Overview
11 DESCRIPTION Dronedarone HCl is a benzofuran derivative with the following chemical name: N -{2-butyl-3-[4-(3-dibutylaminopropoxy)benzoyl]benzofuran-5-yl} methanesulfonamide, hydrochloride. Dronedarone HCl is a white fine powder that is practically insoluble in water and freely soluble in methylene chloride and methanol.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The mechanism of action of dronedarone is unknown. Dronedarone has antiarrhythmic properties belonging to all four Vaughan-Williams classes, but the contribution of each of these activities to the clinical effect is unknown. 12.2 Pharmacodynamics Electrophysiological Effects The effect of dronedarone on 12-lead ECG parameters was investigated in healthy subjects following repeated oral doses up to 1600 mg twice daily for 10 days. Concentration-dependent increases in QTcF and PR were observed and the estimated increases for 400 mg BID with food are 15 and 12 ms, respectively. The contribution of dronedarone and the N-debutyl metabolite to observed changes is unknown.
Indications
- 1 INDICATIONS AND USAGE MULTAQ ® is indicated to reduce the risk of hospitalization for atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistent atrial fibrillation (AF) [see Clinical Studies (14) ] . MULTAQ is an antiarrhythmic drug indicated to reduce the risk of hospitalization for atrial fibrillation (AF) in patients in sinus rhythm with a history of paroxysmal or persistent AF ( 1 , 14 ).
Common Doses
- 400 mg
Dosage
2 DOSAGE AND ADMINISTRATION The recommended dosage of MULTAQ is 400 mg twice daily in adults. MULTAQ should be taken as one tablet with the morning meal and one tablet with the evening meal. Treatment with Class I or III antiarrhythmics (e.g., amiodarone, flecainide, propafenone, quinidine, disopyramide, dofetilide, sotalol) or drugs that are strong inhibitors of CYP3A (e.g., ketoconazole) must be stopped before starting MULTAQ [see Contraindications (4) ] . Verify that females of reproductive potential are not pregnant prior to initiating MULTAQ [see Warnings and Precautions (5.
Black Box Warning
WARNING: INCREASED RISK OF DEATH, STROKE AND HEART FAILURE IN PATIENTS WITH DECOMPENSATED HEART FAILURE OR PERMANENT ATRIAL FIBRILLATION In patients with symptomatic heart failure and recent decompensation requiring hospitalization or NYHA Class IV heart failure, MULTAQ doubles the risk of death [see Clinical Studies (14.3) ] . MULTAQ is contraindicated in patients with symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV heart failure [see Contraindications (4) , Warnings and Precautions (5.1) ] .
Contraindications
- 4 CONTRAINDICATIONS MULTAQ is contraindicated in patients with: • Permanent atrial fibrillation (patients in whom normal sinus rhythm will not or cannot be restored) [see Boxed Warning , Warnings and Precautions (5.2) ] • Symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV symptoms [see Boxed Warning , Warnings and Precautions (5.1) ] • Second or third-degree atrioventricular (AV) block, or sick sinus syndrome (except when used in conjunction with a functioning pacemaker) • Bradycardia 500 ms or PR interval >280 ms • Severe hepatic impairment •...
Side Effects
- 6 ADVERSE REACTIONS The following safety concerns are described elsewhere in the label: • New or worsening heart failure [see Warnings and Precautions (5.4) ] • Liver Injury [see Warnings and Precautions (5.5) ] • Pulmonary toxicity [see Warnings and Precautions (5.6) ] • Hypokalemia and hypomagnesemia with potassium-depleting diuretics [see Warnings and Precautions (5.7) ] • QT prolongation [see Warnings and Precautions (5.
Interactions
- 7 DRUG INTERACTIONS Dronedarone is metabolized by CYP3A and is a moderate inhibitor of CYP3A and CYP2D6 and has potentially important pharmacodynamic interactions ( 7 ) • Class I or III antiarrhythmics: Contraindicated. ( 4 , 7.1 ) • Digoxin: Consider discontinuation or halve dose of digoxin before treatment and monitor digoxin levels. ( 7.1 , 7.3 ) • Calcium channel blockers (CCB): Initiate CCB with low dose and increase after ECG verification of tolerability. ( 7.1 , 7.2 , 7.3 ) • Beta-blockers: May provoke excessive bradycardia.