Summary Public Assessment Report. Generics. Etoricoxib Aurobindo. 30 mg, 60 mg, 90 mg, 120 mg Film-coated tablet (Etoricoxib) PT/H/1603/ /DC

Transcription

1 Summary Public Assessment Report Generics 30 mg, 60 mg, 90 mg, 120 mg Film-coated tablet (Etoricoxib) Date: Summary PAR Generics 1/10

2 Summary Public Assessment Report Generics 30 mg, 60 mg, 90 mg, 120 mg Film-coated tablet Etoricoxib 30 mg, 60 mg, 90 mg, 120 mg Film-coated tablet This is a summary of the public assessment report (PAR) for. It explains how 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 Etoricoxib Aurobindo. For practical information about using patients should read the package leaflet or contact their doctor or pharmacist. What is and what is it used for? 30 mg, 60 mg, 90 mg, 120 mg Film-coated tablet is a generic medicine. This means that is similar to a reference medicine already authorised in the European Union (EU) called Arcoxia 30 mg, 60 mg, 90 mg, 120 mg Film-coated tablet helps to reduce the pain and swelling (inflammation) in the joints and muscles of people 16 years of age and older with osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and gout. is also used for the short-term treatment of moderate pain after dental surgery in people 16 years of age and older. How does work? contains the active substance etoricoxib. is one of a group of medicines called selective COX-2 inhibitors. These belong to a family of medicines called nonsteroidal anti-inflammatory drugs (NSAIDs). How is used? The pharmaceutical form of is Film-coated tablet and the route of administration is oral. Please read section 3 of the PL for detailed information on dosing recommendations, the route of administration, and the duration of treatment. Summary PAR Generics 2/10

3 The medicine can only be obtained with a prescription. What benefits of have been shown in studies? Because is a generic medicine, studies in patients have been limited to tests to determine that it is bioequivalent to the reference medicine, Arcoxia. Two medicines are bioequivalent when they produce the same levels of the active substance in the body. The company provided data from the published literature on Etoricoxib. What are the possible side effects of? Because 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 restrictions, see the package leaflet. Why is approved? It was concluded that, in accordance with EU requirements, 30 mg, 60 mg, 90 mg, 120 mg Film-coated tablet has been shown to have comparable quality and to be bioequivalent/be comparable to Arcoxia. Therefore, the INFARMED, I.P. decided that, as for reference medicine called Arcoxia 30 mg, 60 mg, 90 mg, 120 mg, 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 Etoricoxib Aurobindo? A risk management plan has been developed to ensure that 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, 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 The marketing authorisation for 30 mg, 60 mg, 90 mg, 120 mg Film-coated tablet was granted on The full PAR for 30 mg, 60 mg, 90 mg, 120 mg Film-coated tablet can be found on the website For more information about treatment with, read the package leaflet or contact your doctor or pharmacist. This summary was last updated in MM-YYYY. Summary PAR Generics 3/10

4 Public Assessment Report Scientific discussion 30 mg, 60 mg, 90 mg, 120 mg Film-coated tablet (Etoricoxib) Date: This module reflects the scientific discussion for the approval of. The procedure was finalised at For information on changes after this date please refer to the module Update. Summary PAR Generics 4/10

5 I. INTRODUCTION Based on the review of the quality, safety and efficacy data, the Member States have agreed in granting a marketing authorisation for 30 mg, 60 mg, 90 mg, 120 mg Film-coated tablet, from Aurobindo Pharma (Portugal), Unipessoal Limitada is indicated in adults and adolescents 16 years of age and older for the symptomatic relief of osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis, and the pain and signs of inflammation associated with acute gouty arthritis. is indicated in adults and adolescents 16 years of age and older for the shortterm treatment of moderate pain associated with dental surgery. A comprehensive description of the indications and posology is given in the SmPC. This decentralized application according to concerns a generic version of etoricoxib with the Portugal acting as Reference Member State and BE, DE, ES, FR, NL, RO and UK as Concerned Member States. The EU reference medicinal product is Arcoxia of MAH Merck Sharp & Dohme Limited. The product has been registered since The marketing authorization was granted on based on Directive 2001/83/EC article 10.1 (a) (iii) first paragraph and the Marketing Authorisation Holder is Aurobindo Pharma (Portugal), Unipessoal Limitada. II. QUALITY ASPECTS II.1 Introduction Film-coated tablet. 30 mg film-coated tablets Blue-green, apple-shaped, biconvex film coated tablet, debossed with 30 on one side and plain on the other, with dimensions of 5.8 x 5.9 mm ± 7.5%. 60 mg film-coated tablets Dark green, apple-shaped, biconvex film coated tablet, debossed with 60 on one side and plain on the other, with dimensions of 7.1 x 7.3 mm ± 7.5%. 90 mg film-coated tablets White, apple-shaped, biconvex film coated tablet, debossed with 90 on one side and plain on the other, with dimensions of 8.1 x 8.3 mm ± 7.5%. Summary PAR Generics 5/10

