Public Assessment Report
Decentralised Procedure
Codeine/Paracetamol 30mg/500mg film-coated tablets
Codeine/Paracetamol 60mg/1000mg film-coated tablets
(Codeine phosphate hemihydrate and paracetamol)
PL 36687/0140-0141
UK/H/5715/002-003/DC
Torrent Pharma (UK) Limited
Codeine/Par acetamol 30mg/500mg film-coated tablets
Codeine/Par acetamol 60mg/1000mg film-coated tablets
UK/H/5715/002/DC
UK/H/5715/003/DC
Lay Summary
Codeine/Paracetamol 30mg/500mg film-coated tablets
Codeine/Paracetamol 60mg/1000mg film-coated tablets
(Codeine phosphate hemihydrate and paracetamol)
This is a summary of the Public Assessment Report (PAR) for Codeine/Paracetamol
30mg/500mg film-coated tablets and Codeine/Paracetamol 60mg/1000mg film-coated tablets
(PL 36687/0140-0141; UK/H/5715/002-003/DC). Codeine/Paracetamol 30mg/500mg
film-coated tablets and Codeine/Paracetamol 60mg/1000mg film-coated tablets will be
referred to as Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets throughout this
report, for ease of reading. It explains how Codeine/Paracetamol 30mg/500mg and
60mg/1000mg 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
Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets.
For practical information about using Codeine/Paracetamol 30mg/500mg and 60mg/1000mg
tablets, patients should read the package leaflet or contact their doctor or pharmacist.
What are Codeine/Paracetamol 30mg/500 mg and 60mg/1000mg tablets and what are
they used for?
Codeine/Paracetamol 30mg/500mg tablets are a ‘generic medicine’. This means that they are
similar to a ‘reference medicine’, already authorised in the European Union (EU) called
Solpadol 30mg/500mg Caplets (PL 04425/0637). Codeine/Paracetamol 30mg/500mg tablets
can be used in adults and children over 12 years of age for the short-term relief of moderate
or severe pain that is not relieved by other painkillers such as paracetamol or ibuprofen alone.
Codeine/Paracetamol 60mg/1000mg tablets are a ‘hybrid medicine’. This means that they are
similar to a reference medicine, Solpadol 30mg/500mg Caplets, containing the same active
substances but are available as a different strength: there is 60 mg codeine phosphate
hemihydrate and 1000 mg paracetamol in Codeine/Paracetamol 60mg/1000mg tablets
compared with 30 mg codeine phosphate hemihydrate and 500 mg paracetamol in Solpadol
30mg/500mg Caplets.
Codeine/Paracetamol 60mg/1000mg tablets can be used in adults and children over 16 years
of age for the short-term relief of moderate or severe pain that is not relieved by other
painkillers such as paracetamol or ibuprofen alone.
How do Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets work?
Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets each contain two different
analgesics (painkillers) called paracetamol and codeine (as codeine phosphate hemihydrate).
Codeine belongs to a group of medicines called opioid analgesics, which act to relieve pain.
How are Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets used?
Codeine/Paracetamol 30mg/500mg or 60mg/1000mg tablets should be taken by mouth and
swallowed whole with a drink of water. If necessary, the tablets may be broken in half to
make them easier to swallow.
Please read Section 3 of the package leaflet for detailed information on dosing
recommendations, the route of administration and the duration of treatment.
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Codeine/Paracetamol 30mg/500mg or 60mg/1000mg tablets should not be taken for more
than 3 days.
The recommended dose for Codeine/Paracetamol 30mg/500mg tablets:
- in adults is 1 or 2 tablets. The patient should wait at least 4 hours before taking
another dose and should not take more than 8 tablets in any 24-hour period. Elderly
people may be prescribed a lower dose and patients with kidney problems may
require longer intervals between doses.
- in adolescents over 50 kg of body weight aged 16 years and above is 1 or 2 tablets.
The patient should wait at least 6 hours before taking another dose and should not
take more than 8 tablets in any 24-hour period.
