Trade Names:Multaq- Tablets 400 mg
Exact mechanism is not known; has antiarrhythmic properties belonging to all 4 Vaughn-Williams classes.
Bioavailability is 4% without food; it increases to 15% when administered with a high-fat meal. T max is 3 to 6 h and steady-state concentrations are reached in 4 to 8 days.
More than 98% protein bound, mostly to albumin. Vd after IV administration is about 1,400 L.
Extensively metabolized by CYP3A to the N-debutyl metabolite (active), which is 1/10 to 1/3 as potent as dronedarone, and the propanoic acid metabolite (inactive).
Elimination half-life is 13 to 19 h. Excreted primarily in the feces (84%), with 6% excreted in the urine. Cl after IV administration is 130 to 150 L/h.
No pharmacokinetic difference was observed.Hepatic Function Impairment
Patients with moderate hepatic impairment had an increase in mean exposure of 1.3-fold and a decrease in mean exposure of the N-debutyl metabolite by 50% compared with patients with healthy hepatic function. The effect of severe hepatic impairment on pharmacokinetics was not assessed and dronedarone is contraindicated in these patients.Elderly
Dronedarone exposure is 23% higher in patients 65 yr of age and older compared with those younger than 65 yr of age.Gender
Dronedarone exposure is 30% higher in females than in males.Race
After single-dose administration, Asian (Japanese) males had a 2-fold higher exposure than white males.
To reduce the risk of CV hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL and associated CV risk factors (ie, older than 70 yr of age, hypertension, diabetes, prior cerebrovascular accident, left atrial diameter at least 50 mm or left ventricular ejection fraction [LVEF] less than 40%), who are in sinus rhythm or who will be cardioverted.
NYHA class IV heart failure or NYHA class II or III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic; second- or third-degree AV block or sick sinus syndrome (except when used in conjunction with a functioning pacemaker); bradycardia less than 50 bpm; concomitant use of strong CYP3A inhibitors; concomitant use of drugs or herbal products that prolong the QT interval and might increase the risk of torsades de pointes; QTc Bazett interval at least 500 ms or PR interval greater than 280 ms; severe hepatic impairment; pregnancy; breast-feeding mothers.
PO 400 mg twice daily.
Store between 59° and 86°F.
Increased plasma levels; give lower doses of beta-blockers and calcium channel blockers and increase only after ECG verification of good tolerability. Verapamil and diltiazem increase dronedarone exposure.CYP2D6 (eg, SSRIs) and CYP3A4 (eg, sirolimus, tacrolimus) substrates
Plasma concentrations of drugs metabolized by these CYP enzymes may be elevated, increasing the risk of adverse reactions.CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin, St. John's wort)
Dronedarone plasma levels may be reduced. Avoid coadministration.CYP3A inhibitors (eg, clarithromycin, cyclosporine, itraconazole, ketoconazole, nefazodone, ritonavir, telithromycin, voriconazole)
Concomitant use is contraindicated.Digoxin and other P-glycoprotein substrates
Digoxin levels are increased and may result in toxicity. Reduce digoxin dose by approximately 50% and monitor serum levels closely or discontinue digoxin.Drugs known to increase the QT interval (eg, class I and III antiarrhythmics, macrolide antibiotics, phenothiazines, tricyclic antidepressants)
Risk of life-threatening arrhythmias, including torsades de pointes, may be increased. Coadministration is contraindicated.Grapefruit juice
Dronedarone exposure increased with coadministration. Avoid concomitant use.HMG-CoA reductase inhibitors (eg, simvastatin)
Simvastatin plasma levels may be elevated, increasing the risk of adverse reactions.Warfarin
S-warfarin levels may be increased. Monitor INR.
Asthenic conditions (7%).
Skin conditions, including allergic dermatitis, dermatitis, eczema, pruritus, rash (5%).
Diarrhea (9%); nausea (5%); abdominal pain (4%); dyspeptic signs and symptoms, vomiting (2%).
Serum creatinine increased more than 10% five days after initiation (51%); QTc Bazett prolonged (28%).
Dronedarone is contraindicated in patients with NYHA class IV heart failure or NYHA class II or III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic.
Category X .
Safety and efficacy not established.
Contraindicated in patients with severe hepatic function impairment.
Hypokalemia or hypomagnesemia may occur with coadministration of potassium-sparing diuretics. Potassium levels should be within the normal range prior to administration of dronedarone and maintained in the normal range during administration.
New or worsening heart failure may develop during treatment with dronedarone. If heart failure develops or worsens, consider suspending or discontinuing dronedarone.
Dronedarone induces a moderate QTc prolongation. If the QTc Bazett interval is 500 ms or greater, discontinue dronedarone.
Serum creatinine levels increase about 0.1 mg/dL after initiation of dronedarone. The elevation onset is rapid, reaches a plateau after 7 days, and is reversible upon discontinuation.
Changes in cardiac rhythm and blood pressure.
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