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Find Lowest Prices on MULTAQ (dronedarone) Tablets 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. MULTAQ is contraindicated in patients with symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV heart failure. In patients with permanent atrial fibrillation, MULTAQ doubles the risk of death, stroke and hospitalization for heart failure. MULTAQ is contraindicated in patients in atrial fibrillation (AF) who will not or cannot be cardioverted into normal sinus rhythm. DESCRIPTION Dronedarone HCl is a benzofuran derivative with the following chemical name: N-{2-butyl-3-[4-(3-dibutylaminopropoxy)benzoyl]benzofuran-5-yl} methanesulfonamide, hydrochloride. Dronedarone HCl is a white fine powder that is practically insoluble in water and freely soluble in methylene chloride and methanol. Its empirical formula is C31H44N2O5 S, HCl with a relative molecular mass of 593.2. Its structural formula is: MULTAQ is provided as tablets for oral administration. Each tablet of MULTAQ contains 400 mg of dronedarone (expressed as base). The inactive ingredients are: Core of the tablets-hypromellose, starch, crospovidone, poloxamer 407, lactose monohydrate, colloidal silicon dioxide, magnesium stearate. Coating / polishing of the tablets-hypromellose, polyethylene glycol 6000, titanium dioxide, carnauba wax.

INDICATIONS MULTAQ® is indicated to reduce the risk of hospitalization for atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistent atrial fibrillation (AF) [see Clinical Studies]. DOSAGE AND ADMINISTRATION The recommended dosage of MULTAQ is 400 mg twice daily in adults. MULTAQ should be taken as one tablet with the morning meal and one tablet with the evening meal. Treatment with Class I or III antiarrhythmics (e.g., amiodarone, flecainide, propafenone, quinidine, disopyramide, dofetilide, sotalol) or drugs that are strong inhibitors of CYP3A (e.g., ketoconazole) must be stopped before starting MULTAQ [see CONTRAINDICATIONS]. HOW SUPPLIED Dosage Forms And Strengths MULTAQ 400 mg tablets are provided as white film-coated tablets for oral administration, oblong-shaped, engraved with a double wave marking on one side and “4142” code on the other side. Storage And Handling MULTAQ 400-mg tablets are provided as white film-coated tablets for oral administration, oblong-shaped, engraved with a double wave marking on one side and “4142” code on the other side in: Bottles of 60 tablets, NDC 0024-4142-60 Bottles of 180 tablets, NDC 0024-4142-18 Bottles of 500 tablets NDC 0024-4142-50 Box of 10 blisters (10 tablets per blister) NDC 0024-4142-10 Store at 25°C (77°F): excursions permitted to 15-30°C (59-86°F), [see WARNINGS AND PRECAUTIONS]. Manufactured by Sanofi Winthrop Industrie 1, rue de la Vierge 33440 Ambares, France. sanofi-aventis U.S. LLC Bridgewater, NJ 08807 A Sanofi Company. Revised: Jan 2014.

