Dronedarone

Dronedarone
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]

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Black Box Warning

WARNING See full prescribing information for complete Boxed Warning. To minimize the risk of induced arrhythmia, patients initiated or re-initiated on TIKOSYN should be placed for a minimum of 3 days in a facility that can provide calculations of creatinine clearance, continuous electrocardiographic monitoring, and cardiac resuscitation. For detailed instructions regarding dose selection, see DOSAGE AND ADMINISTRATION. TIKOSYN is available only to hospitals and prescribers who have received appropriate TIKOSYN dosing and treatment initiation education; see DOSAGE AND ADMINISTRATION.

Overview

Dronedarone is an Antiarrhythmic that is FDA approved for the {{{indicationType}}} of atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistent atrial fibrillation (AF). There is a Black Box Warning for this drug as shown here. Common adverse reactions include Abdominal pain, Diarrhea, Indigestion, Nausea, Vomiting, Asthenia , Serum creatinine raised.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Atrial Fibrillation

• Dosing Information

• 400 mg PO bid ( taken as one tablet with the morning meal and one tablet with the evening meal)

Off-Label Use and Dosage (Adult)

Non–Guideline-Supported Use

Atrial flutter, Paroxysmal or persistent

• Dosing information

• 400 mg/day PO

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Dronedarone FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

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 and Warnings and Precautions (5.2)]
• Symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV symptoms [see Boxed Warning and 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 <50 bpm
• Concomitant use of strong CYP 3A inhibitors, such as ketoconazole, itraconazole, voriconazole, cyclosporine, telithromycin, clarithromycin, nefazodone, and ritonavir [see Drug Interactions (7.2)]
• Concomitant use of drugs or herbal products that prolong the QT interval and might increase the risk of Torsade de Pointes, such as phenothiazine anti-psychotics, tricyclic antidepressants, certain oral macrolide antibiotics, and Class I and III antiarrhythmics
• Liver or lung toxicity related to the previous use of amiodarone
• QTc Bazett interval ≥500 ms or PR interval >280 ms
• Severe hepatic impairment
• Pregnancy (Category X): MULTAQ may cause fetal harm when administered to a pregnant woman. MULTAQ is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations (8.1)].
• Nursing mothers [see Use in Specific Populations (8.3)]
• Hypersensitivity to the active substance or to any of the excipients

Warnings

WARNING See full prescribing information for complete Boxed Warning. To minimize the risk of induced arrhythmia, patients initiated or re-initiated on TIKOSYN should be placed for a minimum of 3 days in a facility that can provide calculations of creatinine clearance, continuous electrocardiographic monitoring, and cardiac resuscitation. For detailed instructions regarding dose selection, see DOSAGE AND ADMINISTRATION. TIKOSYN is available only to hospitals and prescribers who have received appropriate TIKOSYN dosing and treatment initiation education; see DOSAGE AND ADMINISTRATION.

• Cardiovascular Death in NYHA Class IV or Decompensated heart failure

• MULTAQ is contraindicated in patients with NYHA Class IV heart failure or symptomatic heart failure with recent decompensation requiring hospitalization because it doubles the risk of death.

• Cardiovascular Death and heart failure in Permanent AF

• MULTAQ doubles the risk of cardiovascular death (largely arrhythmic) and heart failure events in patients with permanent AF. Patients treated with dronedarone should undergo monitoring of cardiac rhythm no less often than every 3 months. Cardiovert patients who are in atrial fibrillation (if clinically indicated) or discontinue MULTAQ. MULTAQ offers no benefit in subjects in permanent AF.

• Increased Risk of Stroke in Permanent AF

• In a placebo-controlled study in patients with permanent atrial fibrillation, dronedarone was associated with an increased risk of stroke, particularly in the first two weeks of therapy [see Clinical Studies (14.4)]. MULTAQ should only be initiated in patients in sinus rhythm who are receiving appropriate antithrombotic therapy [see Drug interactions (7.3)].

• New Onset or Worsening heart failure

• New onset or worsening of heart failure has been reported during treatment with MULTAQ in the postmarketing setting. In a placebo controlled study in patients with permanent AF increased rates of heart failure were observed in patients with normal left ventricular function and no history of symptomatic heart failure, as well as those with a history of heart failure or left ventricular dysfunction.

Advise patients to consult a physician if they develop signs or symptoms of heart failure, such as weight gain, dependent edema, or increasing shortness of breath. If heart failure develops or worsens and requires hospitalization, discontinue MULTAQ.

