MULTAQ® (dronedarone) Tablet

Navigation

Warnings

(description)

Clinical pharmacology

Indications and usage

Contraindications

Precautions

Adverse reactions

Dosage and administration

How supplied

Reference

Warnings

WARNING: HEART FAILURE
MULTAQ is contraindicated in patients with NYHA Class IV heart failure, or NYHA Class II – III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic [see Contraindications].

In a placebo-controlled study in patients with severe heart failure requiring recent hospitalization or referral to a specialized heart failure clinic for worsening symptoms (the ANDROMEDA Study), patients given dronedarone had a greater than two-fold increase in mortality. Such patients should not be given dronedarone.

(description)

Initial U.S. Approval: 2009
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.

MULTAQ is provided as tablets for oral administration.
Each tablet of MULTAQ contains 400 mg of dronedarone (expressed as base).

The inactive ingredients are:
Core of the tablets- hypromellose, starch, crospovidone, poloxamer 407, lactose monohydrate, colloidal silicon dioxide, magnesium stearate.
Coating / polishing of the tablets- hypromellose, polyethylene glycol 6000, titanium dioxide, carnauba wax.

Clinical pharmacology

CLINICAL PHARMACOLOGY
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.

Indications and usage

INDICATIONS AND USAGE
MULTAQ® is indicated to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors (i.e., age >70, hypertension, diabetes, prior cerebrovascular accident, left atrial diameter ≥50 mm or left ventricular ejection fraction [LVEF] <40%), who are in sinus rhythm or who will be cardioverted

Contraindications

Class IV heart failure or symptomatic heart failure with a recent decompensation
Second- or third- degree atrioventicular (AV) block or sick sinus syndrome (except when used in conjunction with a functioning pacemaker)
Bradycardia <50 bpm
Concomitant use of a strong CYP3A inhibitor
Concomitant use of drugs or herbal products that prolong the QT interval and may induce Torsade de Pointes
Severe hepatic impairment
QTc Bazett interval ≥500 ms
Pregnancy
Nursing mothers

Precautions

WARNINGS AND PRECAUTIONS

Heart failure: If heart failure develops or worsens, consider the suspension or discontinuation of MULTAQ
Liver injury: if hepatic injury is suspected, discontinue MULTAQ
Hypokalemia and hypomagnesemia: Maintain potassium and magnesium levels within the normal range
QT prolongation: Stop MULTAQ if QTc Bazett ≥500ms
Increase in creatinine: Monitor serum creatinine periodically
Teratogen: Women of childbearing potential should use effective contraception while using MULTAQ

DRUG INTERACTIONS
Dronedarone is metabolized by CYP 3A and is a moderate inhibitor of
CYP 3A and CYP 2D6 and has potentially important pharmacodynamic interactions.

Antiarrhythmics: Avoid concomitant use
Digoxin: Consider discontinuation or halve dose of digoxin before treatment and monitor
Calcium channel blockers (CCB): Initiate CCB with low dose and increase after ECG verification of tolerability
Beta-blockers: May provoke excessive bradycardia, Initiate with low dose and increase after ECG verification of tolerability
CYP 3A inducers: Avoid concomitant use
Grapefruit juice: Avoid concomitant use
Statins: Follow label recommendations for concomitant use of certain statins with a CYP 3A and P-gP inhibitor like dronedarone
CYP 3A substrates with a narrow therapeutic index (e.g., sirolimus and tacrolimus): Monitor and adjust dosage of concomitant drug as needed when used with MULTAQ
Warfarin: Monitor INR after initiating dronedarone in patients taking warfarin.

Adverse reactions

Most common adverse reactions (=2%) are diarrhea, nausea, abdominal pain, vomiting, and asthenia

Dosage and administration

DOSAGE AND ADMINISTRATION
The only 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

How supplied

HOW SUPPLIED/STORAGE AND HANDLING
MULTAQ 400-mg tablets are provided as white film-coated tablets for oral administration, oblong-shaped, engraved with a double wave marking on one side and "4142" code on the other side in:

Bottles of 60 tablets, NDC 0024-4142-60
Bottles of 180 tablets, NDC 0024-4142-18
Bottles of 500 tablets NDC 0024-4142-50
Box of 10 blisters (10 tablets per blister) NDC 0024-4142-10

Store at 25°C (77°F): excursions permitted to 15–30°C (59–86°F), [see USP controlled room temperature].

Reference

Package Insert data:
Issued February 2011
Manufactured by Sanofi Winthrop Industrie
1, rue de la Vierge
33440 Ambares, France

MULTAQ is a trademark of sanofi-aventis.

The brands listed are the registered trademarks of their respective owners and are not trademarks of sanofi-aventis U.S. LLC.

sanofi-aventis U.S. LLC
Bridgewater, NJ 08807

Reference(s)

National Institutes of Health, U.S. National Library of Medicine, DailyMed Database.
Provides access to the latest drug monographs submitted to the Food and Drug Administration (FDA). Please review the latest applicable package insert for additional information and possible updates. A local search option of this data can be found here.