Dronedarone

Oral
Atrial fibrillation

Mild to Moderate: No dosage adjustment needed. Severe: Contraindicated.

Mild to Moderate: No dosage adjustment needed. Severe: Contraindicated.

Should be taken with food. Avoid grapefruit juice.

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.

May increase risk of arrhythmia in patients w/ hypokalaemia and hypomagnesaemia. Correct K and Mg deficiency prior to initiation and during treatment.

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.

PO: X

Monitor ECG at least every 3 mth renal function periodically, and hepatic function before and throughout therapy.

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).

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.

Description:
Mechanism of Action: 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.

Store at 25°C.

Cardiac Drugs

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.