A 60-year-old male with persistent AF is started on dronedarone. His physician checks renal and hepatic function. Dronedarone is contraindicated in patients with permanent AF or NYHA class III-IV heart failure because clinical trials demonstrated:

• A Increased incidence of Torsades de pointes due to excessive QTc prolongation in heart failure patients
• B Increased mortality in these patient populations, likely due to pro-arrhythmic and hepatic toxic effects ✓
• C Loss of rhythm-control efficacy due to downregulation of cardiac sodium channels in heart failure
• D Severe pulmonary toxicity analogous to amiodarone in patients with reduced ejection fraction

Explanation

The ANDROMEDA and PALLAS trials demonstrated significantly increased mortality with dronedarone in patients with severe heart failure (NYHA III-IV) and in those with permanent AF, respectively. The PALLAS trial showed increased cardiovascular death, stroke, and hospitalisation. Dronedarone is therefore contraindicated in these groups. Serious hepatic injury (including hepatic failure) is another black-box warning. Unlike amiodarone, dronedarone lacks an iodine moiety and thus does not cause pulmonary or thyroid toxicity. Torsades risk is modest as it also blocks sodium and calcium channels.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.