Drug Interaction Report

GENERALLY AVOID: Coadministration with lasmiditan may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) and/or breast cancer resistance protein (BCRP) transporters. The proposed mechanism, based on in vitro data, involves decreased clearance due to inhibition of P-gp and BCRP by lasmiditan. The clinical relevance is unknown.

MANAGEMENT: Concomitant use of lasmiditan with drugs that are P-gp and/or BCRP substrates should be avoided when possible. If coadministration is required, patients should be carefully monitored for increased adverse reactions of these drugs and dosing adjusted as necessary.

GENERALLY AVOID: Grapefruit and grapefruit juice may significantly increase the plasma concentrations of orally administered ranolazine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Because ranolazine prolongs QT interval in a dose-dependent manner, high plasma levels of ranolazine may increase the risk of ventricular arrhythmias such as ventricular tachycardia, ventricular fibrillation, and torsade de pointes.

MANAGEMENT: Patients treated with ranolazine should avoid consumption of grapefruit juice and other grapefruit products if possible. Otherwise, the dosage of ranolazine should be limited to 500 mg twice a day.