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Included as part of the PRECAUTIONS section.

Patients with New or Worsening Heart Failure during Treatment

Postmarketing cases of new onset and worsening heart failure have been reported during treatment with Multaq (dronedarone tablets) . 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, consider the suspension or discontinuation of MULTAQ (dronedarone tablets) .

Liver Injury

Hepatocellular liver injury, including acute liver failure requiring transplant, has been reported in patients treated with MULTAQ (dronedarone tablets) in the post-marketing setting. Advise patients treated with MULTAQ (dronedarone tablets) 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. 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 (dronedarone tablets) 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 (dronedarone tablets) in patients without another explanation for the observed liver injury.

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 (dronedarone tablets) 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, MULTAQ should be stopped [see CONTRAINDICATIONS].

Increase in Creatinine after Treatment Initiation

Serum creatinine levels increase by about 0.1 mg/dL following dronedarone treatment initiation. The elevation has a rapid onset, reaches a plateau after 7 days and is reversible after discontinuation. If an increase in serum creatinine occurs and plateaus, this increased value should be used as the patient's new baseline. The change in creatinine levels has been shown to be the result of an inhibition of creatinine's tubular secretion, with no effect upon the glomerular filtration rate.

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. Women of childbearing potential should be counseled regarding appropriate contraceptive choices taking into consideration their underlying medical conditions and lifestyle preferences [see Use In Specific Populations].

Patient Counseling Information

[See Medication Guide]

MULTAQ (dronedarone tablets) should be administered with a meal. Warn patients not to take MULTAQ (dronedarone tablets) 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 if they develop signs or symptoms of worsening 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 (dronedarone tablets) 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 (dronedarone tablets) 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/m² basis), 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/m² basis), 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/m² basis).

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 (dronedarone tablets) , a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother [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 (dronedarone tablets) 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].

Last reviewed on RxList: 5/10/2011
This monograph has been modified to include the generic and brand name in many instances.