6 120 mg film-coated tablets Pale green, apple-shaped, biconvex film coated tablet, debossed with 120 on one side and plain on the other, with dimensions of 8.9 x 9.2 mm ± 7.5%. The other excipients are: Tablet Core: Microcrystalline Cellulose (E460), Calcium Hydrogen Phosphate (Anhydrous), Croscarmellose Sodium, Magnesium Stearate (E470b). Tablet coating: Polyvinyl Alcohol (E1203), Titanium Dioxide (E171), Glycerol Monostearate (E471), Indigo Carmine Aluminum Lake (E132) [only for 30 mg, 60 mg & 120 mg], Yellow Iron Oxide (E172) [only for 30 mg, 60 mg & 120 mg], Talc (E553b), Sodium Laurilsulfate. film-coated tablets are supplied in OPA-Aluminium PVC/Aluminium blisters. Blister packs contain 7, 14, 20, 28, 30, 50, 98 and 100 film-coated tablets. Not all pack sizes may be marketed. II.2 Drug Substance Nomenclature International Non proprietary Name (INN), USAN & BAN: : Etoricoxib Chemical names (s), IUPAC name: 5-chloro-6 -methyl-3-[4- (methylsulfonyl)phenyl]-2,3 - bipyridine CAS Registry No. : [ ] Therapeutic Category : Anti-inflammatory; analgesic Structure Molecular formula : C 18 H 15 ClN 2 O 2 S Molecular weight : Structural formula: Summary PAR Generics 6/10

7 General Properties Description: Solubility: Melting Point: White to yellow powder Freely Soluble in Dimethyl sulfoxide and methanol. Soluble in ethanol. Practically insoluble in water º C Dissociation constant (pka): 4.5 Isomerism: Polymorphism: Hygroscopicity: Etoricoxib does not contain any chiral centre therefore it is optically inactive Form I according with the manufacturer Non hygroscopic The chemical-pharmaceutical documentation and Quality Overall Summary in relation to Etoricoxib Aurobindo is of sufficient quality in view of the present European regulatory requirements. The control tests and specifications for drug substance product are adequately drawn up. Based on available long-term stability data supported by Accelerated stability data, two year retest period has been proposed for Etoricoxib Active substance when stored under Preserve in well closed containers, Store at below 25ºC.. II.3 Medicinal Product The development of the product has been described, the choice of excipients is justified and their functions explained. The product specifications cover appropriate parameters for this dosage form. Validations of the analytical methods have been presented. Batch analysis has been performed on three batches. The batch analysis results show that the finished products meet the specifications proposed. The conditions used in the stability studies are according to the ICH stability guideline. The control tests and specifications for drug product are adequately drawn up. Basing on the stability data, a shelf life of 36 months is proposed for the product in the proposed packaging for marketing, without special storage conditions. III. NON-CLINICAL ASPECTS Pharmacodynamic, pharmacokinetic and toxicological properties of etoricoxib are well known. As etoricoxib is a widely used, well-known active substance, the applicant has not provided additional studies and further studies are not required. Overview based on literature review is, thus, appropriate. Summary PAR Generics 7/10

