Skip to main content
SpringerLink
Log in

Amiodarone: A Comprehensive Guide for Clinicians

  • Review Article
  • Published:
American Journal of Cardiovascular Drugs Aims and scope Submit manuscript

Abstract

Amiodarone is an effective antiarrhythmic medication frequently used in practice for both ventricular and atrial arrhythmias. Though classified as a class III antiarrhythmic, it affects all phases of the cardiac action potential. However, the drug has several side effects, including thyroid abnormalities, pulmonary fibrosis, and transaminitis, for which routine monitoring is recommended. It also interacts with several medications, such as warfarin, simvastatin, and atorvastatin, and many HIV antiretroviral medications. Given the common use of this medication in medical practice, it is vital that clinicians understand the indications, contraindications, dosing, side effects, and interactions of this medication. A thorough understanding of these topics is essential for clinicians to ensure safe and effective use of amiodarone.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Williams EMV. A classification of antiarrhythmic actions reassessed after a decade of new drugs. J Clin Pharmacol. 1984;24:129–47.

    Article  CAS  Google Scholar 

  2. Haverkamp W, Israel C, Parwani A. Klinische Besonderheiten der Therapie mit Amiodaron. Herzschr Elektrophys. 2017;28:307–16.

    Article  CAS  Google Scholar 

  3. Vaughan Williams EM. Classification of antidysrhythmic drugs. Pharmacol Ther B. 1975;1:115–38.

    CAS  PubMed  Google Scholar 

  4. Kodama I, Kamiya K, Toyama J. Cellular electropharmacology of amiodarone. Cardiovasc Res. 1997;35:13–29.

    Article  CAS  PubMed  Google Scholar 

  5. Mitchell LB, Wyse DG, Gillis AM, Duff HJ. Electropharmacology of amiodarone therapy initiation. Time courses of onset of electrophysiologic and antiarrhythmic effects. Circulation. 1989;80:34–42.

    Article  CAS  PubMed  Google Scholar 

  6. Shayeganpour A, Jun AS, Brocks DR. Pharmacokinetics of Amiodarone in hyperlipidemic and simulated high fat-meal rat models. Biopharm Drug Dispos. 2005;26:249–57.

    Article  CAS  PubMed  Google Scholar 

  7. Meng X, Mojaverian P, Doedée M, Lin E, Weinryb I, Chiang ST, et al. Bioavailability of amiodarone tablets administered with and without food in healthy subjects. Am J Cardiol. 2001;87:432–5.

    Article  CAS  PubMed  Google Scholar 

  8. Holt DW, Tucker GT, Jackson PR, Storey GCA. Amiodarone pharmacokinetics. Am Heart J. 1983;106:840–7.

    Article  CAS  PubMed  Google Scholar 

  9. Freedman MD, Somberg JC. Pharmacology and Pharmacokinetics of Amiodarone. J Clin Pharmacol. 1991;31:1061–9.

    Article  CAS  PubMed  Google Scholar 

  10. Kudenchuk PJ, Doherty AM, Murray WA. Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation. N Engl J Med. 1999;8.

  11. Dorian P, Cass D, Schwartz B, Cooper R, Gelaznikas R, Barr A. Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation. N Engl J Med. 2002;346:884–90.

    Article  CAS  PubMed  Google Scholar 

  12. Kudenchuk PJ, Brown SP, Daya M, Rea T, Nichol G, Morrison LJ, et al. Amiodarone, lidocaine, or placebo in out-of-hospital cardiac arrest. N Engl J Med. 2016;374:1711–22.

    Article  CAS  PubMed  Google Scholar 

  13. Al-Khatib Sana M, Stevenson William G, Ackerman Michael J, Bryant William J, Callans David J, Curtis Anne B, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Circulation. 2018;138:e272–391.

    PubMed  Google Scholar 

  14. Marill KA, deSouza IS, Nishijima DK, Senecal EL, Setnik GS, Stair TO, et al. Amiodarone or procainamide for the termination of sustained stable ventricular tachycardia: an historical multicenter comparison. Acad Emerg Med. 2010;17:297–306.

    Article  PubMed  Google Scholar 

  15. Tomlinson DR, Cherian P, Betts TR, Bashir Y. Intravenous amiodarone for the pharmacological termination of haemodynamically-tolerated sustained ventricular tachycardia: is bolus dose amiodarone an appropriate first-line treatment? Emerg Med J. 2008;25:15.

