Drug Interaction Report

MONITOR: Sorafenib has the potential to prolong QT interval of the electrocardiogram. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In a multicenter, open-label, nonrandomized trial consisting of 53 patients with advanced cancer, no large changes in the mean QTc interval (i.e., greater than 20 msec) from baseline were detected during treatment with sorafenib 400 mg twice daily. After one 28-day treatment cycle, the largest mean QTc interval change of 8.5 msec was observed at 6 hours postdose on day 1 of cycle 2. In another study, QT/QTc measurements were recorded in 31 cancer patients at baseline and posttreatment. Following one 28-day treatment cycle with sorafenib 400 mg twice a day, QTcF was prolonged by 9 +/-18 msec at the time of maximum concentration of sorafenib, as compared to placebo treatment at baseline. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Caution is recommended if sorafenib is used in combination with cumulative high-dose anthracycline therapy or other drugs that can prolong the QT interval. ECG and serum electrolytes, including potassium, magnesium and calcium, should be monitored before starting sorafenib therapy and periodically during treatment. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

GENERALLY AVOID: Risperidone oral solution is not compatible with either tea or cola. In addition, alcohol may potentiate some of the pharmacologic effects of risperidone. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Risperidone oral solution should not be mixed with tea or cola. It may be taken with water, coffee, orange juice, or lowfat milk. Patients should also be advised to avoid consumption of alcohol.

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of sorafenib. According to the product labeling, sorafenib bioavailability was reduced by 29% when administered with a high-fat meal compared to administration in the fasted state. When given with a moderate-fat meal, bioavailability was similar to that in the fasted state.

MANAGEMENT: To ensure maximal and consistent oral absorption, sorafenib should be taken at least one hour before or two hours after eating.