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PAR Capecitabine Reliance 150 mg and 500 mg Film-coated Tablets
UK/H/6096/001-02/DC
Public Assessment Report
Decentralised Procedure
Capecitabine Reliance 150 mg and 500 mg film-coated tablets
(capecitabine)
Procedure No: UK/H/6096/001-02/DC
UK Licence No: PL 42244/0007-0008
Reliance Genemedix Ltd
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PAR Capecitabine Reliance 150 mg and 500 mg Film-coated Tablets
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LAY SUMMARY
Capecitabine Reliance 150 mg and 500 mg film-coated tablets
(capecitabine)
This is a summary of the Public Assessment Report (PAR) for Capecitabine Reliance 150 mg and 500
mg film-coated tablets (PL 42244/0007-0008; UK/H/6096/001-02/DC). It explains how Capecitabine
Reliance 150 mg and 500 mg 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 Capecitabine
Reliance 150 mg and 500 mg film-coated tablets.
These products will be referred to as Capecitabine Reliance Tablets throughout the lay summary, for
ease of reading.
For practical information about using Capecitabine Reliance Tablets, patients should read the package
leaflets or contact their doctor or pharmacist.
What are Capecitabine Reliance Tablets and what are they used for?
Capecitabine Reliance Tablets are ‘generic medicines’. This means that Capecitabine Reliance Tablets
are similar to ‘reference medicines’ already authorised in the European Union (EU) called Xeloda 150
mg and 500 mg Film-coated Tablets (Roche Registration Limited).
Capecitabine Reliance Tablets are used in the treatment of colon, rectal, gastric or breast cancers.
Furthermore, Capecitabine Reliance is used to prevent new occurrence of colon cancer after complete
removal of the tumor by surgery. Capecitabine Reliance may be used either alone or in combination with
other medicines.
How do Capecitabine Reliance Tablets work?
Capecitabine Reliance Tablets belongs to a group of medicines called "cytostatic medicines", which stop
the growth of cancer cells. Capecitabine Reliance Tablets contains the active ingredient capecitabine,
which itself is not a cytostatic medicine. Only after being absorbed by the body it is changed into an
active anti-cancer medicine (more in tumor tissue than in normal tissue).
How are Capecitabine Reliance Tablets used?
Capecitabine Reliance Tablets are taken by mouth. The whole tablet should be swallowed with water
within 30 minutes of a meal (breakfast and dinner).
The patient must always take this medicine exactly as their doctor has told them too. The patients must
check with their doctor or pharmacist if they are not sure. Capecitabine Reliance should only be
prescribed by a doctor experienced in the use of anticancer medicines.
The dose of Capecitabine Reliance Tablets is based on the body surface area and is calculated using the
height and weight of a patient.
The usual dose for adults is 1250 mg/m2 of body surface area taken two times daily (morning and
evening).
Capecitabine Reliance Tablets are usually taken for 14 days followed by a 7 day rest period (when no
tablets are taken). This 21 day period is one treatment cycle.
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In combination with other medicines the usual dose for adults may be less than 1250 mg/m2 of body
surface area, and the patient may need to take the tablets over a different time period (e.g. every day,
with no rest period).
Please read section 3 of the package leaflets for detailed information on dosing recommendations, the
route of administration, and the duration of treatment.
This medicine can only be obtained with a prescription.
How has Capecitabine Reliance Tablets been studied?
Because Capecitabine Reliance Tablets are generic medicines, studies in patients have been limited to
tests to determine that they are bioequivalent to the reference medicines, Xeloda 150 mg and 500 mg
Film-coated Tablets. Two medicines are bioequivalent when they produce the same levels of the active
substance in the body.
What are the benefits and risks of Capecitabine Reliance Tablets?
Because Capecitabine Reliance Tablets are generic medicines and are bioequivalent to the reference
medicines, their benefits and risks are taken as being the same as those for the reference medicines.
Why was Capecitabine Reliance Tablets approved?
