Dronedarone

⛔ FDA Black Box Warning

WARNING: INCREASED RISK OF DEATH, STROKE AND HEART FAILURE IN PATIENTS WITH DECOMPENSATED HEART FAILURE OR PERMANENT ATRIAL FIBRILLATION In patients with symptomatic heart failure and recent decompensation requiring hospitalization or NYHA Class IV heart failure, MULTAQ doubles the risk of death [see Clinical Studies (14.3) ] . MULTAQ is contraindicated in patients with symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV heart failure [see Contraindications (4) , Warnings and Precautions (5.1) ] . In patients with permanent atrial fibrillation, MULTAQ doubles the risk of death, stroke and hospitalization for heart failure [see Clinical Studies (14.4) ] . MULTAQ is contraindicated in patients in atrial fibrillation (AF) who will not or cannot be cardioverted into normal sinus rhythm [see Contraindications (4) , Warnings and Precautions (5.2) ] . WARNING: INCREASED RISK OF DEATH, STROKE AND HEART FAILURE IN PATIENTS WITH DECOMPENSATED HEART FAILURE OR PERMANENT ATRIAL FIBRILLATION See full prescribing information for complete boxed warning. MULTAQ is contraindicated in patients with symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV heart failure. MULTAQ doubles the risk of death in these patients. ( 4 , 5.1 , 14.3 ) MULTAQ is contraindicated in patients in atrial fibrillation (AF) who will not or cannot be cardioverted into normal sinus rhythm. In patients with permanent AF, MULTAQ doubles the risk of death, stroke, and hospitalization for heart failure. ( 4 , 5.2 , 14.4 )

Contraindications

4 CONTRAINDICATIONS MULTAQ is contraindicated in patients with: • Permanent atrial fibrillation (patients in whom normal sinus rhythm will not or cannot be restored) [see Boxed Warning , Warnings and Precautions (5.2) ] • Symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV symptoms [see Boxed Warning , Warnings and Precautions (5.1) ] • Second or third-degree atrioventricular (AV) block, or sick sinus syndrome (except when used in conjunction with a functioning pacemaker) • Bradycardia <50 bpm • Concomitant use of strong CYP3A inhibitors, such as ketoconazole, itraconazole, voriconazole, cyclosporine, telithromycin, clarithromycin, nefazodone, and ritonavir [see Drug Interactions (7.2) ] • Concomitant use of erythromycin [see Clinical Pharmacology (12.3) ] • Concomitant use of drugs or herbal products that prolong the QT interval and might increase the risk of torsade de pointes, such as phenothiazine antipsychotics, tricyclic antidepressants, certain oral macrolide antibiotics, and Class I and III antiarrhythmics • Liver or lung toxicity related to the previous use of amiodarone • QTc interval >500 ms or PR interval >280 ms • Severe hepatic impairment • Hypersensitivity to the active substance or to any of the excipients • Permanent AF (patients in whom normal sinus rhythm will not or cannot be restored) ( Boxed Warning , 4 ) • Recently decompensated heart failure requiring hospitalization or Class IV heart failure ( Boxed Warning , 4 ) • Second or third-degree atrioventricular (AV) block or sick sinus syndrome (except when used in conjunction with a functioning pacemaker) ( 4 ) • Bradycardia <50 bpm ( 4 ) • Concomitant use of a strong CYP3A inhibitor ( 4 ) • Concomitant use of erythromycin ( 4 ) • Concomitant use of drugs or herbal products that prolong the QT interval and may induce torsade de pointes ( 4 ) • Liver or lung toxicity related to the previous use of amiodarone ( 4 ) • QTc interval >500 ms or PR interval >28

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary MULTAQ may cause fetal harm when administered to a pregnant woman. In animal studies, dronedarone administered to pregnant rats and rabbits during the period of organogenesis caused multiple visceral (rats) and skeletal malformations (rats and rabbits) when administered at doses equivalent to or lower than the maximum recommended human dose (MRHD) (see Data ). There are no available data on dronedarone use in pregnant women to evaluate for a drug-associated risk of major birth defects or miscarriage or other adverse maternal or fetal outcomes. Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal data When pregnant rats in embryofetal development studies received dronedarone at oral doses greater than or equal to the MRHD (on a mg/m 2 basis) during organogenesis (gestational days 6 to 15) fetuses had increased rates of external, visceral and skeletal malformations (cranioschisis, cleft palate, incomplete evagination of pineal body, brachygnathia, partially fused carotid arteries, truncus arteriosus, abnormal lobation of the liver, partially duplicated inferior vena cava, brachydactyly, ectrodactyly, syndactyly, and anterior and/or posterior club feet). When pregnant rabbits in embryofetal development studies received dronedarone, at a dose approximately half the MRHD (on a mg/m 2 basis) during organogenesis (gestational days 6 to 18), fetuses had an increased rate of skeletal abnormalities (anomalous ribcage and vertebrae, pelvic asymmetry) at doses ≥20 mg/kg (the lowest dose tested and approximately half the MRHD on a mg/m 2 basis). Actual animal doses: rat (≥80