Public Assessment Report Levofloxacin 250 mg and … · A Risk Management Plan (RMP) has been...

Public Assessment Report

Levofloxacin 250 mg and 500 mg film-coated tablets

(Levofloxacin hemihydrate)

UK Licence No.: PL 28278/0001-2

Ipca Laboratories UK limited

UKPAR Levofloxacin 250 mg and 500 mg film-coated tablets PL 28278/0001-2

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Lay Summary

Levofloxacin 250 mg and 500 mg film-coated tablets

(Levofloxacin hemihydrate)

This is a summary of the Public Assessment Report (PAR) for Levofloxacin 250 mg

and 500 mg film-coated tablets (PL 28278/0001-2). These medicinal products will be

referred to as Levofloxacin Tablets in the remainder of the summary, for ease of

reading.

This summary explains how Levofloxacin 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 these products.

For practical information about using Levofloxacin Tablets, patients should read the

package leaflet or contact their doctor or pharmacist.

What are Levofloxacin Tablets and what are they used for?

These medicines are the same as Levofloxacin 250 mg and 500 mg film-coated

Tablets (PL 17907/0218-0219), which are already authorised. The company that

makes Levofloxacin 250 mg and 500 mg film-coated Tablets (PL 17907/0218-0219),

Bristol Laboratories Limited, has agreed that its scientific data can be used as a basis

for the grant of identical licences for Levofloxacin Tablets (PL 28278/0001-2).

Levofloxacin Tablets can be used in adults including elderly to treat infections of the:

• Sinuses

• Lungs, in people with long-term breathing problems or pneumonia

• Urinary tract, including the bladder or kidneys

• Skin and underneath the skin, including muscles. This is sometimes called

‘soft tissue’

• Prostate gland, where patients have a long lasting infection

In some special situations, Levofloxacin tablets may be used to lessen the chances of

getting a pulmonary disease named anthrax or worsening of the disease after patients

are exposed to the bacteria causing anthrax.

How do Levofloxacin Tablets work?

Levofloxacin Tablets contain the active substance levofloxacin, which is a quinolone

antibiotic. It works by killing the bacteria that causes infection in the body.

How are Levofloxacin Tablets used?

Levofloxacin Tablets are taken by mouth. The whole tablet should be swallowed with

a drink of water. The tablets may be taken during meals or at any time between meals.

The dose and the length of treatment will depend on the type of infection and the

seriousness of the infection.

Please read Section 3 of the package leaflet for detailed information on dosing

recommendations, the route of administration and the duration of treatment.

Levofloxacin Tablets can only be obtained with a prescription from a doctor.


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What benefits of Levofloxacin Tablets have been shown in studies? As Levofloxacin Tablets (PL 28278/0001-2) are considered to be identical to

Levofloxacin 250 mg and 500 mg film-coated Tablets (PL 17907/0218-0219), their

benefits and risks are taken as being the same as those for Levofloxacin 250 mg and

500 mg film-coated Tablets (PL 17907/0218-0219).

What are the possible side effects from Levofloxacin Tablets?

Like all medicines, Levofloxacin Tablets can cause side effects, although not

everybody gets them.

For the full list of all side effects reported with Levofloxacin Tablets, see section 4 of

the package leaflet.

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

Why are Levofloxacin Tablets approved?

No new or unexpected safety concerns arose from these applications. It was,

therefore, considered that the benefits of Levofloxacin Tablets outweigh the risks, and

the grant of Marketing Authorisations was recommended.

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

Levofloxacin Tablets?

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

Tablets are used as safely as possible. Based on this plan, safety information has been

included in the Summaries of Product Characteristics and the package leaflet for

Levofloxacin Tablets, including the appropriate precautions to be followed by

healthcare professionals and patients.

Other information about Levofloxacin Tablets

Marketing Authorisations were granted in the UK on 05 April 2016.

For more information about taking Levofloxacin Tablets, read the package leaflet, or

contact your doctor or pharmacist.

The full PAR for Levofloxacin Tablets follows this summary.

This summary was last updated in May 2015.