PATIENT INFORMATION MULTAQ (MUL-tak) (dronedarone) Tablets Read this Medication Guide before you start taking MULTAQ and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. What is the most important information I should know about MULTAQ? MULTAQ can cause serious side effects. Do not take MULTAQ if you: 1. have symptoms of heart failure that recently worsened and you were hospitalized, or if you have severe heart failure. MULTAQ doubles your risk of dying if you have these conditions. Heart failure means your heart does not pump blood through your body as well as it should. Call your doctor right away if you have any signs or symptoms of heart failure during treatment with MULTAQ: shortness of breath or wheezing at rest wheezing, chest tightness or coughing up frothy sputum at rest, nighttime or after minor exercise trouble sleeping or waking up at night because of breathing problems using more pillows to prop yourself up at night so you can breathe more easily gaining more than 5 pounds quickly increasing swelling of feet or legs 2. have a type of atrial fibrillation (irregular heart rhythm) called permanent atrial fibrillation (AF). You and your doctor may decide not to try to change your heart rhythm back to a normal heart rhythm or your heart rhythm cannot be changed back to a normal rhythm. If you have permanent AF and take MULTAQ, you have a higher risk of death, stroke, and needing to be treated in a hospital for your heart failure. Your doctor will monitor your heart rhythm regularly to make sure your heartbeat keeps a normal rhythm. Call your doctor right away if you notice that your pulse is irregular during treatment with MULTAQ. This is a sign that you are in atrial fibrillation. MULTAQ may cause liver problems, including life-threatening liver failure. Your doctor may order blood tests to check your liver before you start taking MULTAQ and during treatment. In some cases MULTAQ treatment may need to be stopped. Call your doctor right away if you develop any of these signs and symptoms of liver problems during treatment with MULTAQ: loss of appetite, nausea, vomiting fever, feeling unwell, unusual tiredness itching yellowing of the skin or the whites of the eyes (jaundice) unusual darkening of the urine right upper stomach area pain or discomfort What is MULTAQ? MULTAQ is a prescription medicine used to lower the chance that you will need to go into the hospital for atrial fibrillation. It is meant for people who have had certain types of atrial fibrillation (paroxysmal or persistent AF) in the past, but are now in normal rhythm. It is not known if MULTAQ is safe and effective in children younger than age 18 years old. Who should not take MULTAQ? See “What is the most important information I should know about taking MULTAQ?” Do not take MULTAQ if: you have a certain type of heart problem called heart block, and you do not have an implanted pacemaker you have a slow heart rate, less than 50 beats each minute you have severe liver problems or had liver or lung problems after using amiodarone (a medicine for abnormal heart rhythm) you take certain medicines that can change the amount of MULTAQ that gets into your body. Do not use these medicines with MULTAQ: Nefazodone for depression Norvir® (ritonavir) for HIV infection Nizoral® (ketoconazole), and Sporanox® (itraconazole), and Vfend® (voriconazole) for fungal infections Ketek® (telithromycin), Biaxin® (clarithromycin) for bacterial infections Cyclosporine for organ transplant You take certain medicines that can lead to a dangerous abnormal heart rhythm: Some medicines for mental illness called phenothiazines Some medicines for depression called tricyclic antidepressants Some medicines for abnormal heart rhythm or fast heartbeat Some medicines for bacterial infection Ask your doctor if you are not sure if your medicine is one that is listed above. You are pregnant or plan to become pregnant. It is not known if MULTAQ will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant. Women who may become pregnant should use effective birth control (contraception) while taking MULTAQ. Talk to your doctor about the best birth control methods for you. You are breast-feeding or plan to breastfeed. It is not known if MULTAQ passes