Drug Interactions between procainamide and ranitidine bismuth citrate

MONITOR: A study in healthy volunteers suggests that ranitidine may increase the plasma concentrations of procainamide and its active metabolite, N-acetylprocainamide (NAPA), in a dose-dependent manner. The proposed mechanism is competitive inhibition of renal tubular secretion by ranitidine. In the study, coadministration of ranitidine (150 mg orally every 12 hours) and procainamide (1 gram orally 13 hours after first ranitidine dose) in six healthy subjects led to an approximately 14% increase in procainamide and NAPA systemic exposure (AUC) compared to administration of procainamide alone. The renal clearance of procainamide and NAPA decreased by approximately 18% and 10%, respectively, with ranitidine. Subsequently, three of the subjects were coadministered a higher dosage of ranitidine (300 mg orally once, then 150 mg every four hours for three doses) with procainamide (1 gm orally one hour after first ranitidine dose), which resulted in a 21% and 12% increase in the AUC of procainamide and NAPA, respectively. Renal clearance of procainamide and NAPA reduced by a little over 35% each. The clinical significance of this potential interaction is unknown. Two other studies found no relevant effect of ranitidine 150 mg twice a day on the mean pharmacokinetic parameters of procainamide and NAPA. However, individual changes were observed in one of the study, with subjects exhibiting an approximately 20% mean increase or decrease in procainamide renal clearance depending on their baseline clearance level. Specifically, reductions occurred in subjects with a high baseline clearance rate (mean 539 mL/min), whereas increases occurred in subjects with a lower baseline clearance rate (mean 410 mL/min).

MANAGEMENT: Until more information is available, caution is advised when prescribing procainamide with high dosages of ranitidine such as those used in the treatment of Zollinger-Ellison syndrome. In addition, caution may be advisable in certain patient populations such as the elderly or those with liver disease who may experience elevated ranitidine levels at lower dosages. If an interaction is suspected, a dosage adjustment for procainamide or a switch to famotidine or nizatidine may be considered.