What is dronedarone used for?

dronedarone is evaluated for the following indications with varying evidence strength: Non-valvular atrial fibrillation (evidence tier B), Heart failure with reduced ejection fraction (evidence tier F), Permanent atrial fibrillation (evidence tier F). See the full indication matrix with dosing and citations above on this page.

What are the side effects of dronedarone?

Common side effects of dronedarone (≥ 1 in 100): Diarrhea, nausea, vomiting, abdominal pain, Asthenia, fatigue, Bradycardia, QTc prolongation by 10–20 ms, Creatinine increase by 0.1 mg/dL (due to tubular secretion inhibition, not kidney injury). See the Safety section for uncommon and serious reactions.

Who should not take dronedarone?

dronedarone is contraindicated in: Permanent atrial fibrillation; NYHA class II–IV heart failure; LVEF below 35 percent; Severe hepatic impairment; Liver or lung injury from previous amiodarone therapy. Full list in the Safety section.

Does dronedarone carry an FDA boxed warning?

FDA boxed warning: increased mortality, stroke, and heart failure hospitalization in patients with permanent atrial fibrillation (PALLAS trial). Increased mortality in patients with symptomatic NYHA II–IV heart failure or LVEF below 35 percent (ANDROMEDA trial). Contraindicated in these populations.

Dronedarone maintains sinus rhythm in patients with paroxysmal or persistent non-valvular atrial fibrillation after cardioversion. Efficacy was demonstrated in the ATHENA trial (NEJM 2009): a 24 percent reduction in the composite of cardiovascular death and hospitalization versus placebo. 2024 places dronedarone in the second line for rhythm control in patients without heart failure and without significant structural heart disease. Less effective than amiodarone for rhythm maintenance, but with lower extracardiac toxicity (no thyroid, pulmonary, or cutaneous involvement).

Heart failure with reduced ejection fraction

No recomendado

In NYHA class II–IV heart failure or LVEF below 35 percent, dronedarone is contraindicated. The ANDROMEDA trial (NEJM 2008) was stopped early because of a two-fold increase in mortality with dronedarone in patients with severe heart failure. All international regulators (, ) and guidelines ( 2023, 2023) prohibit its use in this population.

Sources

Permanent atrial fibrillation

No recomendado

In permanent atrial fibrillation, dronedarone is contraindicated. The PALLAS trial (NEJM 2011) was stopped early because of a two-fold increase in cardiovascular death, stroke, and heart failure hospitalization with dronedarone in patients with permanent AF and risk factors. Dronedarone is not used in this population for rhythm control (no rationale) or for rate control (inferior to standard beta-blockers and CCBs).

Sources

Cuándo y cómo tomar

Taken 400 mg twice daily with the morning and evening meals. A fatty meal increases bioavailability 2- to 3-fold, so timing is kept consistent. The tablet is not crushed or chewed.

Titulación de dosis

Dose is fixed: 400 mg twice daily. No effect-based titration. If rhythm is not maintained, switch to a different antiarrhythmic (sotalol, flecainide, amiodarone) rather than escalating dronedarone.

Monitorización

Check ALT, AST, ALP, and bilirubin before initiation and every 6 months (severe hepatitis risk). ECG monitoring: baseline QTc, repeat at 4 weeks and every 6 months. With new dyspnea or cough, chest radiography and spirometry rule out interstitial lung disease. Creatinine rises on average by 0.1 mg/dL; a rise greater than 0.3 mg/dL prompts a cause workup.

Situaciones especiales

Grapefruit and grapefruit juice sharply raise dronedarone concentrations: complete avoidance is recommended. Dronedarone increases digoxin levels 1.5- to 2-fold (halve the digoxin dose and check serum levels). With warfarin, INR rises and more frequent monitoring is required. With simvastatin, rhabdomyolysis risk increases – maximum simvastatin dose is 10 mg.

Mitos frecuentes

Myth: “dronedarone is a safer amiodarone”. Fact: dronedarone lacks the extracardiac toxicity of amiodarone (thyroid, lung) but carries its own risks – severe hepatitis and increased mortality in heart failure and permanent AF. It is not a “light version” but a drug with a different safety profile and narrower indications.

Myth: “if rhythm is not maintained, raise the dose”. Fact: 400 mg twice daily is the maximum fixed dose. Switch drugs if it fails.

Myth: “in permanent AF dronedarone will help control rate”. Fact: dronedarone is contraindicated in permanent AF because of the PALLAS mortality signal. Rate control uses beta-blockers and non-dihydropyridine CCBs.

Mayor

dabigatran

Direct thrombin inhibitor

Mecanismo

Дронедарон ингибирует P-gp, концентрация дабигатрана возрастает на 70–100%. Риск кровотечения.

Manejo

При CrCl 30–50 мл/мин снизить дозу дабигатрана до 75 мг 2 р/сут. При CrCl <30 – не сочетать.

Fuentes

ESC: 2020 ESC Guidelines for the management of atrial fibrillation (2020)

Detalles de la pareja →

Contraindicaciones

Permanent atrial fibrillation
NYHA class II–IV heart failure
LVEF below 35 percent
Severe hepatic impairment
Liver or lung injury from previous amiodarone therapy
Pregnancy and breastfeeding
QTc prolongation above 500 ms
Bradycardia below 50 bpm
Second- and third-degree AV block without a pacemaker
Concomitant strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin)
Concomitant QT-prolonging drugs (phenothiazines, tricyclic antidepressants, macrolides)

Reacciones adversas graves

Severe hepatitis with acute liver failure (post-marketing reports requiring transplantation)
Heart failure decompensation in patients with LVEF below 35 percent
Life-threatening arrhythmias (torsades de pointes) with QT prolongation and QT-prolonging co-medication

Reacciones adversas frecuentes

Diarrhea, nausea, vomiting, abdominal pain
Asthenia, fatigue
Bradycardia
QTc prolongation by 10–20 ms
Creatinine increase by 0.1 mg/dL (due to tubular secretion inhibition, not kidney injury)

Reacciones adversas poco frecuentes

Skin rash, photosensitivity
Interstitial lung disease (much less frequent than with amiodarone)
Dysgeusia

EmbarazoFDA X

FDA category X. Dronedarone is contraindicated in pregnancy: animal studies show fetal malformations. Reliable contraception is mandatory in women of reproductive age throughout therapy.

Lactancia

Breastfeeding is contraindicated: dronedarone is excreted in animal milk at high concentrations, with no human data. If maternal therapy is required, breastfeeding is discontinued.

dronedarone

Mecanismo de acción

Indicaciones

Non-valvular atrial fibrillation