clopidogrel 75mg film-coated tablets pl … · clopidogrel 75mg film-coated tablets contain the...

CLOPIDOGREL 75MG FILM-COATED TABLETS

PL 24668/0116

UKPAR

TABLE OF CONTENTS

Lay Summary

Page 2

Scientific discussion

Page 4

Steps taken for assessment

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Steps taken after authorisation – summary

Page 11

Summary of Product Characteristics

Page 12

Product Information Leaflet

Page 12

Labelling

Page 13

UKPAR Clopidogrel 75mg Film-coated Tablets PL 24668/0116

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LAY SUMMARY

Clopidogrel 75mg Film-coated Tablets

(clopidogrel besilate)

This is a summary of the public assessment report (PAR) for Clopidogrel 75mg Film-coated

Tablets (PL 24668/0116). It explains how Clopidogrel 75mg Film-coated 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 Clopidogrel 75mg Film-coated Tablets.

For practical information about using Clopidogrel 75mg Film-coated Tablets, patients should

read the package leaflet or contact their doctor or pharmacist.

What are Clopidogrel 75mg Film-coated Tablets and what are they used for?

Clopidogrel 75mg Film-coated Tablets contain the active ingredient clopidogrel besilate.

They are used to prevent blood clots (thrombi) forming in hardened blood vessels (arteries), a

process known as atherothrombosis, which can lead to atherothrombotic events (such as

stroke, heart attack or death).

This product is identical to Clopidogrel 75mg Film-coated Tablets (PL 30306/0214), which

are already authorised in the UK to Actavis Group PTC ehf.

How are Clopidogrel 75mg Film-coated Tablets used?

When a patient has experienced severe chest pain (unstable angina or heart attack) they may

be given 300 mg of clopidogrel (4 tablets of 75 mg) once at the start of treatment. Then, the

usual dose is one 75 mg tablet of clopidogrel per day to be taken orally with or without food,

at the same time each day.

This medicine can only be obtained with a prescription.

How do Clopidogrel 75mg Film-coated Tablets work?

Clopidogrel 75mg Film-coated Tablets belong to a group of medicines called antiplatelet

medicinal products. Platelets are very small structures in the blood, which clump together

during blood clotting. By preventing this clumping, antiplatelet medicinal products reduce the

chances of blood clots forming (a process called thrombosis).

How have Clopidogrel 75mg Film-coated Tablets been studied? This application is identical to the previously granted licence for Clopidogrel 75mg Film-

coated Tablets (PL 30306/0214; Actavis Group PTC ehf). The company referred to data

provided for the grant of the licence for Clopidogrel 75mg Film-coated Tablets

(PL 30306/0214) as a basis for the grant of this identical licence for Clopidogrel 75mg Film-

coated Tablets (PL 24668/0116).

What are the benefits and risks of Clopidogrel 75mg Film-coated Tablets? As Clopidogrel 75mg Film-coated Tablets are considered identical to Clopidogrel 75mg

Film-coated Tablets (PL 30306/0214), their benefits and risks are taken as being the same as

for Clopidogrel 75mg Film-coated Tablets (PL 30306/0214).


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Why are Clopidogrel 75mg Film-coated Tablets approved? No new or unexpected safety concerns arose from this duplicate application of Clopidogrel

75mg Film-coated Tablets (PL 30306/0214). Therefore, the view was that, as for Clopidogrel

75mg Film-coated Tablets (PL 30306/0214), the benefit outweighs the identified risk.

What measures are being taken to ensure the safe and effective use of Clopidogrel 75mg

Film-coated Tablets?

A risk management plan has been developed to ensure that Clopidogrel 75mg Film-coated

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 Clopidogrel

75mg Film-coated Tablets, including the appropriate precautions to be followed by healthcare

professionals and patients.

Other information about Clopidogrel 75mg Film-coated Tablets

A Marketing Authorisation was granted for Clopidogrel 75mg Film-coated Tablets on 09

May 2014. For more information about treatment with Clopidogrel 75mg Film-coated

Tablets, read the package leaflet or contact your doctor or pharmacist.

The full PAR for Clopidogrel 75mg Film-coated Tablets follows this summary.

This summary was last updated in June 2014.


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PL 24668/0116

SCIENTIFIC DISCUSSION

TABLE OF CONTENTS

Introduction

Page 5

Pharmaceutical assessment

Page 6

Non-clinical assessment

Page 8

Clinical assessment

Page 8

Overall conclusions and risk benefit assessment

Page 9


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INTRODUCTION

The UK granted a Marketing Authorisation to Caduceus Pharma Limited for the medicinal

product Clopidogrel 75mg Film-coated Tablets (PL 24668/0116) on 09 May 2014.

