Can dronedarone (Multaq) be restarted after discontinuation if the reason for stopping has been resolved and there are no contraindications?

Can Multaq Be Restarted After Discontinuation?

Yes, dronedarone (Multaq) can be restarted after discontinuation if the patient remains in or is cardioverted back to sinus rhythm, the reason for stopping has been resolved, and there are no new contraindications—but it must never be restarted in patients who have developed permanent atrial fibrillation. 1

Critical Decision Point: Rhythm Status

The ability to restart dronedarone hinges entirely on whether the patient is in sinus rhythm versus permanent AF:

Patients in Sinus Rhythm (Paroxysmal or Persistent AF)

• Dronedarone can be restarted if the patient is in sinus rhythm, either spontaneously or after cardioversion 1
• European regulatory approval specifically permits dronedarone use for maintenance of sinus rhythm after cardioversion, whether spontaneous or induced 1
• The patient may or may not be taking dronedarone at the time of cardioversion 1
• If AF recurs but remains paroxysmal or persistent, you must decide: either cardiovert the patient back to sinus rhythm (in which case dronedarone may be continued), or accept permanent AF (in which case dronedarone must be stopped) 1

Patients with Permanent AF

• Dronedarone must NOT be restarted in patients with permanent atrial fibrillation 1, 2, 3
• The PALLAS trial was stopped early due to doubled cardiovascular death (HR 2.11), increased stroke (HR 2.32), and increased heart failure hospitalizations (HR 1.81) in permanent AF patients treated with dronedarone 1, 3
• This contraindication is absolute, particularly in patients with significant cardiovascular disease burden 1

Absolute Contraindications Before Restarting

Before restarting dronedarone, verify the patient does NOT have any of these conditions:

• Permanent atrial fibrillation (defined as >6 months duration without cardioversion attempt) 1, 2, 3
• NYHA Class IV heart failure or Class II-III with recent decompensation 1, 2
• History of heart failure or left ventricular dysfunction (based on ANDROMEDA trial showing increased mortality) 1, 2
• Unstable hemodynamic conditions 1
• QTc interval ≥500 ms 2
• Hepatic injury from prior dronedarone use (do not restart without alternative explanation for liver injury) 2
• Concomitant use of QT-prolonging drugs or powerful CYP3A4 inhibitors 4, 2

Monitoring Requirements Upon Restart

When restarting dronedarone, implement this monitoring protocol:

Cardiac Rhythm Monitoring

• Monitor cardiac rhythm no less than every 3 months 2
• Cardiovert patients who develop AF (if clinically indicated) or discontinue dronedarone 2
• Obtain baseline ECG before restarting 4
• If QTc exceeds 500 ms, discontinue immediately 4, 2

Hepatic Monitoring

• Consider obtaining periodic hepatic enzymes (AST, ALT, alkaline phosphatase, bilirubin), especially during first 6 months 2
• Advise patients to report symptoms of hepatic injury immediately (anorexia, nausea, vomiting, fever, malaise, fatigue, right upper quadrant pain, jaundice, dark urine, itching) 2
• If hepatic injury suspected, promptly discontinue and test liver enzymes 2

Renal and Electrolyte Monitoring

• Expect small increases in creatinine (about 0.1 mg/dL) within 7 days due to inhibition of tubular secretion—this is reversible 2
• Monitor renal function periodically for larger increases 2
• Ensure potassium and magnesium levels are normal before restarting and maintain normal range during therapy 2

Heart Failure Surveillance

• Advise patients to report signs of heart failure (weight gain, dependent edema, increasing shortness of breath) 2
• If heart failure develops or worsens requiring hospitalization, discontinue dronedarone 2

Special Consideration: Rapid Switch from Amiodarone

If the patient was previously on amiodarone and you're considering restarting dronedarone:

• A rapid switch (within 2 days of amiodarone discontinuation) may be feasible in certain patients 5
• However, this approach was associated with higher incidence of serious heart failure events and heart failure hospitalizations compared to patients without recent amiodarone use 5
• There was also a higher incidence of bradyarrhythmic events with rapid switching 5
• Exercise extreme caution with rapid switching, particularly in patients with any heart failure history or left ventricular dysfunction 5

Supervision Requirements

• Dronedarone management must be supervised by a specialist (hospital or office-based staff familiar with antiarrhythmic drugs) 1
• It should not be initiated in general or family practice 1
• Subsequent monitoring should include input from an appropriate specialist 1

Common Pitfalls to Avoid

• Do not restart in permanent AF patients, even if they were previously tolerating the drug well—the PALLAS trial definitively showed harm in this population 1, 3
• Do not ignore small creatinine increases (0.1 mg/dL is expected), but investigate larger increases as they may indicate true renal dysfunction 2
• Do not restart without ensuring appropriate anticoagulation is in place, as dronedarone should only be initiated in patients receiving appropriate antithrombotic therapy 2
• Do not overlook the need for specialist supervision—this is not a drug for primary care management 1