Dronedarone Dosing for Atrial Tachyarrhythmias
The recommended dose of dronedarone for atrial fibrillation or atrial flutter is 400 mg twice daily (800 mg total daily dose), taken with morning and evening meals. 1, 2
Standard Dosing Regimen
Dronedarone 400 mg twice daily is the only approved and effective dose established through the DAFNE dose-finding study, which tested 400 mg, 600 mg, and 800 mg twice daily regimens 1
Higher doses (600 mg and 800 mg twice daily) were not more effective and resulted in significantly higher discontinuation rates of 7.6% and 22.6% respectively, compared to the standard 400 mg dose 1
The medication must be taken with food to optimize absorption, as bioavailability increases from approximately 4% (fasting) to 15% (with high-fat meal) 2
Steady-state plasma concentrations are reached within 4-8 days of initiating therapy at the standard dose 2
No Dose Adjustments Required
No dose adjustment is needed for elderly patients, even though dronedarone exposures are 23% higher in patients ≥65 years old 2
No dose adjustment is needed for renal impairment because renal excretion of dronedarone is minimal 2
No dose adjustment is recommended for moderate hepatic impairment, though dronedarone is extensively metabolized by the liver 2
Female patients have 30% higher exposures than males, but no dose adjustment is recommended 2
Critical Contraindications to Dronedarone Use
Absolutely contraindicated in permanent atrial fibrillation (>6 months duration), as the PALLAS trial demonstrated doubled cardiovascular mortality and was terminated early 1, 3
Contraindicated in NYHA Class IV heart failure or recent decompensation requiring hospitalization, as the ANDROMEDA trial showed increased mortality (25 deaths in dronedarone group vs 12 in placebo) and was stopped prematurely 1, 3
Contraindicated in patients with severe heart failure (EF <35%) or unstable NYHA Class II-III heart failure within the past month 1, 3
Clinical Context and Efficacy
Dronedarone is indicated for paroxysmal or persistent atrial fibrillation/flutter in patients with cardiovascular risk factors to reduce cardiovascular hospitalizations 1, 3
The drug is less effective than amiodarone for maintaining sinus rhythm (DIONYSOS trial showed amiodarone superiority, P <0.001) but has a significantly better safety profile 1
Dronedarone demonstrates both rhythm-control and rate-control properties, reducing ventricular rate by approximately 10-12 beats per minute during AF recurrence 1, 4
The ATHENA trial demonstrated a 24% reduction in cardiovascular hospitalization or death (HR 0.76, P <0.0001) and a 34% reduction in stroke risk (HR 0.66, P = 0.027) in appropriate patient populations 1, 3, 5
Important Clinical Pearls
Dronedarone should be initiated by specialists familiar with antiarrhythmic drugs, not in general or family practice settings 3
Concomitant digoxin dose must be reduced by 50% when starting dronedarone, as dronedarone increases digoxin exposure 6
Monitor liver function tests, thyroid function (TSH), and creatinine at baseline and 6 months 6
Dronedarone moderately increases serum creatinine (reflecting reduced tubular secretion, not true kidney dysfunction), so expect a mild elevation 6
The elimination half-life is only 13-19 hours, much shorter than amiodarone's 20-100 day half-life, allowing for more rapid titration and discontinuation if needed 6, 2