For doctors

What is it?

Multaq is a medicine that contains the active substance dronedarone. It is available as white, oblong tablets (400 mg).

What is it used for?

Multaq is used in adults who have had atrial fibrillation in the past or who currently have non-permanent fibrillation. Atrial fibrillation happens when the atria (the upper chambers of the heart) contract irregularly and rapidly. Multaq is used to prevent the fibrillation coming back or to lower the heart rate.
The medicine can only be obtained with a prescription.

How is it used?

The recommended dose of Multaq is one tablet taken twice a day, with the morning and evening meals. The tablets should not be taken together with grapefruit juice.

How does it work?

The active substance in Multaq, dronedarone, is an anti-arrhythmic medicine. It works mainly by blocking channels through which charged particles of potassium move in and out of the muscle cells. The flow of charged particles in and out of the muscle cells produces the excessive electrical activity that leads to atrial fibrillation and rapid heart rate. By reducing the flow of potassium through the channels, Multaq prevents the fibrillation from happening and lowers the heart rate.

How has it been studied?

The effects of Multaq were first tested in experimental models before being studied in humans. There were five main studies of Multaq in adults who had had atrial fibrillation. Three of these studies involving 1411 patients compared Multaq with placebo. The main measures of effectiveness were how long it took before the patients had an episode of atrial fibrillation again or the change in the patients’ heart rate after two weeks.

The fourth study compared Multaq with amiodarone (another medicine used to prevent atrial fibrillation) in 504 patients and looked at the number of patients in whom atrial fibrillation came back or who had to stop treatment because it was causing side effects or not working. The fifth study compared Multaq with placebo in almost 5,000 patients and looked at whether Multaq is effective at reducing and delaying death or hospitalisation due to cardiovascular problems (problems affecting the heart and blood vessels).

What benefits has it shown during the studies?

Multaq was more effective than placebo at preventing atrial fibrillation from reoccurring. In the first three placebo studies, it took an average of 116 days for fibrillation to come back in the patients taking Multaq compared with 53 days in the patients taking placebo. In addition, heart rates reduced by an average of 11.0 beats per minute (bpm) in the patients who took Multaq, compared with a rise of 0.7 bpm in the patients who took placebo.
In the fourth study, Multaq was less effective than amiodarone at maintaining normal rhythm: after a year, atrial fibrillation had come back or treatment had been stopped in 75% of the patients taking Multaq, compared with 59% of the patients receiving amiodarone. Atrial fibrillation came back more often in patients receiving Multaq, but more patients receiving amiodarone had to stop treatment because of side effects.
The fifth study provided further support for the use of Multaq in maintaining normal rhythm and reducing the heart rate. The study showed a reduction in the number of cardiovascular hospitalisations, particularly those related to atrial fibrillations.

What is the risk associated?

The most common side effects with Multaq (seen in more than 1 patient in 10) are increased blood levels of creatinine (a breakdown product of muscle) and a prolonged ‘QTc Bazett’ (an alteration of the electrical activity of the heart). For the full list of all side effects reported with Multaq, see the Package Leaflet.
Multaq should not be used in people who may be hypersensitive (allergic) to the active substance or any of the other ingredients. It must not be taken with medicines that can cause torsades de pointes (a type of rapid heart beat). Multaq must not be used in patients with certain heart problems, such as some types of altered electrical activity of the heart, very slow heart beats or when the heart cannot pump enough blood around the body. It must also not be used in patients who have severe problems with their liver or kidneys. For the full list of restrictions, see the Package Leaflet.

Why has it been approved?

The Committee for Medicinal Products for Human Use (CHMP) noted that although Multaq was less effective than the comparator medicine at maintaining normal rhythm, it may be associated with fewer side effects. Multaq was also more effective than placebo at preventing atrial fibrillation coming back and at controlling the heart rate. The number of patients in the main studies who had taken Multaq and the length of time they had taken the medicine for also allowed the Committee to carry out an adequate assessment of its benefits and risks.
Based on the available evidence, the CHMP decided that Multaq’s benefits are greater than its risks and recommended that Multaq be given marketing authorisation.

How has it been studied?

The company that makes Multaq will ensure that healthcare professionals who prescribe the medicine in all Member States and pharmacists are provided with list of medicines that interact with Multaq and information reminding them how to use Multaq safely.

Further information

The European Commission granted a marketing authorisation valid throughout the European Union for Multaq to Sanofi-Aventis on 26 November 2009. The marketing authorisation is valid for five years, after which it can be renewed.

Name

MULTAQ 400 mg film-coated tablets

Composition

Each tablet contains 400 mg of dronedarone (as hydrochloride).

Excipients:
Each tablet also contains 41.65 mg of lactose (as monohydrate).
For a full list of excipients, see section 6.1.

Pharmaceutical Form

Film-coated tablet (tablet).

White, oblong shaped tablets, engraved with a double wave marking on one side and “4142”code on the other side.