Amiodarone: a unique antiarrhythmic agent.

Abstract

The chemistry, pharmacology, pharmacokinetics, clinical use and efficacy, adverse effects, and dosage of amiodarone, an investigational antiarrhythmic agent, are reviewed. Amiodarone hydrochloride (L3428, Cordarone; Labaz Laboratories) is a benzofuran derivative and contains iodine. Amiodarone is a noncompetitive antagonist of alpha- and beta-adrenergic receptors. It is a type III antiarrhythmic agent and causes prolongation of the action potential of atrial and ventricular tissue. The drug is incompletely and variably absorbed following oral administration; bioavailability ranges from 22 to 86%. Peak serum concentrations occur 2-10 hours after an oral dose. Amiodarone has a large volume of distribution and is widely distributed in body tissues. It is metabolized by the liver; half-life following a single dose is 5-20 hours, but terminal half-lives of 14-58 days have been found following discontinuation of long-term therapy. Amiodarone has been effective in treating supraventricular tachycardias in patients with Wolff-Parkinson-White syndrome whose arrhythmias are refractory to other drugs. Preliminary data suggest a potential use for amiodarone in treating atrial fibrillation/flutter and bradycardia-tachycardia syndrome. The drug has also been tested in patients with ventricular arrhythmias with promising results. Amiodarone has many side effects, some of them serious. The cardiovascular, pulmonary, neurologic, and hepatic systems may be affected; the drug also has deleterious effects on the eyes, thyroid gland, and skin. The usual oral adult dose of amiodarone hydrochloride is 600 mg daily for seven days followed by maintenance doses of 200-400 mg daily during initial therapy. Intravenous initial doses of amiodarone hydrochloride 5 or 10 mg/kg via a central line have been used; these are often followed by infusions of 10 mg/kg/day for three to five days. Amiodarone is an effective antiarrhythmic agent whose use is limited by numerous and sometimes serious side effects. Until more clinical data are available, its use should be restricted to treatment of serious arrhythmias refractory to other agents.