It was concluded that, in accordance with EU requirements, Capecitabine Reliance Tablets have been
shown to have comparable quality and to be bioequivalent to Xeloda 150 mg and 500 mg Film-coated
Tablets. Therefore, the MHRA decided that, as for Xeloda 150 mg and 500 mg Film-coated Tablets, the
benefits are greater than the risks and recommended that they can be approved for use.
What measures are being taken to ensure the safe and effective use of Capecitabine Reliance
Tablets?
A risk management plan (RMP) has been developed to ensure that Capecitabine Reliance Tablets are
used as safely as possible. Based on this plan, safety information has been included in the Summaries of
Product Characteristics and the package leaflets for Capecitabine Reliance 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 Capecitabine Reliance Tablets
Germany and the UK agreed to grant Marketing Authorisations for Capecitabine Reliance 150 mg and
500 mg film-coated tablets (PL 42244/0007-0008; UK/H/6096/001-02/DC) on 07 January 2016.
Marketing Authorisations were granted in the UK on 08 February 2016.
The full PAR for Capecitabine Reliance Tablets follows this summary. For more information about use
of Capecitabine Reliance Tablets, read the package leaflets, or contact your doctor or pharmacist.
This summary was last updated in March 2016.
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PAR Capecitabine Reliance 150 mg and 500 mg Film-coated Tablets
TABLE OF CONTENTS
I
II
III
IV
V
VI
Introduction
Quality aspects
Non-clinical aspects
Clinical aspects
User consultation
Overall conclusion, benefit/risk assessment and
recommendation
Page 5
Page 7
Page 9
Page 9
Page 18
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Table of content of the PAR update for MRP and DCP
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I
INTRODUCTION
Based on the review of the data on quality, safety and efficacy, the Reference Member State (RMS) and
Concerned Member State (CMS) considered that the applications for Capecitabine Reliance 150 mg and
500 mg film-coated tablets (PL 42244/0007-0008; UK/H/6096/001-02/DC), are approvable.
These products are prescription-only medicines (POM) indicated for:
- the adjuvant treatment of patients following surgery of stage III (Dukes' stage C) colon
cancer
- the treatment of metastatic colorectal cancer
- first-line treatment of advanced gastric cancer in combination with a platinum-based regimen
- Capecitabine Reliance in combination with docetaxel is indicated for the treatment of patients
with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy.
Previous therapy should have included an anthracycline. Capecitabine Reliance is also
indicated as monotherapy for the treatment of patients with locally advanced or metastatic
breast cancer after failure of taxanes and an anthracycline-containing chemotherapy regimen
or for whom further anthracycline therapy is not indicated.
These applications were submitted using the Decentralised Procedure, with the UK as Reference
Member State (RMS) and Germany as Concerned Member State (CMS). The applications were
submitted under Article 10(1) of Directive 2001/83/EC, as amended. The applicant has cross referred to
Xeloda 150 mg and 500 mg film-coated tablets, which were first licensed to Roche Registration Limited
on 02 February 2001 via the Centralised Procedure (EU/1/00/163/002).
Capecitabine is a non-cytotoxic fluoropyrimidine carbamate, which functions as an orally administered
precursor of the cytotoxic moiety 5-fluorouracil (5-FU). Capecitabine is activated via several enzymatic
steps. The enzyme involved in the final conversion to 5-FU, thymidine phosphorylase (ThyPase), is
found in tumour tissues, but also in normal tissues, albeit usually at lower levels. In human cancer
xenograft models capecitabine demonstrated a synergistic effect in combination with docetaxel, which
may be related to the upregulation of thymidine phosphorylase by docetaxel.
One bioequivalence study was submitted to support these applications comparing the test product
Capecitabine 500 mg tablet (Reliance Life Sciences Pvt. Ltd) with the reference product Xeloda 500 mg
Tablets (Roche pharma AG, Germany) in adult human cancer patients under fed conditions. The
applicant has stated that the bioequivalence study was carried out in accordance with Good Clinical
Practice (GCP). A biowaiver was requested for the lower tablet strength (150 mg).
With the exception of the bioequivalence study, no new non-clinical or clinical studies were conducted,
which is acceptable given that the applications were based on being generic medicinal products of
originator products that have been licensed for over 10 years.
