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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/665546/2012

EMEA/H/C/001043

EPAR summary for the public

Multaq

dronedarone

This is a summary of the European public assessment report (EPAR) for Multaq. It explains how the Committee for Medicinal Products for Human Use (CHMP) assessed the medicine to reach its opinion in favour of granting a marketing authorisation and its recommendations on the conditions of use for Multaq.

What is Multaq?

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

What is Multaq used for?

Multaq is used to maintain normal heart rhythm in adults with types of non-permanent atrial fibrillation known as 'persistent' or 'paroxysmal' after normal heart rhythm has been restored. Atrial fibrillation happens when the atria (the upper chambers of the heart) contract irregularly and rapidly.

Multaq should only be prescribed after alternative treatment options have been considered.

Multaq should not be given to patients with left ventricular systolic dysfunction (a problem affecting the left side of the heart) or patients who have or have had heart failure (when the heart cannot pump enough blood around the body).

The medicine can only be obtained with a prescription.

How is Multaq used?

Treatment with Multaq should be started and monitored under specialist supervision.

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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 Multaq 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 Multaq been studied?

There were six main studies of Multaq in adults who had had atrial fibrillation. Three of these studies involving 1,411 patients compared Multaq with placebo (a dummy treatment). The main measure of effectiveness was 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 was effective at reducing and delaying death or hospitalisation due to cardiovascular problems (problems affecting the heart and blood vessels).

A sixth study (PALLAS) compared Multaq with placebo in patients over 65 years of age with permanent atrial fibrillation and several risk factors. The study was stopped early because of the occurrence of severe cardiovascular events (such as cardiovascular death or hospitalisation and stroke) in some patients taking Multaq.

What benefit has Multaq 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 events leading to hospitalisations particularly those related to atrial fibrillations.

What is the risk associated with Multaq?

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), a prolonged 'QTc Bazett' (an alteration of the

Multaq electrical activity of the heart) and congestive heart failure (a type of heart disease), but this side effect occurred at a similar rate in patients who took placebo in clinical studies. For the full list of all side effects reported with Multaq, see the package leaflet.

Multaq must not be used in people who are 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), or with dabigatran (a medicine to prevent blood clotting). It must not be used in patients with permanent atrial fibrillation of unknown duration or lasting for more than six months when the doctor has decided not to try to restore normal rhythm. It must also not be used in patients with some other heart problems, such as some problems with the electrical activity, very slow heart beats or heart failure.

Multaq must not be used in patients who have severe problems with their liver or kidneys. Patients who have had previous liver or lung injury following treatment with amiodarone (another antiarrhythmic medicine) must not be given Multaq. For the full list of restrictions, see the package leaflet.

Why has Multaq been approved?

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.

Multaq was originally approved to prevent atrial fibrillation from coming back or to lower the heart rate in adults who have had or have non-permanent atrial fibrillation. In September 2011 this indication was restricted to the maintenance of normal heart rhythm in 'persistent' or 'paroxysmal' atrial fibrillation after normal heart rhythm has been restored. This followed a review of data that became available since its authorisation including data from the PALLAS study.¹

What measures are being taken to ensure the safe use of Multaq?

The company that makes Multaq must ensure that healthcare professionals who prescribe and dispense the medicine in all Member States are provided with a 'prescriber checklist' and a special 'information card'. The prescriber checklist will help healthcare professionals select patients for whom Multaq is appropriate. The information card will remind prescribers how to use the medicine safely. It will also include information on when not to use Multaq, medicines that interact with Multaq, and the need to monitor the function of the liver, lung, heart and kidneys before and during treatment to help manage the risk of severe complications.

Other information about Multaq

The European Commission granted a marketing authorisation valid throughout the European Union for Multaq on 26 November 2009.

The full EPAR for Multaq can be found on the Agency's website ema.europa.eu/Find medicine/Human medicines/European Public Assessment Reports. For more information about treatment with Multaq, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 11-2012.

¹ In the context of a procedure under Article 20 of Regulation (EC) No 726/2004.

Multaq

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