Dronedarone


Concise Prescribing Info
Indications/Uses
AF.
Dosage/Direction for Use
Adult : PO 400 mg bid.
Dosage Details
Oral
Atrial fibrillation
Adult: 400 mg bid (morning and evening).
Renal Impairment
Mild to Moderate: No dosage adjustment needed. Severe: Contraindicated.
Hepatic Impairment
Mild to Moderate: No dosage adjustment needed. Severe: Contraindicated.
Administration
Should be taken with food. Avoid grapefruit juice.
Contraindications
Permanent AF; symptomatic heart failure w/ recent decompensation requiring hospitalisation or NYHA Class IV symptoms; bradycardia <50 bpm; 2nd- or 3rd-degree AV block, or sick sinus syndrome; QTc Bazett interval ≥500 msec; hepatic and lung toxicity associated w/ previous amiodarone therapy; history of or current heart failure or left ventricular systolic dysfunction. Concomitant use w/ phenothiazines antipsychotics, tricyclic antidepressants, class I and III antiarrhythmics, some macrolides (e.g. erythromycin), bepridil, terfenadine, CPY3A4 inhibitor (e.g. ciclosporin, cimetidine, clarithromycin, ketoconazole, HIV-protease inhibitors, grapefruit juice, nefazodone) or inducers (e.g. phenytoin, phenobarbital, rifampicin, carbamazepine, St John's wort). Severe hepatic and renal impairment. Pregnancy and lactation.
Special Precautions
May increase risk of arrhythmia in patients w/ hypokalaemia and hypomagnesaemia. Correct K and Mg deficiency prior to initiation and during treatment.
Adverse Reactions
Hypokalaemia, hypomagnesaemia, bradycardia, diarrhoea, nausea, vomiting, abdominal pain, and dyspepsia, rashes and asthenia, pneumonitis and pulmonary fibrosis.
Potentially Fatal: Stroke, new or worsening heart failure, hepatocellular liver injury and hepatic failure, QT prolongation.
MonitoringParameters
Monitor ECG at least every 3 mth renal function periodically, and hepatic function before and throughout therapy.
Drug Interactions
Increased risk of bradycardia w/ β-blockers, Ca channel blockers and other antiarrhythmics. May increase plasma concentrations of statins, sirolimus and tacrolimus, vit K antagonists, warfarin and digoxin.
Potentially Fatal: Increased risk of QT prolongation and torsade de pointes w/ phenothiazines antipsychotics, tricyclic antidepressants, class I and III antiarrhythmics, some macrolides (e.g. erythromycin), bepridil and terfenadine. Decreased plasma concentration w/ CYP3A4 inducers (e.g. phenytoin, phenobarbital, rifampicin, carbamazepine). Increased plasma concentration w/ CPY3A4 inhibitor (e.g. ciclosporin, cimetidine, clarithromycin, ketoconazole, HIV-protease inhibitors, nefazodone).
Food Interaction
Avoid grapefruit juice as this may increase the serum levels of dronedarone. Avoid St John's wort as this may decrease the serum levels of dronedarone.
Action
Description: Dronedarone is an antiarrhythmic agent structurally related to amiodarone but w/o the iodine moiety to reduce the risk of non-target organ adverse effects associated w/ amiodarone. It exhibits all the properties of the 4 antiarrhythmic classes. It prolongs cardiac action potential duration and refractory periods by inhibiting K channels, inhibits Na and Ca channels, and has noncompetitive antiadrenergic activity.
Pharmacokinetics:
Absorption: Absolute bioavailability: Approx 4% (w/o food) and approx 15% (w/ food). Time to peak plasma concentration: 3-6 hr.
Distribution: Volume of distribution: Approx 20 L/kg. Plasma protein binding: >98% (mainly albumin).
Metabolism: Hepatic metabolism mainly via CYP3A4 isoenzyme to N-butyl metabolite. Initial metabolic pathway includes N-debutylation, oxidative deamination and direct oxidation.
Excretion: Via faeces: Approx 84% (as metabolites and unchanged drug); urine: Approx 6% (as metabolites). Elimination half-life: 13-19 hr.
Storage
Store at 25°C.
MIMS Class
References
Anon. Dronedarone. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 29/08/2013.

Buckingham R (ed). Dronedarone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 29/12/2012.

FDA Drug Safety Communication: Review Update of Multaq (Dronedarone) and Increased Risk of Death and Serious Cardiovascular Adverse Events. U.S. FDA. https://www.fda.gov/. Accessed 29/08/2013.

McEvoy GK, Snow EK, Miller J et al (eds). Dronedarone Hydrochloride. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 29/08/2013.

MULTAQ Film Coated [Sanofi-Aventis U.S. LLC]. DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 29/08/2013.

Disclaimer: This information is independently developed by MIMS based on Dronedarone from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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