Nexavar Special Precautions

Dermatological Toxicities: Hand-foot skin reaction (palmar-plantar erythrodysesthesia) and rash represent the most common adverse reactions with sorafenib. Rash and hand-foot skin reaction are usually National Cancer Institute Common Toxicity Criteria (CTC) grade 1 and 2 and generally appear during the first 6 weeks of treatment with sorafenib.
Management of dermatologic toxicities may include topical therapies for symptomatic relief, temporary treatment interruption and/or dose modification of sorafenib, or in severe or persistent cases, permanent discontinuation of sorafenib (see Adverse Reactions).
Hypertension: An increased incidence of hypertension was observed in sorafenib-treated patients. Hypertension was usually mild to moderate, occurred early in the course of treatment and was amenable to management with standard antihypertensive therapy. Blood pressure should be monitored regularly and treated, if required, in accordance with standard medical practice. In cases of severe or persistent hypertension or hypertensive crisis despite adequate antihypertensive therapy, permanent discontinuation of sorafenib should be considered (see Adverse Reactions).
Hemorrhage: An increase in the risk of bleeding may occur following sorafenib administration. The incidence of severe bleeding events is uncommon. If any bleeding event necessitates medical intervention, it is recommended that permanent discontinuation of sorafenib should be considered (see Adverse Reactions).
Warfarin: Infrequent bleeding events or elevations in the international normalized ratio (INR) have been reported in some patients taking warfarin while on sorafenib therapy. Patients taking warfarin concomitantly should be monitored regularly for changes in prothrombin time, INR and for clinical bleeding episodes (see Adverse Reactions).
Wound Healing Complications: No normal studies of the effect of sorafenib on wound healing have been conducted. In patients undergoing major surgical procedures, temporary interruption of sorafenib therapy is recommended for precautionary reasons. There is limited clinical experience regarding the timing of reinitiation of therapy following major surgical intervention. Therefore, the decision to resume sorafenib therapy following a major surgical intervention should be based on clinical judgment of adequate wound healing.
Cardiac Ischemia and/or Infarction: In Study 11213, the incidence of treatment-emergent cardiac ischemia/infarction events was higher in the sorafenib group (4.9%) compared with the placebo group (0.4%). In Study 100554, the incidence of treatment-emergent cardiac ischemia/infarction events was 2.7% in sorafenib patients compared with 1.3% in the placebo group. Patients with unstable coronary artery disease or recent myocardial infarction were excluded from this study. Temporary or permanent discontinuation of Nexavar should be considered in patients who develop cardiac ischemia and/or infarction (see Pharmacology: Clinical Efficacy and Safety under Actions and Adverse Reactions).
QT Interval Prolongation: Nexavar has been shown to prolong the QT/QTc interval (see Pharmacology under Actions), which may lead to an increased risk for ventricular arrhythmias. Use sorafenib with caution in patients who have, or may develop prolongation of QTc eg, patients with a congenital long QT syndrome, patients treated with a high cumulative dose of anthracycline therapy, patients taking certain antiarrhythmic medicines or other medicinal products that lead to QT prolongation, and those with electrolyte disturbances eg, hypokalemia, hypocalcemia, or hypomagnesemia. When using Nexavar in these patients, periodic monitoring with on-treatment electrocardiograms and electrolytes (magnesium, potassium, calcium) should be considered.
Gastrointestinal Perforation: Gastrointestinal perforation is an uncommon event and has been reported in <1% of patients taking sorafenib. In some cases, this was not associated with apparent intra-abdominal tumor. Sorafenib therapy should be discontinued (see Adverse Reactions).
Hepatic Impairment: No data is available on patients with Child-Pugh C (severe) hepatic impairment. Since sorafenib is mainly eliminated via the hepatic route, exposure might be increased in patients with severe hepatic impairment (see Pharmacokinetics under Actions).
Women of Childbearing-Potential: In animals, sorafenib has been shown to be teratogenic and embryotoxic. Adequate contraception should be used during therapy and for at least 2 weeks after completion of therapy (see Toxicology: Preclinical Safety Data under Actions).
Drug-Drug Interactions: UGT1A Pathway: Caution is recommended when administering sorafenib together with compounds that are metabolized/eliminated predominantly by the UGT1A1 pathway (eg, irinotecan) (see Interactions).
Docetaxel: Concomitant use of docetaxel (75 or 100 mg/m²) with sorafenib (200 or 400 mg twice daily), administered with a 3-day break in dosing around administration of docetaxel, resulted in a 36-80% increase in docetaxel AUC. Caution is recommended when sorafenib is co-administered with docetaxel.
Neomycin: Co-administration of neomycin may cause a decrease in sorafenib concentration.
Effects on the Ability to Drive or Operate Machinery: No studies on the effects of sorafenib on the ability to drive or use machines have been performed. There is no evidence that sorafenib affects the ability to drive or operate machinery.
Impairment of Fertility: Results from animal studies indicate that sorafenib can impair male and female fertility (see Toxicology: Preclinical Safety Data under Actions).
Use in Pregnancy: Based on the proposed mechanism of multikinase inhibition and multiple adverse effects seen in animals at exposure levels significantly below the clinical dose, sorafenib should be assumed to cause fetal harm when administered to a pregnant woman.
There are no adequate and well-controlled studies in pregnant women using sorafenib. Studies in animals have shown reproductive toxicity including malformations. In rats, sorafenib and its metabolites were demonstrated to cross the placenta and sorafenib is anticipated to inhibit angiogenesis in the fetus.
Women should avoid becoming pregnant while on therapy. Women of childbearing potential must be apprised of the potential hazard to the fetus, which includes severe malformation (teratogenicity), failure to thrive and fetal death (embryotoxicity).
Sorafenib should not be used during pregnancy. Prescribers may only consider it to be used, if the potential benefits justify the potential risks to the fetus (see Toxicology: Preclinical Safety Data under Actions).
Use in Lactation: It is not known whether sorafenib is excreted in human milk. In animals, sorafenib and/or its metabolites were excreted in milk. Because many drugs are excreted in human milk and because the effects of sorafenib on infants have not been studied, woman should discontinue breastfeeding during sorafenib treatment.