Combination of disopyramide and mexiletine for better tolerance and additive effects for treatment of ventricular arrhythmias

The efficacy and tolerance of disopyramide and mexiletine used alone and in combination were studied in 21 patients with frequent (≥30/h) ventricular premature complexes. Ambulatory electrocardiographic monitoring was performed at baseline and during therapy with disopyramide alone, mexiletine alone and a combination of disopyramide and mexiletine. During single drug therapy, the dose of disopyramide was 602 +- 152 mg/day and that of mexiletine was 738 ± 144 mg/day. During combination therapy with smaller doses of disopyramide (524 ± 134 mg/day) and mexiletine (652 ± 146 mg/day), no patient had side effects. At baseline before therapy, the mean number of ventricular premature complexes per hour, was 608 ± 757, of couplets per hour was 22.4 ± 45.8 and of episodes of nonsustained ventricular tachycardia/24 h was 219.7 ± 758.2. The mean number of ventricular premature complexes per hour was reduced to 156 ± 217 with disopyramide alone, 188 ± 298 with mexiletine alone and 76 ± 144 with combination therapy (p < 0.05 for combination therapy versus disopyramide or mexiletine alone; p=NS for disopyramide versus mexiletine). Individually, an effective regimen (>;83% reduction in ventricular premature complexes and abolition of nonsustained ventricular tachycardia) was found in 5 (24%) of 21 patients during therapy with disopyramide alone, in 3 (14%) receiving mexiletine alone and in 13 (62%) receiving combination therapy (p < 0.05 for combination therapy versus disopyramide or mexiletine; p = NS for disopyramide versus mexiletine). Thus, the antiarrhythmic effects of disopyramide and mexiletine are additive. A combination of disopyramide and mexiletine in smaller and well tolerated doses may avoid dose-related side effects and is more effective than either drug used alone at higher doses. Therefore, when disopyramide or mexiletine is ineffective because dose-related side effects limit the maximal tolerated dose, combination therapy in smaller and more tolerable doses may avoid side effects and may be more effective than treatment with either drug alone at the maximal tolerated dose.