Public Assessment Report - GOV.UK

1 Public Assessment Report Decentralised Procedure Acamprosate 333 mg Gastro-resistant Tablets (acamprosate calcium) Procedure No: UK/H/5445/001/DC UK Licence No: PL 17871/0206 Jenson Pharmaceutical Services Ltd PAR Acamprosate 333 mg Gastro-resistant Tablets UK/H/5445/001/DC 2 LAY SUMMARY Acamprosate 333 mg Gastro-resistant Tablets (acamprosate calcium) This is a summary of the Public Assessment Report (PAR) for Acamprosate 333 mg Gastro-resistant Tablets (PL 17871/0206). It explains how Acamprosate 333 mg Gastro-resistant Tablets were assessed and their authorisation recommended as well as their conditions of use. It is not intended to provide practical advice on how to use Acamprosate 333 mg Gastro-resistant Tablets. For practical information about using Acamprosate 333 mg Gastro-resistant Tablets, patients should read the package leaflet or contact their doctor or pharmacist.

2 What are Acamprosate 333 mg Gastro-resistant Tablets and what are they used for? Acamprosate 333 mg Gastro-resistant Tablets is a generic medicine . This means that Acamprosate 333 mg Gastro-resistant Tablets are similar to a reference medicine already authorised in the European Union (EU) called Campral EC (Merck Sant ; PL 13466/0001). Acamprosate 333 mg Gastro-resistant Tablets are used for the treatment of alcohol dependence. Acamprosate in combination with counselling will help a patient to maintain abstinence in alcohol-dependent patients. How are Acamprosate 333 mg Gastro-resistant Tablets used? Acamprosate 333 mg Gastro-resistant Tablets are taken by mouth. The tablet should be swallowed whole. Patients should avoid chewing or crushing the tablet as this may damage the gastro-resistant coating. The recommended dose in adults (18-65 years) with body weight of 60 kg or more is 6 tablets a day (2 tablets in the morning, 2 tablets at noon and 2 tablets in the evening with meals).

3 In patients with body weight less than 60 kg, the recommended dose is 4 tablets a day (2 in the morning, 1 at noon and 1 in the evening with meals). It is advised that the patient keeps taking this medicinal product for one year. Acamprosate 333 mg Gastro-resistant Tablets can only be obtained on prescription from a doctor. For further information on how Acamprosate 333 mg Gastro-resistant Tablets are used, please see the Summary of Product Characteristics and package leaflet available on the MHRA website. How do Acamprosate 333 mg Gastro-resistant Tablets work? Acamprosate 333 mg Gastro-resistant Tablets is a medicine which acts on the central nervous system (the brain and the spinal cord). This product works by acting on the chemical changes that have taken place in the brain during the years that the patient has been drinking alcohol.

4 It does not prevent the harmful effects of continuous alcohol abuse. How have Acamprosate 333 mg Gastro-resistant Tablets been studied? Because Acamprosate 333 mg Gastro-resistant Tablets is a generic medicine, studies in patients have been limited to tests to determine that it is bioequivalent to the reference medicine, Campral EC (Merck Sant ; PL 13466/0001). Two medicines are bioequivalent when they produce the same levels of the active substance in the body. What are the benefits and risks of Acamprosate 333 mg Gastro-resistant Tablets? As Acamprosate 333 mg Gastro-resistant Tablets is a generic medicine that is bioequivalent to Campral EC, its benefits and risks are taken as being the same as those for Campral EC (Merck Sant ; PL 13466/0001). PAR Acamprosate 333 mg Gastro-resistant Tablets UK/H/5445/001/DC 3 Why are Acamprosate 333 mg Gastro-resistant Tablets approved?

5 It was concluded that, in accordance with EU requirements, Acamprosate 333 mg Gastro-resistant Tablets have been shown to have comparable quality and to be bioequivalent to Campral EC (Merck Sant ; PL 13466/0001). Therefore, the view was that, as for Campral EC (Merck Sant ; PL 13466/0001) the benefit outweighs the identified risk. What measures are being taken to ensure the safe and effective use of Acamprosate 333 mg Gastro-resistant Tablets? A risk management plan has been developed to ensure that Acamprosate 333 mg Gastro-resistant Tablets are 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 Acamprosate 333 mg Gastro-resistant Tablets, including the appropriate precautions to be followed by healthcare professionals and patients.

