IMPORTANT SAFETY INFORMATION

NEXAVAR in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer. Nexavar may cause fetal harm when administered to a pregnant woman. Women of childbearing potential are advised to avoid becoming pregnant and female patients should also be advised against breastfeeding while receiving Nexavar. Cardiac ischemia and/or myocardial infarction may occur. continue reading below »

Managing hand-foot skin reaction (HFSR)

Prior to initiating therapy with Nexavar, take the following measures to prevent or reduce the severity of HFSR¹:

Conduct full body skin exam, with emphasis on hyperkeratotic areas on palms and soles and any deformities
Use dermal therapy creams and ointments on hands and feet on day 1 of tyrosine kinase inhibitor therapy and continuously thereafter
Maintain frequent communication with patients during weeks 2 to 4 of treatment to ensure that symptoms are detected early

Suggested Dose Modifications for Skin Toxicity

Patient counseling considerations for managing HFSR

To minimize HFSR, advise patients to^1-4:

Diligently apply topical creams/moisturizers to hands and feet on day 1 of therapy and daily thereafter
- Wear cotton gloves and/or socks after applying dermal therapies
Monitor for changes in skin such as sensitivity, burning, redness, or swelling
Wear loose-fitting clothing and shoes
Elevate hands and feet when in a sitting or lying position
Apply ice packs or cool compresses indirectly to hands and feet for up to 20 minutes
Gently pat skin dry after bathing or washing
Avoid:
- Exposure to heat sources such as saunas or direct sun
- Activities that result in unnecessary force or friction on the hands or feet, such as using gardening tools, jogging, or aerobics
- Contact with laundry detergents or cleaning products with strong chemicals

Indication

Nexavar is indicated for the treatment of patients with unresectable hepatocellular carcinoma.

Important Safety Considerations

Nexavar in combination with carboplatin and paclitaxel is contraindicated in patients with squamous cell lung cancer
Nexavar may cause fetal harm when administered to a pregnant woman. Women of childbearing potential are advised to avoid becoming pregnant and female patients should also be advised against breastfeeding while receiving Nexavar
Cardiac ischemia and/or myocardial infarction may occur. Temporary or permanent discontinuation of Nexavar should be considered in patients who develop cardiac ischemia and/or myocardial infarction
Gastrointestinal perforation was an uncommon adverse reaction and has been reported in less than 1% of patients taking Nexavar
Uncommon but serious adverse reactions, including keratoacanthomas/squamous cell cancer of the skin and Stevens-Johnson Syndrome, have been reported in clinical trials
An increased risk of bleeding may occur following Nexavar administration. If bleeding necessitates medical intervention, consider discontinuation of Nexavar
Hypertension may occur early in the course of treatment. Monitor blood pressure weekly during the first 6 weeks and periodically thereafter and treat, as required
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
Nexavar can prolong the QT/QTc interval and increase the risk for ventricular arrhythmias. Avoid use in patients with congenital long QT syndrome and monitor patients with congestive heart failure, bradyarrhythmias, drugs known to prolong the QT interval, and electrolyte abnormalities
Elevations in serum lipase and reductions in serum phosphate of unknown etiology have been associated with Nexavar. Monitor patients taking concomitant warfarin regularly for changes in prothrombin time, INR, or clinical bleeding episodes. Avoid concomitant use of strong CYP3A4 inducers, when possible, because inducers can decrease the systemic exposure of sorafenib. Nexavar exposure decreases when co-administered with oral neomycin. Effects of other antibiotics on Nexavar pharmacokinetics have not been studied
Most common adverse reactions reported for Nexavar-treated patients vs placebo-treated patients in unresectable HCC, respectively, were: 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% vs 32%
During postapproval use of Nexavar, the following adverse drug reactions have been identified: angioedema and drug-induced hepatitis, including reports of hepatic failure and death

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch, or call 1.800.FDA.1088. For important risk and use information, please see the full Prescribing Information.

References: 1. Lacouture ME, Wu S, Robert C, et al. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist. 2008;13(9):1001-1011. 2. Anderson R, Jatoi A, Robert C, Wood LS, Keating KN, Lacouture ME. Search for evidence-based approaches for the prevention and palliation of hand-foot skin reaction (HFSR) caused by multikinase inhibitors. Oncologist. 2009;14(3):291-302 3. Wood LS. Managing the side effects of sorafenib and sunitinib. Commun Oncol. 2006;3(9):558-562. 4. Cancer.net. Hand-foot syndrome or palmar-plantar erythrodysesthesia. http://www.cancer.net/patient/Diagnosis+and+Treatment/Treating+Cancer/managing+Side+Effects/Hand-Foot+Syndrome+or+Plantar+Erythrodysesthesia#mainContent%20idmainContent. Accessed April 3, 2008.