Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of zonisamide, which is metabolized by the isoenzyme. While clinical data are lacking, the possibility of prolonged and/or increased pharmacologic effects of zonisamide should be considered.

MANAGEMENT: Dosage adjustments as well as clinical and laboratory monitoring may be appropriate whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy. Patients should be advised to notify their physician if they experience symptoms such as severe drowsiness, confusion, loss of coordination, depression, aphasia, decreased sweating, fever, loss of seizure control, or slow pulse.

ADJUST DOSING INTERVAL: Food may reduce the oral absorption and bioavailability of zafirlukast. In two separate studies, one using a high-fat and the other a high-protein meal, administration of zafirlukast with food reduced the mean bioavailability by approximately 40%.

MANAGEMENT: To ensure maximal oral absorption, zafirlukast should be administered at least 1 hour before or 2 hours after meals.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.