Drug Interaction Report

MONITOR: Coadministration of lasmiditan and agents that lower heart rate may increase the risk of bradycardia. In clinical trials, lasmiditan was associated with heart rate decreases of 5 to 10 beats per minute (bpm) while placebo was associated with decreases of 2 to 5 bpm. In a drug interaction study, a single 200 mg dose of lasmiditan led to an additional heart rate decrease of 5 bpm when given with propranolol.

MANAGEMENT: Caution is advised during coadministration of lasmiditan and agents that lower heart rate if the estimated decrease in heart rate may present a clinical risk. Consider monitoring heart rate in patients for whom the estimated decrease in heart rate may not be tolerated.

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of ivabradine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. According to the product labeling, administration with grapefruit juice (quantity unknown) resulted in an approximately twofold increase in ivabradine systemic exposure (AUC). Elevated plasma levels of ivabradine may increase the risk of excessive bradycardia and conduction disturbances.

ADJUST DOSING INTERVAL: Food delays the absorption of ivabradine by approximately 1 hour and increases plasma exposure by 20% to 40% compared to fasting conditions.

MANAGEMENT: Patients treated with ivabradine should avoid or limit consumption of grapefruit or grapefruit juice. The manufacturer recommends taking ivabradine with meals to reduce variability in exposure.