This product is a prescription-only medicine (legal status POM). It is indicated in:

• Adult patients suffering from myocardial infarction (from a few days until less than

35 days), ischaemic stroke (from 7 days until less than 6 months) or established

peripheral arterial disease.

• Adult patients suffering from acute coronary syndrome:

- Non ST segment elevation acute coronary syndrome (unstable angina or non

Q wave myocardial infarction), including patients undergoing a stent

placement following percutaneous coronary intervention, in combination with

acetylsalicylic acid (ASA).

- ST segment elevation acute myocardial infarction, in combination with ASA

in medically treated patients eligible for thrombolytic therapy.

• Combination with ASA for the prevention of atherothrombotic and thromboembolic

events, including stroke, in adult patients with atrial fibrillation who have at least one

risk factor for vascular events, who are not suitable for treatment with Vitamin K

antagonists and who have a low bleeding risk.

This application was submitted as an abridged simple application, according to Article 10c of

Directive 2001/83/EC, as amended, cross-referring to Clopidogrel 75mg Film-coated Tablets

(PL 30306/0214), which was granted to Actavis Group PTC ehf on 05 November 2009.

This product contains the active substance clopidogrel besilate. Clopidogrel is a prodrug, one

of whose metabolites is an inhibitor of platelet aggregation. The active metabolite of

clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet

P2Y12 receptor and the subsequent ADP mediated activation of the glycoprotein GPIIb/IIIa

complex, thereby inhibiting platelet aggregation. Due to the irreversible binding, platelets

exposed are affected for the remainder of their lifespan (approximately 7-10 days) and

recovery of normal platelet function occurs at a rate consistent with platelet turnover. Platelet

aggregation induced by agonists other than ADP is also inhibited by blocking the

amplification of platelet activation by released ADP.


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PHARMACEUTICAL ASSESSMENT

LICENCE NO: PL 24668/0116

PROPRIETARY NAME: Clopidogrel 75mg Film-coated Tablets

ACTIVE(S): Clopidogrel besilate

COMPANY NAME: Caduceus Pharma Limited

E.C. ARTICLE: Article 10c

LEGAL STATUS: POM

1. INTRODUCTION This is a simple, piggyback application for Clopidogrel 75mg Film-coated Tablets, submitted

under Article 10c of Directive 2001/83/EC, as amended. The proposed MA holder is

Caduceus Pharma Limited, 6th floor, 94 Wigmore Street, London, W1U 3RF, United

Kingdom.

The application cross-refers to Clopidogrel 75mg Film-coated Tablets (PL 30306/0214),

which was granted to Actavis Group PTC ehf on 05 November 2009.

The current application is considered valid.

2. MARKETING AUTHORISATION APPLICATION FORM 2.1 Name(s)

The proposed name of the product is Clopidogrel 75mg Film-coated Tablets. The product has

been named in line with current requirements.

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

Each film-coated tablet contains 111.86 mg clopidogrel besilate, corresponding to 75 mg

clopidogrel.

The finished product is packaged in the following presentations and pack sizes:

• Aluminium/aluminium blister packs in pack sizes of 10, 20, 28, 30, 50 x 1, 56, 60, 84,

98 and 100 tablets.

• High-density polyethylene (HDPE) tablet containers closed with low-density

polyethylene (LDPE) snap-on caps, with tamper evident rings and with a desiccant

(silica gel) in pack sizes of 100 tablets.

Not all pack sizes may be marketed. However, the Marketing Authorisation Holder has

committed to submitting mock-ups to the regulatory authorities for approval before

marketing any pack size.

The proposed shelf-life (3 years) and storage conditions (no special storage conditions) are

consistent with the details registered for the cross-reference product.

2.3 Legal status On approval, the product will be available as a prescription-only medicine (POM).

2.4 Marketing authorisation holder/Contact Persons/Company

Caduceus Pharma Limited, 6th floor, 94 Wigmore Street, London, W1U 3RF, United

Kingdom.


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The QP responsible for pharmacovigilance is stated and their CV is included.

2.5 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.

2.6 Qualitative and quantitative composition

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

product.

2.7 Manufacturing process

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

cross-reference product.

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

reference product.

2.9 Drug substance specification

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

cross-reference product.