The RMS has been assured that acceptable standards of Good Manufacturing Practice (GMP) are in
place for these product types at all sites responsible for the manufacture, assembly and batch release of
these products.
For manufacturing sites within the Community, the RMS has accepted copies of current manufacturer
authorisations issued by inspection services of the competent authorities as certification that acceptable
standards of GMP are in place at those sites.
For manufacturing sites outside the Community, the RMS has accepted copies of current GMP
Certificates of satisfactory inspection summary reports, as certification that acceptable standards of
GMP are in place at those non-Community sites.
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The procedure was referred to the Commission on Human Medicines on 16 July 2015.
The major issue under consideration was the analysis of the bioequivalence study and whether the
Applicant was justified to use widened acceptance limits for peak plasma concentration (Cmax) in
addition to other points.
The Commission concluded at the time that insufficient justification for a widening of acceptance limits
for Cmax had been provided. A re-analysis of the data was requested given that some subject data had
been incorrectly excluded. As discussed in more detail further on this assessment report, a revised
CHMP opinion in relation to draft product specific bioequivalence guidance for capecitabine has been
issued which gives scope for the possibility to widen acceptance limits for Cmax for capecitabine, in
recognition of its property as a highly variable drug product (HVDP), if this can be clinically justified.
In the event, the Applicant did not need to invoke widened limits for Cmax as the re-analysis of the data
requested by the Commission – to include subject data that had been incorrectly excluded – revealed that
the 90% confidence interval for Cmax lay within the conventional acceptance limits of 80.00 -125.00%.
Nonetheless, the Applicant’s argumentation for the potential widening of acceptance limits for Cmax was
considered in light of the CHMP’s revised recommendations for capecitabine to be in principle correct.
Following the revised analysis, bioequivalence was considered to have been demonstrated between
Capecitabine Reliance 500 mg tablets and Xeloda 500 mg tablets and that a conclusion of
bioequivalence could be extrapolated to the 150 mg tablet strength.
A Risk Management Plan (RMP) and a summary of the pharmacovigilance system have been provided
with these applications and are satisfactory.
All involved Member States agreed to grant Marketing Authorisations for the above products at the end
of the procedure (Day 210 – 07 January 2016). After a subsequent national phase, the UK granted
Marketing Authorisations (PL 42244/0007-0008) for these products on 08 February 2016.
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II
QUALITY ASPECTS
II.1 Introduction
These products are film-coated tablets and contain 150 mg or 500 mg of capecitabine, as the active
ingredient. The excipients present are anhydrous lactose, croscarmellose sodium, hypromellose,
microcrystalline cellulose, magnesium stearate making up the core, and the film-coating is composed of
Opadry pink (hypromellose, titanium dioxide (E171), macrogol/PEG, yellow and red iron oxide (E172)
and talc). Appropriate justification for the inclusion of each excipient has been provided.
All excipients used comply with their respective European Pharmacopoeia monographs with the
exception of Opadry pink which complies with an in-house specification.
The finished products are packaged in polyvinylchloride (PVC)/ACLAR–aluminium blister containing
60 film-coated tablets (6 blisters of 10 tablets).
Satisfactory specifications and Certificates of Analysis have been provided for all packaging
components. All primary packaging complies with the current European regulations concerning
materials in contact with food.
II.2. Drug Substance
INN:
Capecitabine
Chemical names:
Pentyl [1-(5-deoxy-β-D-ribofuranosyl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4yl]carbamate.
Structural formula:
Molecular formula:
Molecular mass:
Appearance:
Solubility:
C15H22FN3O6
359.35 g/mol
white to almost white powder.
Capecitabine sparingly soluble in water, freely soluble in anhydrous ethanol and
practically insoluble in heptane.
Capecitabine is the subject of an active substance master file (ASMF).
Synthesis of the drug substance from the designated starting materials has been adequately described and
appropriate in-process controls and intermediate specifications are applied. Satisfactory specification
tests are in place for all starting materials and reagents, and these are supported by relevant Certificates
of Analysis.
An appropriate specification is provided for the drug substance. Analytical methods have been
appropriately validated and are satisfactory for ensuring compliance with the relevant specifications.
