public assessment report ciprofloxacin 500 mg film … ciprofloxacin 500 mg film-coated tablets pl...

Public Assessment Report

Ciprofloxacin 500 mg film-coated tablets

(ciprofloxacin hydrochloride)

UK Licence No.: PL 44041/0007

Noumed Life Sciences

UKPAR Ciprofloxacin 500 mg film-coated tablets PL 44041/0007

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Lay Summary Ciprofloxacin 500 mg film-coated tablets

(ciprofloxacin hydrochloride)

This is a summary of the Public Assessment Report (PAR) for Ciprofloxacin 500 mg

film-coated tablets (PL 44041/0007). It explains how Ciprofloxacin 500 mg film-

coated tablets were assessed and their authorisation recommended, as well as the

conditions of use. It is not intended to provide practical advice on how to use

Ciprofloxacin 500 mg film-coated tablets.

This medicinal product will be referred to as Ciprofloxacin tablets in this lay summary

for ease of reading.

For practical information about using Ciprofloxacin tablets, patients should read the

package leaflet or contact their doctor or pharmacist.

What are Ciprofloxacin tablets and what are they used for?

This medicine is the same as Ciprofloxacin 500 mg Tablets (PL 21880/0032), which

is already authorised. The company that makes Ciprofloxacin 500 mg Tablets,

Medreich PLC, has agreed that its scientific data can be used as a basis for the grant

of an identical licence for Ciprofloxacin tablets (Noumed Life Sciences; PL

44041/0007).

Adults

Ciprofloxacin is used in adults to treat the following bacterial infections:

• Respiratory tract infections

• Long lasting or recurring ear or sinus infections

• Urinary tract infections

• Genital tract infections in men and women

• Gastro-intestinal tract infections and intra-abdominal infections

• Skin and soft tissue infections

• Bone and joint infections

• To prevent infections due to the bacterium Neisseria meningitidis

• Anthrax inhalation exposure

Ciprofloxacin may also be used in patients with low white blood cell counts

(neutropenia) who have a fever that is suspected to be due to a bacterial infection.

Children and adolescents

Ciprofloxacin is only used in children and adolescents under specialist medical

supervision. It is used to treat the following bacterial infections:

• Lung and bronchial infections in children and adolescents suffering from cystic

fibrosis

• Complicated urinary tract infections, including infections that have reached the

kidneys (pyelonephritis)

• Anthrax inhalation exposure

Ciprofloxacin may also be used to treat other severe infections in children and

adolescents when considered necessary by a doctor.


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How do Ciprofloxacin tablets work?

The active substance, ciprofloxacin, is an antibiotic which belongs to a group of

antibiotic medicines called quinolones which work by killing bacteria that cause

infections.

How are Ciprofloxacin tablets used?

Ciprofloxacin tablets are taken by mouth. The whole tablet should be swallowed with

plenty of fluid. This medicine should be taken at the same time every day at meal

times or between meals, and not chewed.

The prescribing doctor will explain how many tablets 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.

Ciprofloxacin tablets can only be obtained with a prescription.

For further information on how Ciprofloxacin tablets are used, please refer to the

package leaflet and Summary of Product Characteristics available on the Medicines

and Healthcare products Regulatory Agency (MHRA) website.

What benefits of Ciprofloxacin tablets have been shown in studies? As Ciprofloxacin tablets (PL 44041/0007) are considered to be identical to

Ciprofloxacin 500 mg Tablets (PL 21880/0032), their benefits and risks are taken as

being the same as those for Ciprofloxacin 500 mg Tablets (PL 21880/0032).

What are the possible side effects from Ciprofloxacin tablets?

Like all medicines, this medicine can cause side effects, although not everybody gets

them.

The common side effect Ciprofloxacin tablets which may affect 1 in 10 people are

nausea, diarrhoea and joint pains in children.

For the full list of all side effects reported with Ciprofloxacin tablets, see section 4 of

the package leaflet.

For the full list of restrictions, see the package leaflet.

Why are Ciprofloxacin tablets approved?

This medicine is the same as the already approved Ciprofloxacin 500 mg Tablets (PL

21880/0032). No new or unexpected safety concerns arose from this application. It

was, therefore, considered that the benefits of Ciprofloxacin tablets outweigh the

risks, and the grant of a Marketing Authorisation was recommended.

What measures are being taken to ensure the safe and effective use of

Ciprofloxacin tablets?

