Azithromycin 500mg Powder for Solution for Infusion PL ...

1 UKPAR Azithromycin 500mg Powder for Solution for Infusion PL 10622/0306 1 Azithromycin 500mg Powder for Solution for Infusion PL 10622/0306 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 16 Steps taken after authorisation Page 17 Summary of Product Characteristics Page 18 Product Information Leaflet Page 29 Labelling Page 35 UKPAR Azithromycin 500mg Powder for Solution for Infusion PL 10622/0306 2 Azithromycin 500mg Powder for Solution for Infusion PL 10622/0306 LAY SUMMARY The Medicines and Healthcare products Regulatory Agency (MHRA) granted PLIVA Pharma Limited a Marketing Authorisation (licence) for the medicinal product Azithromycin 500mg Powder for Solution for Infusion (PL 10622/0306) on 27 September 2011.

2 This is a prescription-only medicine (POM). Azithromycin is one of a group of antibiotics called macrolides. This medicine is used to treat the following serious infections when these require admission to hospital and when the infection is caused by micro-organisms that are susceptible to Azithromycin : Pneumonia acquired outside of hospital Infection of the internal female sex organs (Pelvic Inflammatory Disease) This medicinal product is used when you require treatment by intravenous Infusion (a drip ). The medicine is ready to be reconstituted (dissolved in liquid) to be given by Infusion . Azithromycin 500mg Powder for Solution for Infusion was considered to be a generic version of a European reference product, Azitromax 500mg Powder for Solution for Infusion (MA number 16698, Pfizer AB, Sweden), based on the data submitted by PLIVA Pharma Limited.

3 No new or unexpected safety concerns arose from this application. It was judged that the benefits of Azithromycin 500mg Powder for Solution for Infusion outweigh the risks; hence a Marketing Authorisation has been granted. UKPAR Azithromycin 500mg Powder for Solution for Infusion PL 10622/0306 3 Azithromycin 500mg Powder for Solution for Infusion PL 10622/0306 SCIENTIFIC DISCUSSION TABLE OF CONTENTS Introduction Page 4 Pharmaceutical assessment Page 6 Non-clinical assessment Page 10 Clinical assessment Page 11 Overall conclusion and risk benefit assessment Page 15 UKPAR Azithromycin 500mg Powder for Solution for Infusion PL 10622/0306 4 INTRODUCTION Based on the review of the data on quality, safety and efficacy.

4 The MHRA granted PLIVA Pharma Limited a Marketing Authorisation for the medicinal product Azithromycin 500mg Powder for Solution for Infusion (PL 10622/0306) on 27 September 2011. The product is a prescription-only medicine (POM). This is a generic application for Azithromycin 500 mg Powder for Solution for Infusion , submitted according to Article , 3rd Paragraph of Directive 2001/83/ EC, as amended. The application refers to a European reference medicinal product, Azitromax 500mg Powder for Solution for Infusion , which was authorised to Pfizer AB in Sweden on 12 December 2003 (MA number 16698). The European reference medicinal product has been authorised in the EU for more than 10 years, thus the period of data exclusivity has expired.

5 Azithromycin (Zithromax, Pfizer) oral products have been continuously marketed in the UK since 1991. An intravenous preparation of Azithromycin has not been authorised in the UK but this route has been licensed in Sweden (2003), Denmark (2003), Canada (1999) and the USA (1998). The UK reference product is Azithromax 500 mg Tablets (PL 00057/0391), authorised to Pfizer Limited on 17 September 1996. The application was referred to the Commission on Human Medicines (CHM) who met in October 2008 for consideration whether the safety, quality and efficacy of the product was demonstrated. Following consideration of the applicant s responses and further data that were submitted, the approval of the Marketing Authorisation was recommended.

6 Azithromycin 500mg Powder for Solution for Infusion is indicated for the treatment of the following infections in adult patients who require intravenous therapy (see sections and ): Community-acquired pneumonia Pelvic Inflammatory Disease Consideration should be given to official guidance regarding the appropriate use of antibacterials. Azithromycin is a macrolide antibiotic (ATC classification: J01FA10) belonging to the azalide group. The molecule is constructed by adding a nitrogen atom to the lactone ring of erythromycin A. The chemical name of Azithromycin is 9-deoxy-9a-aza-9a-methyl-9a-homoerythrom ycin A. The molecular weight is The mechanism of action of Azithromycin is based upon the suppression of bacterial protein synthesis by means of binding to the ribosomal 50s sub-unit and inhibition of peptide translocation.

7 resistance to Azithromycin may be inherent or acquired. There are three main mechanisms of resistance in bacteria: target site alteration, alteration in antibiotic transport and modification of the antibiotic. UKPAR Azithromycin 500mg Powder for Solution for Infusion PL 10622/0306 5 Complete cross- resistance exists among Streptococcus pneumoniae, beta-haemolytic streptococcus of group A, Enterococcus faecalis and Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) to erythromycin, Azithromycin , other macrolides and lincosamides. The medicinal product is supplied in a lyophilised form in a 14 ml vial containing 500 mg Azithromycin , as monohydrate.

8 After reconstitution with sterile water for injection, the product contains 100mg/ml. The reconstituted Solution requires further dilution to a final Infusion concentration of 1 or 2 mg/ml prior to administration. No new non-clinical or clinical efficacy studies were conducted for this application, which is acceptable given that this is a generic application cross-referring to a product that has been licensed for over 10 years. Bioequivalence studies are not necessary to support this application for a parenteral product. The MHRA has been assured that acceptable standards of Good Manufacturing Practice (GMP) are in place for this product type at all sites responsible for the manufacture and assembly of this product.

9 The MHRA considers that the pharmacovigilance system as described by the Marketing Authorisation Holder (MAH) fulfils the requirements and provides adequate evidence that the MAH has the services of a Qualified Person (QP) responsible for pharmacovigilance and has the necessary means for the notification of any adverse reaction suspected of occurring either in the Community or in a third country. The MAH has provided adequate justification for not submitting a detailed Risk Management Plan (RMP). As the application is for a generic version of an already authorised reference products, for which safety concerns requiring additional risk minimisation have not been identified, routine pharmacovigilance activities are proposed and a risk minimisation system is not considered necessary.

10 The reference product has been in use for many years and the safety profile of the active is well-established. The MAH has provided adequate justification for not submitting an Environmental Risk Assessment (ERA). This was an application for a generic product and there is no reason to conclude that marketing of this product will change the overall use pattern of the existing market. There are no environmental concerns associated with the method of manufacture or formulation of the product. UKPAR Azithromycin 500mg Powder for Solution for Infusion PL 10622/0306 6 PHARMACEUTICAL ASSESSMENT ACTIVE SUBSTANCE Azithromycin monohydrate Nomenclature: INN: Azithromycin Chemical names.