In patients with paroxysmal or persistent AFib

MUltaq® demonstrated efficacy across multiple measures1-3

AFib recurrence study (EURIDIS/ADONIS) data1:

25% RRR in 1st AFib recurrence (P<0.001) with patients remaining in sinus rhythm 2.2x LONGER:

The absolute difference in rate of first recurrence at Year 1 for MULTAQ vs placebo was 11%.

The median time in sinus rhythm for MULTAQ patients was 116 days vs 53 days for placebo.

AFib recurrence study (EURIDIS/ADONIS) data1:

No recurrence of symptomatic AFib in 62.3% of MULTAQ patients at Year 1 vs 54% in placebo (P<0.001).

Symptomatic AFib recurrence included 1 or more of the following symptom(s): palpitations, dizziness, fatigue, chest pain, and/or dyspnea.1

Hospitalization study (ATHENA) data2,*:

24% RRR of CV hospitalization or all-cause mortality (combined endpoint), entirely attributable to reduction in CV hospitalization vs placebo.

MULTAQ reduced the relative risk of CV hospitalization or all-cause mortality by 24% (HR=0.76; 95% CI: 0.68-0.83; P<0.0001). Hospitalization/mortality rates were 31.6% with MULTAQ vs 39.2% with placebo.

Hospitalization study (ATHENA) data2,*:

39% RRR of AFib hospitalization vs placebo

MULTAQ reduced the risk of AFib hospitalization by 39% (HR=0.61; 95% CI: 0.53-0.71; P<0.0001). AFib hospitalization rates were 12.7% with MULTAQ vs 19.6% with placebo.

AFib hospitalization was a component of the CV hospitalization secondary endpoint (26% RRR; HR=0.74; 95% CI: 0.67-0.82; P<0.0001). CV hospitalization rates were 29.1% with MULTAQ vs 36.8% with placebo.

*Median follow-up was 22 months; maximum follow-up was 30 months.3

Most Common Adverse Reactions:

The most frequent adverse reactions observed with MULTAQ 400 mg twice daily in clinical studies were diarrhea, nausea, abdominal pain, vomiting, and asthenia.

View a full list of AEs from the EURIDIS/ADONIS trials

View a full list of AEs from the ATHENA trial

Discontinuation rates were generally similar between MULTAQ and placebo (11.8% and 7.7%, respectively). The most common reasons were GI disorders (3.2%) and QT prolongation (1.5%).

EURIDIS/ADONIS study design:

Multicenter study evaluating efficacy and safety of MULTAQ in maintaining sinus rhythm in 1237 patients with nonpermanent AFib/AFL. Patients in sinus rhythm with at least one episode of AFib/AFL observed on an ECG 3 months prior to study enrollment and in sinus rhythm for at least 1 hour prior to randomization were assigned to 400 mg MULTAQ (n=828) twice daily or placebo (n=409) for 12 months. The primary endpoint was first documented recurrence of AFib/AFL, defined as an episode lasting for ≥10 minutes and confirmed by 2 consecutive ECGs taken 10 minutes apart on ECG or transtelephonic monitoring (TTEM), within the 12-month period.1

ATHENA study design:

A double-blind, placebo-controlled study to evaluate the efficacy and safety of MULTAQ in 4628 patients ≥70 years of age with paroxysmal or persistent AFib/AFL and an additional CV risk factor. Patients who experienced AFib/AFL within 6 months, and were in sinus rhythm, were randomized 1:1 to receive MULTAQ 400 mg twice daily or placebo. The primary efficacy endpoint was first hospitalization due to CV event or death from any cause.3

Expand All | Collapse All

EURIDIS/ADONIS: Median time in sinus rhythm was prolonged by 2.2 times vs placebo1

img img

Primary endpoint: MULTAQ significantly reduced the risk of AFib recurrence by 25% at Year 1 (HR=0.75; 95% CI: 0.65-0.87; P<0.001).1

The median time to first recurrence in patients taking placebo was 53 days. Among patients on the MULTAQ arm, the median time to first recurrence was 116 days, more than doubling the time they remained in sinus rhythm.1

The absolute difference in rate of 1st recurrence at Year 1 for MULTAQ vs placebo was 11%. The majority of first recurrences were symptomatic.1

EURIDIS/ADONIS: After 1 year, 62.3% of patients free from symptomatic recurrence (vs 54% for placebo)1

img img

This analysis was a preplanned assessment of the primary endpoint data that excluded patients who discontinued treatment or experienced recurrence of atrial fibrillation before reaching 5 days of study drug exposure.1

Symptomatic AFib recurrence included 1 or more of the following symptom(s): palpitations, dizziness, fatigue, chest pain, and/or dyspnea.1