into your breast milk. You and your doctor should decide if you will take MULTAQ or breastfeed. You should not do both. You are allergic to dronedarone or any of the other ingredients in MULTAQ. See the end of this Medication Guide for a complete list of ingredients in MULTAQ. What should I tell my doctor before taking MULTAQ? Before taking MULTAQ, tell your doctor if you: have any other heart problems have any other medical conditions Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins and herbal supplements. MULTAQ and certain other medicines can react with each other, causing serious side effects. Especially tell your doctor and pharmacist if you take: medicine for high blood pressure, chest pain, or other heart conditions statin medicine to lower blood cholesterol medicine for TB (tuberculosis) medicine for seizures digoxin (Lanoxin) warfarin (Coumadin, Jantoven), a blood thinner medicine medicine for organ transplant herbal supplement called St. John's wort Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine. How should I take MULTAQ? Take MULTAQ exactly as your doctor tells you. Take MULTAQ two times a day with food, once with your morning meal and once with your evening meal. Do not stop taking MULTAQ without first talking to your doctor, even if you are feeling well for a long time. If you miss a dose, wait and take your next dose at your regular time. Do not take 2 doses at the same time. Do not try to make up for a missed dose. If you take too much MULTAQ, call your doctor or go to the nearest hospital emergency room right away. What should I avoid while taking MULTAQ? Do not drink grapefruit juice while you are being treated with MULTAQ. Grapefruit juice can increase the amount of MULTAQ in your blood and increase the likelihood that you will have a side effect of MULTAQ. What are the possible side effects of MULTAQ? MULTAQ may cause serious side effects, including: See “What is the most important information I should know about MULTAQ?” Slowed heartbeat, (bradycardia) Inflammation of the lungs, including scarring and thickening. Call your doctor if you develop shortness of breath or a dry cough during treatment with MULTAQ. Low potassium and magnesium levels in your blood. This can happen if you take certain water pills (diuretics) during treatment with MULTAQ. Your doctor may check you for this problem before and during treatment. Changes in kidney function blood tests after starting MULTAQ. Your doctor may check you for this during treatment. The most common side effects of MULTAQ include: diarrhea nausea vomiting stomach area (abdominal) pain indigestion feeling tired and weak skin problems such as redness, rash, and itching Tell your doctor about any side effect that bothers you or that does not go away. These are not all the possible side effects of MULTAQ. For more information ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store MULTAQ? Store MULTAQ at room temperature (59 -86°F or 15 -30°C). Keep MULTAQ and all medicines out of the reach of children. General information about MULTAQ Medicines are sometimes used for purposes other than those listed in a Medication Guide. Do not use MULTAQ for a condition for which it was not prescribed. Do not give MULTAQ to other people, even if they have the same symptoms or condition. It may harm them. This Medication Guide summarizes the most important information about MULTAQ. If you would like more information: Talk with your doctor Ask your doctor or pharmacist for information about MULTAQ that was written for health-care professionals For the latest information and Medication Guide, visit www.sanofiaventis.us or call sanofi-aventis Medical Information Services at 1-800633-1610 option 1. The Medication Guide may have changed since this copy was printed. What are the ingredients in MULTAQ? Active ingredient: dronedarone Inactive ingredients: hypromellose, starch, crospovidone, poloxamer 407, lactose monohydrate, colloidal silicon dioxide, magnesium stearate, polyethylene glycol 6000, titanium dioxide, carnauba wax

