[UPDATED 12/19/2011] FDA completed a safety review of dronedarone (Multaq). This review showed that dronedarone increased the risk of serious cardiovascular events, including death, when used by patients in permanent atrial fibrillation (AF). The review was based on data from two clinical trials, PALLAS and ATHENA. FDA is providing new information and recommendations for the use of dronedarone to manage the potential serious cardiovascular risks with the drug.
The dronedarone drug label has been revised with the following changes and recommendations:
- Healthcare professionals should not prescribe dronedarone to patients with AF who cannot or will not be converted into normal sinus rhythm (permanent AF), because dronedarone doubles the rate of cardiovascular death, stroke, and heart failure in such patients.
- Healthcare professionals should monitor heart (cardiac) rhythm by electrocardiogram (ECG) at least once every 3 months. If the patient is in AF, dronedarone should be stopped or, if clinically indicated, the patient should be cardioverted.
- Dronedarone is indicated to reduce hospitalization for AF in patients in sinus rhythm with a history of non-permanent AF (known as paroxysmal or persistent AF)
- Patients prescribed dronedarone should receive appropriate antithrombotic therapy.
For additional information, including a data summary, read the updated FDA Drug Safety Communication. For more information visit the FDA website at: Web Siteand Web Site.
[Posted 07/21/2011]ISSUE:FDA notified healthcare professionals that it is reviewing data from a clinical trial that evaluated the effects of the antiarrhythmic drug dronedarone (Multaq) in patients with permanent atrial fibrillation. The study was stopped early after the data monitoring committee found a two-fold increase in death, as well as two-fold increases in stroke and hospitalization for heart failure in patients receiving dronedarone compared to patients taking a placebo. FDA is evaluating whether and how the preliminary results of the PALLAS study apply to patients taking dronedarone for paroxysmal or persistent atrial fibrillation or atrial flutter. The PALLAS study results are considered preliminary at this time because the data have not undergone quality assurance procedures and have not been completely adjudicated. FDA will update the public when more information is available.
BACKGROUND:Dronedarone is approved for use to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors, who are in sinus rhythm or who will be cardioverted.
RECOMMENDATION:At this time, patients taking dronedarone should talk to their healthcare professional about whether they should continue to take dronedarone for non-permanent atrial fibrillation. Patients should not stop taking dronedarone without talking to a healthcare professional. Healthcare professionals should not prescribe dronedarone to patients with permanent atrial fibrillation. See the Data Summary in the Drug Safety Communication for additional details at: Web Site. For more information visit the FDA website at: Web Siteand Web Site.
You should not take dronedarone if you have severe heart failure. Dronedarone may increase the risk of death in people who have severe heart failure. Tell your doctor if you have heart failure that is severe enough to cause shortness of breath while you are at rest, after a small amount of exercise, or after any physical activity. Also tell your doctor if you have been hospitalized for heart failure during the past month even if you are feeling better. Your doctor will not prescribe dronedarone for you.
Your doctor or pharmacist will give you the manufacturer's patient information sheet (Medication Guide) when you begin treatment with dronedarone and each time you refill your prescription. Read the information carefully and ask your doctor or pharmacist if you have any questions. You can also visit the Food and Drug Administration (FDA) website ( Web Site) or the manufacturer's website to obtain the Medication Guide.
Dronedarone is used to treat people who have had atrial fibrillation (a heart rhythm disorder that may cause the heartbeat to be fast and irregular) or atrial flutter (a heart rhythm disorder that may cause the heartbeat to be fast but regular) during the past 6 months and who also have certain other conditions that increase the risk that they will develop heart problems. Dronedarone decreases the risk that people who have these conditions will need to be hospitalized to treat heart problems. Dronedarone is in a class of medications called antiarrhythmics. It works by helping the heart to beat normally.
Dronedarone comes as a tablet to take by mouth. It is usually taken twice a day, with the morning meal and the evening meal. Take dronedarone at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take dronedarone exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Dronedarone will help control your heartbeat only as long as you continue to take it. Continue to take dronedarone even if you feel well and have felt well for a long time. Do not stop taking dronedarone without talking to your doctor.