Certificates of Analysis for all working standards have been provided.
Batch analyses data are provided that comply with the proposed specification.
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Satisfactory specifications and Certificates of Analysis have been provided for all packaging used to
store the drug substance. Confirmation has been provided that the primary packaging complies with
current guidelines concerning materials in contact with food.
Appropriate stability data have been provided, supporting a suitable retest period when the drug
substance is stored in the packaging proposed.
II.3. Medicinal Product
Pharmaceutical Development
The objective of the development programme was to formulate safe, efficacious, tablets containing 150
mg and 500 mg capecitabine that are bioequivalent to the reference products Xeloda 150 mg and 500 mg
Film-coated Tablets (Roche Registration Ltd).
A satisfactory account of the pharmaceutical development has been provided.
Comparative impurity and in-vitro dissolution profiles have been provided for the proposed and
originator products.
Manufacture of the products
Satisfactory batch formulae have been provided for the manufacture of the products, along with an
appropriate account of the manufacturing processes. The manufacturing processes have been validated
and have shown satisfactory results. Process validation data on commercial scale batches have been
provided.
Finished Product Specifications
The finished product specifications proposed are acceptable. The test methods have been described that
have been adequately validated. Batch data have been provided that comply with the release
specifications. Certificates of Analysis have been provided for all working standards used.
Stability of the Products
Finished product stability studies were performed in accordance with current guidelines on batches of
finished products in the packaging proposed for marketing. The data from these studies support a
shelf-life of 2 years with a special storage condition “Do not store above 30°C”.
Suitable post approval stability commitments have been provided to continue stability testing on batches
of finished products.
II.4 Discussion on chemical, pharmaceutical and biological aspects
There are no objections to the approval of these applications from a pharmaceutical viewpoint.
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III
NON-CLINICAL ASPECTS
III.1 Introduction
As the pharmacodynamic, pharmacokinetic and toxicological properties of capecitabine are well-known,
no new non-clinical studies are required and none have been provided. An overview based on the
literature review is, thus, appropriate.
The applicant’s non-clinical expert report has been written by an appropriately qualified person and is
satisfactory, providing an appropriate review of the relevant non-clinical pharmacology,
pharmacokinetics and toxicology.
III.2 Pharmacology
Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.
III.3 Pharmacokinetics
Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.
III.4 Toxicology
Not applicable for this product type. Refer to section ‘III.1; Introduction’ detailed above.
III.5 Ecotoxicity/environmental risk assessment (ERA)
Since these products are intended for generic substitution, this will not lead to an increased exposure to
the environment. An environmental risk assessment is therefore not deemed necessary.
III.6 Discussion on the non-clinical aspects
No new non-clinical studies were conducted, which is acceptable given that the applications were based
on being generic medicinal products of originator products that have been licensed for over 10 years.
There are no objections to the approval of these applications from a non-clinical viewpoint.
IV
CLINICAL ASPECTS
IV.1 Introduction
The clinical pharmacology of capecitabine is well-known. With the exception of data from the
bioequivalence study detailed below, no new pharmacodynamic or pharmacokinetic data are provided or
are required for these applications.
No new efficacy or safety studies have been performed and none are required for this type of
application. A comprehensive review of the published literature has been provided by the applicant,
citing the well-established clinical pharmacology, efficacy and safety of capecitabine.
Based on the data provided, Capecitabine 150 mg and 500 mg Film-coated Tablets can be considered
bioequivalent to Xeloda 150 mg and 500 mg Tablets (Roche pharma AG, Germany).
IV.2 Pharmacokinetics
In support of these applications, the applicant submitted the following bioequivalence study:
STUDY 1
A multi-centre, randomised, open-label, single dose, two-treatment, three-period, three-sequence,
partial replicate, crossover, pivotal bioequivalence study of the test product, Capecitabine 500 mg
tablet manufactured by Reliance Life Sciences Pvt. Ltd, versus the reference product, Xeloda® 500
mg Tablets (Roche Pharma AG, Germany) in adult, human, cancer patients under fed conditions.