SIDE EFFECTS The following safety concerns are described elsewhere in the label: New or worsening heart failure [see WARNINGS AND PRECAUTIONS] Liver Injury [see WARNINGS AND PRECAUTIONS] Pulmonary toxicity [see WARNINGS AND PRECAUTIONS] Hypokalemia and hypomagnesemia with potassium-depleting diuretics [see WARNINGS AND PRECAUTIONS] QT prolongation [see WARNINGS AND PRECAUTIONS] Clinical Trials Experience The safety evaluation of dronedarone 400 mg twice daily in patients with AF or AFL is based on 5 placebo controlled studies, ATHENA, EURIDIS, ADONIS, ERATO and DAFNE. In these studies, a total of 6285 patients were randomized and treated, 3282 patients with MULTAQ 400 mg twice daily, and 2875 with placebo. The mean exposure across studies was 12 months. In ATHENA, the maximum follow-up was 30 months. In clinical trials, premature discontinuation because of adverse reactions occurred in 11.8% of the dronedarone-treated patients and in 7.7% of the placebo-treated group. The most common reasons for discontinuation of therapy with MULTAQ were gastrointestinal disorders (3.2 % versus 1.8% in the placebo group) and QT prolongation (1.5% versus 0.5% in the placebo group). The most frequent adverse reactions observed with MULTAQ 400 mg twice daily in the 5 studies were diarrhea, nausea, abdominal pain, vomiting, and asthenia. Table 1 displays adverse reactions more common with dronedarone 400 mg twice daily than with placebo in AF or AFL patients, presented by system organ class and by decreasing order of frequency. Adverse laboratory and ECG effects are presented separately in Table 2. Table 1: Adverse Drug Reactions that Occurred in at Least 1% of Patients and Were More Frequent than Placebo Placebo (N=2875) Dronedarone 400 mg twice daily (N=3282) Gastrointestinal Diarrhea 6% 9% Nausea 3% 5% Abdominal pain 3% 4% Vomiting 1% 2% Dyspeptic signs and symptoms 1% 2% General Asthenic conditions 5% 7% Cardiac Bradycardia 1% 3% Skin and subcutaneous tissue Including rashes (generalized, macular, maculo-papular, erythematous), pruritus, eczema, dermatitis, dermatitis allergic 3% 5% Photosensitivity reaction and dysgeusia have also been reported at an incidence less than 1% in patients treated with MULTAQ. The following laboratory data/ECG parameters were reported with MULTAQ 400 mg twice daily. Table 2: Laboratory data/ECG parameters not necessarily reported as adverse events Placebo MULTAQ 400 mg twice daily (N=2875) (N=3282) Early increases in creatinine ≥ 10% 21% 51% (N=2237) (N=2701) QTc prolonged 19% 28% Assessment of demographic factors such as gender or age on the incidence of treatment-emergent adverse events did not suggest an excess of adverse events in any particular sub-group. Postmarketing Experience The following adverse reactions have been identified during post-approval use of MULTAQ. Because these reactions are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Cardiac: New or worsening heart failure [see WARNINGS AND PRECAUTIONS] Atrial flutter with 1:1 atrioventricular conduction has been reported very rarely. Hepatic: Liver Injury [see WARNINGS AND PRECAUTIONS] Respiratory: Interstitial lung disease including pneumonitis and pulmonary fibrosis [see WARNINGS AND PRECAUTIONS] Immune: Anaphylactic reactions including angioedema Vascular: Vasculitis, including leukocytoclastic vasculitis DRUG INTERACTIONS Pharmacodynamic Interactions Drugs prolonging the QT interval (inducing Torsade de Pointes) Co-administration of drugs prolonging the QT interval (such as certain phenothiazines, tricyclic antidepressants, certain macrolide antibiotics, and Class I and III antiarrhythmics) is contraindicated because of the potential risk of Torsade de Pointes-type ventricular tachycardia [see CONTRAINDICATIONS, CLINICAL PHARMACOLOGY]. Digoxin In the ANDROMEDA (patients with recently decompensated heart failure) and PALLAS (patients with permanent AF) trials baseline use of digoxin was associated with an increased risk of arrhythmic or sudden death in dronedarone-treated patients compared to placebo. In patients not taking digoxin, no difference in risk of sudden death was observed in the dronedarone vs. placebo groups. [See Clinical Trials]. Digoxin can potentiate the electrophysiologic effects of dronedarone (such as decreased AV-node conduction). Dronedarone increases exposure to digoxin [see CLINICAL PHARMACOLOGY]. Consider discontinuing digoxin. If digoxin treatment is continued, halve the dose of