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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/83596/2015

EMEA/H/C/003687

EPAR summary for the public

Mysimba

naltrexone / bupropion

This is a summary of the European public assessment report (EPAR) for Mysimba. It explains how the Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is not intended to provide practical advice on how to use Mysimba.

For practical information about using Mysimba, patients should read the package leaflet or contact their doctor or pharmacist.

What is Mysimba and what is it used for?

Mysimba is a medicine used along with diet and exercise to help manage weight in adults:

• who are obese (have a body-mass index - BMI - of 30 or more);

• who are overweight (have a BMI between 27 and 30) and have weight-related complications such as diabetes, abnormally high levels of fat in the blood, or high blood pressure.

BMI is a measurement that indicates body weight relative to height.

Mysimba contains the active substances naltrexone and bupropion, which are licensed individually in the EU for other uses.

How is Mysimba used?

Mysimba is available as prolonged-release tablets containing 7.2 mg naltrexone and 78 mg bupropion and can only be obtained with a prescription. Prolonged-release means that naltrexone and bupropion are released slowly from the tablet over a few hours.

Treatment with Mysimba is started with a single tablet each morning, with the dose gradually increased over 4 weeks to the recommended dose of two tablets twice a day, preferably taken with food.

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Patients should have their response and tolerability to the medicine checked regularly and treatment should be stopped in patients who have certain side effects such as an increase in blood pressure. Mysimba should also be stopped if patients have not lost at least 5% of their initial body weight after 4 months of treatment.

For further information, see the package leaflet.

How does Mysimba work?

The exact way that Mysimba works is not fully understood, but the two active substances, naltrexone and bupropion, act on the parts of the brain that control food intake and energy balance, as well as reducing the effect of the part of the brain that controls the pleasure associated with eating food.

When given together, their actions reduce appetite and the amount that patients eat, and increase energy expenditure, helping them to stick to a calorie-controlled diet and to reduce their body weight.

What benefits of Mysimba have been shown in studies?

The effects of Mysimba in reducing body weight have been shown in 4 main studies involving around 4,500 obese or overweight patients, in which Mysimba was compared with placebo (a dummy treatment). Patients in the studies were given the medicine as part of a weight loss programme involving counselling and advice on diet and exercise. The main measures of effectiveness were the percentage reduction in body weight over 28 or 56 weeks of treatment, and the proportion of patients who achieved at least a 5% weight reduction; the studies also looked at the number of patients who achieved at least a more stringent 10% reduction in weight, and the results were analysed using various methods to take account of the number of patients who did not complete the studies (around 50% over one year).

In three of the studies, the average weight loss in patients treated with Mysimba was around 3.7 to 5.7%, compared with 1.3 to 1.9% with placebo; the proportion of Mysimba-treated patients who achieved 5% weight loss ranged from 28 to 42% compared with 12 to 14% with placebo. About 13 to 22% of those taking Mysimba achieved at least a 10% reduction in weight, while 5 to 6% of placebo-treated patients did so.

In the other study, in which patient counselling was also more intensive, the overall weight loss was greater over the study period: 8.1% with Mysimba and 4.9% with placebo. Some 46% and 30% of patients given Mysimba achieved 5 and 10% weight reductions respectively, compared with 34% and 17% respectively with placebo.

The degree of improvement with Mysimba over placebo was similar using different methods of analysis, although the benefits were smallest with the most conservative methods that assumed patients who did not complete the study would not have seen any improvement. The treatment effect was more marked in patients who completed 56 weeks of treatment, or who had lost at least 5% of their original body weight by 4 months.

What are the risks associated with Mysimba?

The most common side effects with Mysimba (which may affect more than 1 in 10 people) are nausea and vomiting (feeling and being sick) and constipation; dizziness and dry mouth were also common (seen in up to 1 patient in 10). For the full list of all side effects reported with Mysimba, see the package leaflet.

Mysimba must not be used in certain patients at particular risk of side effects, including patients with severely reduced kidney or liver function, those with high blood pressure that is not under control, those who have ever had seizures (fits), certain psychological problems or who have a brain tumour or are undergoing withdrawal from alcohol or certain drugs. For the full list of restrictions, see the package leaflet.

Why is Mysimba approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) considered that although the effectiveness of the medicine in promoting weight loss was limited, it was sufficient to be clinically significant, and mandatory re-assessment of treatment after 4 months should ensure that the medicine only continues to be used in those in whom the medicine provides adequate benefit. Regarding safety, although the CHMP had some concerns about possible effects on the heart and blood vessels (cardiovascular outcomes) and a slightly increased risk of seizures (fits), the most common side effects were largely manageable, as patients could stop taking the medicine if they were bothersome. Interim data from an ongoing study of cardiovascular outcomes were reviewed during the assessment although the CHMP also recommended ongoing monitoring of the medicine's cardiovascular effects. On the balance of the available evidence the CHMP decided that Mysimba's benefits are greater than its risks and recommended that it be approved for use in the EU.

What measures are being taken to ensure the safe and effective use of Mysimba?

A risk management plan has been developed to ensure that Mysimba is used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the package leaflet for Mysimba, including the appropriate precautions to be followed by healthcare professionals and patients.

In addition, the company that markets Mysimba will produce an information pack for doctors prescribing the medicine, including guidance on stopping treatment in patients who do not respond or if there are concerns about side effects. It will also carry out a further study to assess the effect of the medicine on the heart and blood vessels.

Further information can be found in the summary of the risk management plan.

Other information about Mysimba

The European Commission granted a marketing authorisation valid throughout the European Union for Mysimba on 26 March 2015.

The full EPAR and risk management plan summary for Mysimba 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 Mysimba, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 03-2015.

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Mysimba

EMA/83596/2015