Drug Interaction Report

MONITOR: Hydantoins may increase the CYP450 hepatic metabolism of quinidine. Serum quinidine levels and quinidine effectiveness may be decreased.

MANAGEMENT: Quinidine levels and effectiveness should be monitored frequently after a hydantoin is added to or deleted from the patient's regimen. An increase in quinidine dosage may be required. Patients should be advised to notify their physician if they experience increased irregular heartbeats or worsening of their symptoms.

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.