Low dose quinidine-mexiletine combination therapy versus quinidine monotherapy for treatment of ventricular arrhythmias

Abstract

Low dose quinidine-mexiletine combination therapy was compared with quinidine monotherapy in 15 patients with frequent ventricular premature complexes and nonsustained ventricular tachycardia in a dose escalation crossover study. Oral combination therapy was initiated with quinidine gluconate (165 mg) plus mexiletine (150 mg) every 8 h. If ventricular premature complexes were not suppressed ≥80% and nonsustained ventricular tachycardia ≥90%, the dose was increased to a maximum of 330 mg of quinidine plus 200 mg of mexiletine. Quinidine monotherapy was initiated with 330 mg and escalated to a maximum of 660 mg every 8 h if criteria for effectiveness were not met.Combination quinidine-mexiletine therapy suppressed 80% of ventricular premature complexes in 13 of 14 patients and suppressed 100% of episodes of ventricular tachycardia in 6 of 8 patients (mean quinidine dose 200 ±70 mg; mean mexiletine dose 146 ± 24 mg every 8 h). The mean effective trough quinidine and mexiletine concentration was 1.0 ± 0.7 and 0.9 ± 0.4 μg/ml, respectively. Monotherapy was less effective; that is, ≥80% suppression of ventricular premature complexes was observed in 5 of 15 patients and 100% suppression of ventricular tachycardia in 2 of 9 patients. The mean quinidine monotherapy dose was 462 ± 155 mg every 8 h; the mean quinidine concentration was 1.8 ± 0.8 μg/ml.Adverse systemic effects occurred in 3 patients on quinidine-mexiletine therapy and in 11 on quinidine monotherapy. Neither treatment prolonged PR or QRS intervals, but monotherapy prolonged the QTc interval (p < 0.05); both treatments prolonged the coupling interval (p < 0.05). Low dose quinidine-mexiletine is more effective and better tolerated than are standard doses of quinidine.