OVERVIEW

PRODUCT INFORMATION

REPRESENTATIVE TRADE NAMES

Dronedarone – Multaq®

DRUG CLASS

Antiarrhythmic Agents

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH

CHEMICAL FORMULA AND STRUCTURE

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DRUG	CAS REGISTRY NO.	MOLECULAR FORMULA	STRUCTURE
Dronedarone	141626-36-0	C31-H44-N2-O5-S

ANNOTATED BIBLIOGRAPHY

References updated: 10 February 2026

Abbreviations: iv, intravenous; ULN, upper limit of normal.

• Zimmerman HJ. Hepatotoxic effects of oncotherapeutic and immunosuppressive agents. In, Zimmerman HJ. Hepatotoxicity: the adverse effects of drugs and other chemicals on the liver. 2nd ed. Philadelphia: Lippincott, 1999, pp. 648-52.

  (Expert review of hepatotoxicity published in 1999; patterns of liver injury associated with amiodarone include frequent minor serum enzyme elevations [14-83%] and, less commonly, chronic liver disease resembling alcoholic hepatitis and cirrhosis, acute hepatitis with jaundice, phospholipidosis, Reye syndrome and cholestasis; dronedarone is not discussed).
• De Marzio DH, Navarro VJ. Antiarrhythmics. Hepatotoxicity of cardiovascular and antidiabetic drugs. In, Kaplowitz N, DeLeve LD, eds. Drug-induced liver disease. 3rd ed. Amsterdam: Elsevier, 2013, pp. 520-22.

  (Review of hepatotoxicity of cardiovascular drugs mentions that two cases of acute liver failure attributed to dronedarone that were reported after its approval in 2009, which led to an FDA warning and recommendation for routine periodic monitoring of liver tests, the effectiveness of which has not been shown).
• Knollman BC, Roden DM. Antiarrhythmic drugs. In, Brunton LL, Hilal-Dandan R, Knollman BC, eds. Goodman & Gilman's The pharmacological basis of therapeutics. 13th ed. New York: McGraw-Hill, 2018, pp. 547-572.

  (Textbook of pharmacology and therapeutics).
• Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J, Yang H, Rochon J; Drug Induced Liver Injury Network(DILIN). Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology 2008; 135: 1924-34. [PMC free article: PMC3654244] [PubMed: 18955056]

  (Among 300 cases of drug induced liver disease in the US collected between 2004 and 2008, 2 were attributed to amiodarone, but none to dronedarone, which however was not approved in the United States until 2009).
• Singh BN, Connolly SJ, Crijns HJ, Roy D, Kowey PR, Capucci A, Radzik D, et al; EURIDIS and ADONIS Investigators. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med 2007; 357: 987-99. [PubMed: 17804843]

  (Prospective study of dronedarone, a benzofuran derivative of amiodarone, versus placebo in 828 patients with atrial fibrillation or flutter for up to one year: abnormalities in liver tests occurred in 12.2% of dronedarone vs 13.6% of placebo recipients; no mention of clinically apparent liver injury).
• Davy JM, Herold M, Hoglund C, Timmermans A, Alings A, Radzik D, Van Kempen L; ERATO Study Investigators. 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. [PubMed: 18760136]

  (Controlled trial of dronedarone vs placebo for 6 months in 174 patients with permanent atrial fibrillation; no specific mention of ALT elevations or hepatotoxicity but authors conclude: "dronedarone was well tolerated with no evidence of organ toxicities").
• Køber L, Torp-Pedersen C, McMurray JJ, Gøtzsche O, Lévy S, Crijns H, Amlie J, et al; Dronedarone Study Group. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med 2008; 358: 2678-87. [PubMed: 18565860]

  (Controlled trial of dronedarone vs placebo in 627 patients with symptomatic heart failure was terminated early because of excess mortality in dronedarone [8.1%] compared to placebo treated subjects [3.8%], largely due to worsening of heart failure; no mention of hepatotoxicity).
• Dronedarone (Multaq) for atrial fibrillation. Med Lett Drugs Ther 2009; 51 (1322): 78-80. [PubMed: 19798011]

  (Concise review of the mechanism of action, clinical efficacy and safety of dronedarone shortly after its approval in the United States).
• Patel C, Yan GX, Kowey PR. Dronedarone. Circulation 2009; 120: 636-44. [PubMed: 19687370]

  (Review of the chemical structure, mechanism of action, pharmacokinetics, clinical efficacy and safety of dronedarone; in the 4640-patient ATHENA trial, liver test abnormalities occurred no more frequently in dronedarone than in placebo treated subjects [0.5% vs 0.6%]).
• Le Heuzey JY, De Ferrari GM, Radzik D, Santini M, Zhu J, Davy JM. 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: 597-605. [PubMed: 20384650]

  (Controlled trial of dronedarone vs amiodarone in 504 patients with persistent atrial fibrillation found higher rate of recurrence with dronedarone, whereas thyroid, neurologic, skin and ocular adverse events were less; ALT or AST elevations [2 times ULN] occurred at similar rates [12% vs 10.6%]).
• Christiansen CB, Torp-Pedersen C, Køber L. Efficacy and safety of dronedarone: a review of randomized trials. Expert Opin Drug Saf 2010; 9: 189-99. [PubMed: 20001756]

  (Review of efficacy and safety of dronedarone based on results of 7 controlled trials; no mention of ALT elevations or hepatotoxicity).
• Reuben A, Koch DG, Lee WM; Acute Liver Failure Study Group. Drug-induced acute liver failure: results of a U.S. multicenter, prospective study. Hepatology 2010; 52: 2065-76. [PMC free article: PMC3992250] [PubMed: 20949552]

  (Among 1198 patients with acute liver failure enrolled in a US prospective study between 1998 and 2007, 133 were attributed to drug induced liver injury, but none were attributed to amiodarone, dronedarone or other antiarrhythmic agents).
• Connolly SJ, Camm AJ, Halperin JL, Joyner C, Alings M, Amerena J, Atar D, et al; PALLAS Investigators. Dronedarone in high-risk permanent atrial fibrillation. N Engl J Med 2011; 365: 2268-76. [PubMed: 22082198]

  (Among 3236 elderly adults with persistent atrial fibrillation treated with dronedarone or placebo, there was an increased rate of primary outcomes including death in the dronedarone treated group, and the study was terminated early; ALT elevations above 3 times ULN occurred in 1.5% on dronedarone versus 0.6% on placebo).
• In brief: FDA warning on dronedarone (Multaq). Med Lett Drugs Ther 2011; 53 (1359): 17. [PubMed: 21383666]

  (Warning from FDA of several cases of severe liver injury and liver failure, two requiring transplantation after 4.5 and 6 months of dronedarone therapy).
• Safety of dronedarone (Multaq). Med Lett Drugs Ther 2011; 53 (1379-1380): 103-4. [PubMed: 22173456]

  (Discussion of safety of dronedarone mentioning studies showing that it is associated with an increased risk of stroke, heart failure, and cardiovascular death).
• Joghetaei N, Weirich G, Huber W, Büchler P, Estner H. Acute liver failure associated with dronedarone. Circ Arrhythm Electrophysiol 2011; 4: 592-3. [PubMed: 21846890]

  (70 year old woman developed jaundice 6 months after starting dronedarone for atrial fibrillation [peak bilirubin 30.3 mg/dL, ALT and Alk P not provided], with progressive hepatic failure leading to emergency liver transplantation 20 days after presentation).
• Del Pozo Ruiz JJ, Martín Sanz A, Alvarez Vicente G, Arenas Monzo C. [Dronedarone-associated hepatotoxicity. A propos of a case]. Farm Hosp 2012; 36: 545-7. Spanish. PMID: 23461450 [PubMed: 23461450]

  (75 year old man developed abdominal pain, nausea and liver test abnormalities a week after starting dronedarone [bilirubin 1.9 mg/dL, ALT 478 U/L, Alk P normal], symptoms resolving rapidly and all values falling into the normal range within 3 weeks of stopping).
• De Ferrari GM, Dusi V. Drug safety evaluation of dronedarone in atrial fibrillation. Expert Opin Drug Saf 2012; 11: 1023-45. [PubMed: 22971242]

  (Extensive review of structure, mechanism of action, pharmacokinetics, clinical efficacy, and safety of dronedarone in comparison to amiodarone).
• Jahn S, Zollner G, Lackner C, Stauber RE. Severe toxic hepatitis associated with dronedarone. Curr Drug Saf 2013; 8: 201-2. [PubMed: 23789833]

  (69 year old woman developed jaundice 11 months after starting dronedarone and 4 months after starting phenprocoumon [bilirubin 4.9 rising to 33.5 mg/dL, ALT 1314 U/L, Alk P 244 U/L, ANA 1:160, peak INR 1.4], subsequently worsening, but ultimately recovering fully within 6 months of onset).
• Friberg L. Safety of dronedarone in routine clinical care. J Am Coll Cardiol 2014; 63: 2376-84. [PubMed: 24727250]

