Public Assessment Report Levetiracetam 250 mg film-coated ...

1 Public Assessment Report Decentralised Procedure Levetiracetam 250 mg film - coated tablets PL 36390/0168; UK/H/5630/001/DC. Levetiracetam 500 mg film - coated tablets PL 36390/0169; UK/H/5630/002/DC. Levetiracetam 750 mg film - coated tablets PL 36390/0170; UK/H/5630/003/DC. Levetiracetam 1000 mg film - coated tablets PL 36390/0171; UK/H/5630/004/DC. Levetiracetam Cipla (EU) Limited PAR Levetiracetam 250, 500, 750 & 1000mg film - coated tablets UK/H/5630/001-004/DC. LAY SUMMARY. This is a summary of the Public Assessment Report (PAR) for Levetiracetam 250, 500, 750. & 1000mg film - coated tablets (PL 36390/0168-0171; UK/H/5630/001-004/DC). Levetiracetam 250, 500, 750 & 1000mg film - coated tablets will be termed Levetiracetam film - coated tablets throughout this PAR for ease of reading. It explains how Levetiracetam film - coated tablets were assessed and their authorisations recommended, as well as their conditions of use.

2 It is not intended to provide practical advice on how to use these products. For practical information about using Levetiracetam film - coated tablets, patients should read the Package Leaflet or contact their doctor or pharmacist. What are Levetiracetam film - coated tablets and what are they used for? Levetiracetam film - coated tablets are a generic medicine'. This means that they are similar to a reference medicine', already authorised in the European Union (EU) called Keppra film - coated tablets. Levetiracetam film - coated tablets are treatments for epilepsy. They are to be used: on their own in adults and adolescents from 16 years of age with newly diagnosed epilepsy, to treat partial onset seizures with or without secondary generalisation. as an add-on to other antiepileptic drugs to treat o partial onset seizures with or without generalisation in adults, adolescents, children and infants from one month of age o myoclonic seizures in adults and adolescents from 12 years of age with juvenile myoclonic epilepsy o primary generalised tonic-clonic seizures in adults and adolescents from 12 years of age with idiopathic generalised epilepsy How do Levetiracetam film - coated tablets work?

3 Levetiracetam film - coated tablets contain the active substance Levetiracetam . This is an antiepileptic medicine. Epilepsy is caused by excessive electrical activity in the brain. The exact way that Levetiracetam works is still unclear, but it seems to interfere with a protein called synaptic vesicle protein 2A', which is found in the spaces between nerves and is involved in the release of chemical messengers from nerve cells. This helps Levetiracetam to stabilise electrical activity in the brain and prevent seizures. Each film - coated tablet contains 250, 500, 750 or 1000mg Levetiracetam . How are Levetiracetam film - coated tablets used? Levetiracetam film - coated tablets should be taken twice a day, once in the morning and once in the evening, at about the same time each day. They should be taken as per the doctor's instructions.

4 The tablets should be swallowed with a sufficient quantity of liquid ( a glass of water). Please read Section 3 of the Package Leaflet for detailed information on dosing recommendations, the route of administration and the duration of treatment. This medicine can only be obtained with a prescription. How have Levetiracetam film - coated tablets been studied? Because Levetiracetam film - coated tablets are generic medicines, studies in patients have been limited to tests to determine that they are bioequivalent to the reference medicine, 2 . PAR Levetiracetam 250, 500, 750 & 1000mg film - coated tablets UK/H/5630/001-004/DC. Keppra film coated tablets. Two medicines are bioequivalent when they produce the same levels of the active substance in the body. What are the possible side effects of Levetiracetam film - coated tablets?

5 Because Levetiracetam film - coated tablets are a generic medicine, their benefits and possible side-effects are taken as being the same as the reference medicine, Keppra film - coated tablets. For further information, please see Section 4 the Package Leaflet. Why are Levetiracetam film - coated tablets approved? It was concluded that, in accordance with EU requirements, Levetiracetam film - coated tablets have been shown to have comparable quality and be bioequivalent to Keppra film - coated tablets. Therefore, the view was that, as for Keppra film - coated tablets, the benefits outweigh the identified risks and it was recommended that Levetiracetam film - coated tablets can be approved for use. What measures are being taken to ensure the safe and effective use of Levetiracetam film - coated tablets?

