Public Assessment Report UKPAR Metformin 500 mg and … · Metformin 500 mg and 850 mg film-coated tablets (Metformin hydrochloride) This is a summary of the Public Assessment Report

PAR Metformin 500 and 850 mg film-coated tablets PL 21880/0199-0200

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Public Assessment Report

UKPAR

Metformin 500 mg and 850 mg film-coated tablets

(Metformin hydrochloride)

UK Licence No: PL 21880/0199-0200

Medreich Plc


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LAY SUMMARY Metformin 500 mg and 850 mg film-coated tablets

(Metformin hydrochloride)

This is a summary of the Public Assessment Report (PAR) for Metformin 500 mg and 850 mg film-

coated tablets (PL 21880/0199-0200). This medicinal product will be referred to as Metformin Tablets in

the remainder of this report, for ease of reading.

This summary explains how Metformin Tablets were assessed and their authorisations recommended, as

well as their conditions of use. It is not intended to provide practical advice on how to use this product.

For practical information about using Metformin Tablets, patients should read the package leaflet or

contact their doctor or pharmacist.

What are Metformin Tablets and what are they used for?

This medicine is the same as Metformin 500 mg and 850 mg tablets (PL 39484/0032-0033; Fouurts UK

Pharmacare Ltd), which is already authorised in the UK. The licence holder (Fouurts UK Pharmacare

Ltd) for Metformin 500 mg and 850 mg tablets (PL 39484/0032-3) has agreed that its own scientific data

can be used as a basis for the grant of an identical licence for Metformin Tablets (PL 21880/0199-0200)

(informed consent).

Metformin tablets are used for the treatment of type II diabetes (a condition in which the body does not

make enough insulin or where the insulin that the body produces does not work as well as it should) not

controlled by diet and exercise alone. A doctor may prescribe Metformin tablets for a patient to take on

its own or in combination with other oral anti-diabetic medicines called sulphonylureas, or insulin.

How do Metformin Tablets work?

Metformin Tablets contain the active ingredient metformin hydrochloride. Metformin is one of a group

of medicines called oral hypoglycaemics, which works by reducing the level of sugar in the blood.

How are Metformin Tablets used?

Metformin Tablets are taken orally. The whole tablet should be swallowed with water during or after

manls. The tablets must not be chewed.

Patients should always take Metformin Tablets exactly as a doctor has told them. Patients must check

with a doctor or pharmacist if they are not sure.

If a patient is taking Metformin tablets continuously, she/he should have regular blood tests to check the

blood glucose levels, kidney function and vitamin B12 levels.

The usual starting dose in adults and elderly is one 500mg tablet three times a day or one 850mg tablet

twice a day, which is gradually increased until the right dose for a patient is found. The maximum dose

is six 500mg tablets or three 850mg tablets daily taken in divided doses.

Metformin Tablets should not be taken by children.

This medicine can only be obtained with a prescription.

For further information on how Metformin Tablets are used, please see the Summaries of Product

Characteristics or the package leaflet available on the MHRA website.


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What benefits of Metformin Tablets have been shown in studies?

As Metformin Tablets (PL 21880/0199-0200) are considered to be identical to the reference products,

Metformin 500 mg and 850 mg tablets (PL 39484/0032-0033), their benefits and risks are taken as being

the same as those for the reference products.

What are the possible side effects from Metformin Tablets?

Like all medicines, Metformin Tablets can cause side effects, although not everybody gets them.

For the full list of all side effects reported with Metformin Tablets, see section 4 of the package leaflet.

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

Why are Metformin Tablets approved?

No new or unexpected safety concerns arose from this application. It was, therefore, considered that the

benefits of Metformin 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 Metformin Tablets?

A risk management plan (RMP) has been developed to ensure that Metformin Tablets are used as safely

as possible. Based on this plan, safety information has been included in the Summaries of Product

Characteristics and the patient information leaflet for Metformin 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 and reviewed continuously.

Other information about Metformin Tablets

A Marketing Authorisation was granted in the UK on 24 August 2017.

The full PAR for Metformin Tablets follows this summary.

This summary was last updated in October 2017.


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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 10

VI Overall conclusion, benefit/risk assessment and

recommendation

Page 10

Table of content of the PAR update Page 17


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I INTRODUCTION

The Medicines and Healthcare products Regulatory Agency (MHRA) granted Medreich Plc a Marketing

Authorisation for the medicinal product Metformin 500 mg and 850 mg film-coated tablets (PL

21880/0199-0200) on 24 August 2017.

This is a prescription only medicine (POM), and is indicated for Treatment of type 2 diabetes mellitus,

particularly in overweight patients, when dietary management and exercise alone does not result in

adequate glycaemic control.

