Drug Interaction Report

MONITOR: Coadministration with cimetidine may increase the plasma concentrations of pentoxifylline. The proposed mechanism is cimetidine inhibition of the CYP450 1A2-mediated metabolism of pentoxifylline. In 10 healthy study subjects given pentoxifylline controlled-release 400 mg every 8 hours, mean pentoxifylline systemic exposure (AUC) increased by approximately 26% and apparent oral clearance decreased by nearly 22% following the addition of cimetidine 300 mg four times daily for 7 days. Some adverse effects such as headache, nausea, and vomiting were reportedly increased during coadministration with cimetidine.

MANAGEMENT: Pharmacologic response to pentoxifylline should be monitored more closely whenever cimetidine is added to or withdrawn from therapy, and the pentoxifylline dosage adjusted as necessary. Patients should be advised to seek medical attention if they experience serious adverse effects such as bleeding, angina, or arrhythmias. Alternatively, agents that do not inhibit CYP450 1A2 such as famotidine, ranitidine, or proton pump inhibitors may be considered when acid suppression is required in patients receiving pentoxifylline.

Concurrent use of cimetidine and ethanol may result in increased ethanol concentrations. The mechanism appears to be due to inhibition of gastric alcohol dehydrogenase by cimetidine, leading to increased bioavailability of the alcohol and inhibition of hepatic metabolism of alcohol. The clinical significance of this interaction is limited. More importantly, patients requiring cimetidine for gastrointestinal disease should be counseled to avoid alcohol to prevent worsening of their disease. The other H-2 receptor antagonists appear to have minimal effects on the concentrations of alcohol.

Caffeine effects may be increased in patients also taking cimetidine. The mechanism may be due to decreased caffeine metabolism induced by cimetidine. Although adequate clinical data are lacking, a reduction in dose or elimination of caffeine may be needed if excess CNS stimulation is observed.

H2 antagonists may reduce the clearance of nicotine. Cimetidine, 600 mg given twice a day for two days, reduced clearance of an intravenous nicotine dose by 30%. Ranitidine, 300 mg given twice a day for two days, reduced clearance by 10%. The clinical significance of this interaction is not known. Patients should be monitored for increased nicotine effects when using the patches or gum for smoking cessation and dosage adjustments should be made as appropriate.