- in children and adolescents 12 to 15 years the recommended dose is one tablet. The
patient should wait at least 6 hours before taking another dose and should not take
more than 4 tablets in any 24-hour period.
The recommended dose for Codeine/Paracetamol 60mg/1000mg tablets:
- in adults is one tablet. The patient should wait at least 4 hours before taking another
dose and should not take more than 4 tablets in any 24-hour period. Elderly people
may be prescribed a lower dose and patients with kidney problems may require longer
intervals between doses.
- in adolescents over 50 kg of body weight aged 16 years and above is one tablet. The
patient should wait at least 6 hours before taking another dose and should not take
more than 4 tablets in any 24-hour period.
Codeine/Paracetamol 60mg/1000mg tablets should not be given to children under 16 years of
age.
These medicines can only be obtained with a prescription.
What benefits of Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets have
been shown in studies?
Codeine/Paracetamol 60mg/1000mg tablets are a hybrid medicine of a reference product,
Solpadol 30mg/500mg Caplets, but with a higher strength dose of codeine phosphate
hemihydrate and paracetamol (i.e. 60 mg rather than 30 mg of codeine phosphate
hemihydrate, and 1000 mg rather than 500 mg of paracetamol). This higher dose of
paracetamol, alone and in combination with codeine, is already widely used and the applicant
has referred to the scientific literature in support of this combination. Studies in patients have
been limited to tests to determine that single doses of Codeine/Paracetamol 60mg/1000mg
tablets are bioequivalent to double doses of the reference medicine, Solpadol 30mg/500mg
Caplets. Two medicines are bioequivalent when they produce the same levels of the active
substance(s) in the body.
Because Codeine/Paracetamol 30mg/500mg tablets are a generic medicine, and
bioequivalence has been shown between equivalent doses of Codeine/Paracetamol
60mg/1000mg tablets and the reference product Solpadol 30mg/500mg Caplets, it was
concluded that the results could be applied to the lower fixed dose combination product such
that Codeine/Paracetamol 30mg/500mg tablets can be considered to be bioequivalent to the
reference medicine Solpadol 30mg/500mg Caplets.
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What are the possible side effects of Codeine/Paracetamol 30mg/500mg and
60mg/1000mg tablets?
Like all medicines, these medicines can cause side effects, although not everybody gets them.
For information about side effects that may occur with using Codeine/Paracetamol
30mg/500mg or 60mg/1000mg tablets, please refer to the package leaflet or the Summaries
of Product Characteristics (SmPC) available on the Medicines and Healthcare products
Regulatory Agency website.
Why are Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets approved?
The MHRA decided that the benefits of Codeine/Paracetamol 30mg/500mg and
60mg/1000mg tablets outweigh the identified risks and recommended that these medicines be
approved for use.
What measures are being taken to ensure the safe and effective use of
Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets?
A risk management plan has been developed to ensure that Codeine/Paracetamol
30mg/500mg and 60mg/1000mg tablets are used as safely as possible. Based on this plan,
safety information has been included in the Summaries of Product Characteristics (SmPCs)
and the package leaflets for Codeine/Paracetamol 30mg/500mg and 60mg/1000mg 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 and healthcare professionals will be monitored and reviewed continuously as well.
Other information about Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets
Germany, Lithuania, Romania and the UK agreed to grant Marketing Authorisations for
Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets on 13 April 2015. The
Marketing Authorisations in the UK were granted to Torrent Pharma (UK) Limited on
02 July 2015.
The full PAR for Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets follows this
summary.
For more information about taking Codeine/Paracetamol 30mg/500mg and 60mg/1000mg
tablets, read the package leaflet or contact your doctor or pharmacist.
This summary was last updated in April 2016.
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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 6
Page 8
Page 10
Page 11
Page 16
Page 17
Table of content of the PAR update for MRP and DCP
Page 23
Annex – 1
Page 27
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I
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Introduction
Based on the review of the data on quality, safety and efficacy, the Member States have
granted Marketing Authorisations (MAs) for the medicinal products Codeine/Paracetamol
30mg/500mg and 60mg/1000mg tablets.