A Risk Management Plan (RMP) has been developed to ensure that Ciprofloxacin

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


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for Ciprofloxacin tablets, including the appropriate precautions to be followed by

healthcare professionals and patients.

Other information about Ciprofloxacin tablets

A Marketing Authorisation was granted in the UK on 31 August 2016.

For more information about taking Ciprofloxacin tablets, read the package leaflet, or

contact your doctor or pharmacist.

The full PAR for Ciprofloxacin tablets follows this summary.

This summary was last updated in October 2016.


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Table of Contents

I Introduction Page 6

II Quality aspects Page 8

III Non-clinical aspects Page 9

IV Clinical aspects Page 9

V User consultation Page 13

VI Overall conclusion, benefit/risk assessment and

recommendation

Page 13

Table of content of the PAR update

Page 16


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I Introduction The Medicines and Healthcare products Regulatory Agency (MHRA) granted

Noumed Life Sciences, a Marketing Authorisation for the medicinal product

Ciprofloxacin 500 mg film-coated tablets (PL 44041/0007) on 31 August 2016. This

product is a prescription only medicine (POM), indicated for the treatment of the

following infections caused by sensitive bacteria.

Special attention should be paid to available information on resistance to

ciprofloxacin before commencing therapy.

Consideration should be given to official guidance on the appropriate use of

antibacterial agents.

Adults:

• Lower 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

• Genital tract infections

- gonococcal uretritis and cervicitis due to susceptible Neisseria

gonorrhoeae

- epididymo-orchitis including cases due to susceptible Neisseria

gonorrhoeae

- pelvic inflammatory disease including cases due to susceptible

Neisseria gonorrhoeae

• 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

• Prophylaxis of invasive infections due to Neisseria meningitidis

• Inhalation anthrax (post-exposure prophylaxis and curative treatment)

Ciprofloxacin may be used in the management of neutropenic patients with fever that

is suspected to be due to a bacterial infection.

Children and adolescents

• 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.

Treatment should be initiated only by physicians who are experienced in the treatment

of cystic fibrosis and/or severe infections in children and adolescents.


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Consideration should be given to official guidance on the appropriate use of

antibacterial agents.

This application was submitted as an abridged simple application, according to Article

10c of Directive 2001/83/EC, as amended. The applicant has cross-referred to

Ciprofloxacin 500 mg Tablets, which was first authorised to Karib Kemi Pharm

Limited (PL 18224/0009) on 19 September 2003. This reference licence underwent a

change of ownership procedure to current Marketing Authorisation holder, Medreich

PLC (PL 21880/0032), on 22 October 2008.

Ciprofloxacin is a synthetic 4-quinolone derivative, with bactericidal activity. It acts

via inhibition of bacterial DNA gyrase, ultimately resulting in interference with DNA

function. Ciprofloxacin is highly active against a wide range of Gram-positive and

Gram-negative organisms and has shown activity against some anaerobes, Chlamydia

spp. and Mycoplasma spp. Killing curves demonstrate the rapid bactericidal effect

against sensitive organisms and it is often found that minimum bactericidal

concentrations are in the range of minimum inhibitory concentrations.

No new data were submitted nor were they necessary for this simple application, as

the data are identical to those of the previously granted cross-reference product.

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 this product.

A Risk Management Plan (RMP) and a summary of the pharmacovigilance system

have been provided with this application, and these are satisfactory.

No new or unexpected safety concerns arose during the review of information

provided by the Marketing Authorisation Holder and it was, therefore, judged that the

benefits of taking Ciprofloxacin 500 mg film-coated tablets outweigh the risks and

Marketing Authorisations were granted.


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II Quality aspects II.1 Introduction This is an abridged simple, informed consent application for Ciprofloxacin 500 mg

film-coated tablets (PL 44041/0007), submitted under Article 10c of Directive

2001/83/EC, as amended. The applicant has cross-referred to Ciprofloxacin 500 mg

Tablets, which was first authorised to Karib Kemi Pharma Limited (PL 18224/0009)

on 19 September 2003. This reference licence underwent a change of ownership

procedure to current Marketing Authorisation holder, Medreich PLC (PL

21880/0032), on 22 October 2008.

II.2. Drug Substance

Drug substance specification

The proposed drug substance specification is consistent with the details registered for

the cross-reference product.

