Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 1A2 may increase the plasma concentrations of asenapine, which is partially metabolized by the isoenzyme. According to the product labeling, administration of asenapine (5 mg single dose) in combination with the potent CYP450 1A2 inhibitor fluvoxamine (25 mg twice daily for 8 days) resulted in a 13% increase in asenapine peak plasma concentration (Cmax) and a 29% increase in systemic exposure (AUC). The full therapeutic dose of fluvoxamine would be expected to cause a greater increase in asenapine plasma concentrations.

MANAGEMENT: Caution is advised if asenapine is prescribed in combination with CYP450 1A2 inhibitors. Pharmacologic response to asenapine should be monitored more closely whenever a CYP450 1A2 inhibitor is added to or withdrawn from therapy, and the asenapine dosage adjusted as necessary.

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.