6 Other information about Acamprosate 333 mg Gastro-resistant Tablets Slovak Republic and the UK agreed to grant a Marketing Authorisation for Acamprosate 333 mg Gastro-resistant Tablets on 12th September 2014. A Marketing Authorisation was granted in the UK on 14th October 2014. The full PAR for Acamprosate 333 mg Gastro-resistant Tablets follows this summary. For more information about treatment with Acamprosate 333 mg Gastro-resistant Tablets, read the package leaflet or contact your doctor or pharmacist. This summary was last updated in December 2014. PAR Acamprosate 333 mg Gastro-resistant Tablets UK/H/5445/001/DC 4 Information about initial procedure Product Name Acamprosate 333 mg Gastro-resistant Tablets Type of Application Generic, Article 10(1) Active Substances Acamprosate calcium Form Gastro-resistant Tablets Strength 333 mg MA Holder Jenson Pharmaceutical Services Ltd Carradine House, 237 Regent s Park Road, London, N3 3LF United Kingdom Reference Member State (RMS) UK Concerned Member States (CMSs)

7 Slovak Republic Procedure Numbers UK/H/5445/001/DC Timetable Day 208 12th September 2014 PAR Acamprosate 333 mg Gastro-resistant Tablets UK/H/5445/001/DC 5 TABLE OF CONTENTS I Introduction Page 6 II Quality aspects Page 7 III Non-clinical aspects Page 8 IV Clinical aspects Page 8 V User consultation Page 12 VI Overall conclusion, benefit/risk Assessment and Page 12 Recommendation Annex 1 Table of content of the PAR update for Page 13 MRP and DCP PAR Acamprosate 333 mg Gastro-resistant Tablets UK/H/5445/001/DC 6 I INTRODUCTION Based on the review of the data on quality, safety and efficacy, the Reference Member State (RMS) and Concerned Member State (CMS) considered that the application for Acamprosate 333 mg Gastro-resistant Tablets (PL 17871/0206; UK/H/5445/001/DC), indicated as therapy to maintain abstinence in alcohol-dependent patients combined with counselling is approvable.

8 The application was submitted using the Decentralised Procedure (DCP), with the UK as the RMS and Slovak Republic as CMS. The application was submitted under Article 10(1) of Directive 2001/83/EC, as amended. The originator product is Aotal 333 mg, comprim enrob gastro-r sistant, authorised to Merck Sant (Exploitant: Merck Serono SAS) on 24th July 1987. The applicant has cross referred to Campral EC, which was first licensed to Merck Sant in the UK (PL 13466/0001) on 18th December 1995. Acamprosate (calcium acetylhomotaurinate) has a chemical structure similar to that of amino acid neuromediators, such as taurine or gamma-amino-butyric acid (GABA), including an acetylation to permit passage across the blood brain barrier. The applicant has submitted two bioequivalence studies comparing the test product, Acamprosate calcium 333 mg Gastro-resistant Tablets (Mylan Laboratories Limited), with the reference product Aotal (acamprosate calcium) 333 mg gastro-resistant Tablets (Merck Serono ) in healthy, adult, human subjects under fasting and fed conditions.

9 Bioequivalence studies were carried out in accordance with Good Clinical Practice (GCP). With the exception of the bioequivalence studies, no new non-clinical or clinical studies were conducted, which is acceptable given that the application was based on being a generic medicinal product of an originator product that has been licensed for over 10 years. The RMS has been assured that acceptable standards of Good Manufacturing Practice are in place for this product type at all sites responsible for the manufacture, assembly and batch release of this product. For manufacturing sites within the Community, the RMS has accepted copies of current manufacturer authorisations issued by inspection services of the competent authorities as certification that acceptable standards of GMP are in place at those sites. For manufacturing sites outside the community, the RMS has accepted copies of current GMP Certificates or satisfactory inspection summary reports, close-out letters or exchange of information issued by the inspection services of the competent authorities (or those countries with which the EEA has a Mutual Recognition Agreement for their own territories) as certification that acceptable standards of GMP are in place at those non-Community sites.

10 All involved Member States agreed to grant a Marketing Authorisation for the above product at the end of the procedure (Day 208 12th September 2014). After a subsequent national phase, the UK granted a Marketing Authorisation (PL 17871/0206) for this product on 14th October 2014. PAR Acamprosate 333 mg Gastro-resistant Tablets UK/H/5445/001/DC 7 II QUALITY ASPECTS Introduction This product is a gastro-resistant tablet and contains mg of acamprosate calcium, as the active ingredient. The excipients are glycerol dibehenate, cellulose, microcrystalline, hypromellose, silica, colloidal anhydrous, magnesium stearate making up the tablet core, and hypromellose (tablet seal coating), methacrylic acid-ethyl acrylate copolymer, talc and propylene glycol (tablet gastro-resistant coating) and the printing ink (shellac, black iron oxide (E172), propylene glycol (E1520) and ammonium hydroxide (E527)).