the patient is no longer clinically benefiting from therapy or until unacceptable toxicity occurs. Management of suspected adverse drug reactions may require temporary interruption and/or dose reduction of Sorafenib therapy. When dose reduction is necessary, the Sorafenib dose may be reduced to 400 mg once daily. If additional dose reduction is required, Sorafenib may be reduced to a single 400 mg dose every other day. Recommended regimens and treatment duration for Sorafenib therapy. Grade 1: Numbness, dysesthesia, paresthesia, tingling, painless swelling, erythema or discomfort of the hands or feet which does not disrupt the patient's: Any occurrence : Continue treatment with Sorafenib and consider topical therapy for symptomatic relief. Grade 2: Painful erythema and swelling of the hands or feet and/ or discomfort affecting the patient’s normal activities 1st occurrence : Continue treatment with Sorafenib and consider topical therapy for symptomatic relief. If no improvement within 7 days, see below. No improvement within 7 days or 2nd or 3rd occurrence : Interrupt Sorafenib treatment until toxicity resolves to Grade 0-1 When resuming treatment, decrease Sorafenib dose by one dose level (400 mg daily or 400 mg every other day). 4th occurrence : Discontinue Sorafenib treatment. Grade 3: Moist desquamation, ulceration, blistering or severe pain of the hands or feet, or severe discomfort that causes the patient to be unable to work or perform activities of daily living: 1st or 2nd occurrence : Interrupt Sorafenib treatment until toxicity resolves to Grade 0-1 When resuming treatment, decrease Sorafenib dose by one dose level (400 mg daily or 400 mg every other day). 3rd occurrence : Discontinue Sorafenib treatment. No dose adjustment is required on the basis of patient age, gender, or body weight. Missed doses: If a dose of Sorafenib is missed, skip the missed dose, and take next dose at regular time. Do not double your dose of Sorafenib.

Contraindications

Sorafenib is contraindicated in patients with known severe hypersensitivity to Sorafenib or any other component of Sorafenib. Sorafenib in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer.

Side Effects

Serious adverse reactions are cardiac ischemia, infarction, hemorrhage, hypertension, hand-foot skin reaction and rash, gastrointestinal perforation, wound healing complications.

Pregnancy & Lactation

Based on its mechanism of action and findings in animals, Sorafenib may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant while on Sorafenib. It is not known whether Sorafenib is excreted in human milk.

Precautions & Warnings

Cardiac ischemia, infarction : Temporary or permanent discontinuation of Sorafenib should be considered in patients who develop cardiac ischemia and/or infarction. Risk of Hemorrhage : An increased risk of bleeding may occur following Sorafenib administration. There was one fatal hemorrhage in each treatment group in RCC Study. If any bleeding necessitates medical intervention, permanent discontinuation of Sorafenib should be considered. Risk of Hypertension : In the HCC study, hypertension was reported in approximately 9.4% and In RCC Study, hypertension was reported in approximately 16.9% of Sorafenib -treated patients. In cases of severe or persistent hypertension, despite institution of antihypertensive therapy, temporary or permanent discontinuation of Sorafenib should be considered. Risk of Dermatologic Toxicities : Hand-foot skin reaction and rash represent the most common adverse reactions attributed to Sorafenib. Risk of Gastrointestinal Perforation : In the event of a gastrointestinal perforation, Sorafenib therapy should be discontinued. Warfarin Co-Administration : Patients taking concomitant warfarin should be monitored regularly for changes in prothrombin time, INR or clinical bleeding episodes. Wound Healing Complications : Resume Sorafenib therapy following a major surgical intervention should be based on clinical judgment of adequate wound healing. Use of Sorafenib in combination with Carboplatin and Paclitaxel in Non-small Cell Lung Cancer : Patients with squamous cell carcinoma (prospectively stratified), higher mortality was observed with the addition of Sorafenib compared to those treated with carboplatin and paclitaxel alone. Interactions with UGT1A1 Substrates : Sorafenib can cause increases in plasma concentrations of drugs that are substrates of UGT1A1. Interaction with Docetaxel & Doxorubicin : Sorafenib can cause increases in plasma concentrations of Docetaxel and Doxorubicin. Hepatic Impairment : Hepatic impairment may reduce plasma concentrations of Sorafenib. Neomycin : Co-administration of oral Neomycin causes a decrease in Sorafenib exposure.

Therapeutic Class

Targeted Cancer Therapy

Storage Conditions

Store at room temperature below 30°C. Do not remove desiccant. Dispense in original bottle.