Maintenance of sinus rhythm Dronedarone (400 mg twice daily) is used for the maintenance of sinus rhythm in patients with paroxysmal or persistent AF or atrial flutter and no evidence of heart failure or left ventricular systolic dysfunction who have spontaneously reverted to sinus rhythm or in whom cardioversion is planned. Hepatic function testing should be performed at the time of dronedarone initiation and repeated once or twice within the first six months and yearly thereafter. An electrocardiogram should be performed annually and at the time of any clinical change (ie, recurrent arrhythmia). (See 'Maintenance of sinus rhythm' above.) Not as a rate control medication Dronedarone should NOT be prescribed exclusively as a rate control medication given the availability of other agents for this purpose and the results of the PALLAS trial, which demonstrated an increase in cardiovascular mortality when dronedarone was used solely as a rate controlling agent. Dronedarone is only rarely https://www.uptodate.com/contents/clinical-uses-of-dronedarone/print 12/21 7/5/23, 9:13 AM Clinical uses of dronedarone - UpToDate effective for the chemical cardioversion of AF or atrial flutter to sinus rhythm (less than 10 percent of patients). As such, dronedarone should NOT be used for this purpose. However, as there is a potential for cardioversion during drug initiation, standard precautions should be taken to minimize the risk of thromboembolic events (ie, therapeutic anticoagulation for at least three weeks or a transesophageal echocardiogram for assessment of left atrial thrombus). (See 'Ventricular rate control in AF' above and 'Effect on cardiovascular mortality' above and 'Chemical cardioversion of AF' above.) Changing to another medication In patients who have developed recurrent AF despite antiarrhythmic therapy, it may be necessary to switch antiarrhythmic drugs. Because of the potential for QT prolongation and torsades de pointes, concomitant use of dronedarone and class I or III antiarrhythmic drugs ( table 1) that prolong the QT interval is contraindicated, and at least five half-lives should be allowed between changes in antiarrhythmic agents with the exception of amiodarone. While there are no specific recommendations concerning the transition from amiodarone to dronedarone, dronedarone can usually be started immediately after amiodarone discontinuation unless there is clinically significant bradycardia or QT prolongation. (See 'Changing to another antiarrhythmic drug' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Singh BN, Connolly SJ, Crijns HJ, et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med 2007; 357:987. 2. Varr A, Tak cs J, N meth M, et al. Electrophysiological effects of dronedarone (SR 33589), a noniodinated amiodarone derivative in the canine heart: comparison with amiodarone. Br J Pharmacol 2001; 133:625. 3. MULTAQ Dronedarone tablets prescribing information products.sanofi.us/Multaq/Multaq.p df (Accessed on June 16, 2011). 4. Hoy SM, Keam SJ. Dronedarone. Drugs 2009; 69:1647. 5. Tschuppert Y, Buclin T, Rothuizen LE, et al. Effect of dronedarone on renal function in healthy subjects. Br J Clin Pharmacol 2007; 64:785. 6. Hohnloser SH, Crijns HJ, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med 2009; 360:668. 7. Zafar MU, Santos-Gallego CG, Smith DA, et al. Dronedarone exerts anticoagulant and antiplatelet effects independently of its antiarrhythmic actions. Atherosclerosis 2017; https://www.uptodate.com/contents/clinical-uses-of-dronedarone/print 13/21 7/5/23, 9:13 AM Clinical uses of dronedarone - UpToDate 266:81. 8. 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; 18:113. 9. Hohnloser SH, Halperin JL, Camm AJ, et al. Interaction between digoxin and dronedarone in the PALLAS trial. Circ Arrhythm Electrophysiol 2014; 7:1019. 10. 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; 156:527.e1. 11. Vallakati A, Chandra PA, Pednekar M, et al. Dronedarone-induced digoxin toxicity: new drug, new interactions. Am J Ther 2013; 20:e717. 12. Dorian P. Clinical pharmacology of dronedarone: implications for the therapy of atrial fibrillation. J Cardiovasc Pharmacol Ther 2010; 15:15S. 13. Dronedarone tablets. European Medicines Agency (EMA) Summary of product characteristic s. Last updated October 29, 2014. European Medicines Agency. www.ema.europa.eu/ema/in dex.jsp. 14. Shirolkar SC, Fiuzat M, Becker RC. Dronedarone and vitamin K antagonists: a review of drug- drug interactions. Am Heart J 2010; 160:577. 15. Patel C, Yan GX, Kowey PR. Dronedarone. Circulation 2009; 120:636. 