Springer Nature is making Coronavirus research free. View research | View latest news | Sign up for updates

Dronedarone

  • 165 Accesses

  • 16 Citations

Abstract

  • ▴ Oral dronedarone is a non-iodinated benzofurane derivative structurally related to amiodarone. Although it is considered a class III antiarrhythmic agent like amiodarone, it demonstrates multi-class electrophysiological activity.

  • ▴ Data from the ATHENA study demonstrated that patients receiving oral dronedarone 400 mg twice daily for 12–30 months had a significantly lower risk of experiencing first hospitalization due to a cardiovascular event or death from any cause than those receiving placebo.

  • ▴ Dronedarone exhibited rate- and rhythm-controlling properties in patients with atrial fibrilation (AF) or atrial flutter, significantly reducing the risk of a first recurrence of AF versus placebo following 12 months’ therapy in the ADONIS and EURIDIS studies.

  • ▴ In the ERATO study, dronedarone was also significantly more effective than placebo in terms of ventricular rate control. Furthermore, the beneficial effects of oral dronedarone on ventricular rate control were maintained during exercise and sustained with continued therapy.

  • ▴ Oral dronedarone was generally well tolerated in the treatment of adult patients with AF and/or atrial flutter in clinical studies. The incidence of diarrhoea, nausea, bradycardia, rash and QT-interval prolongation was significantly higher with oral dronedarone than placebo in the large ATHENA study; however, serious cardiac-related adverse events were observed in <1% of oral dronedarone recipients.

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

References

  1. 1.

    Lip GY, Tse HF. Management of atrial fibrillation. Lancet 2007; 370(9587): 604–18

  2. 2.

    Singh BN, Aliot E. Newer antiarrhythmic agents for maintaining sinus rhythm in atrial fibrillation: simplicity or complexity? Eur Heart J Suppls 2007; 9 Suppl. G: G17–25

  3. 3.

    Musco S, Conway EL, Kowey PR. Drug therapy for atrial fibrillation. Med Clin North Am 2008; 92(1): 121–41

  4. 4.

    Brendorp B, Pedersen OD, Torp-Pedersen C, et al. A benefit-risk assessment of class III antiarrhythmic agents. Drug Saf 2002; 25(12): 847–65

  5. 5.

    Tafreshi MJ, Rowles J. A review of the investigational antiarrhythmic agent dronedarone. J Cardiovasc Pharmacol Ther 2007 Mar; 12(1): 15–26

  6. 6.

    Zimetbaum PJ. Dronedarone for atrial fibrillation: an odyssey. N Engl J Med 2009 Apr 30; 360(18): 1811–3

  7. 7.

    Lombardi F, Terranova P. Pharmacological treatment of atrial fibrillation: mechanisms of action and efficacy of class III drugs. Curr Med Chem 2006; 13(14): 1635–53

  8. 8.

    sanofi-aventis. MULTAQ (dronedarone) tablets: prescribing information [online]. Available from URL: http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022425lbl.pdf [Accessed 2009 Jul 8]

  9. 9.

    Sun W, Chen F, Esmailian F, et al. Acute effects of dronedarone on the potassium currents in human atrial cells. J Am Coll Cardiol 2002 Mar 6; 39 Suppl. A: 105

  10. 10.

    Gautier P, Guillemare E, Marion A, et al. Electrophysiologic characterization of dronedarone in guinea pig ventricular cells. J Cardiovasc Pharmacol 2003 Feb; 41(2): 191–202

  11. 11.

    Guillemare E, Marion A, Nisato D, et al. Inhibitory effects of dronedarone on muscarinic K+ current in guinea pig atrial cells. J Cardiovasc Pharmacol 2000 Dec; 36(6): 802–5

  12. 12.

    Altomare C, Barbuti A, Viscomi C, et al. Effects of dronedarone on acetylcholine-activated current in rabbit SAN cells. Br J Pharmacol 2000 Jul; 130(6): 1315–20

  13. 13.

    Thomas D, Kathofer S, Zhang W, et al. Acute effects of dronedarone on both components of the cardiac delayed rectifier K+ current, HERG and KvLQT1/minK potassium channels. Br J Pharmacol 2003 Nov; 140(5): 996–1002

  14. 14.

    Lalevée N, Barrère-lemaire S, Gautier P, et al. Effects of amiodarone and dronedarone on voltage-dependent sodium current in human cardiomyocytes. J Cardiovasc Electrophysiol 2003 Aug; 14(8): 885–90

  15. 15.