These products are prescription-only medicines (POMs).
Codeine/Paracetamol 30mg/500mg tablets are indicated for the relief of moderate to severe
pain in adults and children above 12 years.
Codeine/Paracetamol 60mg/1000mg tablets are indicated for the relief of moderate to severe
pain in adults and adolescents 16 years and older.
Codeine is indicated in patients 12 years and older for the treatment of acute moderate pain
which is not considered to be relieved by other analgesics such as paracetamol or ibuprofen
(alone).
These applications were submitted using the Decentralised Procedure (DCP), with the UK as
Reference Member State (RMS) and Germany, Lithuania and Romania as Concerned
Member States (CMSs).
The application for Codeine/Paracetamol 30mg/500mg tablets was made under Article 10(1)
of Directive 2001/83/EC, as amended, claiming to be a generic medicinal product. The
reference medicinal product, which has been authorised in accordance with Community
provisions in force for not less than 10 years in the European Economic Area (EEA), is
Solpadol 30mg/500mg Caplets; this product was authorised to Sterling-Winthrop Group
Limited in the UK on 19 December 1989 (PL 00071/0329). The licence for Solpadol
30mg/500mg Caplets subsequently underwent a change of ownership procedure on
02 October 1993 to Sanofi Winthrop Limited (PL 11723/0071). During the history of this
licence, the company name was changed to Sanofi-Synthelabo Limited via a variation on
27 November 2001. On 27 January 2009 the licence held by Sanofi-Synthelabo Limited
underwent a further chnage of ownership procedure to the current MA holder, Aventis
Pharma Limited (PL 04425/0637).
Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets contain the active ingredients
codeine phosphate hemihydrate and paracetamol.
Paracetamol, chemically 4´-hydroxyacetanilide (or N-acetyl-p-aminophenol, acetaminophen),
is an analgesic and antipyretic drug. Paracetamol has both analgesic and antipyretic effects.
However, it does not have an anti-inflammatory effect. The mechanism of analgesic action
has not been fully determined. The main action of paracetamol is the inhibition of
cyclo-oxygenase, an enzyme which is important for prostaglandin synthesis. Central nervous
system cyclo-oxygenase is more sensitive for paracetamol than peripheral cyclo-oxygenase
and this explains why paracetamol has an antipyretic and analgesic efficacy. Paracetamol
probably produces antipyresis by acting centrally on the hypothalamic heat regulating centre.
For several decades paracetamol has proven its clinical efficacy and safety in the treatment of
various acute and chronic pain states. It occupies a unique position among analgesic drugs.
Unlike non-steroidal anti-inflammatory drugs (NSAIDs) it is almost unanimously considered
to have no anti-inflammatory activity and does not produce gastrointestinal damage or
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untoward cardio-renal effects. Unlike opiates it is almost ineffective in intense pain and has
no depressant effect on respiration.
Codeine, chemically 7, 8-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol, is
the prototype of the weak opioid analgesics with weak affinity for μ opioid receptors.
Codeine exerts its effect through µ opioid receptors, although codeine has low affinity for
these receptors, and its analgesic effect is due to its conversion to morphine. There is some
evidence that the metabolite codeine-6 glucuronide is also active. Codeine, particularly in
combination with other analgesics such as paracetamol, has been shown to be effective in
acute nociceptive pain.
No new non-clinical studies were conducted, which is acceptable given that these
applications were based on being a generic medicinal product and a hybrid medicinal product
of an originator product that has been licensed for over 10 years.
Since Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets are intended for generic
substitution, this will not lead to an increased exposure to the environment. An
Environmental Risk Assessment (ERA) is, therefore, not deemed necessary.
