MULTAQ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MULTAQ (MULTAQ).
Dronedarone is a multichannel blocker that inhibits potassium currents (IKr, IKs, IK-ACh), sodium current (INa), and L-type calcium current (ICaL), and has antiadrenergic properties via noncompetitive blockade of beta-adrenergic receptors.
| Metabolism | Primarily metabolized by CYP3A4 to active metabolite N-debutyldronedarone; also metabolized by CYP2D6 to a minor extent. |
| Excretion | Primarily fecal (84%) after biliary excretion; renal excretion accounts for <6% as unchanged drug and metabolites. |
| Half-life | Terminal elimination half-life is approximately 24 hours (range 20-30 hours) after oral administration, allowing for twice-daily dosing. |
| Protein binding | Approximately 96% bound to serum proteins, mainly albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is about 20 L/kg, indicating extensive tissue distribution and accumulation in cardiac tissue. |
| Bioavailability | Oral bioavailability is ~72% (range 58-86%) due to first-pass metabolism; absorption is increased with food. |
| Onset of Action | Oral: Maximum effect on atrial effective refractory period prolongation occurs within 2-6 hours after a single dose. |
| Duration of Action | Antiarrythmic effect persists for approximately 12 hours, corresponding to dosing interval; steady-state is achieved within 4-8 days. |
| Action Class | Class III Agents- anti arrhythmic |
| Brand Substitutes | Dilsave 400mg Tablet |
400 mg orally twice daily with morning and evening meals.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required. CrCl <10 mL/min: not studied, use with caution. |
| Liver impairment | Contraindicated in Child-Pugh class B and C. Child-Pugh class A: no adjustment. |
| Pediatric use | Safety and efficacy not established; no recommended dose. |
| Geriatric use | No specific dose adjustment; monitor renal function and electrolyte balance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MULTAQ (MULTAQ).
| Breastfeeding | Unknown if excreted in human milk. M/P ratio not established. Due to potential for serious adverse reactions (e.g., bradycardia, QT prolongation) in nursing infants, breast-feeding is not recommended during therapy. |
| Teratogenic Risk | Pregnancy Category X. First trimester: Contraindicated due to risk of fetal bradycardia, heart block, and developmental toxicity. Second and third trimesters: Same risks; avoid use. Animal studies show embryocidal and teratogenic effects at subclinical doses. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: INCREASED RISK OF DEATH IN PATIENTS WITH DECOMPENSATED HEART FAILURE OR RECENT HOSPITALIZATION FOR HEART FAILURE. Dronedarone is contraindicated in patients with NYHA Class IV heart failure or NYHA Class II-III heart failure with a recent decompensation requiring hospitalization. In the ANDROMEDA trial, dronedarone doubled the risk of death in such patients.
| Serious Effects |
["NYHA Class IV heart failure or NYHA Class II-III heart failure with recent decompensation requiring hospitalization.","Second- or third-degree AV block or sick sinus syndrome (except in presence of functioning pacemaker).","Bradycardia (<50 bpm).","Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, voriconazole, telithromycin, clarithromycin, nefazodone, ritonavir).","Concomitant use of Class I or III antiarrhythmics (e.g., flecainide, propafenone, quinidine, disopyramide, dofetilide, sotalol, amiodarone).","Concomitant use of certain QT-prolonging drugs (e.g., some antipsychotics, macrolide antibiotics, tricyclic antidepressants).","Severe hepatic impairment.","Pregnancy (based on animal data and potential risk)."]
| Precautions | ["Increased cardiovascular mortality in patients with recent decompensated heart failure (NYHA IV or recent hospitalization).","Elevation of serum creatinine (reversible on discontinuation).","Hepatotoxicity: Hepatocellular liver injury, including acute liver failure with fatal cases; monitor liver enzymes periodically.","Pulmonary toxicity: Interstitial lung disease and pneumonitis, including fatal cases.","QT prolongation (dose-dependent); avoid use with other QT-prolonging drugs.","Increased risk of stroke: Discontinue dronedarone if AF recurs and transition to appropriate anticoagulation.","Hypokalemia or hypomagnesemia: Correct before initiation.","Pregnancy: Avoid unless benefit outweighs risk; potential fetal harm.","Nursing mothers: Discontinue drug or nursing based on importance."] |
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| Monitor maternal ECG for PR interval prolongation, QRS widening, and QT prolongation; monitor hepatic function (LFTs) monthly for first 6 months, then at 9 and 12 months; pulmonary function tests if respiratory symptoms develop; fetal echocardiography to assess heart rate and rhythm if exposure occurs. |
| Fertility Effects | No clinical studies on human fertility. In animal studies, no impairment of fertility observed. Dronedarone may reduce testosterone levels and spermatogenesis in rats, but clinical relevance unknown. |