Drugs Information Online
Drugs and diseases reference index

Drugs and diseases reference index
Search
EN

Drugs A-Z List

Diseases & Conditions A-Z List

Herbs & Supplements

Medical Dictionary

Full Article

Popular Drugs

Popular Diseases & Conditions

Drugs reference index «Dronedarone»

Dronedarone

Pronunciation: DROE-NA-da-roneClass: Antiarrhythmic agent

Trade Names:Multaq- Tablets 400 mg

Pharmacology

Exact mechanism is not known; has antiarrhythmic properties belonging to all 4 Vaughn-Williams classes.

Pharmacokinetics

Absorption

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.

Distribution

More than 98% protein bound, mostly to albumin. Vd after IV administration is about 1,400 L.

Metabolism

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

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.

Special Populations

Renal Function Impairment

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.

Indications and Usage

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.

Contraindications

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.

Dosage and Administration

PO 400 mg twice daily.

General Advice

  • Administer 1 tablet with the morning meal and 1 tablet with the evening meal.

Storage/Stability

Store between 59° and 86°F.

Drug Interactions

Beta-blockers and calcium channel blockers

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.

Adverse Reactions

Cardiovascular

Bradycardia (3%).

CNS

Asthenic conditions (7%).

Dermatologic

Skin conditions, including allergic dermatitis, dermatitis, eczema, pruritus, rash (5%).

GI

Diarrhea (9%); nausea (5%); abdominal pain (4%); dyspeptic signs and symptoms, vomiting (2%).

Lab Tests

Serum creatinine increased more than 10% five days after initiation (51%); QTc Bazett prolonged (28%).

Precautions

Warnings

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.

Pregnancy

Category X .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hepatic Function

Contraindicated in patients with severe hepatic function impairment.

Electrolyte disturbances

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.

Heart failure

New or worsening heart failure may develop during treatment with dronedarone. If heart failure develops or worsens, consider suspending or discontinuing dronedarone.

QTc prolongation

Dronedarone induces a moderate QTc prolongation. If the QTc Bazett interval is 500 ms or greater, discontinue dronedarone.

Serum creatinine increase

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.

Overdosage

Symptoms

Changes in cardiac rhythm and blood pressure.

Patient Information

  • Advise patient or caregiver to read the Medication Guide carefully before starting therapy, and to read and check for new information each time the medication is refilled.
  • Advise patient to take each dose with food.
  • Instruct patient to avoid drinking grapefruit juice while taking dronedarone.
  • Advise patient to inform their health care provider of any history of heart failure, rhythm disturbance other than atrial fibrillation or flutter, or predisposing conditions such as uncorrected hypokalemia.
  • Instruct patient to contact health care provider if they develop symptoms of worsening heart failure such as acute weight gain, dependent edema, or increasing shortness of breath.
  • Caution women of childbearing potential to avoid becoming pregnant during treatment with dronedarone.
  • Advise mothers not to breast-feed.

Copyright © 2009 Wolters Kluwer Health.

  • Dronedarone MedFacts Consumer Leaflet (Wolters Kluwer)
  • dronedarone Advanced Consumer (Micromedex) - Includes Dosage Information
  • Multaq Prescribing Information (FDA)
  • Multaq Consumer Overview

Comment «Dronedarone»