Symptomatic Bradycardia,Syncope,and Prolonged QTc Interval Associated with Dronedarone Therapy

Abstract

Objective

To report a case of symptomatic bradycardia, prolonged QT interval, and syncope associated with dronedarone in a patient with atrial fibrillation who was maintained in sinus rhythm.

Case Summary

A 58-year-old man presented to the emergency department with a chief complaint of chest pain and “passing out.” Three months prior, dronedarone had been initiated for maintenance of sinus rhythm. An initial electrocardiogram (ECG) revealed normal sinus rhythm with a prolonged corrected QT (QTc) interval of 645 ms. Upon hospital admission, dronedarone was discontinued. Approximately 17 hours after hospitalization and 35 hours after the last ingested dronedarone dose, a repeat ECG revealed a QTc interval of 457 ms, and the patient reported symptomatic improvement. The patient was discharged home after a 3-day hospital stay without further event. The Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship between the patient's symptoms and dronedarone.

Discussion

Dronedarone is an antiarrhythmic drug that exhibits multiple mechanisms of action, including potassium, sodium, and calcium channel blockade, in addition to antiadrenegic activity. In clinical evaluations of dronedarone therapy, dronedarone was associated with a mean decrease in resting heart rate and potential to prolong the QT interval by 10 ms. These effects may result in clinically significant outcomes, as was observed in this patient.

Conclusions

This case of symptomatic bradycardia and prolonged QTc interval emphasizes the importance of monitoring the heart rate and ECG in patients prescribed dronedarone, particularly in those on concomitant drug therapy that may precipitate these events.

Keywords

adverse drug reaction bradycardia dronedarone drug-induced arrhythmia prolonged QT interval syncope

Get full access to this article

View all access options for this article.

References

Estrada

J.C.

Darbar

Clinical use of and future perspectives on antiarrhythmic drugs. Eur J Clin Pharmacol. 2008; 64: 1139–1146. doi: 10.1007/s00228-008-0555-x.

Crouch

M.A.

Limon

Cassano

A.T.

Clinical relevance and management of drug-related QT interval prolongation. Pharmacotherapy. 2003; 23(7): 881–908.

Haverkamp

Eckardt

Mönning

Clinical aspects of ventricular arrhythmias associated with QT prolongation. Eur Heart J. 2001; 3(suppl K): K81–88.

Multaq (dronedarone hydrochloride) [package insert]. Bridgewater, NJ: sanofi-aventis; 2011.

Piccini

J.P.

Hasselblad

Peterson

E.D.

Washam

J.B.

Califf

R.M.

Comparative efficacy of dronedarone and amiodarone for the maintenance of sinus rhythm in patients with atrial fibrillation. J Am Coll Cardiol. 2009; 54: 1089–1095. doi: 10.1016/j.jacc.2009.04.085.

Singh

B.N.

Connolly

S.J.

Grijns

H.J.G.M.

Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. New Engl J Med. 2007; 357: 987–999.

US Department of Health and Human Resources, Food and Drug Administration (FDA). US FDA Postmarket Drug Safety Information for Patient and Providers Web site. FDA drug safety communication: severe liver injury associated with the use of dronedarone (marketed as Multaq). http://www.fda.gov/Drugs/DrugSafety/ucm240011.htm. Accessed October 27, 2011.

US Department of Health and Human Resources, Food and Drug Administration (FDA). US FDA Postmarket Drug Safety Information for Patient and Providers Web site. FDA drug safety communication: Multaq (dronedarone) and increased risk of death and serious cardiovascular adverse events. http://www.fda.gov/Drugs/DrugSafety/ucm264059.htm. Accessed October 27, 2011.

Dale

K.M.

White

C.M.

Dronedarone: an amiodarone analog for the treatment of atrial fibrillation and atrial flutter. Ann Pharmacother. 2007; 41: 599–605. doi: 10.1345.aph.lH524

10.

Boutitie

Boissel

J.P.

Connolly

S.J.

Amiodarone interaction with beta-blockers: analysis of the merged EMIAT (European Myocaridal Infarct Amdioarone Trial) and CAMIAT (Canadian Amiodarone Myocardial Infarction Trial) databases. Circulation. 1999; 99: 2268–2275.

11.

Zimetbaum

P.J.

Dronedarone for atrial fibrillation – an Odyssey. N Engl J Med. 2009; 360: 1811–1813.

12.

Pacerone (amiodarone hydrochloride) [package insert]. Minneapolis, MN: Upser-Smith Laboratories; 2009.

13.

Arizona Center for Education and Research on Therapeutics. Drugs that prolong the QT interval and/or induce torsades de pointes ventricular arrhythmia. Arizona Center for Education and Research on Therapeutic Web site. http://www.azcert.org/medical-pros/drug-lists/drug-lists.cfm. Accessed August 25, 2011.

14.

Zipes

D.A.

Camm

A.J.

Borggrefe

ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines. J Am Coll Cardiol. 2006; 48: e247–346. doi: 10.1016/j.jacc.2006.07.010.

15.

Naranjo

C.A.

Busto

Sellers

E.M.

A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981; 20: 239–245.