Ciprofloxacin 100 mg Film-Coated Tablets PL … 100 mg Film-Coated Tablets PL 36390/0142 Ciprofloxacin 250 mg Film-Coated Tablets PL 36390/0143 Ciprofloxacin 500 mg Film-Coated Tablets

Ciprofloxacin 100 mg Film-Coated Tablets PL 36390/0142




UKPAR

TABLE OF CONTENTS Lay Summary

Page 2

Scientific discussion

Page 5

Steps taken for assessment

Page 12

Steps taken after authorisation – summary

Page 13

Summary of Product Characteristics

Page 14

Patient Information Leaflet

Page 14

Labelling

Page 15

UKPAR Ciprofloxacin 100, 250, 500 & 750 mg Film-Coated Tablets PL 36390/0142-0145

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LAY SUMMARY

Ciprofloxacin 100 mg Film-Coated Tablets Ciprofloxacin 250 mg Film-Coated Tablets Ciprofloxacin 500 mg Film-Coated Tablets Ciprofloxacin 750 mg Film-Coated Tablets

(ciprofloxacin hydrochloride) This is a summary of the Public Assessment Report (PAR) for Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets (PL 36390/0142 - 0145). It explains how Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated 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 these products. For practical information about using Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets, patients should read the patient information leaflet (PIL) or contact their doctor or pharmacist. What are Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets and what are they used for? Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets contain the active substance ciprofloxacin hydrochloride. These tablets are used in adults to treat the following bacterial infections: • respiratory tract infections • long-lasting or recurring ear or sinus infections • urinary tract infections • infections of the testicles • genital organ infections in women • gastro-intestinal tract infections and intra-abdominal infections • skin and soft tissue infections • bone and joint infections • to treat infections in patients with a very low white blood cell count • to prevent infections in patients with a very low white blood cell count • to prevent infections due to the bacterium Neisseria meningitidis • anthrax inhalation exposure The tablets are used in children and adolescents, under specialist medical supervision, to treat the following bacterial infections: • lung and bronchial infections in children and adolescents suffering from cystic fibrosis (a hereditary disease affecting multiple organs of the body mainly the lung) • complicated urinary tract infections, including infections that have reached the kidneys • anthrax inhalation exposure Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets are identical to Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets which were originally authorised to Neolab Limited (PL 08137/0049 - 0052) on 15 May 2002. Following


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change of ownership, the current marketing authorisation holder is Aptil Pharma Limited (PL 40378/0161 - 0164). How are Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets used? Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets can only be obtained with a prescription (legal status POM). The prescribing doctor will explain how many tablets of a particular strength will need to be taken, as well as how often and for how long. This will depend on the type of infection and how bad it is. The treatment usually lasts from 5 to 21 days, but may take longer for severe infections. These tablets should be swallowed whole, with plenty of fluid, and not chewed. How do Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets work? The active substance, ciprofloxacin, kills bacteria that cause infections. Ciprofloxacin is an antibiotic which belongs to the fluoroquinolone family, and it works by inhibiting bacterial enzymes responsible for DNA synthesis, but this inhibition is only effective on specific strains of bacteria.

How have Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets been studied? Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets (PL 36390/0142 - 0145; Cipla (EU) Limited) are identical to Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets (PL 40378/0161 - 0164; Aptil Pharma Limited) . Aptil Pharma Limited, has agreed that scientific data presented for Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets (PL 40378/0161 - 0164) can be used for these applications for Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets (PL 36390/0142 - 0145). What are the benefits and risks of Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets? Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets (PL 36390/0142 - 0145; Cipla (EU) Limited) are considered identical to Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets (PL 40378/0161-0164; Aptil Pharma Limited) and, therefore, their benefits and risks are taken as being the same. Why are Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets approved? No new or unexpected safety concerns arose from this application. It was, therefore, considered that the benefits of Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets outweigh their risks, and the grant of these marketing authorisations was recommended. What measures are being taken to ensure the safe and effective use of Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets? A risk management plan has been developed to ensure that Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets are used as safely as possible. Based on this plan, safety information has been included in the summary of product characteristics and the patient information leaflet for Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets, including the appropriate precautions to be followed by healthcare professionals and patients.


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Known side effects are continuously monitored. Furthermore, new safety signals reported by patients and healthcare professionals will be monitored and reviewed continuously as well. Other information about Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets The marketing authorisations were granted in the UK on 15 August 2014. For more information about taking Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets, read the patient information leaflet, or contact your doctor or pharmacist. This summary was last updated in October 2014. The full PAR for Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets follows this summary.