digoxin, monitor serum levels closely, and observe for toxicity. Calcium channel blockers Calcium channel blockers with depressant effects on the sinus and AV nodes could potentiate dronedarone's effects on conduction. Give a low dose of calcium channel blockers initially and increase only after ECG verification of good tolerability [see CLINICAL PHARMACOLOGY]. Beta-blockers In clinical trials, bradycardia was more frequently observed when dronedarone was given in combination with beta-blockers. Give a low dose of beta-blockers initially, and increase only after ECG verification of good tolerability [see CLINICAL PHARMACOLOGY]. Effects Of Other Drugs On Dronedarone Ketoconazole and other potent CYP 3A inhibitors Concomitant use of ketoconazole as well as other potent CYP 3A inhibitors such as itraconazole, voriconazole, ritonavir, clarithromycin, and nefazodone is contraindicated because exposure to dronedarone is significantly increased [see CONTRAINDICATIONS, CLINICAL PHARMACOLOGY]. Grapefruit juice Patients should avoid grapefruit juice beverages while taking MULTAQ because exposure to dronedarone is significantly increased [see CLINICAL PHARMACOLOGY]. Rifampin and other CYP 3A inducers Avoid rifampin or other CYP 3A inducers such as phenobarbital, carbamazepine, phenytoin, and St John's wort because they decrease exposure to dronedarone significantly [see CLINICAL PHARMACOLOGY]. Calcium channel blockers Verapamil and diltiazem are moderate CYP 3A inhibitors and increase dronedarone exposure. Give a low dose of calcium channel blockers initially and increase only after ECG verification of good tolerability [see CLINICAL PHARMACOLOGY]. Effects Of Dronedarone On Other Drugs Simvastatin Dronedarone increased simvastatin/simvastatin acid exposure. Avoid doses greater than 10 mg once daily of simvastatin [see CLINICAL PHARMACOLOGY]. Other statins Because of multiple mechanisms of interaction with statins (CYPs and transporters), follow statin label recommendations for use with CYP 3A and P-gp inhibitors such as dronedarone. Calcium channel blockers Dronedarone increased the exposure of calcium channel blockers (verapamil, diltiazem or nifedipine). Give a low dose of calcium channel blockers initially and increase only after ECG verification of good tolerability [see CLINICAL PHARMACOLOGY]. Sirolimus, tacrolimus, and other CYP3A substrates with narrow therapeutic range Dronedarone can increase plasma concentrations of tacrolimus, sirolimus, and other CYP 3A substrates with a narrow therapeutic range when given orally. Monitor plasma concentrations and adjust dosage appropriately. Beta-blockers and other CYP 2D6 substrates Dronedarone increased the exposure of propranolol and metoprolol. Give low doses of beta-blockers initially, and increase only after ECG verification of good tolerability. Other CYP 2D6 substrates, including other beta-blockers, tricyclic antidepressants, and selective serotonin reuptake inhibitors (SSRIs) may have increased exposure upon co-administration with dronedarone [see CLINICAL PHARMACOLOGY]. P-glycoprotein substrates Digoxin Dronedarone increased digoxin exposure by inhibiting the P-gp transporter. Consider discontinuing digoxin. If digoxin treatment is continued, halve the dose of digoxin, monitor serum levels closely, and observe for toxicity [see CLINICAL PHARMACOLOGY]. Dabigatran Exposure to dabigatran is higher when it is administered with dronedarone than when it is administered alone. Other P-gp substrates are expected to have increased exposure when co-administered with dronedarone. Warfarin When co-administered with dronedarone exposure to S-warfarin was slightly higher than when warfarin was administered alone. There were no clinically significant increases in INR [see CLINICAL PHARMACOLOGY]. More patients experienced clinically significant INR elevations ( ≥ 5) usually within 1 week after starting dronedarone vs. placebo in patients taking oral anticoagulants in ATHENA. However, no excess risk of bleeding was observed in the dronedarone group. Postmarketing cases of increased INR with or without bleeding events have been reported in warfarin-treated patients initiated on dronedarone. Monitor INR after initiating dronedarone in patients taking warfarin.