• In adults, Glucophage may be used as monotherapy or in combination with other oral

antidiabetic agents or with insulin.

• In children from 10 years of age and adolescents, Glucophage may be used as

monotherapy or in combination with insulin.

A reduction of diabetic complications has been shown in overweight type 2 diabetic adult patients

treated with metformin as first-line therapy after diet failure.

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 Metformin 500 mg and 850 mg tablets,

which were originally authorised to OBG Pharmaceuticals Limited (PL 15755/0019-0020) on 09

February 2001. These licenses underwent changes of ownership procedures to LPC Medical (UK)

Limited (PL 19348/0013-0014) on 22 April 2002 and then to the current to the current Marketing

Authorisation Holder (MAH), Fouurts UK Pharmacare Ltd (PL 39484/0032-0033) on 04 June 2011.

Metformin is a biguanide with antihyperglycaemic effects, lowering both basal and postprandial plasma

glucose. It does not stimulate insulin secretion and therefore does not produce hypoglycaemia.

Metformin may act via 3 mechanisms:

• reduction of hepatic glucose production by inhibiting gluconeogenesis and

glycogenolysis.

• in muscle, by increasing insulin sensitivity, improving peripheral glucose uptake and

utilization.

• and delay of intestinal glucose absorption.

Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthase.

Metformin increases the transport capacity of all types of membrane glucose transporters (GLUTs)

known to date.

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 this product type at all sites responsible for the manufacture and assembly of these product.


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II QUALITY ASPECTS

II.1 Introduction

This is a simple (informed consent) application for Metformin 500 mg and 850 mg film-coated tablets

(PL 21880/0199-0200), submitted under Article 10c of Directive 2001/83/EC, as amended. The

applicant has cross-referred to Metformin 500 mg and 850 mg tablets, which were originally authorised

to OBG Pharmaceuticals Limited (PL 15755/0019-0020) on 09 February 2001. These licenses

underwent changes of ownership procedures to LPC Medical (UK) Limited (PL 19348/0013-0014) on

22 April 2002 and then to the current to the current Marketing Authorisation Holder (MAH), Fouurts

UK Pharmacare Ltd (PL 39484/0032-0033) on 04 June 2011. 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

product.

II.3. Medicinal Product

Name

The proposed product name is Metformin 500 mg and 850 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 500 or 850 mg of metformin hydrochloride, as active ingredient. The

route of administration is oral.

The finished product is packed either in polyvinylchloride (PVC) and ard temper aluminium foil

contained in a carton with pack sizes of 28, 84, 504 tablets.

or

in a tablet container (securitainers made up of high density polyethylene (HDPE))

Not all pack sizes may be marketed.

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

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

the cross-reference products.

Marketing Authorisation Holder/Contact Persons/Company

Medreich Plc, Warwick House, Plane Tree Crescent, Feltham, TW13 7HF

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

Vitae (CV) has been provided.

Manufacturer

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 composition is 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 specification

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 this simple abridged application as the proposed product

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

Metformin 500 mg and 850 mg tablets (PL 39484/0032-0033).

Expert Report

The applicant cross-refers to the data for Metformin 500 mg and 850 mg tablets (PL 39484/0032-0033),

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 Metformin 500 mg and

850 mg tablets (PL 39484/0032-0033) 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.

Risk Management Plan (RMP)

The Marketing Authorisation Holder (MAH) has submitted a risk management plan, 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 Metformin 500 mg

and 850 mg film-coated tablets.


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

is listed below:


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Discussion on the clinical aspects

The grant of Marketing Authorisations is recommended for these applications.

V User consultation

The package leaflet has been evaluated via a user consultation study, in accordance with the

requirements of Articles 59(3) and 61(1) of Directive 2001/83/EC, as amended. The language used for

the purpose of user testing the PIL was English.

The results show that the package leaflet meets the criteria for readability, as set out in the guideline on

the readability of the label and package leaflet of medicinal products for human use.

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 product is identical to the reference product. Extensive clinical experience

with metformin hydrochloride 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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Summary of Product Characteristics (SmPC), Patient Information Leaflet (PIL) and Labels

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

Information Leaflets (PIL) for products granted Marketing Authorisations at a national level are

available on the MHRA website.

The approved labelling for Metformin 500 mg and 850 mg film-coated tablets 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 (Type II

variations, PSURs, commitmen

Date

submitted

Application

type

Scope Outcome

Documents

Public Assessment Report UKPAR Metformin 500 mg and … · Metformin 500 mg and 850 mg film-coated tablets (Metformin hydrochloride) This is a summary of the Public Assessment Report