ATHENA: Relative risk of combined primary endpoint of CV hospitalization or all-cause mortality reduced by 24% (entirely attributable to reduction in CV hospitalization)2

img img

Hospitalization/mortality rates were 31.6% with MULTAQ vs 39.2% with placebo.2

ATHENA: Relative reduction for AFib hospitalization risk was 39% (12.7% AFib hospitalization rate with MULTAQ vs 19.6% with placebo)2

img img

AFib hospitalization was a component of the CV hospitalization secondary endpoint (26% RRR; HR=0.74; 95% CI: 0.67-0.82; P<0.0001). CV hospitalization rates were 29.1% with MULTAQ vs 36.8% with placebo.2

Components of CV hospitalization included AFib and other supraventricular disorders.2

img img

Specific initiation and monitoring features

Looking for MULTAQ samples?

Symptomatic recurrence in recently cardioverted patients

ADONIS=American–Australian–African Trial With Dronedarone in Patients With Atrial Fibrillation or Atrial Flutter Patients for the Maintenance of Sinus Rhythm

AE=adverse event

AFib=atrial fibrillation

AFL=atrial flutter

ATHENA=A Placebo-Controlled, Double-Blind, Parallel Arm Trial to Assess the Efficacy of Dronedarone 400 mg bid for the Prevention of Cardiovascular Hospitalization or Death from any Cause in Patients with Atrial Fibrillation/Atrial Flutter

CI=confidence interval

CV=cardiovascular

ECG=electrocardiogram

EURIDIS=European Trial in Atrial Fibrillation or Flutter Patients Receiving Dronedarone for the Maintenance of Sinus Rhythm

HR=hazard ratio

RRR=relative risk reduction

INDICATION

MULTAQ is an antiarrhythmic drug indicated to reduce the risk of hospitalization for atrial fibrillation (AFib) in patients in sinus rhythm with a history of paroxysmal or persistent AFib.

IMPORTANT SAFETY INFORMATION

WARNING: INCREASED RISK OF DEATH, STROKE AND HEART FAILURE IN PATIENTS WITH DECOMPENSATED HEART FAILURE OR PERMANENT ATRIAL FIBRILLATION

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

MULTAQ is contraindicated in patients in atrial fibrillation (AFib) who will not or cannot be cardioverted into normal sinus rhythm. In patients with permanent AFib, MULTAQ doubles the risk of death, stroke, and hospitalization for heart failure.

MULTAQ is also contraindicated in patients:

  • With second- or third-degree atrioventricular (AV) block or sick sinus syndrome (except when used in conjunction with a functioning pacemaker), bradycardia <50 bpm, QTc Bazett interval ≥500 ms or PR interval >280 ms
  • Who are or may become pregnant (Category X) or nursing. MULTAQ may cause fetal harm when administered to a pregnant woman
  • With concomitant use of strong CYP 3A inhibitors, such as ketoconazole, itraconazole, voriconazole, cyclosporine, telithromycin, clarithromycin, nefazodone, ritonavir, or drugs or herbal products that prolong the QT interval and might increase the risk of Torsade de Pointes, such as phenothiazine antipsychotics, tricyclic antidepressants, certain oral macrolide antibiotics, and Class I and III antiarrhythmics
  • With liver or lung toxicity related to the previous use of amiodarone
  • With severe hepatic impairment
  • With hypersensitivity to the active substance or to any of the excipients

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 AFib

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

Increased Risk of Stroke in Permanent AFib

In a placebo-controlled study in patients with permanent AFib, dronedarone was associated with an increased risk of stroke, particularly in the first two weeks of therapy. MULTAQ should only be initiated in patients in sinus rhythm who are receiving appropriate antithrombotic therapy.

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 AFib, 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. 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. 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 and 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

MULTAQ induces a moderate (average of about 10 ms but much greater effects have been observed) QTc (Bazett) prolongation. If the QTc Bazett interval is ≥500 ms, discontinue MULTAQ.

Renal Impairment and Failure

Marked increase in serum creatinine, pre-renal azotemia and acute renal failure, often in the setting of heart failure 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 MULTAQ 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.

Drug-Drug Interactions

  • Treatment with Class I or III antiarrhythmics or drugs that are strong inhibitors of CYP 3A must be stopped before starting MULTAQ (see Contraindications)
  • Patients should be instructed to avoid grapefruit juice beverages while taking MULTAQ
  • Calcium channel blockers with depressant effects and beta-blockers could increase the bradycardia effects of MULTAQ on conduction
  • In the ANDROMEDA (patients with recently decompensated heart failure and PALLAS (patients with permanent AFib) trials, baseline use of digoxin was associated with an increased risk of arrhythmic or sudden death in MULTAQ-treated patients compared to placebo. In patients not taking digoxin, no difference in risk of sudden death was observed in the MULTAQ vs placebo groups

     

    Digoxin can potentiate the electrophysiologic effects of MULTAQ (such as decreased AV-node conduction). MULTAQ increases exposure to digoxin.

