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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 U.S. 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 95% protein bound in blood, with a volume of distribution of 60 L/kg. Amiodarone elimination is quite prolonged, with a mean half-life of 53 days. CYP3A4 converts amiodarone to its equally active metabolite, N-desethylamiodarone (DEA), which displays very similar pharmacokinetics and serum concentrations, compared to 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.
Monitoring amiodarone therapy, especially when amiodarone is coadministered with other drugs that may interact
Evaluation of possible amiodarone toxicity
Assessment of patient compliance
Clinical effects generally require serum concentrations >0.5 mcg/mL. Increased risk of toxicity is associated with amiodarone concentrations >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.
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.
Therapeutic concentration: 0.5-2.0 mcg/mL
Toxic concentration: >2.5 mcg/mL
No therapeutic range established; activity and serum concentration are similar to parent drug.
1. Goldschlager N, Epstein AE, Naccarelli GV, et al: A practical guide for clinicians who treat patients with amiodarone. Heart Rhythm 2007;4:1250-1259
2. Klotz U: Antiarrhythmics: elimination and dosage considerations in hepatic impairment. Clin Pharmacokinet.2007;46(12):985-996
3. Campbell TJ, Williams KM: Therapeutic drug monitoring: antiarrhythmic drugs. Br J Clin Pharmacol.2001;52 Suppl1:21S-34S