    Article  CAS  PubMed  Google Scholar 

  16. Ortiz M, Martín A, Arribas F, Coll-Vinent B, del Arco C, Peinado R, et al. Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study. Eur Heart J. 2016;ehw230.

  17. Panchal Ashish R, Berg Katherine M, Kudenchuk Peter J, Marina Del Rios, Hirsch Karen G, Link Mark S, et al. American Heart Association Focused Update on advanced cardiovascular life support use of antiarrhythmic drugs during and immediately after cardiac arrest: an update to the american heart association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2018;2018(138):e740–9.

    Google Scholar 

  18. Connolly SJ, Dorian P, Roberts RS, Gent M, Bailin S, Fain ES, et al. Comparison of β-blockers, amiodarone plus β-Blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC study: a randomized trial. JAMA. 2006;295:165–71.

    Article  CAS  PubMed  Google Scholar 

  19. Sapp JL, Wells GA, Parkash R, Stevenson WG, Blier L, Sarrazin J-F, et al. Ventricular tachycardia ablation versus escalation of antiarrhythmic drugs. N Engl J Med. 2016;375:111–21.

    Article  CAS  PubMed  Google Scholar 

  20. Bardy GH, Boineau R, Johnson G, Davidson-Ray LD, Ip JH. Amiodarone or an implantable cardioverter–defibrillator for congestive heart failure. N Engl J Med. 2005;13.

  21. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC, et al. AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American college of Cardiology/American heart association task force on clinical practice guidelines and the heart rhythm society in collaboration with the society of thoracic surgeons. Circulation. 2019;2019:140.

    Google Scholar 

  22. Chevalier P, Durand-Dubief A, Burri H, Cucherat M, Kirkorian G, Touboul P. Amiodarone versus placebo and class ic drugs for cardioversion of recent-onset atrial fibrillation: a meta-analysis. J Am Coll Cardiol. 2003;41:255–62.

    Article  CAS  PubMed  Google Scholar 

  23. Gwag HB, Chun KJ, Hwang JK, Park S-J, Kim JS, Park K-M, et al. Which antiarrhythmic drug to choose after electrical cardioversion: A study on non-valvular atrial fibrillation patients. PLoS One [Internet]. 2018 [cited 2020 Jan 30];13. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5963785/.

  24. Di Biase L, Mohanty P, Mohanty S, Santangeli P, Trivedi C, Lakkireddy D, et al. Ablation versus amiodarone for treatment of persistent atrial fibrillation in patients with congestive heart failure and an implanted device. Circulation. 2016;133:1637–44.

    Article  PubMed  CAS  Google Scholar 

  25. Essebag V, Reynolds MR, Hadjis T, Lemery R, Olshansky B, Buxton AE, et al. Sex differences in the relationship between amiodarone use and the need for permanent pacing in patients with atrial fibrillation. Arch Intern Med. 2007;167:1648–53.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Cadrin-Tourigny J, Wyse DG, Roy D, Blondeau L, Levesque S, Talajic M, et al. Efficacy of amiodarone in patients with atrial fibrillation with and without left ventricular dysfunction: a pooled analysis of AFFIRM and AF-CHF trials. J Cardiovasc Electrophysiol. 2014;25:1306–13.

    Article  PubMed  Google Scholar 

  27. Doyle JF, Ho KM. Benefits and risks of long-term amiodarone therapy for persistent atrial fibrillation: a meta-analysis. Mayo Clin Proc. 2009;84:234–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Brugada J, Katritsis DG, Arbelo E, Arribas F, Bax JJ, Blomström-Lundqvist C, et al. 2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC)Developed in collaboration with the Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J [Internet]. [cited 2020 Jan 30]; Available from: https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehz467/5556821.

  29. 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;81:594–8.

    Article  CAS  PubMed  Google Scholar 

  30. Lewis JH, Stine JG. Review article: prescribing medications in patients with cirrhosis—a practical guide. Aliment Pharmacol Ther. 2013;37:1132–56.

    Article  CAS  PubMed  Google Scholar 

  31. Arnouk S, Aberle C, Altshuler D, Merchan C, Piper GL, Papadopoulos J. Clinical effects of intravenous to oral amiodarone transition strategies in critically ill adult patients. J Clin Pharm Ther. 2019;44:693–700.

