Dronedarone Property

Melting point:

65.3°

Boiling point:

683.9±65.0 °C(Predicted)

Density 

1.143±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

≥27.84 mg/mL in DMSO; insoluble in H2O; ≥49.8 mg/mL in EtOH

form 

solid

pka

7.40±0.30(Predicted)

color 

White to off-white

CAS DataBase Reference

141626-36-0(CAS DataBase Reference)

Safety

Hazardous Substances Data

141626-36-0(Hazardous Substances Data)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H332Harmful if inhaled

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

Dronedarone Chemical Properties,Usage,Production

Description

AF is the most common form of sustained cardiac arrhythmia, with an increasing prevalence in the aging population. AF accounts for 34.5% of arrhythmia-related hospital admissions in the United States. The most significant consequences of AF include congestive heart failure, a 5-fold increased risk of stroke, and increased rate of mortality. Although a 90% conversion rate from AF to normal sinus rhythm (NSR) can be achieved with electrical cardioversion, up to 70% of these patients require additional therapy with antiarrhythmic drugs in order to maintain NSR.
Dronedarone, a close analog of amiodarone, is structurally modified to provide improved safety and pharmacokinetic profile. With the introduction of a sulfonamide group, dronedarone is less lipophilic, has lower tissue accumulation, and has a much shorter serum half-life (～24 h) compared with amiodarone. Additionally, dronedarone lacks the iodine moieties that are responsible for thyroid dysfunctions associated with amiodarone. Dronedarone is specifically indicated to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent AF or AFL, with a recent episode of AF/AFL and associated cardiovascular risk factors, who are in sinus rhythm or who will be cardioverted. Similar to amiodarone, dronedarone is a potent blocker of multiple ion currents (including the rapidly activating delayed-rectifier potassium current, the slowly activating delayed-rectifier potassium current, the inward rectifier potassium current, the acetylcholine-activated potassium current, peak sodium current, and L-type calcium current) and exhibits antiadrenergic effects. Overall, dronedarone was well tolerated. The most common side effects were gastrointestinal in nature and included nausea, vomiting, and diarrhea.

Originator

Sanofi-Aventis (US)

Uses

Dronedarone-d9 is an isotopic labeled form of Dronedarone(D679445). Dronedarone is a drug used for the treatment of atrial fibrillation and atrial flutter in patients who have suffered cardiac arrhythmias.

Definition

ChEBI: A member of the class of 1-benzofurans used for the treatment of cardiac arrhythmias.

brand name

Multaq

Clinical Use

Anti-arrhythmic:
Maintenance of sinus rhythm after successful cardioversion in adult clinically stable patients with paroxysmal or persistent atrial fibrillation

target

Calcium Channel | Sodium Channel | Potassium Channel

Drug interactions

Potentially hazardous interactions with other drugs
Anti-arrhythmics: increased risk of myocardial depression with other anti-arrhythmics; increased risk of ventricular arrhythmias with amiodarone or disopyramide - avoid.
Antibacterials: increased risk of ventricular arrhythmias with clarithromycin, telithromycin and erythromycin; concentration reduced by rifampicin - avoid
Anticoagulants: increased anti-coagulant effect with coumarins and phenindione; increased dabigatran concentration - avoid; avoid with rivaroxaban; concentration of edoxaban increased - reduce dose of edoxaban.
Antidepressants: concentration possibly reduced by St John’s wort - avoid; increased risk of ventricular arrhythmias with tricyclic antidepressants, citalopram and escitalopram - avoid.
Antiepileptics: concentration possibly reduced by fosphenytoin, phenytoin, carbamazepine, phenobarbital and primidone - avoid.
Antifungals: concentration increased by ketoconazole - avoid; avoid with itraconazole, posaconazole and voriconazole.
Antipsychotics: increased risk of ventricular arrhythmias with antipsychotics that prolong the QT interval; increased risk of ventricular arrhythmias with phenothiazines - avoid.
Antivirals: avoid with ritonavir; increased risk of ventricular arrhythmias with saquinavir - avoid.
Beta-blockers: increased risk of myocardial depression; concentration of metoprolol and propranolol possibly increased; increased risk of ventricular arrhythmias with sotalol - avoid.
Calcium channel blockers: concentration increased by nifedipine; increased risk of bradycardia and myocardial depression with diltiazem and verapamil.
Cytotoxics: possibly increases bosutinib concentration - avoid or consider reducing bosutinib dose; possibly increases ibrutinib concentration - reduce ibrutinib dose
Digoxin: increased concentration (halve digoxin maintenance dose).
Fingolimod: possibly increased risk of bradycardia.
Grapefruit juice: concentration of dronedarone increased - avoid.
Lipid-lowering drugs: concentration of atorvastatin and rosuvastatin possibly increased; increased risk of myopathy with simvastatin; concentration of lomitapide possibly increased - avoid.
Tacrolimus: manufacturer advises use with caution.

Metabolism

Dronedarone is extensively metabolised in the liver, mainly by the cytochrome P450 isoenzyme CYP3A4 to a less active N-debutyl metabolite, and several inactive metabolites
About 6% of an oral dose is excreted in the urine (entirely metabolites) and 84% in the faeces (metabolites and unchanged drug).