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CLOPIDOGREL 75MG FILM-COATED TABLETS
PL 24668/0116
UKPAR
TABLE OF CONTENTS
Lay Summary
Page 2
Scientific discussion
Page 4
Steps taken for assessment
Page 10
Steps taken after authorisation – summary
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Summary of Product Characteristics
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Product Information Leaflet
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Labelling
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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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CLOPIDOGREL 75MG FILM-COATED TABLETS
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
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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
applications of this type.
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
applications of this type.
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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CLOPIDOGREL 75MG FILM-COATED TABLETS
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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CLOPIDOGREL 75MG FILM-COATED TABLETS
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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