With the exception of one bioequivalence study, no new clinical data were provided with
these applications. A bioequivalence study was performed, which compared the
pharmacokinetics of the applicant’s Codeine/Paracetamol 60mg/1000mg tablets with those of
the reference product, Solpadol 30mg/500mg Caplets, in healthy subjects under fasting
conditions. The bioequivalence study was conducted in line with current Good Clinical
Practice (GCP).
The RMS 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, 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.
A Risk Management Plan (RMP) and a summary of the pharmacovigilance system have been
provided with these applications and these are satisfactory.
The RMS and CMSs considered that the applications could be approved at the end of
procedure (Day 210) on 13 April 2015. After a subsequent national phase, licences were
granted in the UK to Torrent Pharma (UK) Limited on 02 July 2015.
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II
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Quality aspects
II.1 Introduction
The application for Codeine/Paracetamol 30mg/500mg tablets is submitted according to
Article 10(1) of Directive 2001/83/EC, as amended. The application for Codeine/Paracetamol
60mg/1000mg tablets is submitted according to Article 10(3) of Directive 2001/83/EC, as
amended. The applicant has specified Solpadol 30mg/500mg Caplets (PL 04425/0637) as the
EU reference medicinal product for both applications.
Codeine/Paracetamol 30mg/500mg tablets are formulated as white, oval, 8.5 x 17 mm,
biconvex tablets, marked ‘5 3’ on one side with a score line. The score line is only to
facilitate breaking for ease of swallowing and not to divide into equal doses.
Codeine/Paracetamol 60mg/1000mg tablets are formulated as white, oval, 10.7 x 21.4 mm,
biconvex tablets, marked ‘10 6’ on one side with a score line and side scores. The score line
is only to facilitate breaking for ease of swallowing and not to divide into equal doses
Each Codeine/Paracetamol 30mg/500mg tablet contains 30 mg codeine phosphate
hemihydrate and 500 mg paracetamol. Each Codeine/Paracetamol 60mg/1000mg tablet
contains 60 mg codeine phosphate hemihydrate and 1000 mg paracetamol.
The excipients present in the tablet core for each strength tablet are: povidone K29/32,
magnesium stearate, colloidal anhydrous silica, talc, croscarmellose sodium, copovidone and
microcrystalline cellulose. The excipients in the tablet coating are: hydroxypropyl starch
(E1440), talc, mannitol, lecithin soya (E322) and titanium dioxide (E171).
Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets are presented in white
polyvinylchloride/aluminium (PVC/Al) blisters, white high density polyethylene (HDPE)
tablet containers with white low density polyethylene (LDPE) caps, or white HDPE tablet
containers with white polypropylene child-resistant screw caps. The tablets are packed into
the blisters in pack sizes of 8, 10, 16, 20, 24, 30, 40, 50 and 100 tablets, and into the tablet
containers in pack sizes of 50 and 100 tablets.
II.2
Drug Substance
Codeine phosphate hemihydrate
INN:
Codeine phosphate hemihydrate
Chemical Name:
7,8-Didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-ol
phosphate hemihydrate
Structure:
Molecular formula:
Molecular weight:
C18H24NO7P, ½H20
406.4
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Appearance:
Solubility:
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White or almost white, crystalline powder or small, colourless
crystals.
Freely soluble in water, slightly soluble or very slightly soluble
in ethanol (96%)
Codeine phosphate hemihydrate is the subject of a European Pharmacopoeia monograph.
All aspects of the manufacture and control of the active substance, codeine phosphate
hemihydrate, are covered by European Directorate for the Quality of Medicines and
Healthcare (EDQM) Certificates of Suitability.
Paracetamol
INN:
Chemical Name:
Structure:
Molecular formula:
Molecular weight:
Appearance:
Solubility:
Paracetamol
N-(4-Hydroxyphenyl)acetamide
C8H9NO2
151.2
white to almost white crystalline powder
Sparingly soluble in water, freely soluble in alcohol, very slightly
soluble in methylene chloride.
Paracetamol is the subject of a European Pharmacopoeia monograph.
