Clinical uses of amiodarone
- Elsa-Grace Giardina, MD, MS, FACC, FACP, FAHA
Elsa-Grace Giardina, MD, MS, FACC, FACP, FAHA
- 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 with 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 "Monitoring and management of amiodarone side effects" and "Amiodarone and thyroid dysfunction".)
Oral amiodarone is markedly lipophilic, resulting in a very large volume of distribution (average approximately 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.)
- Goldschlager N, Epstein AE, Naccarelli GV, et al. A practical guide for clinicians who treat patients with amiodarone: 2007. Heart Rhythm 2007; 4:1250.
- Connolly SJ. Evidence-based analysis of amiodarone efficacy and safety. Circulation 1999; 100:2025.
- Vassallo P, Trohman RG. Prescribing amiodarone: an evidence-based review of clinical indications. JAMA 2007; 298:1312.
- Desai AD, Chun S, Sung RJ. The role of intravenous amiodarone in the management of cardiac arrhythmias. Ann Intern Med 1997; 127:294.
- Gomes JA, Kang PS, Hariman RJ, et al. Electrophysiologic effects and mechanisms of termination of supraventricular tachycardia by intravenous amiodarone. Am Heart J 1984; 107:214.
- Scheinman MM, Levine JH, Cannom DS, et al. Dose-ranging study of intravenous amiodarone in patients with life-threatening ventricular tachyarrhythmias. The Intravenous Amiodarone Multicenter Investigators Group. Circulation 1995; 92:3264.
- Clemo HF, Wood MA, Gilligan DM, Ellenbogen KA. Intravenous amiodarone for acute heart rate control in the critically ill patient with atrial tachyarrhythmias. Am J Cardiol 1998; 81:594.
- Kamiya K, Nishiyama A, Yasui K, et al. Short- and long-term effects of amiodarone on the two components of cardiac delayed rectifier K(+) current. Circulation 2001; 103:1317.
- European Heart Rhythm Association, Heart Rhythm Society, Fuster V, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation--executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation). J Am Coll Cardiol 2006; 48:854.
- Darkner S, Chen X, Hansen J, et al. Recurrence of arrhythmia following short-term oral AMIOdarone after CATheter ablation for atrial fibrillation: a double-blind, randomized, placebo-controlled study (AMIO-CAT trial). Eur Heart J 2014; 35:3356.
- Mohanty S, Di Biase L, Mohanty P, et al. Effect of periprocedural amiodarone on procedure outcome in patients with longstanding persistent atrial fibrillation undergoing extended pulmonary vein antrum isolation: results from a randomized study (SPECULATE). Heart Rhythm 2015; 12:477.
- Daoud EG, Strickberger SA, Man KC, et al. Preoperative amiodarone as prophylaxis against atrial fibrillation after heart surgery. N Engl J Med 1997; 337:1785.
- Giri S, White CM, Dunn AB, et al. Oral amiodarone for prevention of atrial fibrillation after open heart surgery, the Atrial Fibrillation Suppression Trial (AFIST): a randomised placebo-controlled trial. Lancet 2001; 357:830.
- Ad N, Holmes SD, Shuman DJ, et al. Amiodarone after surgical ablation for atrial fibrillation: Is it really necessary? A prospective randomized controlled trial. J Thorac Cardiovasc Surg 2016; 151:798.
- Fuster V, Rydén LE, Cannom DS, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 2006; 114:e257.
- Khan IA, Mehta NJ, Gowda RM. Amiodarone for pharmacological cardioversion of recent-onset atrial fibrillation. Int J Cardiol 2003; 89:239.
- Hilleman DE, Spinler SA. Conversion of recent-onset atrial fibrillation with intravenous amiodarone: a meta-analysis of randomized controlled trials. Pharmacotherapy 2002; 22:66.
- Chevalier P, Durand-Dubief A, Burri H, et al. Amiodarone versus placebo and class Ic drugs for cardioversion of recent-onset atrial fibrillation: a meta-analysis. J Am Coll Cardiol 2003; 41:255.
- Guarnieri T, Nolan S, Gottlieb SO, et al. Intravenous amiodarone for the prevention of atrial fibrillation after open heart surgery: the Amiodarone Reduction in Coronary Heart (ARCH) trial. J Am Coll Cardiol 1999; 34:343.
- Beaulieu Y, Denault AY, Couture P, et al. Perioperative intravenous amiodarone does not reduce the burden of atrial fibrillation in patients undergoing cardiac valvular surgery. Anesthesiology 2010; 112:128.
- Cairns JA, Connolly SJ, Roberts R, Gent M. Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Lancet 1997; 349:675.
- Singh SN, Fletcher RD, Fisher SG, et al. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. Survival Trial of Antiarrhythmic Therapy in Congestive Heart Failure. N Engl J Med 1995; 333:77.
- Claro JC, Candia R, Rada G, et al. Amiodarone versus other pharmacological interventions for prevention of sudden cardiac death. Cochrane Database Syst Rev 2015; :CD008093.
- Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. N Engl J Med 1996; 335:1933.
- Buxton AE, Lee KL, Fisher JD, et al. A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter Unsustained Tachycardia Trial Investigators. N Engl J Med 1999; 341:1882.
- European Heart Rhythm Association, Heart Rhythm Society, Zipes DP, et al. ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death). J Am Coll Cardiol 2006; 48:e247.
- Passman R, Subacius H, Ruo B, et al. Implantable cardioverter defibrillators and quality of life: results from the defibrillators in nonischemic cardiomyopathy treatment evaluation study. Arch Intern Med 2007; 167:2226.
- Connolly SJ, Dorian P, Roberts RS, et al. Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC Study: a randomized trial. JAMA 2006; 295:165.
- Hohnloser SH, Dorian P, Roberts R, et al. Effect of amiodarone and sotalol on ventricular defibrillation threshold: the optimal pharmacological therapy in cardioverter defibrillator patients (OPTIC) trial. Circulation 2006; 114:104.
- Perry JC, Fenrich AL, Hulse JE, et al. Pediatric use of intravenous amiodarone: efficacy and safety in critically ill patients from a multicenter protocol. J Am Coll Cardiol 1996; 27:1246.
- Figa FH, Gow RM, Hamilton RM, Freedom RM. Clinical efficacy and safety of intravenous Amiodarone in infants and children. Am J Cardiol 1994; 74:573.
- 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
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS