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dronedarone (Multaq)

Formerly Class III antiarrhythmic agent. [10] Indications: - maintenance of sinus rhythm in patients with atrial fibrillation (AF) & heart failure (FDA-approved)* - currently only approved for nonpermanent AF [6,7,8]* * less effective than amiodarone, avoid [12] Contraindications: - NYHA class 4 heart failure - NYHA class 2 or 3 heart failure with recent myocardial infarction [10] Adverse effects: - bradycardia, QT-interval prolongation - nausea, diarrhea - rash - elevated serum creatinine - average decrease in creatinine clearance of 18% [10] - due to partial inhibition of tubular excretion of creatinine - no change in glomerular filtration rate [10] - worsens heart failure, increases mortality [1]; delays hospitalization for cardiac events [3]; does not increase mortality [3] - increased risk for cardiovascular events in patients taking the drug for permanent atrial fibrillation [6] a) 2-fold increased risk of death b) 2-fold increased risk of stroke c) 2-fold increased risk of hospitalization for heart failure [7] Mechanism of action: - antiarrhythmic drug with electrophysiologic effects similar to amiodarone - does not contain iodine Clinical trials: see ATHENA study Notes: costs over $200/month (2009) [4]

Related

ATHENA study

General

antiarrhythmic multichannel blocker

Database Correlations

PUBCHEM correlations

References

  1. Kober L et al for the Dronedarone Study Group. Increased mortality after dronedarone therapy for severe heart failure. N Engl J Med 2008, 358:2678 PMID: 18565860
  2. Hohnloser SH et al for the ATHENA Investigators. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med 2009 Feb 12; 360:668 PMID: 19213680
  3. Zimetbaum PJ. Dronedarone for atrial fibrillation-an odyssey. N Engl J Med. 2009 Apr 30;360(18):1811-3. PMID: 19403901
  4. Prescriber's Letter 16(8): 2009 COMMENTARY: New Drug: Multaq (Dronedarone) GUIDELINES: Management of Patients with Atrial Fibrillation (ACC/AHA/ESC 2006) Detail-Document#: 250807 (subscription needed) http://www.prescribersletter.com
  5. FDA MedWatch, Jan 14, 2011 Multaq (dronedarone) - Drug Safety Communication: Risk of Severe Liver Injury http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm240110.htm
  6. Sanofi Provides Multaq Phase IIIb PALLAS Trial Update - Indication seeking trial in permanent AF patient population stopped - Benefit-risk of Multaq remains unchanged in non-permanent AF patients - http://en.sanofi.com/binaries/20110707_PALLAS_en_tcm28-33021.pdf
  7. FDA MedWatch: 07/21/2011 Multaq (dronedarone): Drug Safety Communication - Increased Risk of Death or Serious Cardiovascular Events http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm264204.htm
  8. Prescriber's Letter 18(10): 2011 Multaq (Dronedarone) Alternatives for Atrial Fibrillation Detail-Document#: 271009 (subscription needed) http://www.prescribersletter.com
  9. Connolly SJ et al. for the PALLAS Investigators. Dronedarone in high-risk permanent atrial fibrillation. N Engl J Med. 2011 Dec 15;365(24):2268-76. Epub 2011 Nov 14. PMID: 22082198 - Nattel S. Dronedarone and atrial fibrillation - Jekyll and Hyde? N Engl J Med. 2011 Dec 15;365(24):2321-2. Epub 2011 Nov 14 PMID: 22082122
  10. Medical Knowledge Self Assessment Program (MKSAP) 16, 17. American College of Physicians, Philadelphia 2012, 2015
  11. Patel C, Yan GX, Kowey PR. Dronedarone. Circulation. 2009 Aug 18;120(7):636-44. PMID: 19687370
  12. Therapeutics Letter #108. Therapeutics Initiative Drugs to Avoid. http://www.ti.ubc.ca/2018/01/04/108-drugs-avoid/