Amiodarone is a benzofuran that was synthesized and tested as an antianginal agent in the 1960s, but was later discovered to have antiarrhythmic properties. Amiodarone is the most widely prescribed antiarrhythmic medication in the United States, largely due to its efficacy in the management of both supraventricular and ventricular arrhythmias. In addition to the superior efficacy compared to most other antiarrhythmic drugs, amiodarone has very little negative inotropic activity, and a low rate of ventricular proarrhythmia, making it advantageous for use in patients with heart failure . Despite these advantages, the use of amiodarone is associated with a relatively high incidence of side effects, making it a complicated drug to use safely.
This topic will review the electrophysiologic properties of amiodarone, clinical indications, and dosing recommendations for oral and intravenous amiodarone. The side effects of amiodarone are discussed in detail elsewhere. (See "Major side effects of amiodarone" and "Amiodarone and thyroid dysfunction".)
Oral amiodarone is markedly lipophilic, resulting in a very large volume of distribution (average about 66 L/kg) and a prolonged time to reach stable plasma levels . It is incompletely absorbed (approximately 30 to 70 percent) after oral administration and is taken up very extensively by tissue, with marked interindividual variation . Estimates of the elimination half-life of amiodarone vary, depending on how the half-life has been measured and the route of amiodarone administration. The relatively short half-life for disappearance of amiodarone from plasma after a single-dose or short-term intravenous administration is likely a measure of drug redistribution from vascular space into tissue and not true body elimination. After long-term oral therapy, amiodarone has a true elimination half-life between 60 and 142 days [2,3]. Slow and wide distribution to tissue (fat, muscle, highly perfused organs) results in a requirement of long loading periods in an effort to accelerate the onset of drug activity. However, even with loading, arrhythmia recurrence during the first months of therapy does not necessarily predict long-term efficacy. Conversely, intravenous (IV) amiodarone begins to act within one hour, with rapid onset of action within minutes following an IV bolus.
There is little correlation between the plasma concentration of amiodarone or its major active metabolite, desethylamiodarone, and drug efficacy or toxicity .
Amiodarone is a potent inhibitor of CYP3A4, which can lead to significant drug interactions. (See 'Drug interactions' below.)