Public Assessment Report UKPAR Paracetamol 500mg … · UKPAR Paracetamol 500mg Tablets (Paracetamol) ... Paracetamol 500mg Tablets are considered ... predominantly by inhibiting

Public Assessment Report

UKPAR

Paracetamol 500mg Tablets

(Paracetamol)

UK Licence No: PL 16028/0162

Galpharm Healthcare Limited.

PAR Paracetamol 500mg Tablets PL 16028/0162

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LAY SUMMARY

Paracetamol 500mg Tablets

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

(PL 16028/0162). It explains how Paracetamol 500mg 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 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?

Paracetamol 500mg Tablets are used for relief of

• mild to moderate pain including headache, migraine, nerve pain (neuralgia), toothache, sore

throat and period pains

• symptoms of rheumatic and muscular aches and pains, sciatica, back pain (lumbago), joint

swelling and stiffness

• symptoms of colds and flu.

This medicine is the same as Paracetamol 500mg Tablets (PL 16028/0053) which is already authorised.

The company (Galpharm Healthcare Limited) that makes Paracetamol 500mg Tablets (PL 16028/0053)

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

consent) for Paracetamol 500mg Tablets (PL 16028/0162).

How do Paracetamol 500mg Tablets work?

This medicine contains the active ingredient called paracetamol which relieves pain and brings down

high temperatures (reduces fever).

How are Paracetamol 500mg Tablets used?

The pharmaceutical form of this medicine is a tablet and the route of administration is oral (by mouth).

The patient should swallow the tablets, preferably with a drink of water.

Dosage


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The patient must not take more medicine than the label tells them to. If the patient does not get better,

they should talk to their doctor.

The patient should talk to a doctor at once if they take too much of this medicine even if they feel well.

This is because too much paracetamol can cause delayed, serious liver damage.

Please refer to section 3 of the package leaflet for information on how to use this medicine.

This medicine can be obtained without a prescription.

For further information on how Paracetamol 500mg Tablets are used, refer to the package leaflet and

Summary of Product Characteristics available on the Medicines and Healthcare products Regulatory

Agency (MHRA) website.

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

Paracetamol 500mg Tablets are considered identical to previously authorised Paracetamol 500mg

Tablets (PL 16028/0053), with the same benefits and risks. So no new studies have been provided for

Paracetamol 500mg Tablets but reference is made to the studies for Paracetamol 500mg Tablets (PL

16028/0053).

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

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

Paracetamol 500mg Tablets are considered to be identical to the previously authorised application for

Paracetamol 500mg Tablets (PL 16028/0053) with the same benefits and risks.

For a full list of all the side effects reported with Paracetamol 500mg Tablets see section 4 of the

package leaflet, available on the Medicines and Healthcare products Regulatory Agency (MHRA)

website.

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

Why are Paracetamol 500mg Tablets approved?

The MHRA decided that the benefits of Paracetamol 500mg Tablets are greater than their risks and

recommended that they be approved for use.

What measures are being taken to ensure the safe and effective use of Paracetamol 500mg

Tablets?

A Risk Management Plan has been developed to ensure that Paracetamol 500mg Tablets are used as

safely as possible. Based on this plan, 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.

Known side effects are continuously monitored. Furthermore new safety signals reported by

patients/healthcare professionals will be monitored/reviewed continuously.

Other information about Paracetamol 500mg Tablets

A Marketing Authorisation was granted in the UK on 29 June 2017.

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

For more information about treatment with Paracetamol 500mg Tablets read the package leaflet, or

contact your doctor or pharmacist.

This summary was last updated in August 2017.


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TABLE OF CONTENTS

I Introduction Page 5

II Quality aspects Page 5

III Non-clinical aspects Page 7

IV Clinical aspects Page 7

V User consultation Page 8

VI Overall conclusion, benefit/risk assessment and

recommendation

Page 8

Table of content of the PAR update Page 12


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I INTRODUCTION

The Medicines and Healthcare products Regulatory Agency (MHRA) granted Galpharm Healthcare

Limited a Marketing Authorisation for the medicinal product Paracetamol 500mg Tablets (PL

16028/0162) on 29 June 2017. The product is a pharmacy (P) medicine indicated:

• For the relief of mild to moderate pain including headache, migraine, neuralgia, toothache, sore

throat and dysmenorrhoea.

• For the symptomatic relief of rheumatic and muscular aches and pains, sciatica, fibrositis,

lumbago, joint swelling and stiffness.

• For the symptomatic relief of influenza, feverish colds and feverishness.

This application was submitted as a simple abridged (informed consent) application according to Article

10c of Directive 2001/83/EC, as amended.

The application cross-refers to the reference product Paracetamol 500mg Tablets (PL 16028/0053),

which was first authorised to the marketing authorisation holder (MAH) Galpharm Healthcare Limited

on 08 October 2001.

This application is submitted to duplicate the cross-reference product Paracetamol 500mg Tablets (PL

16028/0053) which was authorised with two legal classifications: general sales list (legal status GSL)

and pharmacy (legal status P) medicine. The cross-reference product (PL 16028/0053) was authorised

prior to the introduction of The Medicines for Human Use and Medical Devices (Fees and

Miscellaneous Amendments) Regulations 2002 (SI 2002/542) which came in force on 01 April 2002.

This legislation states that a single marketing authorisation can only have one legal classification. It has

been confirmed by the applicant that the proposed marketing authorisation (PL 16028/0162) will replace

the supply of the drug product (‘pharmacy only’ pack size) from the existing, reference authorisation.

Following the grant of this application, the applicant should delete the relevant legal status from the

current licence (PL 16028/0053) by submitting a variation application.