All aspects of the manufacture and control of the active substance, paracetamol, are covered
by a European Directorate for the Quality of Medicines and Healthcare (EDQM) Certificate
of Suitability.
II.3
Medicinal Product
Pharmaceutical development
The aim of the pharmaceutical development was to formulate compressed oral dosage
forms with the dosages for codeine phosphate hemihydrate/paracetamol of 30
mg/500 mg and 60 mg/1000 mg. The aim was to produce film-coated tablets with an
instant drug release similar to that of the reference product Solpadol 30mg/500mg
Caplets, authorised to Aventis Pharma Limited.
The development of the product has been adequately described. The results from a
comparative dissolution study show that more than 85% of both paracetamol and codeine
from Codeine/Paracetamol 60mg/1000mg tablets and the reference medicinal product,
Solpadol 30mg/500mg Caplets, is dissolved at all test conditions after 15 minutes. It can be
concluded that the test product and reference product show similar dissolution profiles for
paracetamol and codeine at all tested pH levels. Comparative impurity profiles between
Codeine/Paracetamol 60mg/1000mg tablets and Solpadol 30mg/500mg Caplets have shown
that the levels and profile of impurities are comparable between these products.
In order to show that equivalent doses of Codeine/Paracetamol 60mg/1000mg tablets are
equivalent to the reference medicinal product, Solpadol 30mg/500mg Caplets, with regard to
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bioavailability, a bioequivalence study was performed. This is discussed in Section IV –
Clinical aspects.
All the excipients used in the manufacture of the proposed formulation, other than the
film-coating excipients, comply with their respective European Pharmacopoeia monographs.
The film-coating excipients comply with satisfactory in-house specifications.
Satisfactory certificates of analysis have been provided for all excipients showing compliance
with their proposed specifications.
None of the excipients are sourced from animal or human origin. The magnesium stearate is
of vegetable origin.
No genetically modified organisms (GMO) have been used in the preparation of these
excipients.
Manufacture of the product
Satisfactory batch formulae have been provided for the manufacture of the finished products,
together with an appropriate account of the manufacturing process. The manufacturing
process has been validated for pilot-scale batch sizes. A commitment has been made by the
applicant to validate the process at full production scale before marketing.
Product Specifications
The finished product specifications are satisfactory. Satisfactory batch analyses were
performed on two batches of the finished product, for each strength product. Certificates of
analysis have been provided for all working standards used.
Stability of the product
Stability studies were performed in accordance with current guidelines on batches of the
finished products, packed in the packaging proposed for marketing. The data from these
studies support a shelf-life for each product of 2 years. There are no special storage
conditions for these products.
Suitable post approval stability commitments have been provided.
II.4
Discussion on chemical, pharmaceutical and biological aspects
The grant of marketing authorisations is recommended for these products.
III Non-clinical aspects
The pharmacodynamic, pharmacokinetic and toxicological properties of codeine and
paracetamol are well-known. As codeine and paracetamol are widely used, well-known
active substances, the applicant has not provided additional studies and further studies are not
required. The non-clinical overview based on a literature review is, thus, appropriate.
The non-clinical overview has been written by an appropriately qualified person. The
non-clinical overview on the pharmacology, pharmacokinetics and toxicology is adequate.
Since Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets are intended for generic
substitution, they will not lead to an increased exposure to the environment. An environmental
risk assessment is, therefore, not deemed necessary.
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IV Clinical aspects
IV.1 Introduction
With the exception of bioequivalence data, no new clinical data have been submitted and
none are required for applications of this type. The applicant’s clinical overview has been
written by an appropriately qualified person and is considered acceptable.
IV.2 Pharmacokinetics
In support of these applications the marketing authorisation holder has submitted results from
the following bioequivalence study:
A single centre, single-dose, open-label, laboratory-blind, randomized, two-period
crossover study to determine bioequivalence between the test product (tablets
containing 60 mg codeine and 1000 mg paracetamol) and the reference product (caplets
containing 30 mg codeine phosphate hemihydrate and 500 mg paracetamol) in 36
healthy male and female subjects under fasting conditions.
