Public Assessment Report - Medicines and Healthcare ... the introduction of current legislation, no...

Public Assessment Report

Paracetamol 500mg Tablets

(paracetamol)

UK Licence No: PL 20395/0078

Relonchem Limited

PAR Paracetamol 500mg Tablets PL 20395/0078

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LAY SUMMARY Paracetamol 500mg Tablets

(paracetamol)

This is a summary of the Public Assessment Report (PAR) for Paracetamol 500mg Tablets (PL

20395/0078). It explains how Paracetamol 500mg 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 Paracetamol 500mg Tablets.

For practical information about using Paracetamol 500mg Tablets, patients should read the package

leaflet or contact their doctor or pharmacist.

What are Paracetamol 500mg Tablets and what are they used for?

This medicine is the same as Paracetamol 500mg Caplets (PL 39484/0038), which is already authorised.

The company that makes Paracetamol 500mg Caplets (PL 39484/0038), Fourrts (UK) Pharmacare Ltd,

has agreed that its scientific data can be used as a basis for the grant of an identical licence for

Paracetamol 500mg Tablets (PL 20395/0078).

Paracetamol 500mg Tablets are used for the relief of mild to moderate pain including:

- Rheumatic aches and pains

- Neuralgia (severe nerve pain), period pain

- Migraine, headache

- Sore throat, toothache

- Fever, colds, flu and influenza

How do Paracetamol 500mg Tablets work?

Paracetamol 500mg Tablets contain the active ingredient paracetamol, which belongs to a group of

medicines called analgesics (pain killers) and helps relieve mild to moderate pain.

How are Paracetamol 500mg Tablets used?

Paracetamol 500mg Tablets are taken by mouth. The whole tablet should be swallowed with a glass of

water.

The recommended dose in adults, the elderly and childen 16 years and over is one or two tablets up to 4

times a day. Patients should not take more than eight tablets in any 24 hours.

The dose in children 10 to 15 years of age is one tablet up to 4 times a day. Patients should not take

more than four tablets in any 24 hours.

The dose should not be repeated more frequently than every 4 hours and not more than 4 doses should

be taken in any 24 hour period.

Paracetamol 500mg Tablets are not recommended in children under the age of 10.

This medicine should not be given for more than 3 days at a time unless advised by a adoctor.

For further information on how Paracetamol 500mg Tablets are used, please see the Summary of

Product Characteristics or the package leaflet available on the MHRA website.

What benefits of Paracetamol 500mg Tablets have been shown in studies?

As Paracetamol 500mg Tablets (PL 20395/0078) are considered to be identical to Paracetamol 500mg

Caplets (PL 39484/0038), their benefits and risks are taken as being the same as those for Paracetamol


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500mg Caplets (PL 39484/0038).

What are the possible side effects of Paracetamol 500mg Tablets?

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

For information about side effects that may occur with taking Paracetamol 500mg Tablets, please refer

to the package leaflet or the Summary of Product Characteristics available on the MHRA website.

Why is Paracetamol 500mg Tablets approved?

This medicine is the same as the already approved Paracetamol 500mg Caplets (PL 39484/0038). No

new or unexpected safety concerns arose from this application. It was, therefore, considered that the

benefits of Paracetamol 500mg 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 Paracetamol 500mg

Tablets?

Safety information has been included in the Summary of Product Characteristics and the package leaflet

for Paracetamol 500mg Tablets, including the appropriate precautions to be followed by healthcare

professionals and patients.

Other information about Paracetamol 500mg Tablets

A Marketing Authorisation was granted in the UK on 30 June 2011.

The full PAR for Paracetamol 500mg Tablets follows this summary.

This summary was last updated in December 2016.


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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 7

VI Overall conclusion, benefit/risk assessment and Page 8

Recommendation

Table of content of the PAR update Page 14

Annex Page 15


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I INTRODUCTION

Based on the review of the data on quality, safety and efficacy, the UK granted a Marketing

Authorisation for the medicinal product Paracetamol 500mg Tablets (PL 20395/0078) on 30 June 2011.

This product is a prescription only medicine (POM).

This is a simple, abridged, ‘informed consent’ application submitted according to Article 10c of EC

Directive 2001/83 (as amended), cross-referring to the Marketing Authorisation for Paracetamol 500mg

Caplets (PL 39484/0038), licensed to Fourrts (UK) Pharmacare Ltd. The cross-referenced product was

originally awarded a default conversion licence in November 2011, licensed to Rusco Limited (PL

01618/5165R), which underwent a Change of Ownership (CoA) to the current Marketing Authorisation

Holder, Fourrts (UK) Pharmacare Ltd, on 15th

July 2011.

Paracetamol 500mg tablets are indicated for the treatment of mild to moderate pain including headache,

migraine, neuralgia, toothache, sore throat, period pain, aches and pains, symptomatic relief of

rheumatic aches and pains and of influenza, feverishness and feverish colds.

Paracetamol is an effective analgesic and antipyretic agent (ATC code - N02B E01) but has only weak

anti-inflammatory properties. Its mechanism of action is not fully understood, as it is only a weak

inhibitor of prostaglandin bio-synthesis, but it has been suggested that it is more effective against

enzymes in the central nervous system (CNS) than those in the periphery. The drug has no effect on the

cardiovascular and respiratory systems and it does not cause gastric irritation or bleeding like salicylates.

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.

As the application is for a product that is identical to an already authorised reference product, 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.

The reference product has been in use for many years and the safety profile of the active is well-

established.

