Fluconazole 50mg 5ml Powder for Oral …

1 UKPAR Fluconazole 50mg /5ml Powder for oral suspension PL 06831/0220 1 Fluconazole 50mg /5ML Powder FOR oral suspension PL 06831/0220 UKPAR TABLE OF CONTENTS Lay Summary Page 2 Scientific discussion Page 3 Steps taken for assessment Page 12 Steps taken after authorisation summary Page 13 Summary of Product Characteristics Product Information Leaflet Labelling Page 14 Page 25 Page 27 UKPAR Fluconazole 50mg /5ml Powder for oral suspension PL 06831/0220 2 Fluconazole 50mg /5ML Powder FOR oral suspension PL 06831/0220 LAY SUMMARY On 15th June 2011, the MHRA granted Genus Pharmaceuticals Limited a Marketing Authorisation (licence) for Fluconazole 50mg /5ml Powder for oral suspension . Fluconazole 50mg /5ml Powder for oral suspension contains the active ingredient Fluconazole .

2 Fluconazole belongs to a group of medicinal products called triazole antifungal drugs. These medicinal products are used for the treatment of a wide variety of infections caused by fungi. Fluconazole 50mg /5ml suspension is used in the treatment of the following in adults and children: Fungal infections caused by fungi of the Candida genus (called candidiasis) ("Thrush"). This type of infection may occur in the mouth and throat, may cause chest infections, candidiasis in the urinary tract and infection associated with the use of dentures. Generalised infections located in the abdomen, heart and respiratory system may also occur. Fluconazole is also indicated in the prevention of relapse of oral candidiasis in patients with acquired immune deficiency syndrome (AIDS).

3 Infections caused by the fungus Cryptococcus (called Cryptococcosis), including meningitis and infections in other locations (lungs, in the skin, etc.). Fluconazole may be used as a maintenance treatment to prevent cryptococcosis relapses in patients with AIDS. The prevention of infections caused by fungi in patients with cancer or transplanted organs who are predisposed to such infections as a result of the treatment they are receiving. Other generalised fungal infections ( coccidiomycosis, paracoccidiomycosis, sporotrichosis and histoplasmosis). Infections of the skin such as the different types of ringworm. Fluconazole is not indicated for nail infections or tinea capitis in adults and children. No new or unexpected safety concerns arose from this application and it was, therefore, judged that the benefits of taking Fluconazole 50mg /5ml Powder for oral suspension outweigh the risks; hence a Marketing Authorisation has been granted.

4 UKPAR Fluconazole 50mg /5ml Powder for oral suspension PL 06831/0220 3 Fluconazole 50mg /5ML Powder FOR oral suspension PL 06831/0220 SCIENTIFIC DISCUSSION TABLE OF CONTENTS Introduction Page 4 Pharmaceutical assessment Page 6 Non-clinical assessment Page 9 Clinical assessment (including statistical assessment) Page 10 Overall conclusions and risk benefit assessment Page 11 UKPAR Fluconazole 50mg /5ml Powder for oral suspension PL 06831/0220 4 INTRODUCTION Based on the review of the data on quality, safety and efficacy, the UK granted a Marketing Authorisation for the medicinal product Fluconazole 50mg /5ml Powder for oral suspension (PL 06831/0220), to Genus Pharmaceuticals Limited on 15th June 2010. This medicine is available with a prescription only (POM) and is indicated for in the treatment of mycoses caused by Candida, Cryptococcus and other susceptible yeasts, in particular: Mucosal candidiasis: These include oropharyngeal candidiasis, oesophageal, non-invasive bronchopulmonary infections, candiduria, mucocutaneous candidiasis and chronic atrophic oral candidiasis (denture sore mouth).