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Table of Contents

I Introduction Page 5

II Quality aspects Page 6

III Non-clinical aspects Page 7

IV Clinical aspects Page 7

V User consultation Page 11

VI Overall conclusion, benefit/risk assessment and

recommendation

Page 11

Table of content of the PAR update

Page 20


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

Laboratories Limited Marketing Authorisations for the medicinal products for

Levofloxacin 250 mg and 500 mg film-coated tablets (PL 28278/0001-2) on 05 April

2016. These products are prescription only medicines (POM) indicated in adult for the

treatment of the following infections:

Acute bacterial sinusitis

Acute bacterial exacerbations of chronic bronchitis

Community-acquired pneumonia

Complicated skin and soft tissue infections

For the above-mentioned infections, Levofloxacin tablets should be used only when it

is considered inappropriate to use antibacterial agents that are commonly

recommended for the initial treatment of these infections.

Complicated urinary tract infections including pyelonephritis

Chronic bacterial prostatitis

Uncomplicated cystitis

Inhalation Anthrax: post-exposure prophylaxis and curative treatment.

Levofloxacin tablets may also be used to complete a course of therapy in patients who

have shown improvement during initial treatment with intravenous levofloxacin.

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

antibacterial agents.

These applications were submitted as abridged simple applications, according to

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

Levofloxacin 250 mg and 500 mg film-coated Tablets, which were first authorised to

Bristol Laboratories Limited (PL 17907/0218-0219) on 11 November 2016.

The active ingredient, levofloxacin is a synthetic antibacterial agent of the

fluoroquinolone class and is the S (-) enantiomer of the racemic drug substance

ofloxacin. As a fluoroquinolone antibacterial agent, levofloxacin acts on the DNA-

DNA-gyrase complex and topoisomerase IV.

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.


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II Quality aspects II.1 Introduction These are simple, piggyback (informed consent) applications for Levofloxacin 250

mg and 500 mg film-coated tablets (PL 28278/0001-2), submitted under Article 10c

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

Levofloxacin 250 mg and 500 mg film-coated Tablets, which were first authorised to

Bristol Laboratories Limited (PL 17907/0218-0219) on 11 November 2016. The

current applications are considered valid.

II.2. Drug Substance

Drug substance specification

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

the cross-reference products.

II.3. Medicinal Products

Name

The proposed product names are Levofloxacin 250 mg and 500 mg film-coated

tablets. The products have been named in line with current requirements.

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

Each film-coated tablet contains levofloxacin hemihydrate, which is equivalent to 250

mg and 500 mg levofloxacin, as active ingredient. The route of administration is oral.

The finished products are packed into a clear polyvinylchloride (PVC)/aluminium foil

blisters with pack sizes of 1’s, 5’s and 10’s Tablets. Not all pack sizes may be

marketed.

The proposed shelf-life is 36 months with storage conditions “Do not store above

25°C” and “Store in the original package”.

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

cross-reference products. These are satisfactory.

Legal status

These products are prescription only medicines (POM).

Marketing Authorisation Holder/Contact Persons/Company

Ipca Laboratories UK limited, Unit 97-98, Silverbriar Sunderland Enterprise Park

East, Sunderland, SR5 2TQ 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 products and evidence of Good Manufacturing Practice (GMP)

compliance has been provided.


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Qualitative and quantitative composition

The proposed compositions are consistent with the details registered for the

cross-reference products.

Manufacturing process

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

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

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

the cross-reference products.

Bioequivalence

No bioequivalence data are required to support these simple abridged applications as

the proposed products are manufactured to the same formula utilising the same

process as the cross-reference products, Levofloxacin 250 mg and 500 mg film-coated

Tablets (PL 17907/0218-0219).

Expert Report

The applicant cross-refers to the data for Levofloxacin 250 mg and 500 mg film-

coated Tablets (PL 17907/0218-0219) to which these applications are claimed to be

identical. This is acceptable. The applicant has included expert reports of the

applications. 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 these applications are consistent with those approved for

Levofloxacin 250 mg and 500 mg film-coated Tablets (PL 17907/0218-0219) and, as

such, have been judged to be satisfactory. The grant of Marketing Authorisations is

recommended.

III Non-clinical aspects As these are abridged simple applications 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 Marketing Authorisations is recommended.

IV Clinical aspects As these are abridged simple applications submitted under Article 10c of Directive

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

required.


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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.

The grant of Marketing Authorisations 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

Levofloxacin 250 mg and 500 mg film-coated tablets (PL 28278/0001-2).

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 SmPCs. These are considered sufficient. No additional risk minimisation measures

are considered necessary.

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

VI Overall conclusion, benefit/risk assessment and

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

have been identified. The applicant’s products are identical to the reference products.

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 currently approved labels are 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

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