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PL 36390/0142 - 0145

SCIENTIFIC DISCUSSION

TABLE OF CONTENTS Introduction

Page 6

Pharmaceutical assessment

Page 8

Non-clinical assessment

Page 10

Clinical assessment

Page 10

Overall conclusions and risk benefit assessment

Page 11


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INTRODUCTION Based on the review of the data on quality, safety and efficacy, the UK granted marketing authorisations to Cipla (EU) Limited for the medicinal products Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets (PL 36390/0142 - 0145) on 15 August 2014. These are prescription-only medicines (legal status POM). In adults these tablets are used to treat the following bacterial infections:

• respiratory tract infections due to Gram-negative bacteria - exacerbations of chronic obstructive pulmonary disease - broncho-pulmonary infections in cystic fibrosis or in

bronchiectasis - pneumonia

• Chronic suppurative otitis media • Acute exacerbation of chronic sinusitis especially if these are

caused by Gram-negative bacteria • Urinary tract infections • Gonococcal uretritis and cervicitis • Epididymo-orchitis including cases due to Neisseria gonorrhoea • Pelvic inflammatory disease including cases due to Neisseria

gonorrhoea • In the above genital tract infections when thought or known to be

due to Neisseria gonorrhoea it is particularly important to obtain local information on the prevalence of resistance to ciprofloxacin and to confirm susceptibility based on laboratory testing.

• Infections of the gastro-intestinal tract (e.g. travellers’ diarrhoea) • Intra-abdominal infections • Infections of the skin and soft tissue caused by Gram-negative

bacteria • Malignant external otitis • Infections of the bones and joints • Treatment of infections in neutropenic patients • Prophylaxis of infections in neutropenic patients • Prophylaxis of invasive infections due to Neisseria meningitidis • Inhalation anthrax (post-exposure prophylaxis and curative

treatment)

In children and adolescents these tablets are used to treat the following bacterial infections:

• Broncho-pulmonary infections in cystic fibrosis caused by Pseudomonas aeruginosa

• Complicated urinary tract infections and pyelonephritis • Inhalation anthrax (post-exposure prophylaxis and curative

treatment) • Ciprofloxacin may also be used to treat severe infections in

children and adolescents when this is considered to be necessary.


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These applications were submitted as abridged simple applications according to Article 10c of Directive 2001/83/EC, as amended. These applications cross-refer to Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets (PL 40378/0161 - 0164), which were authorised to Neolab Limited (PL 08137/0049 - 0052) on 15 May 2002. On 30 April 2013, the marketing authorisation holder was updated by a change of ownership to the current marketing authorisation holder, Aptil Pharma Limited (PL 40378/0161 - 0164). These medicinal products contain the active substance ciprofloxacin (as ciprofloxacin hydrochloride) which is an antibiotic belonging to the fluoroquinolone family. This active substance works by inhibiting both type II topoisomerase (DNA-gyrase) and topoisomerase IV enzymes required for bacterial DNA replication, transcription, repair and recombination. No new data were submitted nor were they necessary for these simple applications, as the data are identical to those of the previously granted cross-reference products. The MHRA has been assured that acceptable standards of Good Manufacturing Practice (GMP) are in place for these product types at all sites responsible for the manufacture and assembly of these products. A summary of the pharmacovigilance system and risk management plan have been provided with these applications and are satisfactory.


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PHARMACEUTICAL ASSESSMENT LICENCE NO: PL 36390/0142 - 0145 PROPRIETARY NAME: Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets ACTIVE(S): Ciprofloxacin Hydrochloride COMPANY NAME: Cipla (EU) Limited E.C. ARTICLE: Article 10c of Directive 2001/83/EC, as amended LEGAL STATUS: POM 1. INTRODUCTION These are simple, piggyback (informed consent) applications for Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets, submitted under Article 10c of Directive 2001/83/EC, as amended. The proposed MA holder is Cipla (EU) Limited, Hillbrow House, Hillbrow Road, Esher, Surrey, KT10 9NW. The applications cross-refer to licences for Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets (PL 40378/0161 - 0164), which were authorised to Neolab Limited (PL 08137/0049 - 0052) on 15 May 2002. On 30 April 2013, the marketing authorisation holder was updated by a change of ownership to the current marketing authorisation holder, Aptil Pharma Limited (PL 40378/0161 - 0164). The current applications are considered valid. 2. MARKETING AUTHORISATION APPLICATION FORM 2.1 Name(s) The proposed names of the products are Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets. The products have been named in line with current requirements. 2.2 Strength, pharmaceutical form, route of administration, container and pack sizes Each Ciprofloxacin 100, 250, 500 and 750 mg film-coated tablet contains 100, 250, 500 and 750 mg of ciprofloxacin (as ciprofloxacin hydrochloride), respectively. Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets are packaged in polyvinylchloride/aluminium foil blisters, contained in cardboard cartons, in pack sizes of 6, 10, 20, or 100 tablets. The proposed shelf-life for the Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets is 3 years. The storage conditions for Ciprofloxacin 100 mg Film-Coated Tablets are “Do not store above 25°C” and “Store in the original package”. The storage condition for Ciprofloxacin 250, 500 and 750 mg Film-Coated Tablets is “Store in the original package”. These are consistent with the details registered for the cross-reference products. 2.3 Legal status On approval, these products will be available as prescription-only medicines (POM). 2.4 Marketing authorisation holder/Contact Persons/Company Cipla (EU) Limited, Hillbrow House, Hillbrow Road, Esher, Surrey, KT10 9NW, United Kingdom.


