Clinical Information

Amiodarone is an antiarrhythmic agent used to treat life-threatening arrhythmias; it is typically categorized as a Class III drug (antiarrhythmic agents that are potassium channel blockers) but shows several mechanisms of action. The US Food and Drug Administration approved the use of amiodarone for recurrent ventricular fibrillation and recurrent hemodynamically unstable ventricular tachycardia only after demonstrating lack of response to other antiarrhythmics, but more recent studies have shown amiodarone to be the antiarrhythmic agent of choice for many situations, including atrial fibrillation.(1)

Amiodarone can be administered orally or intravenously for cardiac rhythm control. It is approximately 95% protein bound in blood, with a volume of distribution of 60 L/kg. Amiodarone elimination is quite prolonged, with a half-life of 26-107 days for oral, chronic dosing. Cytochrome P450 (CYP) 3A4 converts amiodarone to its equally active metabolite, N-desethylamiodarone (DEA), which displays very similar pharmacokinetics and serum concentrations compared with the parent drug.(2) Current therapeutic ranges are based solely on amiodarone, but most individuals will have roughly equivalent concentrations of DEA at steady state.(3)

Numerous side effects have been associated with amiodarone. The most common adverse effect is disruption of thyroid function (hypo- or hyperthyroidism) due to amiodarone's structural similarity to thyroid hormones. Neurological and gastrointestinal toxicities are concentration-dependent, whereas thyroid dysfunction, pulmonary fibrosis, and hepatotoxicity are more loosely linked to drug concentration. There is significant potential for drug interactions involving amiodarone, including several other cardioactive drugs (eg, digoxin, verapamil, class I antiarrhythmics [sodium channel blockers]), warfarin, statins, and CYP3A4 substrates.