Dosing & Uses
Dosing Forms & Strength
tablet
- 400mg
Atrial Fibrillation/Flutter
Reduces the risk of hospitalization for atrial fibrillation (AF) in patients in sinus rhythm with history of paroxysmal or persistent AF
400 mg PO twice daily with meals
Dosing Considerations
Discontinue class I or III antiarrhythmics or strong CYP3A inhibitors before initiating therapy
Dosing Modifications
Renal impairment: Dose adjustment not necessary
Mild to moderate hepatic impairment: Dose adjustment not necessary
Severe hepatic impairment: Containdicated
Safety and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Adverse Effects
>10%
QTc prolongation (28%)
Early increase in SCr of >10% (51%)
1-10%
Diarrhea (9%)
Asthenia (7%)
Nausea (5%)
Skin reactions (eg, rash, pruritus, eczema, allergic dermatitis) (5%)
Abdominal pain (4%)
Bradycardia (3%)
Vomiting (2%)
Dyspepsia (2%)
Postmarketing Reports
New/worsening HF
Hepatic injury
Cardiac failure
Pulmonary fibrosis
Interstitial lung disease including pneumonitis and PF
Anaphylactic reactions (eg, angioedema)
Vasculitis (eg, leukocytoclastic vasculitis)
Interstitial lung disease, including pneumonitis and pulmonary fibrosis, have been reported
Atrial flutter with 1:1 atrioventricular conduction
Photosensitivity
Dysgeusia
Warnings
Black Box Warnings
Increased risk of death, stroke, and heart failure in patients with decompensated HF or permanent AF
Heart failure
- Symptomatic HF with recent decompensation requiring hospitalization
- NYHA class IV HF
- Referral to specialized HF clinic
- ANDROMEDA study showed mortality increased 2-fold in patients with severe HF requiring hospitalization or those referred to HF clinic for worsening symptoms
Permanent atrial fibrillation
- In patients with permanent AF, risk of death or stroke (particularly in the first 2 weeks of therapy) and hospitalization for HF is doubled; contraindicated in permanent AF (ie, patients who cannot be cardioverted into normal sinus rhythm)
- Patients should undergo cardiac rhythm monitoring at least every 3 months
- Cardiovert patients who are in atrial fibrillation (if clinically indicated) or discontinue drug
- Dronedarone offers no benefit in permanent AF
Contraindications
Hypersensitivity
Permanent AF in patients in whom normal sinus rhythm cannot be restored
Symptomatic HF with recent decompensation requiring hospitalization, or symptoms of NYHA class IV HF due to doubled risk of death
Concomitant strong CYP3A4 inhibitors (eg, grapefruit juice, itraconazole, clarithromycin, erythromycin)
Symptomatic HF with recent decompensation requiring hospitalization
NYHA class IV HF
Referral to HF program
2nd or 3rd degree heart block or sick sinus syndrome (unless used with functioning pacemaker)
Bradycardia <50 bpm
QTc interval >500 ms or PR interval >280 ms
Coadministration with drugs that prolong QT interval may cause torsade de Pointes-type ventricular tachycardia (eg, phenothiazine, TCAs, macrolide antibiotics, class I and III antiarrhythmic agents [amiodarone, flecainide, propafenone, quinidine, disopyramide, dofetilide, sotalol])
Liver toxicity related to previous use of amiodarone
Severe hepatic impairment (ie, Child-Pugh Class C)
Pregnancy (category X)
Breastfeeding women
Cautions
Several cases of hepatocellular liver injury and hepatic failure, including 2 postmarketing reports of acute hepatic failure requiring transplantation; discontinue immediately if hepatic injury is suspected; obtain periodic hepatic serum enzymes, especially during the first 6 months of treatment
Interstitial lung disease (pneumonitis, PF); if pulmonary toxicity is suspected, discontinue immediately
Postmarketing cases of increased INR with or without bleeding events have been reported in warfarin-treated patients initiated on dronedarone; monitor INR after initiating in patients taking warfarin
Increased risk of hypomagnesemia/hypokalemia with potassium-depleting diuretics
Dronedarone induces moderate prolongation of the QT interval; monitor
Discontinue if new or worsening HF develops
Marked increase in serum creatinine, prerenal azotemia, and acute renal failure, often in the setting of heart failure or hypovolemia, reported; typically reversible when drug discontinued; monitor renal function
Small increase in SCr following initiation; elevation has a rapid onset, reaches plateau after 7 days, and is reversible upon discontinuation
Not approved for permanent atrial fibrillation (phase III PALLAS trial halted because preliminary analysis showed 2-fold increase in death, as well as 2-fold increases in stroke and hospitalization for HF)
Women of childbearing potential must exercise caution while on therapy and must be counseled on appropriate contraceptive choices
Pregnancy & Lactation
Pregnancy category: X
Lactation: Unknown if distributed in breast milk; contraindicated
Pregnancy Categories
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Pharmacology
Mechanism of Action
Unknown; noniodinated antiarrhythmic agent structurally related to amiodarone; has properties belonging to all 4 Vaughn-Williams antiarrhythmic classes
Blocks sodium channels, blocks beta1-adrenergic site, and alters adenyl cyclase generation (ie, negative inotropic effects); blocks potassium channels (eg, hERG) and therefore prolongs cardiac repolarization
Absorption
Bioavailability: 4% (without food); 15% (with high-fat meal)
Peak plasma time: 3-6 hr (including major active metabolite); at steady state: 2.6-4.5 hr
Distribution
Protein bound: >98%
Vd: 1400 L (steady state)
Metabolism
CYP3A4 (extensive)
Initial metabolic pathway includes N-debutylation to form active N-debutyl metabolite, oxidative deamination to form the inactive propanoic acid metabolite, and direct oxidation
Metabolites undergo further metabolism to yield over 30 uncharacterized metabolites; N-debutyl metabolite exhibits pharmacodynamic activity (1/10 to 1/3 as potent as dronedarone)
Elimination
Half-life, elimination: 13-19 hr
Clearance: 130-150 L/hr
Excretion: Feces (84%); urine (6%)
Images
Patient Handout
Formulary
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