Action

Unknown.

Availability

Tablets: 400 mg

Indications and dosages

➣ To reduce risk of hospitalization for atrial fibrillation (AF) in patients in sinus rhythm with a history of paroxysmal or persistent AF

Adults: 400 mg P.O. b.i.d. with morning and evening meals

Contraindications

• Permanent AF (patients in whom normal sinus rhythm won't or can't be restored), symptomatic heart failure with recent decompensation requiring hospitalization or New York Heart Association Class IV symptoms, second- or third-degree atrioventricular (AV) block or sick sinus syndrome (except when used with a functioning pacemaker), bradycardia less than 50 beats/minute, QTc Bazett interval at or above 500 ms or PR interval above 280 ms

• Concomitant use of drugs or herbal products that prolong QT interval and may induce torsades de pointes (such as phenothiazine antipsychotics, tricyclic antidepressants, certain oral macrolide antibiotics, Class I and III antiarrhythmics)

• Concomitant use of a strong CYP3A inhibitor (such as clarithromycin, cyclosporine, itraconazole, ketoconazole, nefazodone, ritonavir, telithromycin, voriconazole)

• Hepatotoxicity related to the previous use of amiodarone and severe hepatic impairment

• Patients who are or may become pregnant

• Breastfeeding patients

Precautions

Use cautiously in:

• new or worsening heart failure during treatment, QT-interval prolongation

• hypokalemia, hypomagnesemia

• increased serum creatinine level

• children younger than age 18 (safety and efficacy not established).

Administration

See Be aware that treatment with Class I or III antiarrhythmics or strong CYP3A inhibitors must be stopped before start of dronedarone.

• Note that hypokalemia or hypomagnesemia may occur with concomitant administration of potassium-depleting diuretics. Ensure that potassium levels are within normal range before starting drug.

• Administer with morning and evening meals but not with grapefruit juice.

Adverse reactions

CNS: asthenia

CV: bradycardia, QT-interval prolongation, new or worsening heart failure

GI: diarrhea, nausea, vomiting, abdominal pain, dyspepsia

Hepatic: hepatocellular injury, acute liver injury

Metabolic: hypokalemia, hypomagnesemia, increased creatinine

Skin: rash (generalized, macular, maculopapular, erythematous), pruritus, eczema, dermatitis, allergic dermatitis

Interactions

Drug-drug. Beta blockers, such as metoprolol, propranolol: increased effects to these drugs, increased risk of bradycardia

Calcium channel blockers, with depressant effects on sinus and AV nodes, such as diltiazem, nifedipine, verapamil: increased dronedarone and calcium channel blocker effects; potentiated dronedarone effects on conduction

CYP3A inducers, such as carbamazepine, phenobarbital, phenytoin, rifampin: significantly decreased dronedarone effect

Digoxin: potentiated dronedarone electrophysiologic effects (such as decreased AV node conduction); increased digoxin level; increased GI disorders

Drugs that prolong QT interval: risk of torsades de pointes-type ventricular tachycardia

Other CYP2D6 substrates, such as other beta blockers, selective serotonin reuptake inhibitors, tricyclic antidepressants: increased effects of these drugs

Potent CYP3A inhibitors, such as clarithromycin, cyclosporine, itraconazole, ketoconazole, nefazodone, ritonavir, telithromycin, voriconazole: increased dronedarone effect and C_max

HMG-CoA reductase inhibitors, such as simvastatin: increased simvastatin effect

Sirolimus, tacrolimus, other CYP3A substrates with narrow therapeutic range: increased plasma concentrations of these drugs

Drug-diagnostic tests. Serum creatinine: increased level

Magnesium, potassium: decreased levels

Drug-food. Any food: increased drug bioavailability

Grapefruit juice: increased dronedarone effect and C_max

Drug-herbs. St. John's wort: significantly decreased dronedarone effect

Patient monitoring

See Observe patient closely for worsening heart failure: If heart failure develops or worsens, consider suspending or discontinuing drug.

See Discontinue drug if QT-interval prolongation occurs (QTc Bazett interval at or above 500 ms).

• Monitor patient for hypokalemia and hypomagnesemia, especially with concomitant administration of potassium-depleting diuretics. Maintain potassium and magnesium levels within normal range.

• Monitor renal function and watch for increase in serum creatinine level.

Patient teaching

• Instruct patient to take drug with morning and evening meals and to avoid grapefruit juice.

See Advise patient to immediately notify prescriber if signs and symptoms of worsening heart failure develop, such as acute weight gain, edema in legs or feet, or increasing shortness of breath.

• Instruct patient to consult prescriber before taking other prescription or nonprescription drugs or herbal products, particularly St. John's wort.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, and herbs mentioned above.