MULTAQ significantly reduced the risk of CV hospitalization or all-cause mortality3
Relative risk reduction in the primary composite endpoint was entirely attributable to reduction in CV hospitalization.3
Rates of the primary composite endpoint of CV hospitalization or all-cause mortality were 31.6% with MULTAQ vs 39.2% with placebo.3
*Mean follow-up was 21±5 months.3
MULTAQ reduces the risk of AFib hospitalization with a 39% RRR3,*
CV hospitalization rates were 29.1% with MULTAQ vs 36.8% with placebo (HR 0.74; 95% CI: 0.67-0.82; P<0.001).3
*Hospitalization due to AFib and other supraventricular rhythm disorders was a component of the secondary endpoint
of CV hospitalization.3
Post hoc analysis: Risk of CV hospitalization or all-cause mortality in patients with AFib and CAD with MULTAQ4,*
Post hoc analysis primary composite endpoint: Time to first CV
hospitalization or all-cause mortality (n=1405)
ATHENA post-hoc analysis
Results in the primary composite endpoint were consistent in patients with or without CAD.
This post hoc analysis assessed safety and cardiovascular outcomes of MULTAQ in a total of 1405 patients with CAD from the ATHENA study.4
In the ATHENA study (N=4628), MULTAQ significantly reduced the primary composite endpoint with a 24% RRR, 7.6% RRR, and NNT=13 (HR=0.76; 95% CI: 0.68-0.83; P<0.0001).
- Post hoc analysis where potential bias could be introduced, given that patients were randomized based on CAD status. The analysis was retrospective, exploratory, and based on a much smaller population than the full randomized population in the ATHENA trial
- In patients who had a history of CAD, patients receiving MULTAQ had similar rates of any TEAEs and serious TEAEs as patients receiving placebo, but had significantly higher rates of bradycardia, QT interval prolongation, gastrointestinal events, and increases in serum creatinine
*ATHENA defined coronary artery disease as a documented history of either ischemic dilated cardiomyopathy, evidenced by clinically significant left ventricular dilatation secondary to coronary artery disease, or coronary artery disease, which was defined as acute myocardial infarction and/or the following: significant (≥70%) coronary artery stenosis, history of revascularization procedure (percutaneous transluminal coronary angioplasty, stent implantation in a coronary artery, coronary artery bypass grafting, etc), positive exercise test, and positive nuclear scan of cardiac perfusion.4
ADONIS=American–Australian–African Trial With Dronedarone in Patients With Atrial Fibrillation or Atrial Flutter Patients for the Maintenance of Sinus Rhythm
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
CAD=coronary artery disease
EURIDIS=European Trial in Atrial Fibrillation or Flutter Patients Receiving Dronedarone for the Maintenance of Sinus Rhythm
HFpEF=heart failure with preserved ejection fraction
RRR=relative risk reduction
TEAE=treatment-emergent adverse event
- 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.
- MULTAQ [package insert]. Bridgewater, NJ. sanofi-aventis U.S. LLC; 2017. USPI - NOV-2020 (v2.0).
- 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.
- Pisters R, Hohnloser S, Connolly SJ, et al. Effect of dronedarone on clinical end points in patients with atrial fibrillation and coronary heart disease: insights from the ATHENA trial. Europace. 2014;16:174-181.
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
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 interval >500 ms or PR interval >280 ms
- Concomitant use of strong CYP3A inhibitors, such as ketoconazole, itraconazole, voriconazole, cyclosporine, telithromycin, clarithromycin, nefazodone, ritonavir, erythromycin, 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
- Liver or lung toxicity related to the previous use of amiodarone
- Severe hepatic impairment
- 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 dronedarone 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 2 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.
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.
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 is associated with concentration-dependent QTcF interval prolongation (estimated QTcF increase for 400 mg BID with food is 15 ms). If the QTc 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.
Based on animal data, MULTAQ may cause fetal harm when administered to a pregnant woman. Dronedarone caused multiple visceral and skeletal malformations in animal reproduction studies when pregnant rats and rabbits were administered dronedarone at doses equivalent to recommended human doses. Advise pregnant women of the potential risk to the fetus. Verify that females of reproductive potential are not pregnant prior to initiating MULTAQ. Advise females of reproductive potential to use effective contraception during treatment with MULTAQ and for 5 days (about 6 half-lives) after the final dose.
- Treatment with Class I or III antiarrhythmics or drugs that are strong inhibitors of CYP3A 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 dronedarone-treated patients compared to placebo. In patients not taking digoxin, no difference in risk of sudden death was observed in the dronedarone vs. placebo groups.
- Digoxin can potentiate the electrophysiologic effects of dronedarone (such as decreased AV-node conduction). dronedarone 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 dronedarone. 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 CYP3A and P-gp inhibitors such as dronedarone
In studies, the most common adverse reactions (≥2%) observed with MULTAQ were diarrhea, nausea, abdominal pain, vomiting, dyspepsia, bradycardia, skin issues (rashes, pruritus, eczema, dermatitis, dermatitis allergic), and asthenia.
Use in Specific Populations
Lactation: Do not breastfeed
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