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Related to dronedarone: flecainide, Propafenone
Pharmacologic class: Benzofuran derivative
Therapeutic class: Antiarrhythmic
Pregnancy risk category X
FDA Box Warning
• In patients with symptomatic heart failure and recent decompensation requiring hospitalization or with New York Heart Association Class IV heart failure, dronedarone doubles risk of death and is contraindicated in these patients.
• In patients with permanent AF, dronedarone doubles risk of death, stroke, and hospitalization for heart failure. Dronedarone is contraindicated in patients with AF who won't or can't be cardioverted into normal sinus rhythm.
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
• 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
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).
☞ 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.
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
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 Cmax
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 Cmax
Drug-herbs.St. John's wort: significantly decreased dronedarone effect
☞ Observe patient closely for worsening heart failure: If heart failure develops or worsens, consider suspending or discontinuing drug.
☞ 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.
• Instruct patient to take drug with morning and evening meals and to avoid grapefruit juice.
☞ 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.
Time/action profile (antiarrhythmic effect)
|PO||unknown†||3–6 hr‡||12 hr|
Adverse Reactions/Side Effects
Central nervous system
- weakness (most frequent)
- hf (life-threatening)
- QTc prolongation
- hepatotoxicity (life-threatening)
- abdominal pain (most frequent)
- diarrhea (most frequent)
- taste abnormality
- vomiting (most frequent)
- pneumonitis (life-threatening)
- pulmonary fibrosis (life-threatening)
- ↑ serum creatinine
- angioedema (life-threatening)
Drug-Drug interactionDronedarone is metabolized by CYP3A and is a moderate inhibitor of CYP3A and CYP2D6 enzyme systems; interactions may occur with other drugs that are substrates for or are metabolized by these systems.Dronedarone also inhibits P-gp, which can result in ↑ absorption of certain drugs.Concurrent use of strong CYP3A inhibitors including ketoconazole, itraconazole, voriconazole, cyclosporine, telithromycin, clarithromycin, nefazodone, and ritonavir or drugs that prolong the QT interval including phenothiazine antipsychotics, tricyclic antidepressants, some oral macrolide antibiotics, and other Class I and III antiarrhythmics ↑ risk of serious adverse cardiovascular reactions; concurrent use contraindicated.Concurrent use of CYP3A4 inducers including rifampin, phenobarbital, carbamazepine, or phenytoin ↓ blood levels and effectiveness and should be avoided.↑ digoxin levels and the risk of toxicity (discontinue or ↓ dose of digoxin by 50% before treatment and monitor carefully).May ↑ dabigatran and warfarin levels and the risk of bleeding.Avoid concurrent use of other antiarrhythmics, including amiodarone, flecainide, propafenone, quinidine, disopyramide, dofetilide, and sotalol due to ↑ risk of adverse cardiovascular reactions; discontinue prior to dronedarone therapy (concurrent use is contraindicated).Concurrent use of diltiazem, verapamil, digoxin, or beta-blockers ↑ risk of bradycardia (initiate at lower dose and ↑ only after ECG evaluation).May also ↑ levels and effects oftricyclic antidepressants, and selective serotonin reuptake inhibitors (SSRIs).May ↑ levels and risk of toxicity of some HMG-CoA reductase inhibitors (statins) ; do not exceed simvastatin dose of 10 mg/day.Concurrent use with CYP 3A substrates including sirolimus and tacrolimus may ↑ risk of serious adverse reactions; monitor and adjust dosage carefully.St. John’s wort ↓ blood levels and may ↓ effectiveness; avoid concurrent use.Grapefruit juice may ↑ levels and the risk of toxicity; avoid concurrent ingestion.
- Assess for signs and symptoms of atrial fibrillation or atrial flutter (palpitations, abnormal ECG) periodically during therapy. If atrial fibrillation occurs, cardiovert or discontinue dronaderone; increases risk of stroke, hospitalization for HF, and death.
- Monitor ECG periodically and at least every 3 mo during therapy. If QTc ≥500 ms or PR interval >280 ms, discontinue therapy.
- Assess for signs and symptoms of hepatic injury (anorexia, nausea, vomiting, fever, malaise, fatigue, right upper quadrant pain, jaundice, dark urine, or itching) during therapy. If hepatic injury is suspected, discontinue therapy and test serum enzymes (AST, ALT), alkaline phosphatase, and serum bilirubin to determine liver injury. If liver injury occurs, begin treatment. Do not restart therapy without another explanation for liver injury.
- Assess for signs of pulmonary toxicity (dyspnea, nonproductive cough) periodically during therapy. If pulmonary toxicity occurs, discontinue therapy.
- Lab Test Considerations: Monitor serum hepatic enzymes periodically, especially during first 6 mo of therapy.
- Monitor serum potassium and magnesium levels during therapy and maintain within normal range. May cause hypokalemia and hypomagnesemia.
- Monitor serum creatinine levels periodically during therapy. Serum creatinine levels ↑ by about 0.1 mg/dL following initiation of therapy with a rapid onset and plateau after 7 days; reversible with discontinuation. If ↑ and plateau occurs, use increased value as new baseline.
Potential Nursing DiagnosesDecreased cardiac output (Indications)
- Patient should be on concurrent antithrombotic therapy.
- Oral: Administer twice daily with morning and evening meals; avoid grapefruit juice.
- Instruct patient to take dronedarone as directed. Do not stop taking dronedarone, even if feeling better, without consulting health care professional. If a dose is missed, omit and take next dose at regularly scheduled time; do not double dose. Advise patient to read Medication Guide before starting therapy and with each Rx refill; there may be new information.
- Advise patient to avoid grapefruit juice during therapy.
- Advise patient to notify health care professional if signs and symptoms of heart failure (weight gain, dependent edema, increasing shortness of breath), hepatic injury, or pulmonary toxicity occur.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
- May be teratogenic. Caution female patients of child-bearing age to use effective contraception during therapy and to notify health care professional if pregnancy is planned or suspected or if breast feeding.
- Reduction in hospitalization of patients with paroxysmal or persistent atrial fibrillation or atrial flutter.