  (Among 174,995 patients with atrial fibrillation in a Swedish health registry, there was a lower rate of mortality among the 4856 who received dronedarone [1.3% annually] than among those who did not [14%] and no excess in clinically apparent liver disease [0.2% vs 0.6% annually]).
• Hohnloser SH. Dronedarone: "Real-world" data vis-à-vis data from randomized clinical trials. J Am Coll Cardiol 2014; 63: 2385-7. [PubMed: 24727252]

  (Editorial in response to analysis of a Swedish registry by Friberg [2014]).
• Gao S, Dai W, Zhang L, Juhaeri J, Wang Y, Caubel P. Risk of cardiovascular events, stroke, congestive heart failure, interstitial lung disease, and acute liver injury: dronedarone versus amiodarone and other antiarrhythmics. J Atr Fibrillation 2013; 6: 890. [PMC free article: PMC5153130] [PubMed: 28496906]

  (Analysis of health care database of 10,455 adults with atrial fibrillation or flutter seen between 2009 and 2010 for serious outcomes including myocardial infarction, stroke, congestive heart failure, interstitial lung disease and acute liver injury found no excess of instances of acute liver injury among 1727 who were started on dronedarone therapy).
• Arif SA, Drury R, Ader P. Impact of Food and Drug Administration hepatotoxicity warning on prescribing and monitoring of dronedarone in a tertiary teaching hospital. Int J Pharm Pract 2015; 23: 456-60. [PubMed: 26382915]

  (Retrospective analysis of frequency of prescriptions for dronedarone for the year before and year after the FDA issued a warning letter concerning liver injury at a single medical referral center showed a 50% decrease in number of prescriptions, but no increase in rate of ALT monitoring of recipients).
• Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]

  (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 5 cases were attributed to amiodarone and 2 to dronedarone).
• Gao S, Dai W, Zhang L, Juhaeri J, Wang Y, Caubel P. Risk of cardiovascular events, stroke, congestive heart failure, interstitial lung disease, and acute liver injury: dronedarone versus amiodarone and other antiarrhythmics. J Atr Fibrillation. 2013;6:890. [PMC free article: PMC5153130] [PubMed: 28496906]

  (Analysis of a health database on 10,455 adults with atrial fibrillation or flutter treated with one of five antiarrhthmics, dronedarone [n=1,727, followed for 6 months or more] was not associated with an increased risk of cardiovascular events, stroke, heart failure, interstitial lung disease, or acute liver injury [5 cases, none hospitalized]).
• Felser A, Stoller A, Morand R, Schnell D, Donzelli M, Terracciano L, Bouitbir J, et al. Hepatic toxicity of dronedarone in mice: role of mitochondrial β-oxidation. Toxicology. 2014;323:1-9. [PubMed: 24881592]

  (Studies in mice showed that dronedarone [400 mg/kg/day for 1 week] led to weight loss and increases in serum ALT and bilirubin levels and impaired oxidation in mitochondria).
• Guzmán Ramos MI, Romero García T, Márquez Saavedra E, Suárez García E, Martínez Castillo R. Dronedarone-induced liver injury. A case report. Gastroenterol Hepatol. 2018;41:636-638. [PubMed: 29452933]

  (78 year old woman with heart disease and atrial fibrillation developed fatigue and jaundice 6 months after starting dronedarone [bilirubin 13.6 mg/dL, ALT 453 U/L, Alk P not provided] with progressive hepatic encephalopathy, ascites, and death 18 days later).
• Grimaldi-Bensouda L, Wedemeyer H, Wiegand J, Lohse AW, Benichou J, Rossignol M, Larrey D, et al; PGRx-ALI study group. Dronedarone, amiodarone and other antiarrhythmic drugs, and acute liver injuries: a case-referent study. Int J Cardiol. 2018;266:100-105. [PubMed: 29887424]

  (Comparison of 252 cases of suspected drug-induced liver injury collected by a network of 59 centers in Germany between 2010 and 2014 vs 1081 age and sex matched concurrent controls, showed that dronedarone was used by 1.2% [3 cases] vs 0.4% and amiodarone by 2.4% [6 cases] vs 0.6%, the “adjusted” odds ratio being slightly higher for amiodarone).
• Dilaveris P, Tousoulis D. Do not condemn solely dronedarone for acute liver injury: It's a class effect. Int J Cardiol. 2018;266:149-150. [PubMed: 29887433]

