Dronedarone (Multaq): Benzofuran derivative approved to reduce the risk of CV hospitalization in patients with AF

New molecular entity: Dronedarone (Multaq), a benzofuran derivative, was approved on July 1, 2009, to reduce the risk of CV hospitalization in patients with AF

Dronedarone is a benzofuran derivative with antiarrhythmic properties belonging to all 4 Vaughan-Williams classes. Dronedarone's mechanism of action is unknown. This agent was approved on July 1, 2009, to reduce the risk of cardiovascular (CV) hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL) who have experienced a recent episode of AF/AFL, have associated CV risk factors (age >70 y, hypertension, diabetes, previous cerebrovascular accident, left atrial diameter ≥50 mm or left ventricular ejection fraction <40%), and are in sinus rhythm or will be cardioverted.

Efficacy. The efficacy of dronedarone was assessed in several trials. In 1 trial, patients aged ≥75 years or ≥70 years with ≥1 risk factor and with a recent history of AF/AFL who were in sinus rhythm or were to be converted to sinus rhythm were randomized to treatment with dronedarone 400 mg twice/d or placebo for up to 30 months. The primary end point was time to first hospitalization for CV reasons or death from any cause. Dronedarone reduced the incidence of the primary end point by 24.2% compared with placebo (HR=0.76; 95% CI, 0.68–0.83; P<.0001); this result was entirely attributable to dronedarone's effect on CV hospitalization. In 2 trials, patients in sinus rhythm who had experienced a previous episode of AF/AFL were randomized to treatment with dronedarone 400 mg twice/d or placebo for 12 months. The primary end point was time to first recurrence of AF/AFL. Dronedarone reduced the risk of first AF/AFL recurrence by approximately 25%, with an approximate 11% absolute difference in recurrence rate. In another study, patients who were recently hospitalized with symptomatic heart failure (HF) and severe left ventricular systolic dysfunction were randomized to treatment with dronedarone 400 mg twice/d or placebo. This trial was terminated prematurely because of excess mortality among dronedarone-treated patients (HR=2.13; 95% CI, 1.07–4.25; P=.027).

Safety. Patients who develop signs or symptoms of HF should consult a physician. If HF develops or worsens, suspension or discontinuation of dronedarone should be considered. Concomitant administration of potassium-depleting diuretics may lead to hypokalemia or hypomagnesemia. If QTc Bazett interval is ≥500 ms, dronedarone treatment should be discontinued. Women of childbearing potential must use effective contraception during dronedarone treatment. The most common adverse events associated with dronedarone treatment include diarrhea, nausea, abdominal pain, vomiting, and asthenia.

Dosing. Dronedarone 400-mg tablets should be administered twice/d. Class I or III antiarrhythmics and drugs that strongly inhibit CYP3A must be discontinued before initiation of dronedarone treatment.