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 Lacosamide dose adjustments may be necessary whenever a strong CYP450 3A4 and/or 2C9 inhibitor is added to or withdrawn from therapy in patients with renal and/or hepatic impairment.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 may reduce the systemic bioavailability of amprenavir from fosamprenavir oral suspension. The mechanism of interaction has not been described. According to the product labeling, administration of fosamprenavir oral suspension (1400 mg single dose) with a high-fat meal (967 kcal, 67 g fat, 33 g protein, 58 g carbohydrate) reduced amprenavir peak plasma concentration (Cmax) by 46% and systemic exposure (AUC) by 28% compared to administration in a fasted state. The time to reach peak plasma level (Tmax) was delayed by 0.72 hours. In contrast, the same high-fat meal did not affect the pharmacokinetics of amprenavir from fosamprenavir tablets.

MANAGEMENT: Fosamprenavir suspension should be administered on an empty stomach in adults, but with food in pediatric patients to aid palatability and compliance. If emesis occurs within 30 minutes after dosing the suspension, the dose should be repeated. Fosamprenavir tablets may be taken with or without food.