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Blood samples for measurement of plasma capecitabine were collected prior to administration of the
investigational drug (up to one hour before dosing) and at 0.33, 0.67, 1.00, 1.33, 1.67, 2.00, 2.33, 2.67,
3.00, 5.00 and 8.00 hours after drug administration. There was a washout period of 12 hours.
The observed 90% confidence intervals of the geometric mean ratio for log transformed
pharmacokinetic parameter AUC(0-t) calculated using the average bioequivalence method (ABE) were
85.25 – 99.15 and 85.30 – 99.60 (with and without outliers respectively) of the test to reference
formulation and were therefore within the pre-specified bioequivalence acceptance range of 80.00% to
125.00%.
In recognition that capecitabine is a known highly variable drug product (HVDP) the Applicant
performed a study of partial replicate design in order to establish the within subject variance in Cmax for
the reference product. The intra-subject coefficient of variation (ISCVRef) for reference product Cmax
was confirmed to exceed 30%, and appropriate analysis excluded outliers as the reason for this.
The Applicant pre-specified use of scaled average bioequivalence evaluation (SABE) in order to derive
widened acceptance limits for the 90% confidence interval for test/reference ratio for Cmax, on the basis
of the observed coefficient of variation (47.147% and 46.617% with and without outliers).
Using the average bioequivalence method (ABE) the 90% confidence intervals for the geometric mean
of the Test/Reference ratio for ln-transformed Cmax (with and without outliers) were calculated to be as
follows:
Observed 90% CI for ln Cmax (with outliers) 97.54 – 131.46
Observed 90% CI for ln Cmax (without outliers) 96.01 – 129.41
The observed 90% confidence intervals (CIs) for Cmax (calculated using ABE) were within a widened
acceptance limit (calculated using the SABE formula in the EMA bioequivalence guidance
CPMP/EWP/QWP/1401/98 Rev. 1/ Corr **) of 71.14 – 140.56%.
Although this methodology was in principle correct for a HVDP, and in accordance with the EMA
bioequivalence guidance CPMP/EWP/QWP/1401/98 Rev. 1/ Corr **, a key concern was that the
principle applies only to “Those HVDP for which a wider difference in Cmax is considered clinically
irrelevant.” The widening of acceptance limits for Cmax was also at odds with the draft product specific
bioequivalence guidance for capecitabine CHMP/PKWP/EMA/423732/2013 which considers
capecitabine a ”critical dose” drug and that acceptance limits for Cmax should therefore not be widened.
Robust justification was therefore requested for the Applicant’s case that a wider degree of variability in
Cmax than would ordinarily be permitted for bioequivalence demonstration does not compromise clinical
safety and efficacy. It is not sufficient to accept that it is an intrinsic property of the active substance
which is unalterable.
The Applicant has put forward argumentation that the efficacy and safety of capecitabine is principally
related to exposure (AUC) rather than peak plasma concentrations (Cmax), supported by the published
literature. The Applicant has not sought to apply widened acceptance limits to the critical parameter
AUC(0-t) which has been demonstrated to lie within the conventional bioequivalence acceptance limits of
80.00 – 125.00%. The Applicant presents a number of lines of evidence, supported by published
literature, to support that efficacy and safety are principally related to cumulative exposure rather than
peak plasma concentration.
Following stakeholder consultation, CHMP issued amended bioequivalence study guidance for
capecitabine, contained in an updated document Compilation of individual product-specific guidance on
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demonstration of bioequivalence EMA/CHMP/736403/2014 Rev 2 (21st May 2015) in which the
specified acceptance limits for AUC(0-t) and Cmax for capecitabine remain unchanged at 80.00 – 125.00%;
however, this is qualified with the statement that “* Since high intra-individual variability (CVintra > 30
%) is expected, the applicants might follow respective guideline recommendations.” This is understood
by the RMS to mean that it would in principle be acceptable to follow a pre-specified replicate or partial
replicate trial design and to use scaled average bioequivalence evaluation to derive widened limits for
Cmax, as specified in the guidance on highly variable drug products, but that this has to be clinically
justified. The RMS considers that the Applicant has in principle provided sufficient clinical justification
for this approach, as outlined in the original clinical study report. The guideline also does not consider a
need to impose limits for Cmax narrower than 80.00 – 125.00%, which can be required for drugs
considered to have a narrow therapeutic index.
