droe-NED-a-rone

• Reduces the risk of hospitalization for atrial fibrillation (AF) in patients in sinus rhythm with a history of paroxysmal or persistent AF.

• Has several antiarrhythmic properties; prolongs PR and QTc intervals.

• Suppression of AF.

Absorption: Poor bioavailability (4%) due to extensive first-pass hepatic metabolism (4%); food ↑ bioavailability (15%).

Distribution: Unknown.

Protein Binding: >98%.

Metabolism/Excretion: Undergoes extensive first-pass hepatic metabolism; mostly by the CYP3A enzyme system. 6% excreted in urine as metabolites, 84% was excreted in feces as metabolites. Minimal elimination as unchanged drug.

Half-life: 13–19 hr.

Contraindicated in:

• Class IV heart failure or Class II–III heart failure with recent decompensation requiring hospitalization
• Permanent AF
• Second- or third-degree atrioventricular (AV) block or sick sinus syndrome (unless a pacemaker is present)
• Heart rate <50 bpm
• Concurrent use of strong CYP3A inhibitors or drugs/herbal products that prolong the QT interval
• liver or lung toxicity related to previous amiodarone use
• QTc interval 500 msec
• PR interval >280 msec
• Concurrent use of Class I or III antiarrhythmics including amiodarone, flecainide, propafenone, quinidine, disopyramide, dofetilide, and sotalol; must be discontinued prior to treatment
• Severe hepatic impairment
• OB: Pregnancy (may cause fetal harm)
• Lactation: Lactation.

Use Cautiously in:

• New/worsening heart failure
• Hypokalemia or hypomagnesemia (may ↑ risk of arrhythmias)
• Mild or moderate hepatic impairment
• Rep: Women of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CV: HF, QTc prolongation.

GI: HEPATOTOXICITY, abdominal pain, diarrhea, nausea, taste abnormality, vomiting.

Neuro: weakness.

Resp: PNEUMONITIS, PULMONARY FIBROSIS.

GU: ACUTE RENAL FAILURE, renal impairment.

Derm: photosensitivity.

Misc: ANGIOEDEMA.

Drug-Drug:

• Dronedarone 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, clarithromycin, nefazodone, and ritonavir or drugs that prolong the QT interval including phenothiazine antipsychotics, tricyclic antidepressants, 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 levels and risk of bleeding; ↓ dabigatran dose to 75 mg twice daily in patients with moderate renal impairment (CCr 30–50 mL/min); avoid concurrent use in severe renal impairment (CCr 15–30 mL/min).
• May ↑ warfarin levels and risk of bleeding; closely monitor INR.
• 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 of tricyclic 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.

Drug-Natural Products:

• St. John’s wort ↓ blood levels and may ↓ effectiveness; avoid concurrent use.

Drug-Food:

• Grapefruit juice may ↑ levels and the risk of toxicity; avoid concurrent ingestion.

• PO (Adults): 400 mg twice daily.

• Patient should be on concurrent antithrombotic therapy.
• PO: Administer twice daily with morning and evening meals.

Multaq

Therapeutic Classification: antiarrhythmics

Pharmacologic Classification: benzofurans

• Tablets: 400 mg;

(antiarrhythmic effect)

†Steady state blood levels are attained at 4–8 days.

†Peak levels after individual doses.

• Assess for signs and symptoms of atrial fibrillation (palpitations, abnormal ECG) periodically during therapy. If atrial fibrillation occurs, cardiovert or discontinue dronedarone; 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.

• 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.

• Decreased cardiac output (Indications).

• 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 in case of changes.
• Advise patient to avoid grapefruit juice during therapy; may increase drug levels.
• Advise patient to notify health care professional if signs and symptoms of HF (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.
• Rep: May be teratogenic. Caution female patients of reproductive potential to use effective contraception, to avoid breastfeeding during therapy, and to notify health care professional promptly if pregnancy is suspected.

• Reduction in hospitalization of patients with paroxysmal or persistent atrial fibrillation or atrial flutter.

NDC Code^*

• 0024- sanofi-aventis U.S. LLC
  • 0024-4142- Multaq
    • 0024-4142-06- 8 BLISTER PACK in 1 BOX (0024-4142-06) > 6 TABLET, FILM COATED in 1 BLISTER PACK

• 0024- sanofi-aventis U.S. LLC
  • 0024-4142- Multaq
    • 0024-4142-10- 10 BLISTER PACK in 1 BOX (0024-4142-10) > 10 TABLET, FILM COATED in 1 BLISTER PACK

• 0024- sanofi-aventis U.S. LLC
  • 0024-4142- Multaq
    • 0024-4142-50- 500 TABLET, FILM COATED in 1 BOTTLE (0024-4142-50)

• 0024- sanofi-aventis U.S. LLC
  • 0024-4142- Multaq
    • 0024-4142-60- 60 TABLET, FILM COATED in 1 BOTTLE (0024-4142-60)

• 55154- Cardinal Health
  • 55154-8104- Multaq
    • 55154-8104-2- 1260 TABLET, FILM COATED in 1 BOTTLE (55154-8104-2)