    Article  CAS  PubMed  Google Scholar 

  32. Sandler M. Amiodarone dosage in older patients with atrial fibrillation: an open, multi-centre study. Curr Med Res Opin. 1992;13:31–6.

    Article  CAS  PubMed  Google Scholar 

  33. Antonelli D, Atar S, Freedberg NA, Rosenfeld T. Torsade de pointes in patients on chronic amiodarone treatment: contributing factors and drug interactions. Isr Med Assoc J. 2005;7:3.

    Google Scholar 

  34. Hauser TH, Pinto DS, Josephson ME, Zimetbaum P. Safety and feasibility of a clinical pathway for the outpatient initiation of antiarrhythmic medications in patients with atrial fibrillation or atrial flutter. Am J Cardiol. 2003;91:1437–41.

    Article  PubMed  Google Scholar 

  35. Nademanee K, Kannan R, Hendrickson J, Ookhtens M, Kay I, Singh BN. Amiodarone-digoxin interaction: clinical significance, time course of development, potential pharmacokinetic mechanisms and therapeutic implications. J Am Coll Cardiol. 1984;4:111–6.

    Article  CAS  PubMed  Google Scholar 

  36. Robinson K, Johnston A, Walker S, Mulrow JP, McKenna WJ, Holt DW. The digoxin-amiodarone interaction. Cardiovasc Drug Ther. 1989;3:25–8.

    Article  CAS  Google Scholar 

  37. Fenner K, Troutman M, Kempshall S, Cook J, Ware J, Smith D, et al. Drug–drug interactions mediated through P-glycoprotein: clinical relevance and in vitro–in vivo correlation using digoxin as a probe drug. Clin Pharmacol Ther. 2009;85:173–81.

    Article  CAS  PubMed  Google Scholar 

  38. Shea P, Lal R, Kim SS, Schechtman K, Ruffy R. Flecainide and amiodarone interaction. J Am Coll Cardiol. 1986;7:1127–30.

    Article  CAS  PubMed  Google Scholar 

  39. Becquemont L, Neuvonen M, Verstuyft C, Jaillon P, Letierce A, Neuvonen PJ, et al. Amiodarone interacts with simvastatin but not with pravastatin disposition kinetics. Clin Pharmacol Ther. 2007;81:679–84.

    Article  CAS  PubMed  Google Scholar 

  40. Research C for DE and. FDA Drug Safety Communication: Revised dose limitation for Zocor (simvastatin) when taken with amiodarone. FDA [Internet]. 2018 [cited 2019 Jun 7]; Available from: http://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-revised-dose-limitation-zocor-simvastatin-when-taken-amiodarone.

  41. O’Reilly RA, Trager WF, Rettie AE, Goulart DA. Interaction of amiodarone with racemic warfarin and its separated enantiomorphs in humans. Clin Pharmacol Ther. 1987;42:290–4.

    Article  PubMed  Google Scholar 

  42. Holm J, Lindh JD, Andersson ML, Mannheimer B. The effect of amiodarone on warfarin anticoagulation: a register-based nationwide cohort study involving the Swedish population. J Thromb Haemost. 2017;15:446–53.

    Article  CAS  PubMed  Google Scholar 

  43. Wei A, Peng J, Gu Z, Li J. QTc prolongation and torsades de pointes due to a coadministration of fluoxetine and amiodarone in a patient with implantable cardioverter–defibrillator: case report and review of the literature. Medicine. 2017;96:e9071.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Nitsch J, Lüderitz B. Beschleunigte elimination von amiodaron durch Colestyramin*. Dtsch Med Wochenschr. 1986;111:1241–4.

    Article  CAS  PubMed  Google Scholar 

  45. Chauffert B, Martin M, Hammann A, Michel MF, Martin F. Amiodarone-induced enhancement of doxorubicin and 4′-Deoxydoxorubicin cytotoxicity to rat colon cancer cells in vitro and in vivo. Cancer Res. 1986;46:825–30.

    CAS  PubMed  Google Scholar 

  46. Crouch MA, Limon L, Cassano AT. clinical relevance and management of drug-related QT interval prolongation. Pharmacotherapy. 2003;23:881–908.