Paracetamol is an effective analgesic and antipyretic agent but has only weak anti-inflammatory

properties. Its mechanism of action is not fully understood. It has been suggested that it may act

predominantly by inhibiting prostaglandin synthesis in the CNS and to a lesser extent through a

peripheral action by blocking pain-impulse generation. The peripheral action may also be due to

inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that

sensitise pain receptors to mechanical or chemical stimulation.

Paracetamol probably produces an antipyretic action by a central effect on the hypothalamic heat-

regulating centre to produce peripheral vasodilation resulting in increased blood flow through the skin,

sweating and heat loss. The central action probably involves inhibition of prostaglandin synthesis in the

hypothalamus. The drug has no effect on the cardiovascular and respiratory systems, and unlike

salicylates it does not cause gastric irritation or bleeding.

No new data were submitted nor were necessary to be submitted for this application, as the data are

identical to the data for the previously granted cross-referenced product.

II QUALITY ASPECTS

II.1 Introduction

This is an abridged application for Paracetamol 500mg Tablets (PL 16028/0162) submitted under Article

10c of Directive 2001/83/EC, as amended.

II.2. Drug Substance

Drug substance specification


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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 for this application is Paracetamol 500mg Tablets. The product has been

named in line with current requirements.

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

Each tablet contains 500 mg paracetamol. The finished product is packed into blisters comprised of:

• 30 micron hard temper aluminium lidding foil with 250 – 300 micron polyvinyl chloride (PVC)

base material.

or

• 30 micron hard temper aluminium lidding foil with 250 micron PVC/polyvinylidene chloride

[PVdC] (40-90 gsm) base material.

or

• 20 micron aluminium/15 micron PVC lidding foil with 250 – 300 micron PVC base material.

or

• 20 micron aluminium/15 micron PVC lidding foil with 250 micron PVC/PVdC (40-90 gsm) base

material.

and is available in a pack size of 32 tablets.

The proposed shelf life is 3 years with no special storage conditions.

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

the cross-reference product.

Legal status

Pharmacy (P).

Marketing Authorisation Holder/Contact Persons/Company

Galpharm Healthcare Limited, Wrafton, Braunton, Devon, EX33 2DL, United Kingdom.

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

Qualitative and quantitative composition

The proposed composition is consistent with the details registered for the cross-reference product.

Manufacturing process

The proposed manufacturing processes are 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.

TSE Compliance

None of the excipients contain materials of animal or human origin.


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No genetically modified organisms (GMO) have been used in the preparation of this product.

Bioequivalence

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

product is manufactured to the same formula utilising the same processes as the cross-reference product,

Paracetamol 500mg Tablets (PL 16028/0053).

Expert Reports

The applicant cross-refers to the data for Paracetamol 500mg Tablets (PL 16028/0053) to which this

application is claimed to be identical. This is acceptable.

Product Name and Appearance

See Section II.3 ‘Medicinal Product; Name’ for details of the proposed product name. The appearance of

the product is identical to that of the cross-reference product.

II.4 Discussion on chemical, pharmaceutical and biological aspects

The data submitted with the application is acceptable. The grant of a Marketing Authorisation is

recommended.

III NON-CLINICAL ASPECTS

Introduction

As this is an abridged application submitted under Article 10c of Directive 2001/83/EC, as amended, no

new non-clinical data have been supplied and none are required.

Ecotoxicity/environmental risk assessment (ERA)

Suitable justification has been provided for non-submission of an Environmental Risk Assessment. As

the application is an identical version of an already authorised product, it is not expected that

environmental exposure will increase following approval of the Marketing Authorisation for the

proposed product.

Discussion on the non-clinical aspects

The grant of a Marketing Authorisation is recommended.

IV CLINICAL ASPECTS

Introduction

As this is an abridged application submitted under Article 10c of Directive 2001/83/EC, as amended, no

new clinical data have been supplied and none are required.

Risk Management Plan (RMP)

The marketing authorisation holder (MAH) has submitted a risk management plan (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 Paracetamol

500mg Tablets.

A summary of safety concerns and planned risk minimisation activities, as approved in the RMP, are

listed below:


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Summary table of safety concerns:

Routine pharmacovigilance and routine risk minimisation are proposed for all safety concerns.

Discussion on the clinical aspects

The grant of a Marketing Authorisation is recommended.

V User consultation

A user consultation with target patient groups on the package information leaflet (PIL) has been

performed on the basis of a bridging report making reference to the PIL for Paracetamol 500mg Tablets

(PL 16028/0053). The bridging report submitted by the applicant is acceptable.

VI Overall conclusion, benefit/risk assessment and recommendation

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

identified. The applicant’s product is identical to the cross-reference product. Extensive clinical

experience with paracetamol is considered to have demonstrated the therapeutic value of the compound.

The benefit/risk balance is, therefore, considered to be positive.


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Summaries of Product Characteristics (SmPC), Patient Information Leaflets (PIL) and Labels

The SmPC and PIL are consistent with the details registered for the cross-reference product.

In accordance with Directive 2010/84/EU the SmPCs and PILs for products granted Marketing

Authorisations at a national level are available on the MHRA website.

The approved labelling for this medicine is presented below:


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Annex 1

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)

Scope Procedure

number

Product

information

affected

Date of

start of the

procedure

Date of end

of

procedure

Approval/

non

approval

Assessment

report

attached

Y/N

(version)

Documents

Public Assessment Report UKPAR Paracetamol 500mg … · UKPAR Paracetamol 500mg Tablets (Paracetamol) ... Paracetamol 500mg Tablets are considered ... predominantly by inhibiting