    Watanabe Y, Kimura J. Acute inhibitory effect of dronedarone, a noniodinated benzofuran analogue of amiodarone, on Na+/Ca2+ exchange current in guinea pig cardiac ventricular myocytes. Naunyn Schmiedebergs Arch Pharmacol 2008 Jun; 377(4–6): 371–6

  16. 16.

    Hodeige D, Heyndrickx JP, Chatelain P, et al. SR 33589, a new amiodarone-like antiarrhythmic agent: anti-adrenoceptor activity in anaesthetized and conscious dogs. Eur J Pharmacol 1995 Jun 6; 279: 25–32

  17. 17.

    Djandjighian L, Planchenault J, Finance O, et al. Hemodynamic and antiadrenergic effects of dronedarone and amiodarone in animals with a healed myocardial infarction. J Cardiovasc Pharmacol 2000 Sep; 36: 376–83

  18. 18.

    Sun W, Sarma JS, Singh BN. Chronic and acute effects of dronedarone on the action potential of rabbit atrial muscle preparations: comparison with amiodarone. J Cardiovasc Pharmacol 2002 May; 39(5): 677–84

  19. 19.

    Sun W, Sarma JS, Singh BN. Electrophysiological effects of dronedarone (SR33589), a noniodinated benzofuran derivative, in the rabbit heart: comparison with amiodarone. Circulation 1999 Nov 30; 100(22): 2276–81

  20. 20.

    Manning A, Thisse V, Hodeige D, et al. SR 33589, a new amiodarone-like antiarrhythmic agent: electrophysiological effects in anesthetized dogs. J Cardiovasc Pharmacol 1995 Feb; 25(2): 252–61

  21. 21.

    Moro S, Ferreiro M, Celestino D, et al. In vitro effects of acute amiodarone and dronedarone on epicardial, endocardial, and M cells of the canine ventricle. J Cardiovasc Pharmacol Ther 2007 Dec; 12(4): 314–21

  22. 22.

    Varro A, Takacs J, Nemeth M, et al. Electrophysiological effects of dronedarone (SR 33589), a noniodinated amiodarone derivative in the canine heart: comparison with amiodarone. Br J Pharmacol 2001 Jul; 133(5): 625–34

  23. 23.

    Celestino D, Medei E, Moro S, et al. Acute in vitro effects of dronedarone, an iodine-free derivative, and amiodarone, on the rabbit sinoatrial node automaticity: a comparative study. J Cardiovasc Pharmacol Ther 2007 Sep; 12(3): 248–57

  24. 24.

    Aimond F, Beck L, Gautier P, et al. Cellular and in vivo electrophysiological effects of dronedarone in normal and postmyocardial infarcted rats. J Pharmacol Exp Ther 2000 Jan; 292: 415–24

  25. 25.

    Manning AS, Bruyninckx C, Ramboux J, et al. SR 33589, a new amiodarone-like agent: effect on ischemia- and reperfusion-induced arrhythmias in anesthetized rats. J Cardiovasc Pharmacol 1995 Sep; 26: 453–61

  26. 26.

    Rochetaing A, Barbe C, Kreher P. Beneficial effects of amiodarone and dronedarone (SR 33589b), when applied during low-flow ischemia, on arrhythmia and functional parameters asssessed during reperfusion in isolated rat hearts. J Cardiovasc Pharmacol 2001 Oct; 38(4): 500–11

  27. 27.

    Verduyn SC, Vos MA, Leunissen HDM, et al. Evaluation of the acute electrophysiologic effects of intravenous dronedarone, an amiodarone-like agent, with special emphasis on ventricular repolarization and acquired torsade de pointes arrhythmias. J Cardiovasc Pharmacol 1999 Feb; 33: 212–22

  28. 28.

    Verduyn SC, Leunissen JD, Vos MA. Intravenous administration of an amiodarone like agent, dronedarone (SR33589), does not evoke but suppresses torsade de pointes arrhythmias. Circulation 1996 Oct 15; 94 (8 Suppl.): 745

  29. 29.

    Finance O, Manning A, Chatelain P. Effects of a new amiodarone-like agent, SR 33589, in comparison to amiodarone, D,L-sotalol, and lignocaine, on ischemia-induced ventricular arrhythmias in anesthetized pigs. J Cardiovasc Pharmacol 1995 Oct; 26: 570–6

  30. 30.

