Drug Interaction Report

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.

ADJUST DOSING INTERVAL: Bulk-forming laxatives such as guar gum, psyllium, polycarbophil, or methylcellulose may affect the bioavailability of concomitantly administered substances due to their effect on the rate of gastrointestinal transit and gastric emptying.

MANAGEMENT: In general, oral medications should be administered at least 2 hours before or 2 hours after dosing of the bulk-forming laxative.