    Article  PubMed  Google Scholar 

  47. Rushworth GF, Lambrakis P, Leslie SJ. Ivabradine: a new rate-limiting therapy for coronary artery disease and heart failure. Ther Adv Drug Saf. 2011;2:19–28.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Nolan PE, Marcus FI, Hoyer GL, Bliss M, Gear K. Pharmacokinetic interaction between intravenous phenytoin and amiodarone in healthy volunteers. Clin Pharmacol Ther. 1989;46:43–9.

    Article  CAS  PubMed  Google Scholar 

  49. Antiretroviral therapy increases serum concentrations of amiodarone. Ann Pharmacother. 1999;33:645–6

  50. Research C for DE and. FDA Drug Safety Communication: FDA warns of serious slowing of the heart rate when antiarrhythmic drug amiodarone is used with hepatitis C treatments containing sofosbuvir (Harvoni) or Sovaldi in combination with another Direct Acting Antiviral drug. FDA [Internet]. 2019 [cited 2019 May 24]; Available from: http://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-serious-slowing-heart-rate-when-antiarrhythmic-drug.

  51. CORDARONE® (amiodarone HCl) Dosage and Administration | Pfizer Medical Information - US [Internet]. [cited 2019 Jun 8]. Available from: https://www.pfizermedicalinformation.com/en-us/cordarone/dosage-admin.

  52. Dosing | NEXTERONE (amiodarone HCl) [Internet]. [cited 2019 Jun 8]. Available from: http://www.nexterone.com/dosing.html.

  53. NEXTERONE (amiodarone HCI) Premixed Injection [Internet]. [cited 2019 Jun 8]. Available from: http://www.nexterone.com/about_nexterone.html.

  54. Trohman RG, Sharma PS, McAninch EA, Bianco AC. Amiodarone and thyroid physiology, pathophysiology, diagnosis and management. Trends Cardiovasc Med. 2019;29:285–95.

    Article  CAS  PubMed  Google Scholar 

  55. Ruzieh M, Moroi MK, Aboujamous NM, Ghahramani M, Naccarelli GV, Mandrola J, et al. Meta-analysis comparing the relative risk of adverse events for amiodarone versus placebo. Am J Cardiol. 2019;124:1889–93.

    Article  CAS  PubMed  Google Scholar 

  56. Basaria S, Cooper DS. Amiodarone and the thyroid. Am J Cardiol. 2005;118:706–14.

    CAS  Google Scholar 

  57. Papiris SA, Triantafillidou C, Kolilekas L, Markoulaki D, Manali ED. Amiodarone. Drug Saf. 2010;33:539–58.

    Article  CAS  PubMed  Google Scholar 

  58. Kumar S, Bangalore S, Kumari R, Grosu H, Jean R. Amiodarone-induced acute respiratory distress syndrome masquerading as acute heart failure. J Emerg Med. 2012;43:e311–4.

    Article  PubMed  Google Scholar 

  59. Azzam I, Tov N, Elias N, Naschitz JE. Amiodarone toxicity presenting as pulmonary mass and peripheral neuropathy: the continuing diagnostic challenge. Postgrad Med J. 2006;82:73–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Rodrı́guez-Garcı́a JL, Garcı́a-Nieto JC, Ballesta F, Prieto E, Villanueva MA, Gallardo J. Pulmonary mass and multiple lung nodules mimicking a lung neoplasm as amiodarone-induced pulmonary toxicity. Eur J Intern Med. 2001;12:372–6.

  61. Gonzalez-Rothi RJ, Hannan SE, Hood CI, Franzini DA. Amiodarone pulmonary toxicity presenting as bilateral exudative pleural effusions. Chest. 1987;92:179–82.

    Article  CAS  PubMed  Google Scholar 

  62. Singh SN, Fletcher RD, Fisher SG, Singh BN, Lewis HD, Deedwania PC, et al. Amiodarone in patients with congestive heart failure and asymptomatic ventricular arrhythmia. N Engl J Med. 1995;333:77–82.

    Article  CAS  PubMed  Google Scholar 

  63. Connolly Stuart J. Evidence-based analysis of amiodarone efficacy and safety. Circulation. 1999;100:2025–34.

    Article  CAS  PubMed  Google Scholar 

  64. Goldschlager N, Epstein AE, Naccarelli GV, Olshansky B, Singh B, Collard HR, et al. A practical guide for clinicians who treat patients with amiodarone: 2007. Heart Rhythm. 2007;4:1250–9.