16. Connolly SJ, Ezekowitz MD, Yusuf S, et al. Newly identified events in the RE-LY trial. N Engl J Med 2010; 363:1875. 17. Gandhi SK, Reiffel JA, Boiron R, Wieloch M. Risk of Major Bleeding in Patients With Atrial Fibrillation Taking Dronedarone in Combination With a Direct Acting Oral Anticoagulant (From a U.S. Claims Database). Am J Cardiol 2021; 159:79. 18. Multaq [package insert]. Bridgewater, NJ: Sanofi-aventis; 2014. 19. January CT, Wann LS, Alpert JS, et al. 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 Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2014; 64:e1. 20. Touboul P, Brugada J, Capucci A, et al. Dronedarone for prevention of atrial fibrillation: a dose-ranging study. Eur Heart J 2003; 24:1481. 21. Guerra F, Hohnloser SH, Kowey PR, et al. Efficacy and safety of dronedarone in patients previously treated with other antiarrhythmic agents. Clin Cardiol 2014; 37:717. https://www.uptodate.com/contents/clinical-uses-of-dronedarone/print 14/21 7/5/23, 9:13 AM Clinical uses of dronedarone - UpToDate 22. Vamos M, Calkins H, Kowey PR, et al. Efficacy and safety of dronedarone in patients with a prior ablation for atrial fibrillation/flutter: Insights from the ATHENA study. Clin Cardiol 2020; 43:291. 23. Wharton JM, Piccini JP, Koren A, et al. Comparative Safety and Effectiveness of Sotalol Versus Dronedarone After Catheter Ablation for Atrial Fibrillation. J Am Heart Assoc 2022; 11:e020506. 24. Le Heuzey JY, De Ferrari GM, Radzik D, et al. A short-term, randomized, double-blind, parallel-group study to evaluate the efficacy and safety of dronedarone versus amiodarone in patients with persistent atrial fibrillation: the DIONYSOS study. J Cardiovasc Electrophysiol 2010; 21:597. 25. Page RL, Connolly SJ, Crijns HJ, et al. Rhythm- and rate-controlling effects of dronedarone in patients with atrial fibrillation (from the ATHENA trial). Am J Cardiol 2011; 107:1019. 26. Pisters R, Hohnloser SH, Connolly SJ, et al. Effect of dronedarone on clinical end points in patients with atrial fibrillation and coronary heart disease: insights from the ATHENA trial. Europace 2014; 16:174. 27. Connolly SJ, Camm AJ, Halperin JL, et al. Dronedarone in high-risk permanent atrial fibrillation. N Engl J Med 2011; 365:2268. 28. Friberg L. Safety of dronedarone in routine clinical care. J Am Coll Cardiol 2014; 63:2376. 29. K ber L, Torp-Pedersen C, McMurray JJ, et al. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med 2008; 358:2678. 30. Chatterjee S, Ghosh J, Lichstein E, et al. Meta-analysis of cardiovascular outcomes with dronedarone in patients with atrial fibrillation or heart failure. Am J Cardiol 2012; 110:607. 31. Vaduganathan M, Piccini JP, Camm AJ, et al. Dronedarone for the treatment of atrial fibrillation with concomitant heart failure with preserved and mildly reduced ejection fraction: a post-hoc analysis of the ATHENA trial. Eur J Heart Fail 2022; 24:1094. 32. Shaaraoui M, Freudenberger R, Levin V, Marchlinski FE. Suppression of ventricular tachycardia with dronedarone: a case report. J Cardiovasc Electrophysiol 2011; 22:201. Topic 16216 Version 31.0 https://www.uptodate.com/contents/clinical-uses-of-dronedarone/print 15/21 7/5/23, 9:13 AM Clinical uses of dronedarone - UpToDate GRAPHICS Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): https://www.uptodate.com/contents/clinical-uses-of-dronedarone/print 16/21 7/5/23, 9:13 AM Clinical uses of dronedarone - UpToDate Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/clinical-uses-of-dronedarone/print 17/21 7/5/23, 9:13 AM Clinical uses of dronedarone - UpToDate Cytochrome P450 3A (including 3A4) inhibitors and inducers Strong inhibitors Moderate inhibitors Strong inducers Moderate inducers Adagrasib Amiodarone Apalutamide Bexarotene Atazanavir Aprepitant Carbamazepine Bosentan Ceritinib Berotralstat Enzalutamide Cenobamate Clarithromycin Cimetidine Fosphenytoin Dabrafenib Cobicistat and cobicistat- containing coformulations Conivaptan Lumacaftor Dexamethasone Crizotinib Lumacaftor- ivacaftor Dipyrone Cyclosporine Efavirenz Mitotane Diltiazem Elagolix, estradiol, and norethindrone therapy pack Darunavir Phenobarbital Duvelisib Idelalisib Phenytoin Dronedarone Indinavir Eslicarbazepine Primidone Erythromycin Itraconazole Etravirine Rifampin (rifampicin) Fedratinib Ketoconazole Lorlatinib Fluconazole Levoketoconazole Mitapivat Fosamprenavir Lonafarnib Modafinil Fosaprepitant Lopinavir Nafcillin Fosnetupitant- Mifepristone* Pexidartinib palonosetron Nefazodone Rifabutin Grapefruit juice Nelfinavir Rifapentine Imatinib