Drug Interaction Report

MONITOR: Coadministration of strong inhibitors of CYP450 3A4 and/or CYP450 2C9 in patients with renal or hepatic impairment may significantly increase lacosamide plasma concentrations and increase the risk of lacosamide toxicity. The presumed mechanism is additive reduction in lacosamide clearance. Pharmacokinetic studies have shown lacosamide systemic exposure (AUC) may increase by 25% to 60% in patients with renal and/or hepatic impairment. Additional increases in lacosamide plasma concentrations are possible due to inhibition of the CYP450 3A4 and 2C9-mediated formation of O-desmethyl metabolite (inactive). Approximately 30% of a lacosamide dose is excreted as O-desmethyl metabolite in the urine. This interaction has not been established in vivo but is possible based on in vitro data.

MANAGEMENT: For patients with renal and/or hepatic impairment concomitantly receiving a strong CYP450 3A4 and/or CYP450 2C9 inhibitor, lacosamide dose reductions in addition to those recommended for renal and/or hepatic impairment may be necessary. Manufacturer labeling should be consulted for dose recommendations in renal and/or hepatic impairment. Patients should be advised to notify their physician if they experience dizziness, lightheadedness, fainting, or irregular heartbeat. Lacosamide dose adjustments may be necessary whenever a strong CYP450 3A4 and/or 2C9 inhibitor is added to or withdrawn from therapy in patients with renal and/or hepatic impairment.

ADJUST DOSING INTERVAL: Food significantly enhances the oral bioavailability of boceprevir. When given at 800 mg three times daily with food, boceprevir exposure increased by up to 65% relative to administration in the fasting state. The bioavailability of boceprevir was similar regardless of meal type (e.g., high-fat versus low-fat) or whether taken 5 minutes prior to eating, during a meal, or immediately following completion of the meal. Therefore, boceprevir may be taken without regard to either meal type or timing of the meal.

MANAGEMENT: To ensure maximal oral absorption, boceprevir should be administered with a meal or light snack.