Clinical uses of amiodarone
- Elsa-Grace Giardina, MD, MS
Elsa-Grace Giardina, MD, MS
- Professor of Medicine
- Director, Center for Women’s Health
- Columbia University Medical Center
- Rod Passman, MD, MSCE
Rod Passman, MD, MSCE
- Professor of Medicine
- Northwestern University Feinberg School of Medicine
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.)
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- ELECTROPHYSIOLOGIC PROPERTIES
- Oral amiodarone
- Intravenous amiodarone
- Effects on the ECG
- ORAL AMIODARONE FOR THE TREATMENT OF ATRIAL ARRHYTHMIAS
- Oral amiodarone to prevent recurrent paroxysmal atrial fibrillation
- Oral amiodarone for pharmacologic cardioversion of atrial fibrillation
- Oral amiodarone prior to elective cardioversion or catheter ablation for persistent atrial fibrillation
- Oral amiodarone for prophylaxis against atrial fibrillation following cardiac surgery
- INTRAVENOUS AMIODARONE FOR THE TREATMENT OF ATRIAL ARRHYTHMIAS
- IV amiodarone to restore and maintain sinus rhythm in critically ill patients with hemodynamically unstable atrial fibrillation
- IV amiodarone to control the ventricular response in critically ill patients with atrial fibrillation and rapid ventricular response
- IV amiodarone for prophylaxis against atrial fibrillation following cardiac surgery
- CLINICAL USES OF AMIODARONE FOR VENTRICULAR ARRHYTHMIAS
- Oral amiodarone for the treatment of ventricular arrhythmias
- Oral amiodarone for the primary prevention of sudden cardiac death
- Oral amiodarone for the secondary prevention of sudden cardiac death
- Oral amiodarone for the prevention of ventricular arrhythmias in patients with ICDs
- IV amiodarone for the treatment of electrical storm and incessant ventricular tachycardia
- IV amiodarone during resuscitation from cardiac arrest
- SPECIAL CONSIDERATIONS
- Transition from IV to oral therapy
- Dose adjustment
- Drug interactions
- Use in pregnancy
- Use in children
- SIDE EFFECTS
- SUMMARY AND RECOMMENDATIONS