Public Assessment Report Decentralised Procedure

1 Public Assessment Report Decentralised Procedure TRANYLCYPROMINE 10MG TABLETS (tranylcypromine sulfate) Procedure No: UK/H/4625/001/DC UK Licence No: PL 41830/0025 NRIM Limited PAR Tranylcypromine 10 mg Tablets UK/H/4625/001/DC 2 LAY SUMMARY Tranylcypromine 10mg Tablets (tranylcypromine sulfate) This is a summary of the Public Assessment Report (PAR) for Tranylcypromine 10mg Tablets (PL 41830/0025). It explains how Tranylcypromine 10mg 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 Tranylcypromine 10mg Tablets. For practical information about using Tranylcypromine 10mg Tablets, patients should read the package leaflet or contact their doctor or pharmacist. What are Tranylcypromine 10mg Tablets and what are they used for? Tranylcypromine 10 mg Tablets are a generic medicine . This means that Tranylcypromine 10 mg Tablets are similar to a reference medicine already authorised in the European Union (EU) called Parnate 10 mg Tablets.

2 Tranylcypromine 10mg Tablets are used to treat moderate to severe depression in adults. They can also help feelings of fear (phobia), which sometimes occur in depression. This medicine is often used when other types of antidepressant medicines have not worked. How are Tranylcypromine 10mg Tablets used? Tranylcypromine 10mg Tablets should be swallowed whole with a glass of water. The usual dose in adults is one tablet in the morning and one tablet in the afternoon each day. Patients should try to take the last dose before 3 o clock in the afternoon. The dose may be increased by a doctor to three tablets a day and the extra tablet should be taken at midday. Elderly patients will usually be prescribed a lower dose. This medicine can only be obtained with a prescription. How do Tranylcypromine 10mg Tablets work? Tranylcypromine 10mg Tablets contain the active ingredient tranylcypromine sulfate which belongs to a group of antidepressant medicines known as monoamine oxidase inhibitors (MAOIs).

3 Tranylcypromine works by stopping the breakdown of two substances in the brain called serotonin and noradrenaline and should help bring these substances back to normal levels. How have Tranylcypromine 10mg Tablets been studied? Because Tranylcypromine 10mg Tablets are a generic medicine, studies in patients have been limited to tests to determine that they are bioequivalent to the reference medicine, Parnate 10 mg Tablets. Two medicines are bioequivalent when they produce the same levels of the active substance in the body. What are the benefits and risks of Tranylcypromine 10mg Tablets? Because Tranylcypromine 10mg Tablets are a generic medicine that is bioequivalent to the reference medicine, its benefits and risks are taken as being the same as the reference medicine. PAR Tranylcypromine 10 mg Tablets UK/H/4625/001/DC 3 Why are Tranylcypromine 10mg Tablets approved? It was concluded that, in accordance with EU requirements, Tranylcypromine 10mg Tablets have been shown to have comparable quality and to be bioequivalent to Parnate 10 mg Tablets.

4 Therefore, the view was that, as for Parnate 10 mg Tablets, the benefit outweighs the identified risks. What measures are being taken to ensure the safe and effective use of Tranylcypromine 10mg Tablets? A risk management plan has been developed to ensure that Tranylcypromine 10mg Tablets are used as safely as possible. Based on this plan, safety information has been included in the S ummary of Product Characteristics and the package leaflet for Tranylcypromine 10mg Tablets, including the appropriate precautions to be followed by healthcare professionals and patients. Other information about Tranylcypromine 10mg Tablets Germany, Ireland and the UK agreed to grant Marketing Authorisations for Tranylcypromine 10mg Tablets on 06 December 2013. A Marketing Authorisation was granted in the UK on 08 January 2014. The full PAR for Tranylcypromine 10mg Tablets follows this summary. For more information about treatment with Tranylcypromine 10mg Tablets, read the package leaflet or contact your doctor or pharmacist.

5 This summary was last updated in February 2014. PAR Tranylcypromine 10 mg Tablets UK/H/4625/001/DC 4 TABLE OF CONTENTS Module 1: Information about initial Procedure Page 5 Module 2: Summary of Product Characteristics Page 6 Module 3: Patient Information Leaflet Page 7 Module 4: Labelling Page 8 Module 5: Scientific discussion during initial Procedure Page 10 I Introduction II About the product III Scientific overview and discussion Quality aspects Non-clinical aspects Clinical aspects IV Overall conclusion and benefit-risk Assessment Module 6: Steps taken after initial Procedure Page 17 PAR Tranylcypromine 10 mg Tablets UK/H/4625/001/DC 5 Module 1 Information about initial Procedure Product Name Tranylcypromine 10mg Tablets Type of Application Generic, Article 10(1) Active Substances Tranylcypromine sulfate Form Tablets Strength 10 mg MA Holder Lime Pharma Limited McKenzie House Bury Street Ruislip Middlesex HA4 7TL United Kingdom Reference Member State (RMS) UK Concerned Member States (CMS) Germany and Ireland Procedure Number UK/H/4625/001/DC Timetable Day 210 06 December 2013 PAR Tranylcypromine 10 mg Tablets UK/H/4625/001/DC 6 Module 2 Summary of Product Characteristics In accordance with Directive 2010/84/EU the Summaries of Product Characteristics (SmPCs) for products that have been granted Marketing Authorisations at a national level are available on the MHRA website.

