22232 Amiodarone (AMIO)

Cordarone​, Desethylamiodarone, Pacerone (Amiodarone Hydrochloride)

Monitoring Amiodarone therapy, especially when amiodarone is coadministered with other drugs that may interact

Evaluation of possible amiodarone toxicity

Assessment of patient compliance​

Numerous drug interactions have been observed for amiodarone. Clinical follow-up is essential for optimal use of amiodarone. Therapeutic drug monitoring for amiodarone and coadministered medications is highly recommended.

Specimens that are obtained from gel tubes or anticoagulate collections can cause assay interference.

​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.

Clinical effects generally require serum concentrations above 0.5 mcg/mL.

Increased risk of toxicity is associated with amiodarone concentrations above 2.5 mcg/mL.

Although therapeutic and toxic ranges are based only on the parent drug, the active metabolite N-desethylamiodarone should be present in similar concentrations to amiodarone.