Dronedarone

Title: Dronedarone
CAS Registry Number: 141626-36-0
CAS Name: N-[2-Butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]methanesulfonamide
Additional Names: N,N-dibutyl-3-[4-[(2-butyl-5-methylsulfonamido)benzofuran-3-ylcarbonyl]phenoxy]propylamine
Manufacturers' Codes: SR-33589
Molecular Formula: C31H44N2O5S
Molecular Weight: 556.76
Percent Composition: C 66.87%, H 7.97%, N 5.03%, O 14.37%, S 5.76%
Literature References: Noniodinated analog of amiodarone, q.v. Prepn: J. Gubin et al., EP 471609; eidem, US 5223510 (1992, 1993 both to Sanofi). Hemodynamic and antiadrenergic effects in dogs: L. Djandjighian et al., J. Cardiovasc. Pharmacol. 36, 376 (2000). Electrophysiological effects in canine heart: A. Varró et al., Br. J. Pharmacol. 133, 625 (2001). Clinical pharmacokinetics and interaction with metoprolol, q.v.: T. Damy et al., Fundam. Clin. Pharmacol. 18, 113 (2004). Clinical evaluation in atrial fibrillation: P. Touboul et al., Eur. Heart J. 24, 1481 (2003).
Properties: Crystals from hexane, mp 65.3°.
Melting point: mp 65.3°
Derivative Type: Hydrochloride
CAS Registry Number: 141625-93-6
Manufacturers' Codes: SR-33589B
Molecular Formula: C31H45ClN2O5S
Molecular Weight: 593.22
Percent Composition: C 62.76%, H 7.65%, Cl 5.98%, N 4.72%, O 13.49%, S 5.41%
Properties: Colorless solid from acetone, mp 143°.
Melting point: mp 143°
Therap-Cat: Antiarrhythmic (class III).
Keywords: Antiarrhythmic.
Droperidol Droprenilamine Dropropizine Drosera Drosophilin A

Dronedarone
Dronedarone structure.svg
Systematic (IUPAC) name
N-(2-Butyl-3-(p-(3-(dibutylamino)propoxy)benzoyl)-
5-benzofuranyl)methanesulfonamide
Clinical data
Trade names Multaq
AHFS/Drugs.com monograph
MedlinePlus a609034
Licence data US FDA:link
Pregnancy cat. X (US)
Legal status -only (US)
Routes Oral
Pharmacokinetic data
Bioavailability 15% (with a high-fat meal)[1]
Protein binding >98%
Metabolism Extensive hepatic (mainly by CYP3A)
Half-life 13–19 hours
Excretion Feces (84%), urine (~6%)
Identifiers
CAS number 141626-36-0 N
ATC code C01BD07
PubChem CID 208898
ChemSpider 180996 YesY
UNII JQZ1L091Y2 YesY
KEGG D02537 YesY
ChEBI CHEBI:50659 YesY
ChEMBL CHEMBL184412 YesY
Chemical data
Formula C31H44N2O5S 
Mol. mass 556.758 g/mol
 N (what is this?)  (verify)

Dronedarone (development codename SR33589 and marketed as Multaq) is a drug by Sanofi-Aventis, mainly for the indication of cardiac arrhythmias. It was approved by the FDA on July 2, 2009. It was recommended as an alternative to amiodarone for the treatment of atrial fibrillation and atrial flutter in people whose hearts have either returned to normal rhythm or who undergo drug therapy or electric shock treatment i.e. direct current cardioversion (DCCV) to maintain normal rhythm.[2] In the United States, the FDA approved label includes a claim for reducing hospitalization, but not for reducing mortality, as a reduction in mortality was not demonstrated in the clinical development program.[3] A trial of the drug in heart failure was stopped as an interim analysis showed a possible increase in heart failure deaths, in patients with moderate to severe CHF.[4]

The U.S. label for dronedarone includes a black box warning, stating that dronedarone is contraindicated in patients with NYHA Class IV heart failure, with NYHA Class II–III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic, or with permanent atrial fibrillation."[1] Dronedarone is also associated with rare case of severe liver damage, including liver failure.[5]