Efficacy and safety of long-term amiodarone in treatment of cardiac arrhythmias: Dosage experience

The efficacy and safety of long-term oral amiodarone was assessed in 173 patients with symptomatic tachyarrhythmias: 96 with life-threatening ventricular tachycardia and fibrillation (VT-VF), of whom 40 had survived sudden cardiac death (SCD), and 77 with atrial tachyarrhythmias (AT), predominantly atrial fibrillation and flutter, that had been refractory to conventional antiarrhythmic agents in therapeutic dosages. Amiodarone administration consisted of a high-dose loading phase (800 to 1600 mg/day in divided doses) for 8 days to 4 weeks, followed by a low-dose maintenance phase (200 to 400 mg once a day). The regulation of the maintenance dose was aided by frequent monitoring of serum amiodarone concentrations, clinical response, and development of side effects. Amiodarone had long-term effectiveness (mean follow-up 10.1 months; range 1.5 to 62 months) in 139 of 173 patients (79%). It was effective in 82 of 96 patients (83%) with symptomatic VT-VF (35 of 40 survivors [86%] of SCD), whose mean follow-up was 10.3 months. In the 77 AT patients there were 57 long-term responders (74%; mean follow-up 9.1 months; range 1.5 to 60 months). The maintenance (apparent steady-state) serum amiodarone concentrations ranged from 0.6 to 2.8 μg/ml (mean 1.6 μg/ml) in 139 of the 173 responders and were lower than those in the nonresponders (mean 1.9 μg/ml). These differences were not significant. There was a wide intersubject variation of serum levels for a given dose of amiodarone. Arrhythmia relapses occurred in nine patients when their serum concentrations fell to ≤1.0 μg/ml. In eight of these patients, reinstitution of higher amiodarone dosages and elevation of serum amiodarone concentrations restored control of their tachycardia. Side effects occurred in 44 of 173 patients (25%) but precluded long-term use in only 18 patients (10%). Although side effects were generally more common when serum amiodarone concentrations exceeded 2.5 μg/ml, even serious ones occurred over a wide range (0.6 to 4.4 μg/ml) of serum drug concentrations. Important drug interactions occurred with warfarin and class I antiarrhythmic agents.