Dronedarone tablets

Some medicines are not suitable for people with certain conditions, and sometimes a medicine may only be used if extra care is taken. For these reasons, before you start taking dronedarone it is important that your doctor knows:

• If you are pregnant, trying for a baby, or breast-feeding.
• If you have any problems with the way your liver works or with the way your kidneys work.
• If you have any other heart conditions.
• If you have ever had an allergic reaction to a medicine. It is particularly important that you tell your doctor if you have taken a medicine called amiodarone and had problems with your breathing as a result.
• If you are taking any other medicines. This includes any medicines you are taking which are available to buy without a prescription, as well as herbal and complementary medicines.

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.

In the event of overdosage, monitor the patient's cardiac rhythm and blood pressure. Treatment should be supportive and based on symptoms.

It is not known whether dronedarone or its metabolites can be removed by dialysis (hemodialysis, peritoneal dialysis or hemofiltration). There is no specific antidote available.

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

Dronedarone is used to treat intermittent or "temporary" heart rhythm disorders. In some people with "permanent" atrial fibrillation, dronedarone increased the risk of stroke, hospitalization due to heart failure, and death. Talk with your doctor about your individual risk. Do not stop taking this medication without first talking to your doctor. Stopping suddenly may make your condition worse.

You should not use dronedarone if you are allergic to dronedarone, if you are pregnant or breast-feeding, or if you have severe liver disease, certain serious heart conditions, especially severe heart failure, "AV block" or sick sinus syndrome (unless you have a pacemaker), a history of slow heart beats that have caused you to faint, or if you were recently hospitalized for heart failure.

There are many other medicines that can cause serious medical problems if you take them together with dronedarone. You may need to stop taking certain drugs while you are taking dronedarone. Tell your doctor about all other medications you use.

Also tell your doctor if you have kidney disease, liver disease, a history of heart failure, an electrolyte imbalance (such as low levels of potassium or magnesium in your blood), or if you have a pacemaker or defibrillator implanted in your chest.

Dronedarone can harm an unborn baby or cause birth defects. Do not use dronedarone if you are pregnant.

You may need regular medical tests to be sure this medication is not causing harmful effects. Visit your doctor regularly.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

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

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

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

Read the entire FDA prescribing information for Multaq (Dronedarone Tablets)

• Abnormal Heart Rhythms (Heart Rhythm Disorders)
• Atrial Fibrillation (AF, AFib)