Usefulness and safety of cimetidine in patients receiving mexiletine for ventricular arrhythmia.

Cimetidine, a commonly used H2 receptor antagonist, was found to adversely interact with many drugs metabolized by the liver, including class I antiarrhythmic agents, lidocaine and quinidine. Mexiletine is a new class I antiarrhythmic agent similar to lidocaine which when used orally may have significant gastric side effects. Since some patients with peptic ulcer disease or gastric hyperacidity on mexiletine may benefit from the addition of cimetidine, it was important to rule out any significant adverse interaction between the two drugs in such patients. Eleven patients currently receiving long-term oral mexiletine for the treatment of complex ventricular arrhythmia underwent a double-blind crossover trial where they were maintained on their usual dose of mexiletine, and cimetidine, 300 mg orally every 6 hours, or placebo were added for a 1-week period each. Peak and trough mexiletine blood levels were not significantly altered by cimetidine. Similarly, there was no significant change in the frequency and severity of ventricular arrhythmia when cimetidine was added to mexiletine. Cimetidine reduced gastric side effects of mexiletine in 50% of patients who had complained of such symptoms on mexiletine alone or on mexiletine and placebo. We conclude that cimetidine can effectively reduce gastric side effects of mexiletine in many patients without adversely affecting the plasma concentration or the efficacy of the drug.