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 effects of CNS-active and/or CNS-toxic agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

GENERALLY AVOID: Grapefruit and/or grapefruit juice may increase the plasma concentrations and effects of drugs that are substrates of the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4 mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit the 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. It may be advisable for patients to avoid consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with drugs that undergo metabolism by CYP450 3A4. Orange juice is not expected to interact with these drugs.