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Cardiovascular Death In NYHA Class IV Or Decompensated Heart Failure MULTAQ is contraindicated in patients with NYHA Class IV heart failure or symptomatic heart failure with recent decompensation requiring hospitalization because it doubles the risk of death. Cardiovascular Death And Heart Failure In Permanent AF MULTAQ doubles the risk of cardiovascular death (largely arrhythmic) and heart failure events in patients with permanent AF. Patients treated with dronedarone should undergo monitoring of cardiac rhythm no less often than every 3 months. Cardiovert patients who are in atrial fibrillation (if clinically indicated) or discontinue MULTAQ. MULTAQ offers no benefit in subjects in permanent AF. Increased Risk Of Stroke In Permanent AF In a placebo-controlled study in patients with permanent atrial fibrillation, dronedarone was associated with an increased risk of stroke, particularly in the first two weeks of therapy [see Clinical Studies]. MULTAQ should only be initiated in patients in sinus rhythm who are receiving appropriate antithrombotic therapy [see DRUG INTERACTIONS]. New Onset Or Worsening Heart Failure New onset or worsening of heart failure has been reported during treatment with MULTAQ in the postmarketing setting. In a placebo controlled study in patients with permanent AF increased rates of heart failure were observed in patients with normal left ventricular function and no history of symptomatic heart failure, as well as those with a history of heart failure or left ventricular dysfunction. Advise patients to consult a physician if they develop signs or symptoms of heart failure, such as weight gain, dependent edema, or increasing shortness of breath. If heart failure develops or worsens and requires hospitalization, discontinue MULTAQ. Liver Injury Hepatocellular liver injury, including acute liver failure requiring transplant, has been reported in patients treated with MULTAQ in the postmarketing setting. Advise patients treated with MULTAQ to report immediately symptoms suggesting hepatic injury (such as anorexia, nausea, vomiting, fever, malaise, fatigue, right upper quadrant pain, jaundice, dark urine, or itching). Consider obtaining periodic hepatic serum enzymes, especially during the first 6 months of treatment, but it is not known whether routine periodic monitoring of serum enzymes will prevent the development of severe liver injury. If hepatic injury is suspected, promptly discontinue MULTAQ and test serum enzymes, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase, as well as serum bilirubin, to establish whether there is liver injury. If liver injury is found, institute appropriate treatment and investigate the probable cause. Do not restart MULTAQ in patients without another explanation for the observed liver injury. Pulmonary Toxicity Cases of interstitial lung disease including pneumonitis and pulmonary fibrosis have been reported in patients treated with MULTAQ in the post-marketing setting [see ADVERSE REACTIONS]. Onset of dyspnea or non-productive cough may be related to pulmonary toxicity and patients should be carefully evaluated clinically. If pulmonary toxicity is confirmed, MULTAQ should be discontinued. Hypokalemia And Hypomagnesemia With Potassium-Depleting Diuretics Hypokalemia or hypomagnesemia may occur with concomitant administration of potassium-depleting diuretics. Potassium levels should be within the normal range prior to administration of MULTAQ and maintained in the normal range during administration of MULTAQ. QT Interval Prolongation Dronedarone induces a moderate (average of about 10 ms but much greater effects have been observed) QTc (Bazett) prolongation [see CLINICAL PHARMACOLOGY and Clinical Studies]. If the QTc Bazett interval is ≥ 500 ms, discontinue MULTAQ [see CONTRAINDICATIONS]. Renal Impairment And Failure Marked increase in serum creatinine, pre-renal azotemia and acute renal failure, often in the setting of heart failure [see WARNINGS AND PRECAUTIONS] or hypovolemia, have been reported in patients taking MULTAQ. In most cases, these effects appear to be reversible upon drug discontinuation and with appropriate medical treatment. Monitor renal function periodically. Small increases in creatinine levels (about 0.1 mg/dL) following dronedarone treatment initiation have been shown to be a result of inhibition of creatinine's tubular secretion. The elevation has a rapid onset, reaches a plateau after 7 days and is reversible after discontinuation. Women Of Childbearing Potential Premenopausal women who have not undergone a hysterectomy or oophorectomy must use effective contraception while using MULTAQ. Dronedarone caused fetal harm in animal studies at doses