Important Safety Information

Important Safety Considerations When observed, hypertension usually occurred early in the course of treatment and was managed with antihypertensive therapy. Monitor blood pressure weekly during the first 6 weeks and periodically thereafter and treat, as required. An increased risk of bleeding may occur following Nexavar administration. The following bleeding adverse reactions were reported in Nexavar-treated vs placebo-treated patients, respectively: overall bleeding (18% vs 20%), bleeding from esophageal varices (2.4% vs 4%), and bleeding with fatal outcome at any site (2.4% vs 4%). The incidence of treatment-emergent cardiovascular ischemia/infarction was 2.7% in Nexavar-treated patients vs 1.3% for placebo-treated patients. Gastrointestinal perforation was an uncommon adverse reaction and has been reported in less than 1% of patients taking Nexavar. Most common adverse reactions reported for Nexavar-treated patients vs placebo-treated patients, respectively: diarrhea (55% vs 25%), fatigue (46% vs 45%), abdominal pain (31% vs 26%), weight loss (30% vs 10%), anorexia (29% vs 18%), nausea (24% vs 20%), and hand-foot skin reaction (21% vs 3%). Grade 3/4 adverse reactions were 45% for Nexavar vs 32% for placebo. Hand-foot skin reaction and rash are common, and management may include topical therapies for symptomatic relief. In cases of any severe or persistent adverse reactions, temporary treatment interruption, dose modification, or permanent discontinuation of Nexavar should be considered. Temporary interruption of Nexavar therapy is recommended in patients undergoing major surgical procedures. Elevations in serum lipase and reductions in serum phosphate of unknown etiology have been associated with Nexavar. Caution is recommended when administering Nexavar with compounds that are metabolized/eliminated predominantly by the UGT1A9 pathway, UGT1A1 pathway (eg, irinotecan), doxorubicin, docetaxel, fluorouracil, and substrates of CYP2B6 and CYP2C8, and CYP3A4 inducers. Patients taking concomitant warfarin should be monitored regularly for changes in prothrombin time, INR, or clinical bleeding episodes. Women of childbearing potential are advised to avoid becoming pregnant and against breastfeeding.