  (Editorial in response to Grimaldi-Bensouda [2018] argues that while both dronedarone and amiodarone can cause liver injury, it is a class effect and dronedarone may be better tolerated than amiodarone).
• Siddique AS, Siddique O, Einstein M, Urtasun-Sotil E, Ligato S. Drug and herbal/dietary supplements-induced liver injury: A tertiary care center experience. World J Hepatol. 2020;12:207-219. [PMC free article: PMC7280859] [PubMed: 32547688]

  (Among 38 cases of suspected drug induced liver injury that underwent liver biopsy seen at a single referral center in China between 2012 and 2018, one was attributed to dronedarone [bilirubin 3.3 mg/dL, ALT 93 U/L, Alk P 477 U/L], histology showing a mixed-cholestatic hepatitis with steatosis and bile duct injury).
• Khan ZH, Mukhtar K, Ahmed MM, Zaidi SR, Abd Algayoum R. Dronedarone-mediated acute hepatic and renal toxicity. Cureus. 2020;12:e9611. [PMC free article: PMC7478565] [PubMed: 32923213]

  (86 year old man with rapid atrial fibrillation despite long term amiodarone therapy was given 3 doses of dronedarone [amount not provided] without change in rapid heart rate leading to cardioversion 24 hours after which serum ALT was 3151 U/L, AST 3930 U/L, Alk P 144 U/L, INR 6.1, and creatinine 5.4 mg/dL, which then fell towards normal with no further therapy).
• Pop A, Halegoua-DeMarzio D, Barnhart H, Kleiner D, Avigan M, Gu J, Chalasani N, et al. Amiodarone and dronedarone causes liver injury with distinctly different clinical presentations. Dig Dis Sci. 2024;69:1479-1487. [PMC free article: PMC11026178] [PubMed: 38416280]

  (In a U.S. prospective study of drug-induced liver injury conducted between 2004 and 2016, 3 cases of dronedarone vs 10 cases of amiodarone were identified and compared; dronedarone cases were on average younger [median age 58 vs 70 years], with a latency of 2 to 6 months vs longer, a hepatocellular pattern of injury vs mixed or cholestatic, and hepatitis-like histologic findings vs steatohepatitis with Mallory bodies and fibrosis or cirrhosis).
• Torgersen J, Mezochow AK, Newcomb CW, Carbonari DM, Hennessy S, Rentsch CT, Park LS, et al. Severe acute liver injury after hepatotoxic medication initiation in real-world data. JAMA Intern Med. 2024;184:943-952.. [PMC free article: PMC11197444] [PubMed: 38913369]

  (Analysis of the US Veterans Administration electronic health records between 1999 and 2021 identified 1739 hospitalizations for acute liver injury suspected to be due to medications, no mention of dronedarone, but the estimated rate of injury from amiodarone was 1:2,500 persons per year).
• Bessone F, Hernandez N, Medina-Caliz I, García-Cortés M, Schinoni MI, Mendizabal M, Chiodi D, et al. Drug-induced liver injury in Latin America: 10-year experience of the Latin American DILI (LATINDILI) Network. Clin Gastroenterol Hepatol. 2025;23:89-102. [PubMed: 38992407]

  (Among 483 cases of drug-induced liver injury enrolled in a prospective Latin American database between 2012 and 2022, none were attributed to amiodarone or dronedarone).
• Chen VL, Rockey DC, Bjornsson ES, Barnhart H, Hoofnagle JH; Drug-Induced Liver Injury Network Investigators. Incidence of idiosyncratic drug-induced liver Injury caused by prescription drugs. Drug Saf. 2025;48:151-160. 39317916 [PMC free article: PMC11785493] [PubMed: 39317916]

  (Analysis of 1284 cases of drug-induced liver injury enrolled in a U.S. prospective study between 2005 and 2019 included 8 cases [0.6%] attributed to amiodarone, occurring at an estimated rate of 1 per 4100 persons treated [95% confidence intervals 1:1,200 to 1:6,800], while there were too few cases [less than 5] attributed to dronedarone and lack of information on number treated making it impossible to estimate a rate of liver injury from its use).
• Pundi K, Fan J, Kabadi S, Din N, Blomström-Lundqvist C, Camm AJ, Kowey P, et al. Dronedarone versus sotalol in antiarrhythmic drug-naive veterans with atrial fibrillation. Circ Arrhythm Electrophysiol. 2023;16:456-467. [PubMed: 37485722]

  (Analysis of a matched cohort of 3106 patients from the VA Health Administration files who were treated with dronedarone vs a similar number with sotalol for atrial fibrillation after 2012 with uncertain amount of follow up[~1 year] showing no difference in hospitalization for cardiovascular disease or all cause mortality).