Dronedarone

Table of contents

  • Brand Names
  • Chemistry
  • Pharmacologic Category
  • Mechanism of Action
  • Therapeutic Use
  • Pregnancy and Lactation Implications
  • Contraindications
  • Warnings and Precautions
  • Adverse Reactions
  • Genes that may be involved
  • Substrate of
  • Inhibits
  • Drug Interactions
  • Nutrition/Nutraceutical Interactions
  • Dosage
  • Pharmacokinetics and Pharmacodynamics
  • Special Considerations

Brand Names

Austria: Multaq; Bulgaria: Multaq; Czech Republic: Multaq; Denmark: Multaq; Finland: Multaq; Germany: Multaq; Greece: Multaq; Hungary: Multaq; Ireland: Multaq; Italy: Multaq; Latvia: Multaq; Lithuania: Multaq; Malta: Multaq; Netherlands: Multaq; Poland: Multaq; Portugal: Multaq; Romania: Multaq; Slovakia: Multaq; Slovenia: Multaq; Sweden: Multaq; UK: Multaq.

North America

Canada: Multaq; USA: Multaq.

Drug combinations

Chemistry

Dronedarone Hydrochloride: C~31~H~44~N~2~O~5~S HCl. Mw: 593.22. N-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-1-benzofuran-5-yl] methanesulfonamide, hydrochloride. CAS-141625-93-6.

Pharmacologic Category

Antiarrhythmic Agents; Class III Antiarrhythmics. (ATC-Code: C01BD07).

Mechanism of action

Dronedarone has antiarrhythmic properties belonging to all four antiarrhythmic (Vaughan-Williams) classes, but the contribution of each of these activities to the clinical effect is unknown. Inhibits sodium (I~Na~) and potassium (I~kr~, I~kS~, I~k1~, and I~k-ACh~) channels resulting in prolongation of the action potential and refractory period in myocardial tissue without reverse-use-dependent effects. Decreases AV conduction and sinus node function through inhibition of calcium (I~Ca-L~) channels and β~1~-receptor blocking activity. Similar to amiodarone, dronedarone also inhibits α~1~-receptor-mediated increases in blood pressure.

Therapeutic use

Indicated to reduce the risk of hospitalization related to paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFl) in patients with a recent episode of AF/AFl and associated cardiovascular risk factors (e.g., age >70 years, hypertension, diabetes, prior cerebrovascular accident, left atrial diameter ≥50 mm or left ventricular ejection fraction <40%), who are in normal sinus rhythm or will be cardioverted.

Pregnancy and lactiation implications

Fetal harm may occur (pregnancy should be avoided while taking this medication). Breast-feeding is contraindicated.

Unlabeled use

Contraindications

NYHA Class IV heart failure (HF); NYHA Class II-III HF with recent decompensation requiring hospitalization or referral to a specialized HF clinic; second- or third-degree heart block, or sick sinus syndrome (except in patients with a functioning artificial pacemaker). Bradycardia <50 bpm. Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, cyclosporine, telithromycin, clarithromycin, nefazodone, or ritonavir). Concomitant use of drugs or herbal products known to prolong the QT interval, increasing the risk for torsade de pointes (e.g. phenothiazine antipsychotics, tricyclic antidepressants, certain oral macrolide antibiotics, or class I and III antiarrhythmics). QTc (Bazett) interval ≥500 ms or PR interval >280 ms. Severe hepatic impairment. Pregnancy. Breast-feeding.

Warnings and precautions

Dronedarone induces a moderate prolongation of the QT interval (average ~10 ms); much greater effects have been observed. Use in patients with QTc (Bazett) interval ≥500 ms is contraindicated; discontinue use of dronedarone if this occurs during therapy. Following initiation, dronedarone may produce a slight increase in serum creatinine (~0.1 mg/dL) due to inhibition of tubular secretion; glomerular filtration rate is not affected. Chronic administration of antiarrhythmic drugs may affect defibrillation or pacing thresholds. Electrolyte imbalance may occur. Use is contraindicated in patients with NYHA Class IV HF or NYHA Class II-III HF with recent decompensation requiring hospitalization or referral to a specialized HF clinic (consider suspension or discontinuation of dronedarone if heart failure develops or worsens). Use with caution in mild-to-moderate hepatic impairment and avoid use in severe hepatic impairment.

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