It is not considered that this medicinal product represents any risk to the environment. There is no reason

to conclude that marketing of this product will change the overall use pattern of the existing market. The

availability of this medicinal product, which is identical to the cited reference product, will not lead to

any increase in environmental exposure concentrations of the active ingredient, paracetamol. An

Environmental Risk Assessment (ERA) is not considered necessary.

No new data were submitted, nor was it necessary for this simple application, as the data are identical to

that of the previously granted cross-reference product. As the cross-reference product was granted prior

to the introduction of current legislation, no Public Assessment Report (PAR) was generated for it.


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II QUALITY ASPECTS

II.1 Introduction

This is an abridged simple, informed consent application for Paracetamol 500mg tablets (PL

20395/0078), submitted under Article 10c of Directive 2001/83/EC, as amended. The applicant has

cross-referred to Paracetamol 500mg Caplets (PL 39484/0038), licensed to Fourrts (UK) Pharmacare

Ltd. The cross-referenced product was originally awarded a default conversion licence in November

2011, licensed to Rusco Limited (PL 01618/5165R), which underwent a Change of Ownership (CoA) to

the current Marketing Authorisation Holder, Fourrts (UK) Pharmacare Ltd, on 15th

July 2011. The

current application is considered valid.

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 Paracetamol 500mg tablets. The product has been named in line with

current requirements.

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

Each Paracetamol 500mg tablet contains 500mg of the active ingredient, paracetamol. The tablets are

licensed for marketing in polyvinylchloride (PVC) / aluminium foil blister strips, which are packaged

with the Patient Information Leaflet (PIL) into cardboard outer cartons in pack sizes of 48, 60, 96 and

100 tablets. The MAH has stated that not all pack sizes may be marketed.

The approved shelf-life (3 years) and storage conditions (‘Do not store above 25C. Store in the original

package’) are consistent with the details registered for the cross-reference product.

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

Relonchem Limited, Cheshire House, Gorsey Lane, Widnes, Cheshire, WA8 0RP, UK

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 GMP compliance has been provided.

Qualitative and quantitative compositions

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 specifications


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The proposed finished product specification is consistent with the details registered for the cross-

reference product.

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

reference product.

TSE Compliance

There are no materials of human or animal origin contained in, or used in the manufacturing process for,

the proposed product. None of the excipients are sourced from genetically modified organisms.

Expert Report

The applicant cross-refers to the data for Paracetamol 500mg Caplets (PL 39484/0038), 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 Paracetamol 500mg Caplets

(PL 39484/0038) and, as such, have been judged to be satisfactory. The grant of a Marketing

Authorisation was recommended.

III NON-CLINICAL ASPECTS

III.1 Introduction As this is 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

IV.1 Introduction

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.

The grant of a Marketing Authorisation is recommended.

V USER CONSULTATION The approved patient information leaflet (PIL) is satisfactory and in line with the approved SmPC. The

PIL has been prepared in the user-tested format and in line with the details registered for the cross-

reference product.

PIL user-testing has been accepted based on bridging to the successful user-testing of the PIL for the

reference product, Paracetamol 500mg Caplets (PL 39484/0038). The text, content and layout of the

proposed PIL are essentially identical to the approved PIL for the reference product. The bridging is

accepted.


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VI OVERALL CONCLUSION, BENEFIT-RISK ASSESSMENT AND

RECOMMENDATION

QUALITY

The data for this application are consistent with those previously assessed for the cross-reference

product and as such have been judged to be satisfactory.

NON-CLINICAL

No new non-clinical data were submitted and none are required for an application of this type.

CLINCIAL

This application is considered identical to the previously granted licence for Paracetamol 500mg Caplets

(PL 39484/0038, Fourrts (UK) Pharmacare Ltd).

No new or unexpected safety concerns arose from this application.

PRODUCT LITERATURE

The approved SmPC, PIL and labelling are satisfactory and consistent with the details registered for the

cross-reference product.

Mock-up labelling has been provided and is satisfactory. The approved labelling artwork complies with

statutory requirements.

BENEFIT-RISK ASSESSMENT

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 cross-reference product. The benefit: risk ratio is

considered to be positive.


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Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and labelling

In accordance with Directive 2010/84/EU the Summaries of Product Characteristics (SmPCs) and

Patient Information Leaflets (PILs) for products that are granted Marketing Authorisations at a national

level are available on the MHRA website.

The current approved labelling is presented 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 (Variations,

PSURs, commitments)

Date

submitted

Application

type

Scope Outcome

30/08/2016 IB To update sections 4 (Clinical particulars),

and 5 (Pharmacological properties) of the

SmPC and consequentially the leaflet in

line with the brand leader.

Approved on

07/11/2016


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ANNEX 1

Our Reference: PL 20395/0078-0029

Product: Paracetamol 500mg Tablets

Marketing Authorisation Holder: Relonchem Limited

Active Ingredient(s): Paracetamol

Reason:

To update sections 4 (Clinical particulars), and 5 (Pharmacological properties) of the SmPC and

consequentially the leaflet in line with the brand leader.

Supporting Evidence

Revised sections of the SmPC and PIL have been provided.

Evaluation

The proposed changes to the SmPC fragments and the PIL are acceptable. These updated SmPC

fragments and PIL have been incorporated into the Marketing Authorisation.

Conclusion

Following approval of the variation on 07 November 2016 the SmPC and PIL were updated. In

accordance with Directive 2010/84/EU, the current granted UK SmPC and PIL are available on the

MHRA website.

Decision: granted on 07 November 2016.

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