• Liver Injury

• Hepatocellular liver injury, including acute liver failure requiring transplant, has been reported in patients treated with MULTAQ in the postmarketing setting. Advise patients treated with MULTAQ to report immediately symptoms suggesting hepatic injury (such as anorexia, nausea, vomiting, fever, malaise, fatigue, right upper quadrant pain, jaundice, dark urine, or itching). Consider obtaining periodic hepatic serum enzymes, especially during the first 6 months of treatment, but it is not known whether routine periodic monitoring of serum enzymes will prevent the development of severe liver injury. If hepatic injury is suspected, promptly discontinue MULTAQ and test serum enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase, as well as serum bilirubin, to establish whether there is liver injury. If liver injury is found, institute appropriate treatment and investigate the probable cause. Do not restart MULTAQ in patients without another explanation for the observed liver injury.

• Pulmonary Toxicity

• Cases of interstitial lung disease including pneumonitis and pulmonary fibrosis have been reported in patients treated with MULTAQ in the post-marketing setting [see Adverse Reactions (6.2)]. Onset of dyspnea or non-productive cough may be related to pulmonary toxicity and patients should be carefully evaluated clinically. If pulmonary toxicity is confirmed, MULTAQ should be discontinued.

• Hypokalemia and Hypomagnesemia with Potassium-Depleting Diuretics

• Hypokalemia or hypomagnesemia may occur with concomitant administration of potassium-depleting diuretics. Potassium levels should be within the normal range prior to administration of MULTAQ and maintained in the normal range during administration of MULTAQ.

• QT Interval Prolongation

• Dronedarone induces a moderate (average of about 10 ms but much greater effects have been observed) QTc (Bazett) prolongation [see Clinical Pharmacology (12.2) and Clinical Studies (14.1)]. If the QTc Bazett interval is ≥500 ms, discontinue MULTAQ [see Contraindications (4)].

• Renal Impairment and Failure

• Marked increase in serum creatinine, pre-renal azotemia and acute renal failure, often in the setting of heart failure [see Warnings and Precautions (5.4)] or hypovolemia, have been reported in patients taking MULTAQ. In most cases, these effects appear to be reversible upon drug discontinuation and with appropriate medical treatment. Monitor renal function periodically.

Small increases in creatinine levels (about 0.1 mg/dL) following dronedarone treatment initiation have been shown to be a result of inhibition of creatinine's tubular secretion. The elevation has a rapid onset, reaches a plateau after 7 days and is reversible after discontinuation.

• Women of Childbearing Potential

• Premenopausal women who have not undergone a hysterectomy or oophorectomy must use effective contraception while using MULTAQ. Dronedarone caused fetal harm in animal studies at doses equivalent to recommended human doses. Counsel women of childbearing potential regarding appropriate contraceptive choices [see Use in Specific Populations (8.1)].

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Dronedarone Clinical Trials Experience in the drug label.

Postmarketing Experience

There is limited information regarding Dronedarone Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Dronedarone Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Dronedarone in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Dronedarone in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Dronedarone during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Dronedarone in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Dronedarone in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Dronedarone in geriatric settings.

Gender

There is no FDA guidance on the use of Dronedarone with respect to specific gender populations.

Race

There is no FDA guidance on the use of Dronedarone with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Dronedarone in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Dronedarone in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Dronedarone in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Dronedarone in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Dronedarone Administration in the drug label.

Monitoring

There is limited information regarding Dronedarone Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Dronedarone and IV administrations.

Overdosage

There is limited information regarding Dronedarone overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

Mechanism of Action

There is limited information regarding Dronedarone Mechanism of Action in the drug label.

Structure

There is limited information regarding Dronedarone Structure in the drug label.

Pharmacodynamics

There is limited information regarding Dronedarone Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Dronedarone Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Dronedarone Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Dronedarone Clinical Studies in the drug label.

How Supplied

There is limited information regarding Dronedarone How Supplied in the drug label.

Storage

There is limited information regarding Dronedarone Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Dronedarone Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Dronedarone interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Dronedarone Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Dronedarone Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

Dronedarone

File:Dronedarone.svg
Legal status
Legal status	Phase III
Identifiers
IUPAC name N-(2-Butyl-3-(p-(3-(dibutylamino)propoxy)benzoyl)- 5-benzofuranyl)methanesulfonamide
CAS Number	141626-36-0
PubChem CID	208898
E number	{{#property:P628}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C31H44N2O5S
Molar mass	556.758

Dronedarone (also known as SR33589) is a drug under development by Sanofi-Aventis, mainly for the indication of cardiac arrhythmias (irregular heartbeat). It is currently in phase III trials for atrial fibrillation and in patients with an implantable cardioverter-defibrillator (ICD); a trial in heart failure was stopped as an interim analysis showed a possible increase in heart failure deaths.

Chemically it is a benzofuran derivative related to amiodarone, a popular antiarrhythmic the use of which is limited to toxicity due its high iodine content (pulmonary fibrosis, thyroid disease) as well as by liver disease. Dronedarone lacks the iodine, and is expected to have less toxicity, yet it displays amiodarone-like class III antiarrhytmic activity in vitro and in clinical trials.

In a 2007 trial in atrial fibrillation, dronedarone was significantly more effective than placebo in maintaining sinus rhythm, with no difference in lung and thyroid function in the short term.