    Guiraudou P, Pucheu SC, Gayraud R, et al. Involvement of nitric oxide in amiodarone- and dronedarone-induced coronary vasodilation in guinea pig heart. Eur J Pharmacol 2004 Aug 2; 496(1-3): 119–27

  31. 31.

    Pantos C, Mourouzis I, Delbruyere M, et al. Effects of dronedarone and amiodarone on plasma thyroid hormones and on the basal and postischemic performance of the isolated rat heart. Eur J Pharmacol 2002 May 31; 444: 191–6

  32. 32.

    Stoykov I, van Beeren HC, Moorman AF, et al. Effect of amiodarone and dronedarone administration in rats on thyroid hormone-dependent gene expression in different cardiac components. Eur J Endocrinol 2007 Jun; 156(6): 695–702

  33. 33.

    Wadhani N, Sarma JSM, Singh BN, et al. Dose-dependent effects of oral dronedarone on the circadian variation of RR and QT intervals in healthy subjects: implications for antiarrhythmic actions. J Cardiovasc Pharmacol Ther 2006 Sep 1; 11(3): 184–90

  34. 34.

    Tschuppert Y, Buclin T, Rothuizen LE, et al. Effect of dronedarone on renal function in healthy subjects. Br J Clin Pharmacol 2007 Dec; 64(6): 785–91

  35. 35.

    sanofi-aventis. US FDA Cardiovascular & Renal Drugs Advisory Committee: briefing material for dronedarone [online]. Available from URL: http://www.fda.gov/ohrms/dockets/ac/09/briefing/2009-4417b1-01-FDA.pdf [Accessed 2009 Jun 3]

  36. 36.

    Touboul P, Brugada J, Capucci A, et al. Dronedarone for prevention of atrial fibrillation: a dose-ranging study. Eur Heart J 2003 Aug; 24(16): 1481–7

  37. 37.

    Damy T, Pousset F, Caplain H, et al. Pharmacokinetic and pharmacodynamic interactions between metoprolol and dronedarone in extensive and poor CYP2D6 metabolizers healthy subjects. Fundam Clin Pharmacol 2004 Feb; 18(1): 113–23

  38. 38.

    Singh BN, Connolly SJ, Crijns HJ, et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med 2007 Sep 6; 357(10): 987–99

  39. 39.

    Hohnloser SH, Crijns HJ, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med 2009 Feb 12; 360(7): 668–78

  40. 40.

    Hohnloser SH, Connolly SJ, Crijns HJ, et al. Rationale and design of ATHENA: a placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter. J Cardiovasc Electrophysiol 2008 Jan; 19(1): 69–73

  41. 41.

    Davy JM, Herold M, Hoglund C, et al. Dronedarone for the control of ventricular rate in permanent atrial fibrillation: the Efficacy and safety of dRonedArone for the cOntrol of ventricular rate during atrial fibrillation (ERATO) study. Am Heart J 2008 Sep; 156(3): 527.e1-9

  42. 42.

    Hohnloser SH, Connolly SJ, Crijins HJ, et al. Effects of dronedarone on clinical outcomes in patients with atrial fibrillation and congestive heart failure: insights from ATHENA [abstract]. Heart Rhythm Society’s 30th Annual Scientific Sessions; 2009 May 13–16; Boston (MA)

  43. 43.

    Hohnloser SH, Connolly SJ, van Eickels M, et al. Effect of dronedarone on cardiovascular outcomes: a meta-analysis of five randomized controlled trials in 6157 patients with atrial fibrillation/flutter [abstract no. 1020-54]. J Am Coll Cardiol 2009; 53 (10 Suppl. A): A113–4

  44. 44.

    Køber L, Torp-Pedersen C, McMurray JJ, et al. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med 2008 Jun 19; 358(25): 2678–87

  45. 45.

    sanofi-aventis. FDA approved Multaq® for patients with atrial fibrillation or atrial flutter [online]. Available from URL: http://en.sanofi-aventis.com/binaries/20090702_multaq_en_tcm28-25557.pdf [Accessed 2009 Jul 10]

Download references

Author information

Correspondence to Sheridan M. Hoy.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hoy, S.M., Keam, S.J. Dronedarone. Drugs 69, 1647–1663 (2009). https://doi.org/10.2165/11200820-000000000-00000

Download citation

Keywords

  • Atrial Fibrillation
  • Amiodarone
  • Atrial Flutter
  • Ventricular Rate
  • Dronedarone