5 Both normal hosts and immunocompromised patients may be treated. Systemic candidiasis (including disseminated deep infections and peritonitis). Acute cryptococcal meningitis in adults, including patients with AIDS, transplanted patients or other patients with other causes of immunosuppression. Genital candidiasis. Acute or recurrent vaginal candidiasis. Candida balanitis. The treatment of partners who present with symptomatic genital candidiasis should be considered. Prevention of fungal infections in patients predisposed to such infections as a result of chemotherapy or radiotherapy, including bone transplant patients. Dermatomycosis, including infections such as Tinea pedis, Tinea corporis, Tinea cruris, Tinea versicolor. Fluconazole is not indicated for nail infections and tinea capitis.

6 Fluconazole should not be used for tinea capitis in children. This application for Fluconazole 50mg /5ml Powder for oral suspension is submitted as an abridged application according to Article of Directive 2001/83/EC, claiming to be a hybrid medicinal product to Diflucan 150mg Capsules, first authorised to Pfizer Limited on 7th June 1998 (PL 00057/0290). Fluconazole is a triazole agent that acts as a potent and specific inhibitor of the fungal synthesis of sterols. Fluconazole , given both orally and intravenously, has been shown to be active in a broad variety of fungal infection animal models. This activity has been demonstrated in opportunistic mycoses, such as infections by Candida spp, including systemic candidiases in immunocompromised animals; infections by Cryptococcus neoformans, including intracranial infections; infections by Microsporum spp and infections by Trichophyton spp.

7 Fluconazole has also been shown to be active in endemic mycosis animal models, including infections by Blastomyces dermatitidis, infections by Coccidioides immitis, including intracranial infection; and infections by Histoplasma capsulatum in normal and immunocompromised animals. UKPAR Fluconazole 50mg /5ml Powder for oral suspension PL 06831/0220 5 The pharmacovigilance system as described by the applicant fulfils the requirements. It also provides adequate evidence that the applicant has the services of a qualified person responsible for pharmacovigilance and has the necessary means for the notification of any adverse reaction suspected of occurring. A satisfactory justification for the absence of a Risk Management Plan (RMP) has been provided.

8 UKPAR Fluconazole 50mg /5ml Powder for oral suspension PL 06831/0220 6 PHARMACEUTICAL ASSESSMENT DRUG SUBSTANCE INN: Fluconazole Chemical name: 2-(2,4-difluorophenyl)-1,3-bis-(1H-1,2,4 -triazol-1-yl)-2-propanol Structure: Physical form: white to almost white crystalline Powder . Solubility: slightly soluble in water, freely soluble in methanol and soluble in acetone. Molecular formula: C13H12N6OF2 Molecular weight: Fluconazole is the subject of a European Pharmacopoeia monograph. All aspects of the manufacture of the drug substance from its starting materials are controlled by a Certificate of Suitability. Appropriate proof of structure data has been supplied for the drug substance. All potential known impurities have been identified and characterised.

9 An appropriate specification with suitable test methods and limits is provided for the drug substance Fluconazole . The methods of testing and limits for residual solvents are in compliance with current guidelines. Suitable Certificates of Analysis have been provided for all reference standards used. Batch analysis data are provided and comply with the proposed specification. Appropriate stability data have been generated showing the drug substance to be a physically and chemically stable drug, and supporting an appropriate retest period. DRUG PRODUCT Other ingredients Other ingredients consist of the pharmaceutical excipients sucrose, colloidal silica, titanium dioxide, xanthan gum, sodium citrate anhydrous, citric acid monohydrate, sodium benzoate (E-211) and orange flavour (containing maltodextrin and arabic gum).

10 All the ingredients with the exception of sodium citrate anhydrous and orange flavour comply with their relevant European Pharmacopoeia monographs. Sodium citrate anhydrous has a United States Pharmacopoeia (USP) monograph. Orange flavour complies with in-house specifications. None of the excipients used contain material of animal or human origin. UKPAR Fluconazole 50mg /5ml Powder for oral suspension PL 06831/0220 7 Product development The objective of the development programme was to produce a product that could be considered a hybrid medicinal product of Diflucan 150mg Capsules (PL 00057/0290). The reference product used in the bioequivalence study is Triflucan 50mg /5ml suspension , authorised in France to Pfizer Limited. The applicant has provided a suitable product development section.