6 A risk management plan (RMP) has been developed to ensure that Levetiracetam film - coated 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 Levetiracetam film - coated tablets 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 and healthcare professionals will be monitored and reviewed continuously as well. Other information about Levetiracetam film - coated tablets Bulgaria, Cyprus, Czech Republic, Denmark, Greece, France, Croatia, Hungary, Ireland, Italy, Malta, Norway, Romania, Sweden, Slovenia, Slovak Republic and the UK agreed to grant marketing authorisations for Levetiracetam film - coated tablets on 02 December 2014.

7 The marketing authorisations in the UK were granted on 19 January 2015. The full PAR for Levetiracetam film - coated tablets follows this summary. For more information about treatment with Levetiracetam film - coated tablets, read the Package Leaflet or contact your doctor or pharmacist. This summary was last updated in March 2015. 3 . PAR Levetiracetam 250, 500, 750 & 1000mg film - coated tablets UK/H/5630/001-004/DC. TABLE OF CONTENTS. I Introduction Page 5. II Quality aspects Page 7. III Non-clinical aspects Page 8. IV Clinical aspects Page 9. V User consultation Page 13. VI Overall conclusion, benefit/risk Assessment Page 13. and recommendation Table of content of the PAR update for Page 17. MRP and DCP. 4 . PAR Levetiracetam 250, 500, 750 & 1000mg film - coated tablets UK/H/5630/001-004/DC.

8 I INTRODUCTION. Based on the review of the data on quality, safety and efficacy, the Reference Member State (RMS) and Concerned Member States (CMSs) considered that the applications for Levetiracetam 250, 500, 750 & 1000mg film - coated tablets (PL 36390/0168-0171;. UK/H/5630/001-004/DC) could be approved. These products are prescription-only medicines indicated as: monotherapy in the treatment of partial onset seizures with or without secondary generalisation in adults and adolescents from 16 years of age with newly diagnosed epilepsy. adjunctive therapy o in the treatment of partial onset seizures with or without secondary generalisation in adults adolescents, children and infants from 1 month of age with epilepsy o in the treatment of myoclonic seizures in adults and adolescents from 12 years of age with Juvenile Myoclonic Epilepsy o in the treatment of primary generalised tonic-clonic seizures in adults and adolescents from 12 years of age with Idiopathic Generalised Epilepsy Levetiracetam is a pyrrolidone derivative, not chemically related to any existing antiepileptic active substances.

9 The mechanism of action of Levetiracetam is not fully understood, but in vitro studies showed that Levetiracetam affects intraneuronal Ca2+ levels and binds the synaptic vesicle protein 2A. Levetiracetam induces seizure protection in a broad range of animal models of partial and primary generalised seizures, and in man is proved to diminish epileptiform discharge and photoparoxysmal response. These applications were made under Article 10(1) of Directive 2001/83/EC, as amended, claiming to be generic medicinal products of the reference medicinal product Keppra 250, 500, 750 & 1000mg film - coated tablets, which were authorised to UCB Pharma SA via a Centralised Procedure that concluded in September 2000 (EU/1/00/146). The RMS for these procedures was the UK and the CMSs were Bulgaria, Cyprus, Czech Republic, Denmark, Greece, France, Croatia, Hungary, Ireland, Italy, Malta, Norway, Romania, Sweden, Slovenia and Slovak Republic.

10 No new non-clinical studies were conducted, which is acceptable given that the applications are based on being generic medicinal products of the originator products that have been licensed for over 10 years. Since these products are intended for generic substitution, this will not lead to an increased exposure to the environment. An Environmental Risk Assessment (ERA) is, therefore, not deemed necessary. With the exception of one bioequivalence study, no new clinical data were provided with this application. A bioequivalence study was performed, which compared the pharmacokinetics of the applicant's Levetiracetam 1000mg film - coated tablets with those of the reference product, Keppra 1000mg film - coated tablets, in healthy subjects under fasting conditions. The bioequivalence study was conducted in-line with current Good Clinical Practice (GCP).