     

    Consider discontinuing digoxin. If digoxin treatment is continued, halve the dose of digoxin, monitor serum levels closely, and observe for toxicity.

     

  • Postmarketing cases of increased INR with or without bleeding events have been reported in warfarin-treated patients initiated with MULTAQ. Monitor INR after initiating MULTAQ in patients taking warfarin
  • Statins: Avoid simvastatin doses greater than 10 mg daily. Follow statin label recommendations for use with CYP 3A and P-gP inhibitors such as MULTAQ

Adverse Reactions

In studies, the most common adverse reactions observed with MULTAQ were diarrhea, nausea, abdominal pain, vomiting, and asthenia.

References:

  1. 1. MULTAQ [package insert]. Bridgewater, NJ. sanofi-aventis U.S. LLC; 2017.
  2. 2. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. J Am Coll Cardiol. 2014;64(21):e1-e76.
  3. 3. Singh BN, Connolly SJ, Crijns HJ, et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med. 2007;357(10):987-999.
  4. 4. Hohnloser SH, Crijns HJ, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009;360(7):668-678.

References:

  1. 1. Singh BN, Connolly SJ, Crijns HJ, et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med. 2007;357(10):987-999.
  2. 2. Thind M, Crijns HJ, Naccarelli GV, et al. Dronedarone treatment following cardioversion in patients with atrial fibrillation/flutter: a post hoc analysis of the EURIDIS and ADONIS trials. J Cardiovasc Electrophysiol. Published online: February 21, 2020 (doi: 10.1111/jce.14405).

References:

  1. 1. Singh BN, Connolly SJ, Crijns HJ, et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med. 2007;357(10):987-999.
  2. 2. Hohnloser SH, Crijns HJ, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009;360(7):668-678.
  3. 3. MULTAQ [package insert]. Bridgewater, NJ. sanofi-aventis U.S. LLC; 2017.
  4. 4. Vamos M, Calking H, Kowey PR, et al. P1034 Impact of ablation status on the efficacy and safety of dronedarone in patients with atrial fibrillation/flutter: a post hoc analysis of the ATHENA trial. Poster presentation at: European Society of Cardiology Congress 2019; August 31–September 4, 2019; Paris, France.
  5. 5. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. J Am Coll Cardiol. 2014;64(21):e1-e76.

References:

  1. 1. MULTAQ [package insert]. Bridgewater, NJ. sanofi-aventis U.S. LLC; 2017.
  2. 2. Hohnloser SH, Crijns HJ, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009;360(7):668-678.
  3. 3. Pisters R, Hohnloser SH, Connolly SJ, et al; for the ATHENA investigators. Effect of dronedarone on clinical end points in patients with atrial fibrillation and coronary heart disease: insights from the ATHENA trial. Europace. 2014;16(2):174-181.

References:

  1. 1. Singh BN, Connolly SJ, Crijns HJ, et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med. 2007;357(10):987-999.
  2. 2. MULTAQ [package insert]. Bridgewater, NJ. sanofi-aventis U.S. LLC; 2017.
  3. 3. Hohnloser SH, Crijns HJ, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009;360(7):668-678.

References:

  1. 1. MULTAQ [package insert]. Bridgewater, NJ. sanofi-aventis U.S. LLC; 2017.
  2. 2. Singh BN, Connolly SJ, Crijns HJ, et al. Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. N Engl J Med. 2007;357(10):987-999.
  3. 3. Hohnloser SH, Crijns HJ, van Eickels M, et al. Effect of dronedarone on cardiovascular events in atrial fibrillation. N Engl J Med. 2009;360(7):668-678.

References:

  1. 1. MULTAQ [package insert]. Bridgewater, NJ. sanofi-aventis U.S. LLC; 2017.
  2. 2. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. J Am Coll Cardiol. 2014;64(21):e1-e76.

References:

  1. 1. MULTAQ [package insert]. Bridgewater, NJ. sanofi-aventis U.S. LLC; 2017.

*

Back to the top ▲

© 2020 sanofi-aventis U.S. LLC, A SANOFI COMPANY. All rights reserved.

Legal Disclaimer | Privacy Policy | Contact SANOFI

This site is intended for use by U.S. Healthcare Professionals only.

MAT-US-2002101 Last Updated: June 2020

IMPORTANT SAFETY INFORMATION

WARNING: INCREASED RISK OF DEATH, STROKE AND HEART FAILURE IN PATIENTS WITH DECOMPENSATED HEART FAILURE OR PERMANENT ATRIAL FIBRILLATION