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Summary Public Assessment Report

Generics

Levodopa/Carbidopa/Entacapone Mylan 50 mg/12.5 mg/200 mg, film-coated tablets Levodopa/Carbidopa/Entacapone Mylan 75 mg/18.75 mg/200 mg, film-coated tablets Levodopa/Carbidopa/Entacapone Mylan 100 mg/25 mg/200 mg, film-coated tablets Levodopa/Carbidopa/Entacapone Mylan 125 mg/31.25 mg/200 mg, film-coated tablets Levodopa/Carbidopa/Entacapone Mylan 150 mg/37.5 mg/200 mg, film-coated tablets Levodopa/Carbidopa/Entacapone Mylan 175 mg/43.75 mg/200 mg, film-coated tablets Levodopa/Carbidopa/Entacapone Mylan 200 mg/50 mg/200 mg, film-coated tablets

(levodopa/carbidopa/entacapone)

NL/H/3403/001-007/DC

Date: 13 November 2016

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E B M Summary Public Assessment Report

Generics

Levodopa/Carbidopa/Entacapone Mylan 50 mg/12.5 mg/200 mg, 75 mg/18.75 mg/200 mg, 100 mg/25 mg/200 mg, 125 mg/31.25 mg/200 mg, 150 mg/37.5 mg/200 mg, 175 mg/43.75 mg/200 mg and 200 mg/50 mg/200 mg, film-coated tablets

Active substance: levodopa, carbidopa and entacapone

This is a summary of the public assessment report (PAR) for Levodopa/Carbidopa/Entacapone Mylan. It explains how this medicine was assessed and its authorisation recommended as well as its conditions of use. It is not intended to provide practical advice on how to use Levodopa/Carbidopa/Entacapone Mylan.

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

What is Levodopa/Carbidopa/Entacapone Mylan and what is it used for? Levodopa/Carbidopa/Entacapone Mylan is a ‘generic medicine’. This means that it is similar to a ‘reference medicine’ already authorised in the European Union (EU) called Stalevo.

Levodopa/Carbidopa/Entacapone Mylan is used to treat adults with Parkinson’s disease. Parkinson’s disease is a progressive brain disorder that causes shaking, slow movement and muscle stiffness. Levodopa/Carbidopa/Entacapone Mylan is used in patients who are being treated with a combination of levodopa and an inhibitor of dopa decarboxylase (two standard treatments for Parkinson’s disease) but are having ‘fluctuations’ towards the end of the period between two doses of their medication. Fluctuations happen when the effects of the medication wear off and symptoms re-emerge. They are linked with a reduction in the effect of levodopa, when the patient experiences sudden switches between being ‘on’ and able to move, and being ‘off’ and having difficulty moving about. Levodopa/Carbidopa/Entacapone Mylan is used when these fluctuations cannot be treated with the standard combination alone.

How does this medicine work? Levodopa/Carbidopa/Entacapone Mylan is a medicine that contains three active substances: levodopa, carbidopa and entacapone. In patients with Parkinson’s disease, the cells in the brain that produce the neurotransmitter dopamine begin to die and the amount of dopamine in the brain decreases. The patients then lose their ability to control their movements reliably. All of the active substances in Stalevo work to restore the levels of dopamine in the parts of the brain that control movement and co-ordination. Levodopa is converted into dopamine in the brain. Both carbidopa and entacapone block some of the enzymes that are involved in the breakdown of levodopa in the body: carbidopa blocks the enzyme dopa decarboxylase, and entacapone blocks the enzyme catechol-O-methyl transferase (COMT). As a result, levodopa remains active for longer. This helps to improve the symptoms of Parkinson’s disease, such as stiffness and slowness of movement. Entacapone has been authorised in the European Union (EU) as Comtess/Comtan since 1998. The use of combinations of levodopa and carbidopa is well established, having being in use since the mid- 1970s. Having all three substances in the same tablet can lower the number of tablets the patients have to take and help them stick to treatment.

How is this medicine used? The pharmaceutical form of Levodopa/Carbidopa/Entacapone Mylan is a film-coated tablet and the route of administration is oral. The medicine can only be obtained with a prescription. Each Levodopa/Carbidopa/Entacapone Mylan tablet contains one complete dose of levodopa, in seven strengths, with corresponding amounts of carbidopa and entacapone to improve its effectiveness. The strength of Levodopa/Carbidopa/Entacapone Mylan that the patient should use is based on the amount of levodopa they need to control their symptoms. The maximum daily dose of Levodopa/Carbidopa/Entacapone Mylan is 10 tablets, except for the tablets containing 200 mg levodopa and 50 mg carbidopa, for which the maximum daily dose is seven

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E B M tablets. Levodopa/Carbidopa/Entacapone Mylan tablets should be taken whole, with or without food. They should be used with caution in patients with mild to moderate problems with their liver or severe problems with their kidneys. They should not be used in patients with severe liver problems.

Please read section 3 of the PL for detailed information on dosing recommendations, the route of administration, and the duration of treatment.

How has this medicine been studied? Because Levodopa/Carbidopa/Entacapone Mylan is a generic medicine, studies in patients have been limited to tests to determine that it is bioequivalent to the reference medicine, Stalevo. Two medicines are bioequivalent when they produce the same levels of the active substance in the body.

What are the possible side effects of this medicine? Because Levodopa/Carbidopa/Entacapone Mylan is a generic medicine and is bioequivalent to the reference medicine, its benefits and possible side effects are taken as being the same as the reference medicine.

For the full list of all side effects reported with this medicine, see section 4 of the package leaflet.

Why is this medicine approved? It was concluded that, in accordance with EU requirements, this medicine has been shown to have comparable quality and to be bioequivalent to the reference medicine. Therefore, the Medicines Evaluation Board of the Netherlands decided that, as for Stalevo, the benefits are greater than its risk and recommended that it can be approved for use.

What measures are being taken to ensure the safe and effective use of this medicine? A risk management plan has been developed to ensure that this medicine 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 Levodopa/Carbidopa/Entacapone Mylan, including the appropriate precautions to be followed by healthcare professionals and patients. Known side effects are continuously monitored. Furthermore new safety signals reported by patients/healthcare professionals will be monitored/reviewed continuously as well.

Other information about this medicine In the Netherlands, the marketing authorisation for Levodopa/Carbidopa/Entacapone Mylan was granted on 7 January 2016.

The full PAR for this medicine can be found on the website http://mri.medagencies.org/Human. For more information about treatment with Levodopa/Carbidopa/Entacapone Mylan, read the package leaflet (http://mri.medagencies.org/download/NL_H_3403_001_FinalPL.pdf) or contact your doctor or pharmacist.

This summary was last updated in November 2016.

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