Subjects received a single oral dose of 60 mg codeine phosphate and 1000 mg paracetamol in
each study period as either one Codeine/Paracetamol 60/1000mg tablet (test product) or two
Solpadol 30mg/500mg Caplets (reference product). Administration of each dose followed an
overnight fast of at least 10 hours. Blood samples were taken for the measurement of
pharmacokinetic parameters pre-dose and up to 24 hours post-dose. The two treatment
periods were separated by a 7 to 12-day washout period.
The following pharmacokinetic (PK) parameters were estimated for paracetamol and codeine
for each subject and treatment:
Primary pharmacokinetic endpoints:
- Maximum observed plasma concentration (Cmax), obtained directly from the
concentration-time data.
- Area under the plasma concentration versus time curve, from time zero to t, where t is
the time of the last quantifiable concentration (AUC(0-t)).
Secondary pharmacokinetic endpoints:
- Time to maximum observed plasma concentration (tmax).
- Area under the plasma concentration versus time curve, with extrapolation to infinity
(AUC(0-∞)).
- Percentage of AUC(0-∞) obtained by extrapolation (%AUCex).
- Terminal elimination rate constant (λz).
- Apparent terminal elimination half-life (t½z).
- Ratio of AUC(0-t) (Test Product) to AUC(0-t) (Reference Product).
- Ratio of Cmax (Test Product) to Cmax (Reference Product).
- Number of points used to calculate λz.
- Adjusted R-squared value.
For both analytes, the test product was compared to the reference product by means of
statistical analysis with respect to the primary PK parameters using an analysis of variance
with sequence, subject (sequence), product and period effects after logarithmic
transformation of the data. Point estimates and 90% confidence intervals for the
“test/reference” geometric mean ratios of these parameters were tabulated. The main
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pharmacokinetic results are presented below:
The 90% confidence intervals were within the acceptance criteria of 80.00% to 125.00%.
Based on these results, the proposed product, Codeine/Paracetamol 60mg/1000mg tablets,
can be considered to be bioequivalent with the reference product Solpadol 30mg/500mg
Caplets, when dosed at equivalent doses.
Codeine/Paracetamol 30mg/500mg tablets meet the general biowaiver criteria specified in the
Guideline on the Investigation of Bioequivalence (CPMP/EWP/QWP/1401/98 Rev. 1/
Corr**). It is, therefore, justified that the results and conclusions from the bioequivalence
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study on the 60mg/1000mg strength product are extrapolated to the 30mg/500mg strength
product.
IV.3 Pharmacodynamics
No new pharmacodynamics data are required for these applications and none have been
submitted.
IV.4 Clinical efficacy
No new clinical efficacy data are required for these applications and none have been
submitted.
IV.5 Clinical safety
No new clinical safety data have been provided and none are required.
IV.6 Risk Management Plan (RMP)
The marketing authorisation holder has submitted an 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 Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets.
A summary of safety concerns and planned risk minimisation activities, as approved in the
RMP, are listed below:
Planned risk minimisation activities
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V.7
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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 for Codeine/Paracetamol 60mg/1000mg tablets 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
package leaflet was English.
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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.
A user consultation with target patient groups on the package leaflet for Codeine/Paracetamol
30 mg/500 mg tablets has been performed on the basis of a bridging report making reference
to Codeine/Paracetamol 60mg/1000mg tablets (PL 36687/0141; UK/H/5715/003/DC). The
bridging report submitted by the applicant has been found to be acceptable.
VI Overall conclusion, benefit/risk assessment and
recommendation
The quality of the products is acceptable, and no new non-clinical or clinical safety concerns
have been identified. The applications include an adequate review of published non-clinical
and clinical data concerning the efficacy and safety of codeine and paracetamol. The test
products Codeine/Paracetamol 30mg/500mg and 60mg/1000mg tablets can be considered
bioequivalent to the reference product Solpadol 30mg/500mg Caplets based on equivalent
doses. The benefit/risk assessment is, therefore, considered to be positive.