    Article  PubMed  Google Scholar 

  65. Wolkove N, Baltzan M. Amiodarone pulmonary toxicity. J Thorac Dis. 2009;16:6.

    Google Scholar 

  66. Gayam V, Khalid M, Dahal S, Garlapati P, Gill A, Alex R, et al. Fatal acute liver failure with intravenous amiodarone: a case report and literature review. Gastroenterol Res. 2018;11:62–3.

    Article  Google Scholar 

  67. Passman RS, Bennett CL, Purpura JM, Kapur R, Johnson LN, Raisch DW, et al. Amiodarone-associated optic neuropathy: a critical review. Am J Med. 2012;125:447–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Jaworski K, Walecka I, Rudnicka L, Gnatowski M, Kosior DA. Cutaneous adverse reactions of amiodarone. Med Sci Monit. 2014;20:2369–72.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Tan HL, Lie KI. Treatment of tachyarrhythmias during pregnancy and lactation. Eur Heart J. 2001;22:458–64.

    Article  CAS  PubMed  Google Scholar 

  70. Gleadhill IC, Wise RA, Schonfeld SA, Scott PP, Guarnieri T, Levine JH, et al. Serial lung function testing in patients treated with amiodarone: a prospective study. Am J Med. 1989;86:4–10.

    Article  CAS  PubMed  Google Scholar 

  71. Lavon O, Goldman R. Adherence to monitoring guidelines of amiodarone adverse reactions. Health Serv Res Manag Epidemiol. 2019;6:233339281984463.

    Article  Google Scholar 

  72. Bickford CL, Spencer AP. Adherence to the NASPE guideline for amiodarone monitoring at a medical university. JMCP. 2006;12:254–9.

    Article  PubMed  Google Scholar 

  73. Burgess C, Blaikie A, Ingham T, Robinson G, Narasimhan S. Monitoring the use of amiodarone: compliance with guidelines. Intern Med J. 2006;36:289–93.

    Article  CAS  PubMed  Google Scholar 

  74. Dixon DL, Dunn SP, Kelly MS, McLlarky TR, Brown RE. Effectiveness of pharmacist-led amiodarone monitoring services on improving adherence to amiodarone monitoring recommendations: a systematic review. Pharmacotherapy. 2016;36:230–6.

Download references

Author information

Author notes

  1. David Hamilton and Shuktika Nandkeolyar Contributed equally to the writing and editing of the manuscript.

Authors and Affiliations

  1. Division of Cardiology, University of Arizona Sarver Heart Center, Tucson, USA

    David Hamilton Sr.

  2. Division of Cardiology, Department of Medicine, Loma Linda University Medical Center, 112345 Anderson St. SP1637, Loma Linda, CA, 92354, USA

    Shuktika Nandkeolyar, Howard Lan, Islam Abudayyeh, Tahmeed Contractor & Anthony Hilliard

  3. Department of Internal Medicine, University of California Los Angeles Medical Center, Los Angeles, USA

    Pooja Desai

  4. Department of Internal Medicine, University of California, Irvine Medical Center, Orange, USA

    Jonathan Evans

  5. Department of Pharmacy, Loma Linda University Medical Center, Loma Linda, USA

    Christopher Hauschild

  6. Department of Pharmacy, Medical City McKinney, Mckinney, USA

    Dimpa Choksi

Authors
  1. David Hamilton Sr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shuktika Nandkeolyar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Howard Lan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Pooja Desai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jonathan Evans
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christopher Hauschild
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dimpa Choksi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Islam Abudayyeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Tahmeed Contractor
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Anthony Hilliard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shuktika Nandkeolyar.

Ethics declarations

Funding

No external funding was used in the preparation of this manuscript.

Conflicts of interest

David Hamilton Sr., Shuktika Nandkeolyar, Howard Lan, Pooja Desai, Jonathan Evans, Christopher Hauschild, Dimpa Choksi, Islam Abudayyeh, Tahmeed Contractor, and Anthony Hilliard have no potential conflicts of interest that might be relevant to the contents of this manuscript.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hamilton, D., Nandkeolyar, S., Lan, H. et al. Amiodarone: A Comprehensive Guide for Clinicians. Am J Cardiovasc Drugs 20, 549–558 (2020). https://doi.org/10.1007/s40256-020-00401-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40256-020-00401-5

Search

Navigation