PUBLIC ASSESSMENT REPORT …

1 C B GM E B 1 PUBLIC ASSESSMENT REPORT of the Medicines Evaluation Board in the Netherlands Amoxicilline/Clavulaanzuur Pfizer 500/125 and 875 mg/125 mg film-coated tablets Pfizer , the Netherlands amoxicillin (as trihydrate potassium clavulanate) This ASSESSMENT REPORT is published by the MEB pursuant Article 21 (3) and (4) of Directive 2001/83/EC. The REPORT comments on the registration dossier that was submitted to the MEB and its fellow organisations in all concerned EU member states. It reflects the scientific conclusion reached by the MEB and all concerned member states at the end of the evaluation process and provides a summary of the grounds for approval of a marketing authorisation.

2 This REPORT is intended for all those involved with the safe and proper use of the medicinal product, healthcare professionals, patients and their family and carers. Some knowledge of medicines and diseases is expected of the latter category as the language in this REPORT may be difficult for laymen to understand. This ASSESSMENT REPORT shall be updated by a following addendum whenever new information becomes available. General information on the PUBLIC ASSESSMENT Reports can be found on the website of the MEB. To the best of the MEB s knowledge, this REPORT does not contain any information that should not have been made available to the PUBLIC .

3 The MAH has checked this REPORT for the absence of any confidential information. EU-procedure number: NL/H/2241/001- 002/MR Registration number in the Netherlands: RVG 107460-1 Date of first publication: 29 August 2011 Last revision: 21 March 2012 Pharmacotherapeutic group: combinations of penicillins, incl. beta-lactamase inhibitors ATC code: J01CR02 Route of administration: oral Therapeutic indication: acute bacterial sinusitis (adequately diagnosed); acute otitis media; acute exacerbations of chronic bronchitis (adequately diagnosed); community acquired pneumonia; cystitis pyelonephritis; skin and soft tissue infections in particular cellulitis, animal bites, severe dental abscess with spreading cellulitis; bone and joint infections, in particular osteomyelitis.

4 Prescription status: prescription only Date of first authorisation in NL: 28 September 2010 Concerned Member States: Mutual recognition procedure with AT, BE, CY, CZ, DE, DK, EE, EL, ES, FI, HU, IE, IT, LT, LU, MT (not for 875 mg/125 mg strength), NO, PL, PT, RO, SE, SI, SK, and UK Application type/legal basis: Directive 2001/83/EC, Article 10(1). For product information for healthcare professionals and users, including information on pack sizes and presentations, see Summary of Product Characteristics (SPC), package leaflet and labelling. C B GM E B 2I INTRODUCTION Based on the review of the quality, safety and efficacy data, the member states have granted a marketing authorisation for Amoxicilline/Clavulaanzuur Pfizer 500/125 and 875 mg/125 mg film-coated tablets from Pfizer The date of authorisation was on 28 September 2010 in the Netherlands.

5 The product is indicated for the treatment of the following infections in adults and children : Acute bacterial sinusitis (adequately diagnosed) Acute otitis media Acute exacerbations of chronic bronchitis (adequately diagnosed) Community acquired pneumonia Cystitis Pyelonephritis Skin and soft tissue infections in particular cellulitis, animal bites, severe dental abscess with spreading cellulitis. Bone and joint infections, in particular osteomyelitis. Consideration should be given to official guidance on the appropriate use of antibacterial agents. A comprehensive description of the indications and posology is given in the SPC.

6 Amoxicillin Amoxicillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) in the biosynthetic pathway of bacterial peptidoglycan, which is an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which is usually followed by cell lysis and death. Amoxicillin is susceptible to degradation by beta-lactamases produced by resistant bacteria and therefore the spectrum of activity of amoxicillin alone does not include organisms which produce these enzymes. Clavulanic acid Clavulanic acid is a beta-lactam structurally related to penicillins.

7 It inactivates some beta-lactamase enzymes thereby preventing inactivation of amoxicillin. Clavulanic acid alone does not exert a clinically useful antibacterial effect. This mutual recognition procedure concerns a generic application claiming essential similarity with the innovator products Augmentin 500/125 mg and 875/125 mg filmcoated tablets (NL license RVG 09840 and 18553, respectively) which have been registered in the Netherlands by GlaxoSmithKline BV since 1983 (500 mg/ 125 mg) and 1996 (875 mg/ 125 mg). In addition, reference is made to Augmentin authorisations in the individual member states (reference product). The marketing authorisation is granted based on article 10(1) of Directive 2001/83/EC.

8 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, 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 authorised medicinal product, which is legally allowed once the data protection time of the dossier of the reference product has expired.

9 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. To this end the MAH has submitted two bioequivalence study in which the pharmacokinetic profile of the product is compared with the pharmacokinetic profile of the reference products Augmentin 500 mg/ 125 mg and 875 mg/ 125 mg tablets, registered in the UK and Germany, respectively. A bioequivalence study is the widely accepted means of demonstrating that difference of use of different excipients and different methods of manufacture have no influence on efficacy and safety. This generic product can be used instead of its reference product.

10 C B GM E B 3 No new pre-clinical and clinical studies were conducted, which is acceptable for this abridged application. No scientific advice has been given to the MAH with respect to these products, and no paediatric development programme has been submitted, as this is not required for generic medicinal products. II SCIENTIFIC OVERVIEW AND DISCUSSION Quality aspects Compliance with Good Manufacturing Practice The MEB has been assured that acceptable standards of GMP (see Directive 2003/94/EC) are in place for this product type at all sites responsible for the manufacturing of the active substance as well as for the manufacturing and assembly of this product prior to granting its national authorisation.