The Summaries of Product Characteristics (SmPCs), package leaflets and labelling are
satisfactory, in line with current guidelines and consistent with the reference product. In
accordance with Directive 2012/84/EU, the current approved UK versions of the SmPCs and
package leaflets for these products are available on the Medicines and Healthcare products
Regulatory Agency website.
17
Codeine/Par acetamol 30mg/500mg film-coated tablets
Codeine/Par acetamol 60mg/1000mg film-coated tablets
UK/H/5715/002/DC
UK/H/5715/003/DC
Labelling mock-ups for Codeine/Paracetamol 30mg/500mg tablets
18
Codeine/Par acetamol 30mg/500mg film-coated tablets
Codeine/Par acetamol 60mg/1000mg film-coated tablets
UK/H/5715/002/DC
UK/H/5715/003/DC
19
Codeine/Par acetamol 30mg/500mg film-coated tablets
Codeine/Par acetamol 60mg/1000mg film-coated tablets
UK/H/5715/002/DC
UK/H/5715/003/DC
20
Codeine/Par acetamol 30mg/500mg film-coated tablets
Codeine/Par acetamol 60mg/1000mg film-coated tablets
UK/H/5715/002/DC
UK/H/5715/003/DC
Labelling mock-ups for Codeine/Paracetamol 60mg/1000mg tablets
21
Codeine/Par acetamol 30mg/500mg film-coated tablets
Codeine/Par acetamol 60mg/1000mg film-coated tablets
UK/H/5715/002/DC
UK/H/5715/003/DC
22
Codeine/Par acetamol 30mg/500mg film-coated tablets
Codeine/Par acetamol 60mg/1000mg film-coated tablets
UK/H/5715/002/DC
UK/H/5715/003/DC
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)
The following table lists a non-safety update to the Marketing Authorisations for these
products that has been approved by the MHRA since the products were first licensed. The
table includes updates that are detailed in the annex to this PAR. This is not a complete list of
the post-authorisation changes that have been made to these Marketing Authorisations.
Scope
Procedure
number
To update section UK/H/5715
3
/002(Pharmaceutical
003/IB/001
form) of the
Summaries of
Product
Characteristics
(SmPC) to
correct a mistake
in the common
texts with respect
to the appearance
of the filmcoated tablets.
Consequentially
the Patient
Information
Leaflets (PIL)
have been
updated.
Product
information
affected
Date of
start of the
procedure
Date of
end of
procedure
Approval
/ non
approval
SmPC
and PIL
17/02/2016
01/04/2016
Approved
Assessment
report
attached
Y/N
(version)
Yes
23
Codeine/Par acetamol 30mg/500mg film-coated tablets
Codeine/Par acetamol 60mg/1000mg film-coated tablets
UK/H/5715/002/DC
UK/H/5715/003/DC
Annex 1
Reference:
PL 36687/0140-1 - 0003
Product:
Codeine/Paracetamol 30mg/500mg and 60mg/1000mg film-coated
tablets
Marketing Authorisation Holder: Torrent Pharma (UK) Ltd
Active Ingredient:
Codeine Phosphate Hemihydrate and Paracetamol
Reason:
To update section 3 (Pharmaceutical form) of the Summaries of Product Characteristics
(SmPC) to correct mistakes in the common texts with respect to the appearance of the filmcoated tablets. Consequentially the Patient Information Leaflets (PIL) have been updated.
Supporting evidence
The applicant has submitted an updated section 3 of the SmPCs and PILs.
Evaluation
The amended section of the SmPCs and the PILs are satisfactory.
Conclusion
The proposed changes are acceptable. The updated section of the SmPCs and the PILs have
been submitted and are acceptable.
In accordance with Directive 2010/84/EU, the current granted UK SmPCs and PILs are
available on the MHRA website.
Decision
Grant
Date: 01 April 2016
24