This medication may be prescribed for other uses; ask your doctor or pharmacist for more information.
Before taking dronedarone,
- tell your doctor and pharmacist if you are allergic to dronedarone, any other medications, or any of the ingredients in dronedarone tablets. Ask your pharmacist or check the Medication Guide for a list of the ingredients.
- tell your doctor if you are taking any of the following medications: certain antidepressants such as amitriptyline (in Limbitrol), amoxapine, clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil); certain antifungals such as itraconazole (Sporanox), ketoconazole (Nizoral), or voriconazole (Vfend); clarithromycin (Biaxin); cyclosporine (Gengraf, Neoral, Sandimmune); erythromycin (E.E.S., E-Mycin, Erythrocin); medications for irregular heartbeat such as amiodarone (Cordarone, Pacerone), disopyramide (Norpace), dofetilide (Tikosyn), flecainide (Tambocor), propafenone (Rythmol), quinidine, and sotalol (Betapace); nefazodone; phenothiazine medications for mental illness or nausea; ritonavir (Norvir); or telithromycin (Ketek). Your doctor may tell you not to take dronedarone if you are taking one or more of these medications.
- tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, and nutritional supplements you are taking or plan to take. Be sure to mention any of the following: anticoagulants (blood thinners) such as warfarin (Coumadin); beta blockers such as atenolol (Tenormin), labetalol (Normodyne), metoprolol (Lopressor, Toprol XL), nadolol (Corgard), and propranolol (Inderal); calcium channel blockers such as diltiazem (Cardizem, Dilacor, Tiazac), nifedipine (Adalat, Procardia), and verapamil (Calan, Covera, Isoptin, Verelan); carbamazepine (Epitol, Equetro, Tegretol); cholesterol-lowering medications (statins) such as atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravachol), and simvastatin (Zocor); digoxin (Lanoxicaps, Lanoxin); diuretics (water pills); phenobarbital; phenytoin (Dilantin); rifampin (Rifadin, Rimactane); selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), paroxetine (Paxil), and sertraline (Zoloft); sirolimus (Rapamune); and tacrolimus (Prograf). Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
- tell your doctor what herbal products you are taking, especially St. John's wort.
- tell your doctor if you have any other heart problems such as a fast heartbeat, a long QT interval (a heart problem that may cause irregular heartbeat, fainting, or sudden death), or liver disease. Your doctor may tell you not to take dronedarone.
- tell your doctor if you have or have ever had any other medical conditions.
- tell your doctor if you are pregnant or plan to become pregnant. You must use effective birth control during your treatment with dronedarone. Talk to your doctor about birth control methods that will work for you. If you become pregnant while taking dronedarone, call your doctor immediately. Dronedarone may harm the fetus.
- you should not breast-feed during your treatment with dronedarone.
Do not eat grapefruit or drink grapefruit juice while taking this medication.
Unless your doctor tells you otherwise, continue your normal diet.
Skip the missed dose and continue your regular dosing schedule. Do not try to make up for a missed dose or take a double dose to make up for a missed one.
Dronedarone may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:
- shortness of breath
- chest tightness
- coughing up frothy mucus
- difficulty sleeping due to breathing problems
- need to prop yourself up with extra pillows in order to breathe at night
- weight gain (of 5 or more pounds) in a short period of time
- swelling of the feet or legs
- slowed heartbeat
- flu-like symptoms
- yellowing of the skin or eyes
- unusual bruising or bleeding
- loss of appetite
- pain in the upper right part of the stomach
- tiredness or lack of energy
- unusual darkening of the urine
- light colored stools
Dronedarone may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online [at Web Site] or by phone [1-800-332-1088].
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
In case of overdose, call your local poison control center at 1-800-222-1222. If the victim has collapsed or is not breathing, call local emergency services at 911.
Keep all appointments with your doctor and the laboratory. Your doctor may order certain lab tests to check your body's response to dronedarone.
Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.
It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
AHFS® Consumer Medication Information. © Copyright, The American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland. All Rights Reserved. Duplication for commercial use must be authorized by ASHP.
Selected Revisions: February 15, 2012.