2.10 TSE Compliance

With the exception of the excipient lactose anhydrous, no materials of animal or human

origin are included in this product. This is consistent with the cross-reference product. The

company have provided confirmation that the lactose anhydrous is produced from milk that

has been sourced from healthy cows in the same conditions as milk collected for human

consumption.

2.11 Bioequivalence

No bioequivalence data are required to support this informed consent application, as the proposed

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

Clopidogrel 75mg Film-coated Tablets (PL 30306/0214).

3. EXPERT REPORTS The applicant has included expert reports in Module 2 of the application. Signed declarations

and copies of the experts’ CVs are enclosed in Module 1.4 for the quality, non-clinical and

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

4. PRODUCT NAME & APPEARANCE See 2.1 for details of the proposed product name. The appearance of the product is identical

to the cross-reference product.

5. SUMMARY OF PRODUCT CHARACTERISTICS (SmPC) The proposed SmPC is consistent with the details registered for the cross-reference product.


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6. PATIENT INFORMATION LEAFLET (PIL)/LABEL PIL

The PIL has been prepared in line with the details registered for the cross-reference product.

The results of consultations with target patient groups (‘user testing’), in accordance with

Article 59 of Council Directive 2001/83/EC (as amended) for the package leaflet for the

cross-reference product have been submitted and are satisfactory. The results indicate that the

package leaflet is well structured and organised, easy to understand and written in a

comprehensive manner. The test shows that the patients/users are able to act upon the

information that it contains.

Carton and blister

The proposed artwork is comparable with the artwork registered for the cross reference

product and complies with statutory requirements. The applicant has included sufficient space

for a standard UK pharmacy dispensing label.

7. CONCLUSIONS The data submitted with the application is acceptable. From a quality perspective, a

Marketing Authorisation should be granted.

NON-CLINICAL ASSESSMENT

No new non-clinical data have been supplied with this application and none are required for

applications of this type.

An Environmental Risk Assessment (ERA) has not been provided. As this product is

intended for substitution with products that are already marketed, no increase in

environmental burden is anticipated.

The grant of a Marketing Authorisation is recommended.

CLINICAL ASSESSMENT

No new clinical data have been supplied with this application and none are required for


The Pharmacovigilance System, as described by the applicant, fulfils the requirements and

provides adequate evidence that the applicant has the services of a qualified person

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.

A suitable risk management plan has been provided for this product.

The grant of a Marketing Authorisation is recommended.


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OVERALL CONCLUSION AND BENEFIT/RISK ASSESSMENT

QUALITY

The data provided for this application is consistent with that previously assessed for the

cross-reference product and as such have been judged to be satisfactory. There are no

outstanding quality issues that would have a negative impact on the benefit/risk balance.

NON-CLINICAL

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

EFFICACY

This application is identical to the previously granted application for Clopidogrel 75mg Film-

coated Tablets (PL 30306/0214), which was granted to Actavis Group PTC ehf on 05

November 2009. No new clinical pharmacology/efficacy data have been submitted with this

application and none are required for applications of this type.

SAFETY No new safety data have been submitted with this application and none are required for


No new or unexpected safety concerns have arisen from this application.

PRODUCT LITERATURE

The SmPC, PIL and labelling are satisfactory and consistent with the reference product.

BENEFIT-RISK ASSESSMENT

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

have been identified. Extensive clinical experience with clopidogrel besilate is considered to

have demonstrated the therapeutic value of the compound. The benefit/risk is, therefore,

considered to be positive.


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PL 24668/0116

STEPS TAKEN FOR ASSESMENT

1 The MHRA received the Marketing Authorisation application on 01 March

2013.

2 Following standard checks and communication with the applicant, the MHRA

considered the application valid on 08 March 2013.

3 Following assessment of the application, the MHRA requested further

information relating to the dossier on 16 May 2013.

4 The applicant responded to the MHRA’s requests, providing further information

on 17 December 2013.

5 The application was determined on 09 May 2014.


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PL 24668/0116

STEPS TAKEN AFTER AUTHORISATION - SUMMARY

Date

submitted

Application

type

Scope Outcome


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Summary of Product Characteristics and Patient Information Leaflet In accordance with Directive 2010/84/EU, the current approved UK versions of the Summary

of Product Characteristics (SmPC) and Patient Information Leaflet (PIL) for this product are

available on the MHRA website.


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Labelling


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clopidogrel 75mg film-coated tablets pl … · clopidogrel 75mg film-coated tablets contain the...

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