8 III.1 Ecotoxicity/environmental risk assessment (ERA) Since 30 mg, 60 mg, 90 mg, 120 mg Film-coated tablet is intended for generic substitution, this will not lead to an increased exposure to the environment. An environmental risk assessment is therefore not deemed necessary. III.2 Discussion on the non-clinical aspects Since this product has been shown to be essentially similar and refer to a product approved based on a full application with regard to preclinical data, no further such data have been submitted or are considered necessary. IV. CLINICAL ASPECTS To support the application, the applicant has submitted as report one bioequivalence study. This study was performed in order to show bioequivalence between the PharOS Ltd developed Etoricoxib 120 mg film-coated tablets and the originator product, Arcoxia 120 mg tablets marketed in Europe by Merck Sharp & Dohme Limited. PharOS Ltd has developed Etoricoxib 30, 60, 90 and 120 mg film-coated tablet, in line with the originator product s tablet strength which are commercially available. In accordance with the EMA CPMP/EWP/QWP/1401/98 Rev. 1 note for guidance on Bioavailability and Bioequivalence, if the application concerns several strengths of the active substance, a bioequivalence study investigating only one strength may be acceptable if all the following conditions are fulfilled: a) the pharmaceutical products are manufactured by the same manufacturing process. b) the qualitative composition of the different strengths is the same. c) the composition of the strengths are quantitatively proportional. i.e. the ratio between the amount of each excipient to the amount of active substance(s) is the same for all strengths (for immediate release products, coating components, capsule shell, colour agents and flavours are not required to follow this rule). d) appropriate in vitro dissolution data should confirm the adequacy of waiving additional in vivo bioequivalence testing. A biowaiver for additional strengths is acceptable. The choice of the highest strength for the Bioequivalence trial is also acceptable. Conclusion on bioequivalence studies: Based on the submitted bioequivalence study 30 mg, 60 mg, 90 mg, 120 mg Film-coated tablet is considered bioequivalent with Arcoxia 30 mg, 60 mg, 90 mg, 120 mg Filmcoated tablet Summary PAR Generics 8/10

9 IV.1 Risk Management Plan The MAH has submitted a risk management plan, in accordance with the requirements of Directive 2001/83/EC as amended, describing the pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to 30 mg, 60 mg, 90 mg, 120 mg Film-coated tablet. 1. Summary of safety concerns: Important identified risks: - Gastrointestinal bleeding and Gastrointestinal ulceration - Cardiovascular thrombotic events - Renal toxicity, fluid retention, and oedema - Hypertension - Serious hypersensitivity reactions (including angioedema/anaphylactic /anaphylactoid reactions including shock) - Hepatotoxicity - Concomitant use with oral anti-coagulants - Serious skin reactions Important potential risks: - Use in pregnancy and lactation - Congestive heart failure Missing Information: - Use in severe hepatic impairment IV.2 Discussion on the clinical aspects This type of application refers to information that is contained in the pharmacological-toxicological and clinical part of the dossier of the authorisation of the reference product. A reference product is a medicinal product authorised and marketed on the basis of a full dossier, i.e. including chemical, biological, pharmaceutical, pharmacological-toxicological and clinical data. This information is not fully available in the public domain. Authorisations for generic products are therefore linked to the original authorized medicinal product, which is legally allowed once the data protection time of the dossier of the reference product has expired. For this kind of application, it has to be demonstrated that the pharmacokinetic profile of the product is similar to the pharmacokinetic profile of the reference product. This generic product can be used instead of its reference product. V. USER CONSULTATION Summary PAR Generics 9/10

10 The package leaflet has been evaluated via a user consultation study in accordance with the requirements of Articles 59(3) and 61(1) of Directive 2001/83/EC. The language used for the purpose of user testing the PIL was English The results show that the package leaflet meets the criteria for readability as set out in the Guideline on the readability of the label and package leaflet of medicinal products for human use. VI. OVERALL CONCLUSION, BENEFIT/RISK ASSESSMENT AND RECOMMENDATION The application for 30 mg, 60 mg, 90 mg, 120 mg Film-coated tablet contains adequate quality, non-clinical and clinical data and the bioequivalence has been shown. A benefit/risk ratio comparable to the reference product can therefore be concluded. Summary PAR Generics 10/10