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2.5 Manufacturers The proposed manufacturing sites are consistent with those registered for the cross-reference products and evidence of Good Manufacturing Practice (GMP) compliance has been provided. 2.6 Qualitative and quantitative composition The proposed compositions are consistent with the details registered for the cross-reference products. 2.7 Manufacturing process The proposed manufacturing process is consistent with the details registered for the cross-reference products. 2.8 Finished product/shelf-life specification The proposed finished product specifications are in-line with the details registered for the cross-reference products. 2.9 Drug substance specification The proposed drug substance specification is consistent with the details registered for the cross-reference products. 2.10 TSE Compliance No materials of animal or human origin are included in these products. This is consistent with the cross-reference products. 3. EXPERT REPORTS The applicant has included detailed expert reports in Module 2 of the applications. Signed declarations and copies of the experts’ CVs are enclosed in Module 1.4 for the quality, non-clinical and clinical experts. All are considered to have sufficient experience for their responsibilities. 4. PRODUCT NAME & APPEARANCE See Section 2.1 for details of the proposed product names. The appearances of the products are identical to the cross-reference products. 5. SUMMARY OF PRODUCT CHARACTERISTICS (SmPC) The proposed SmPCs are consistent with the details registered for the cross-reference products. 6. PATIENT INFORMATION LEAFLET (PIL)/CARTON PIL The patient information leaflet has been prepared in-line with the details registered for the cross-reference products. Carton and Label The proposed carton and label texts were provided in the Quality Review of Documents (QRD) template word format and were consistent with those of the reference product.


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7. CONCLUSIONS The data submitted with the applications are acceptable. From a quality perspective, Marketing Authorisations should be granted.

NON-CLINICAL ASSESSMENT No new non-clinical data have been supplied with these applications and none are required for applications of this type.

CLINICAL ASSESSMENT

No new clinical data have been supplied with these applications and none are required for applications of this type.


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OVERALL CONCLUSION AND BENEFIT-RISK ASSESSMENT QUALITY The important quality characteristics of Ciprofloxacin 100, 250, 500 and 750 mg Film-Coated Tablets are well-defined and controlled. The specifications and batch analytical results indicate consistency from batch to batch. There are no outstanding quality issues that would have a negative impact on the benefit/risk balance. NON-CLINICAL No new non-clinical data were submitted and none are required for applications of this type. CLINICAL PHARMACOLOGY/EFFICACY No new clinical pharmacology/efficacy data have been submitted with these applications and none are required for applications of this type. SAFETY No new safety data have been submitted with these applications and none are required for applications of this type. No new or unexpected safety concerns arose from these applications. The SmPCs, PIL and labelling are satisfactory. BENEFIT-RISK ASSESSMENT The quality of the products is acceptable and no new non-clinical or clinical safety concerns have been identified. Extensive clinical experience with ciprofloxacin is considered to have demonstrated the therapeutic value of the compound. The benefit-risk assessment is, therefore, considered to be positive.


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PL 36390/0142 - 0145

STEPS TAKEN FOR ASSESMENT

1 The MHRA received the marketing authorisation applications on 03 January

2014

2 Following standard checks and communication with the applicant, the MHRA considered the applications valid on 31 January 2014

3 Following assessment of the applications, the MHRA requested further information relating to the dossiers on 10 April 2014 and 01 July 2014

4 The applicant responded to the MHRA’s requests, providing further information on 23 May 2014 and 15 July 2014

5 The applications were determined on 15 Aug 2014


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PL 36390/0142 - 0145

STEPS TAKEN AFTER AUTHORISATION - SUMMARY

Date submitted

Application type

Scope Outcome


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Summary of Product Characteristics and Patient Information Leaflet In accordance with Directive 2012/84/EU, the current approved UK versions of the Summaries of Product Characteristics (SmPC) and Patient Information Leaflet (PIL) for these products are available on the MHRA website.


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Labelling

100 mg Carton and Label


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