In the event, the approach of applying widened limits for Cmax has been obviated by the Applicant’s reanalysis of the data to take account of subject data that had been incorrectly excluded (due to data being
present for at least one period each of test and reference product) and additional data that had been
wrongly included due to the LLOQ of the bioanalytical assay being insufficiently low to detect 5% of
Cmax in those subject/periods. These data set corrections, and re-analysis, were requested by the RMS.
When the data were re-analysed using a correct data set both of the critical parameters Cmax and AUC(0-t)
now fall within conventional acceptance limits of 80. 00 – 125.00% and therefore widened acceptance
limits, calculated using scaled average bioequivalence evaluation, do not need to be applied.
Results
Table of revised data following the re-analysis:
Summary of geometric means and 90% confidence intervals for test and reference product for
capecitabine.
Pharmacokinetic
Parameter
In Cmax
InAUC0-t
InAUC0-∞
T/R Ratio (%)
91.04
92.77
94.77
90% CI
Limit
80.41
86.96
87.85
Lower 90% CI Upper Limit
103.08
98.97
102.0
In the revised analysis the 90% confidence intervals of the test/reference formulations for AUCO-∞ and Cmax values
lie within the acceptable limits of 80.00% to 125.00%, in line with the ‘Guideline on the Investigation of
Bioequivalence (CPMP/EWP/QWP/1401/98 Rev 1/Corr**). Bioequivalence has been shown for the test
formulation (Capecitabine Reliance 500 mg Tablets) and the reference formulation (Xeloda 500 mg
Tablets) under fed conditions.
Biowaiver
The Applicant has applied for a biowaiver for the lower tablet strength (150 mg) on the grounds that the
proposed tablet strengths (150 mg and 500 mg) display proportional composition in terms of active
substance to excipient composition, the test and reference products are qualitatively and quantitatively
similar, exhibit comparable dissolution profiles at both tablet strengths, that capecitabine displays linear
pharmacokinetics (PK) across the proposed dose range.
As the 150 mg and 500 mg strength products meet all the criteria specified in the “Guideline on the
Investigation of Bioequivalence” (CPMP/EWP/QWP/1401/98 Rev.1 Corr**), the results of the study for
500 mg tablets can be extrapolated to the other strength i.e. 150 mg Tablets. Therefore, bioequivalence
has been shown between the 150 mg and 500 mg strengths of the test products and the respective bio
reference product.
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IV.3 Pharmacodynamics
No new pharmacodynamic data were submitted and none were required for an application of this type.
IV.4 Clinical efficacy
The clinical overview provides an adequate review of published literature to support the proposed
indications.
IV.5 Clinical safety
The clinical overview provides a comprehensive review of known safety issues from the published
literature.
IV.6 Risk Management Plan (RMP) and Pharmacovigilance System
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 Capecitabine Reliance 150 mg and 500 mg film-coated tablets.
A summary of safety concerns and planned risk minimisation activities, as approved in the RMP, is
listed below:
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Routine pharmacovigilance is proposed for all safety concerns.
IV.7 Discussion on the clinical aspects
With the exception of the bioequivalence studies, no new clinical studies were conducted, which is
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acceptable given that the applications were based on being generic medicinal products of originator
products that have been licensed for over 10 years.
Bioequivalence has been demonstrated between the applicant’s Capecitabine Reliance 500 mg Filmcoated Tablets and the reference product Xeloda 500 mg Tablets under fed conditions.
As the 150 mg and 500 mg strength test products meet the biowaiver criteria specified in the current
bioequivalence guidance, the results and conclusions of the bioequivalence studies with the 500 mg
tablet strength can be extrapolated to the 150 mg strength tablets.
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. The language used for the purpose of
user testing the patient information leaflet 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. Extensive clinical experience with capecitabine 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 Capecitabine Reliance 150 mg and 500 mg film-coated tablets is presented
below:
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Table of content of the PAR update for MRP and DCP
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)
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