The interaction of mexiletine with other cardiovascular drugs.

Drug-drug interactions can be adverse or beneficial and can be classified as pharmacokinetic or pharmacodynamic. Several adverse pharmacokinetic drug interactions have been described for mexiletine. Because it is a weak base, mexiletine undergoes several pH-dependent drug interactions in the gastrointestinal tract and kidney. Since mexiletine is metabolized by hepatic mixed-function oxidases, its metabolic rate can be altered by drugs that induce or inhibit this drug metabolizing system. Phenytoin and rifampin have been shown to increase mexiletine clearance and decrease its plasma concentration. Striking examples of beneficial pharmacodynamic interactions occur with mexiletine. Combining mexiletine with either beta-adrenergic blocking drugs or with quinidine markedly increases antiarrhythmic efficacy and substantially decreases the incidence of adverse effects. These beneficial interactions will have a major impact on the clinical use of mexiletine.