Drug Interaction Report

MONITOR: Coadministration with alcohol or other central nervous system (CNS) depressants may enhance the sedative effects of lasmiditan and increase the likelihood and/or severity of cognitive and/or neuropsychiatric adverse reactions. Patients treated with lasmiditan are at risk of CNS depression, including dizziness and sedation, as well as driving impairment. In clinical studies, dizziness and sedation were reported in up to 17% and 7%, respectively, of patients receiving lasmiditan, and dizziness was the most common adverse event resulting in discontinuation (greater than 2%). In a computer-based driving study, a significant, dose-dependent impairment of subjects' ability to drive was observed with single 50, 100, and 200 mg lasmiditan doses at 90 minutes after administration. Concomitant use of lasmiditan and CNS depressants has not been studied clinically.

MANAGEMENT: Caution is advised during coadministration of lasmiditan with alcohol, other CNS depressants, or other agents that cause sedation. Patients should be advised against driving and other activities that require complete mental alertness for at least 8 hours after lasmiditan is administered.

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

Administration with food may increase the bioavailability of paliperidone from the extended release tablets. In healthy ambulatory subjects, administration of a 12 mg paliperidone extended release tablet with a standard high-fat/high-caloric meal resulted in 60% and 54% increases, respectively, in the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of paliperidone compared to administration under fasting conditions. The clinical significance of these changes is unknown.

MANAGEMENT: Patients receiving paliperidone should be advised to avoid the consumption of alcohol. Since clinical trials establishing the safety and efficacy of paliperidone were carried out without regard to the timing of meals, presumably paliperidone may be administered with or without food.