Drug Interaction Report

MONITOR: Coadministration with inhibitors of P-glycoprotein may increase the plasma concentrations of vismodegib, which has been shown in vitro to be a substrate of the efflux transporter. The potential for increased pharmacologic effects of vismodegib, including adverse effects such as muscle spasm, alopecia, dysgeusia/ageusia, weight loss, fatigue, nausea, vomiting, diarrhea, decreased appetite, constipation and arthralgia, should be considered.

MANAGEMENT: Caution is advised if vismodegib is used in combination with P-glycoprotein inhibitors.

GENERALLY AVOID: Alcohol may increase the plasma concentrations of ezogabine. In a study of healthy volunteers, the administration of ezogabine 200 mg in combination with ethanol 1g/kg (5 standard alcohol drinks) over 20 minutes resulted in an increase in the ezogabine peak plasma concentration (Cmax) and systemic exposure (AUC) by 23% and 37%, respectively.

Food does not significantly affect the bioavailability of ezogabine. According to the product labeling, high-fat food does not affect the extent to which ezogabine is absorbed, but increases peak plasma concentration (Cmax) by approximately 38% and delays the time to reach peak concentration (Tmax) by 0.75 hour.

MANAGEMENT: In general, alcohol consumption should be avoided or limited during treatment with CNS-depressant agents. Patients should be advised of the potential for increased dose-related adverse reactions of ezogabine (e.g., dizziness, somnolence, nausea, constipation, urinary retention, blurred vision, memory impairment, tremor) when taken with alcohol, and to avoid hazardous activities that require mental alertness and motor coordination until they know how the medication affects them. Ezogabine can be taken with or without food.