equivalent to recommended human doses. Counsel women of childbearing potential regarding appropriate contraceptive choices [see Use In Specific Populations]. Patient Counseling Information Information for Patients [See Medication Guide] MULTAQ should be administered with a meal. Warn patients not to take MULTAQ with grapefruit juice. If a dose is missed, patients should take the next dose at the regularly scheduled time and should not double the dose. Advise patients to consult a physician before stopping treatment with MULTAQ. Advise patients to consult a physician if they develop signs or symptoms of heart failure such as acute weight gain, dependent edema, or increasing shortness of breath. Advise patients to immediately report any symptoms of potential liver injury (such as anorexia, nausea, vomiting, fever, malaise, fatigue, right upper quadrant abdominal discomfort, jaundice, dark urine or itching) to their physician. Advise patients to inform their physician of any history of heart failure, rhythm disturbance other than atrial fibrillation or flutter or predisposing conditions such as uncorrected hypokalemia. MULTAQ may interact with some drugs; therefore, advise patients to report to their doctor the use of any other prescription, non-prescription medication or herbal products, particularly St. John's wort. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility In studies in which dronedarone was administered to rats and mice for up to 2 years at doses of up to 70 mg/kg/day and 300 mg/kg/day, respectively, there was an increased incidence of histiocytic sarcomas in dronedarone-treated male mice (300 mg/kg/day or 5X the maximum recommended human dose based on AUC comparisons), mammary adenocarcinomas in dronedarone-treated female mice (300 mg/kg/day or 8X MRHD based on AUC comparisons) and hemangiomas in dronedarone-treated male rats (70 mg/kg/day or 5X MRHD based on AUC comparisons). Dronedarone did not demonstrate genotoxic potential in the in vivo mouse micronucleus test, the Ames bacterial mutation assay, the unscheduled DNA synthesis assay, or an in vitro chromosomal aberration assay in human lymphocytes. S-9 processed dronedarone, however, was positive in a V79 transfected Chinese hamster V79 assay. In fertility studies conducted with female rats, dronedarone given prior to breeding and implantation caused an increase in irregular estrus cycles and cessation of cycling at doses ≥ 10mg/kg (equivalent to 0.12X the MRHD on a mg/m² basis). Corpora lutea, implantations and live fetuses were decreased at 100 mg/kg (equivalent to 1.2X the MRHD on a mg/m² basis). There were no reported effects on mating behavior or fertility of male rats at doses of up to 100 mg/kg/day. Use In Specific Populations Pregnancy Pregnancy Category X [see CONTRAINDICATIONS] MULTAQ may cause fetal harm when administered to a pregnant woman. In animal studies, dronedarone was teratogenic in rats at the maximum recommended human dose (MRHD), and in rabbits at half the MRHD. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. When pregnant rats received dronedarone at oral doses greater than or equal to the MRHD (on a mg/m²basis), 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, ectrodactylia, syndactylia, and anterior and/or posterior club feet). When pregnant rabbits received dronedarone, at a dose approximately half the MRHD (on a mg/m²basis), 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/m²basis). Actual animal doses: rat ( ≥ 80 mg/kg/day); rabbit ( ≥ 20 mg/kg) Nursing Mothers It is not known whether MULTAQ is excreted in human milk. Dronedarone and its metabolites are excreted in rat milk. During a pre-and post-natal study in rats, maternal dronedarone administration was associated with minor reduced body-weight gain in the offspring. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from MULTAQ, discontinue nursing or discontinue the drug [see CONTRAINDICATIONS]. Pediatric Use Safety and efficacy in children below the age of 18 years have not been established. Geriatric Use More than 4500 patients with AF or AFL aged 65 years or above were included in the MULTAQ clinical program (of whom more than 2000 patients were 75 years or older). Efficacy and safety were similar in elderly and younger patients. Renal Impairment Patients with renal impairment were included in clinical studies. Because renal excretion of dronedarone is minimal [see CLINICAL PHARMACOLOGY], no dosing alteration is needed. Hepatic Impairment Dronedarone is extensively metabolized by the liver. There is little clinical experience with moderate hepatic impairment and none with severe impairment. No dosage adjustment is recommended for moderate hepatic impairment [see CONTRAINDICATIONS and CLINICAL PHARMACOLOGY].