Nirmatrelvir- ritonavir Sotorasib Isavuconazole (isavuconazonium sulfate) St. John's wort Ombitasvir- paritaprevir- ritonavir Lefamulin Letermovir Ombitasvir- paritaprevir- ritonavir plus dasabuvir Netupitant Nilotinib Ribociclib Schisandra Posaconazole Verapamil Ritonavir and ritonavir-containing coformulations Saquinavir Telithromycin Tucatinib Voriconazole https://www.uptodate.com/contents/clinical-uses-of-dronedarone/print 18/21 7/5/23, 9:13 AM Clinical uses of dronedarone - UpToDate For drug interaction purposes, the inhibitors and inducers of CYP3A metabolism listed above can alter serum concentrations of drugs that are dependent upon the CYP3A subfamily of liver enzymes, including CYP3A4, for elimination or activation. These classifications are based upon US Food and Drug Administration (FDA) guidance. sources may use a different classification system resulting in some agents being classified [1,2] Other differently. Data are for systemic drug forms. Degree of inhibition or induction may be altered by dose, method, and timing of administration. Weak inhibitors and inducers are not listed in this table with exception of a few examples. Clinically significant interactions can occasionally occur due to weak inhibitors and inducers (eg, target drug is highly dependent on CYP3A4 metabolism and has a narrow therapeutic index). Accordingly, specific interactions should be checked using a drug interaction program such as the Lexicomp drug interactions program included within UpToDate. Refer to UpToDate topics on specific agents and indications for further details. Mifepristone is a significant inhibitor of CYP3A4 when used chronically (eg, for hyperglycemia in patients with Cushing syndrome); not in single-dose use. [1] Classified as a weak inhibitor of CYP3A4 according to FDA system. [1] Classified as a weak inducer of CYP3A4 according to FDA system. The fixed-dose combination therapy pack taken in the approved regimen has moderate CYP3A4 induction effects. When elagolix is used as a single agent, it is a weak CYP3A4 inducer. Norethindrone and estradiol are not CYP3A4 inducers. Data from: Lexicomp Online (Lexi-Interact). Copyright 1978-2023 Lexicomp, Inc. All Rights Reserved. References: 1. Clinical Drug Interaction Studies Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Guidance for Industry (January 2020) available at: https://www.fda.gov/regulatory-information/search-fda-guidance- documents/clinical-drug-interaction-studies-cytochrome-p450-enzyme-and-transporter-mediated-drug-interactions. 2. US Food & Drug Administration. Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers. Available at: FDA.gov website. Graphic 76992 Version 90.0 https://www.uptodate.com/contents/clinical-uses-of-dronedarone/print 19/21 7/5/23, 9:13 AM Clinical uses of dronedarone - UpToDate Strategies for rhythm control in patients with paroxysmal* and persistent AF AF: atrial fibrillation; CAD: coronary artery disease; HF: heart failure; LVH: left ventricular hypertrophy; AV: atrioventricular. Catheter ablation is only recommended as first-line therapy for patients with paroxysmal AF (Class IIa recommendation). Drugs are listed alphabetically. Depending on patient preference when performed in experienced centers. Not recommended with severe LVH (wall thickness >1.5 cm). Should be used with caution in patients at risk for torsades de pointes ventricular tachycardia. Should be combined with AV nodal blocking agents. Reproduced from: January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline 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 Heart Rhythm Society. J Am Coll Cardiol 2014. DOI: 10.1016/j.jacc.2014.03.021. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 95079 Version 3.0 https://www.uptodate.com/contents/clinical-uses-of-dronedarone/print 20/21 7/5/23, 9:13 AM Clinical uses of dronedarone - UpToDate Contributor Disclosures Rod Passman, MD, MSCE Grant/Research/Clinical Trial Support: Abbott [Ablation]; AHA [Ablation]; NIH [Stroke prevention]. Consultant/Advisory Boards: Abbott [Ablation]; iRhythm [Monitoring]; Janssen [Atrial fibrillation detection]; Medtronic [Implantable cardiac monitors]. Speaker's Bureau: iRhythm [Monitoring]. All of the relevant financial relationships listed have been mitigated. Elsa-Grace Giardina, MD, MS, FACC, FACP, FAHA No relevant financial relationship(s) with ineligible companies to disclose. Mark S Link, MD No relevant financial relationship(s) with ineligible companies to disclose. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/clinical-uses-of-dronedarone/print 21/21