The cimetidine-lidocaine interaction

Lidocaine is a widely used antiarrhythmic agent whose plasma clearance varies with changes in hepatic blood flow. Cimetidine, an H2-receptor antagonist, has been shown to decrease hepatic blood flow. To ascertain whether cimetidine affected serum lidocaine concentration, we studied 21 patients receiving lidocaine infusions and divided them into two groups. Fifteen patients received cimetidine, 300 mg every 6 hours, in addition to lidocaine; six patients received only lidocaine. In 14 of the 15 patients receiving both lidocaine and cimetidine, a rise in serum lidocaine levels was seen, whereas no change was noted in the control group. Six of the 15 patients were found to have levels in the toxic range and two had symptoms. An additional three patients on lidocaine received diphenhydramine, an H1-receptor antagonist. No elevation in serum lidocaine levels was noted after administration of diphenhydramine. We conclude that there exists an interaction between lidocaine and cimetidine and that the rise in serum lidocaine levels may be mediated by cimetidine's inhibition of the H2 receptor.