II.3. Medicinal Product

Name

The proposed product name is Ciprofloxacin 500 mg film-coated tablets. The product

has been named in line with current requirements.

Strength, pharmaceutical form, route of administration, container and pack size

Each tablet contains 582.0 mg ciprofloxacin hydrochloride equivalent to 500 mg

ciprofloxacin. The route of administration is oral.

The product is packaged in polyvinylchloride (PVC)/aluminium blister strips. The

pack sizes are 10 and 20 tablets.

The proposed shelf-life is 3 years with a storage condition “Do not store above 25°C”.

The proposed packaging and shelf-life are consistent with the details registered for the

cross-reference product.

Legal status

This product is a Prescription Only Medicine (POM).

Marketing Authorisation Holder/Contact Persons/Company

Noumed Life Sciences, Plot 5, Cattle Market, Hexam, Northumberland, NE46 1NJ,

United Kingdom

The Qualified Person (QP) responsible for pharmacovigilance is stated and a

satisfactory Curriculum Vitae (CV) has been provided.

Manufacturers

The proposed manufacturing sites are consistent with those registered for the

cross-reference product and evidence of Good Manufacturing Practice (GMP)

compliance has been provided.


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Qualitative and quantitative composition

The proposed composition is consistent with the details registered for the

cross-reference product.

Manufacturing process

The proposed manufacturing process is consistent with the details registered for the

cross-reference product and the maximum batch size is stated.

Finished product/shelf-life specification The proposed finished product specification is in line with the details registered for

the cross-reference product.

Bioequivalence

No bioequivalence data are required to support this simple abridged application as the

proposed product is manufactured to the same formula utilising the same process as

the cross-reference product, Ciprofloxacin 500 mg Tablets (PL 21880/0032).

Expert Report

The applicant cross-refers to the data for Ciprofloxacin 500 mg Tablets (PL

21880/0032), to which this application is claimed to be identical. This is acceptable.

The applicant has included expert reports for the application. Signed declarations and

copies of the experts’ CVs are enclosed for the quality, non-clinical and clinical

experts. All are considered to have sufficient experience for their responsibilities.

II.4 Discussion on chemical, pharmaceutical and biological aspects

The quality data for this application is consistent with those approved for

Ciprofloxacin 500 mg Tablets (PL 21880/0032) and, as such, have been judged to be

satisfactory. The grant of a Marketing Authorisation was recommended.

III Non-clinical aspects As this is an abridged simple application submitted under Article 10c of Directive

2001/83/EC, as amended, no new non-clinical data has been supplied and none are

required.

A suitable justification has been provided for not submitting an environmental risk

assessment.

The grant of a Marketing Authorisation is recommended.

IV Clinical aspects As this is an abridged simple application submitted under Article 10c of Directive

2001/83/EC, as amended, no new clinical data have been supplied and none are

required.

The Marketing Authorisation Holder has provided details of a suitable

pharmacovigilance system that fulfils the requirements and provides adequate

evidence that they have the services of a qualified person responsible for

pharmacovigilance, and have the necessary means for the notification of any adverse

reaction suspected of occurring either in the Community or in a third country.


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The grant of a Marketing Authorisation is recommended.

Risk Management Plan (RMP)

The applicant has submitted an RMP, 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

Ciprofloxacin 500 mg Tablets.

A summary of safety concerns and planned risk minimisation activities, as

approved in the RMP, is listed below:


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The applicant proposes only routine risk minimisation measures, which are detailed in

the SmPC. These are considered sufficient. No additional risk minimisation measures

are considered necessary.


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V User consultation The package leaflet is identical to the leaflet for the reference product.

VI Overall conclusion, benefit/risk assessment and

recommendation The quality of the product is acceptable, and no new non-clinical or clinical concerns

have been identified. The applicant’s product is identical to the reference product. The

benefit-risk assessment is, therefore, considered to be positive.


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Summary of Product Characteristics, Patient Information Leaflet &

Labels In accordance with Directive 2012/84/EU, the current approved UK versions of the

SmPCs and PIL for this product are available on the MHRA website.

The current approved label is listed below:


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Table of content of the PAR update

Steps taken after the initial procedure with an influence on the Public Assessment

Report (Type II variations, PSURs, commitments)

Date

submitted

Application

type

Scope Outcome

public assessment report ciprofloxacin 500 mg film … ciprofloxacin 500 mg film-coated tablets pl...

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