6 PAR Tranylcypromine 10 mg Tablets UK/H/4625/001/DC 7 Module 3 Patient Information Leaflet In accordance with Directive 2010/84/EU the Patient Information Leaflets for products that are granted Marketing Authorisations at a national level are available on the MHRA website. PAR Tranylcypromine 10 mg Tablets UK/H/4625/001/DC 8 Module 4 Labelling Carton for HDPE container: Label for HDPE container: PAR Tranylcypromine 10 mg Tablets UK/H/4625/001/DC 9 Carton for blister packs: Blister: PAR Tranylcypromine 10 mg Tablets UK/H/4625/001/DC 10 Module 5 Scientific discussion during initial Procedure I INTRODUCTION Based on the review of the data on quality, safety and efficacy, the Member States considered that the application for Tranylcypromine 10mg Tablets (PL 20620/0061, UK/H/4625/001/DC; Lime Pharma Limited) could be approved. The application w as submitted via the Decentralised Procedure , with the UK as Reference Member State (RMS), and Germany and Ireland as Concerned Member States (CMS).

7 This product is a prescription-only medicine (legal classification POM). It is indicated for the treatment of symptoms of depressive illness, especially where phobic symptoms are present or where treatment with other types of anti-depressants has failed. It is not recommended for mild depressive states resulting from temporary situational difficulties. This was an application made under the Decentralised Procedure (DCP), according to Article 10(1) of Directive 2001/83/EC, as amended, claiming to be a generic medicinal product of Parnate 10mg Tablets (Smithkline and French Laboratories Ltd; PL 00002/5040R), which was initially granted a Marketing Authorisation in the UK on 04 August 1984. The current marketing authorisation holder for the reference product is Mercury Pharmaceuticals Ltd (PL 12762/0075), following a change of ownership that was concluded on 15 September 2000. This product contains the active substance tranylcypromine sulfate, which belongs to a class of antidepressant drugs known as monoamine oxidase inhibitors (MAOIs).

8 Tranylcypromine is a non-hydrazine, irreversible inhibitor of MAO. Inhibition of this enzyme increases the levels of amines including 5-hydroxytryptamine (5-HT, serotonin), dopamine and noradrenaline. Tranylcypromine undergoes considerable metabolism, including breakdown of the side chain and probably conjugation. Inhibition of MAO (both MAOA and MAOB) lasts for some time, and clinically is considered to have reversed within 14 days. With the exception of the bioequivalence study, 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. A bioequivalence study was performed, which compared the pharmacokinetics of the test product Tranylcypromine 10mg Tablets to those of the reference product Parnate 10mg Tablets (Mercury Pharmaceuticals Ltd). The bioequivalence study was carried out in accordance with Good Clinical Practice (GCP).

9 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. The RMS and CMS considered that the application could be approved at the end of Procedure on 06 December 2013. After a subsequent national phase, a licence was granted in the UK on 08 January 2014. On 21 January 2014, the licence subsequently underwent a change of ownership from Lime Pharma Limited (PL 20620/0061) to NRIM Limited (PL 41830/0025).PAR Tranylcypromine 10 mg Tablets UK/H/4625/001/DC 11 II. ABOUT THE PRODUCT Name of the product in the Reference Member State Tranylcypromine 10mg Tablets Name(s) of the active substance(s) (INN) Tranylcypromine sulfate Pharmacotherapeutic classification (ATC code) Monoamine Oxidase Inhibitors, non-selective (N06AF04) Pharmaceutical form and strength(s) Tablets, 10 mg Reference numbers for the Decentralised Procedure UK/H/4625/001/DC Reference Member State UK Member States concerned Germany and Ireland Marketing Authorisation Number(s) PL 20620/0061 Name and address of the authorisation holder Lime Pharma Limited McKenzie House Bury Street Ruislip Middlesex HA4 7TL United Kingdom PAR Tranylcypromine 10 mg Tablets UK/H/4625/001/DC 12 III SCIENTIFIC OVERVIEW AND DISCUSSION QUALITY ASPECTS S.

10 Active substance Tranylcypromine Sulfate rINN: Tranylcypromine Sulfate Chemical name(s): i. (1RS,2SR)-2- Phenylcyclopropylamine Sulphate (2:1) ii. Cyclopropanamine, 2-phenyl-, trans-(+)-, sulfate (2: 1) iii. (+) Trans-2-phenylcyclopropylamine Sulphate (2:1) Structure: Molecular formula: [C9H11N]2 .H2SO4 Molecular weight: Appearance: White to off-white crystalline powder Solubility: Sparingly soluble in dimethylformamide, slightly soluble in methanol, very slightly soluble in water and practically insoluble in hydrochloric acid. An Active Substance Master File (ASMF) has been provided by the active substance manufacturer, covering the manufacture and control of the active substance tranylcypromine sulfate. Synthesis of the drug substance from the designated starting materials has been adequately described and appropriate in-process controls and intermediate specifications are applied. Satisfactory specification tests are in place for all starting materials and reagents and these are supported by relevant certificates of analysis.