UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
GAVISCON PEPPERMINT FLAVOUR TABLETS
(sodium alginate, sodium hydrogen carbonate, calcium carbonate)
PL 00063/0627
UKPAR
TABLE OF CONTENTS
Lay Summary
Page 2
Scientific discussion
Page 3
Steps taken for assessment
Page 11
Steps taken after authorisation
Page 12
Summary of Product Characteristics
Page 13
Patient Information Leaflets
Page 16
Labelling
Page 19
1
UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
Gaviscon Peppermint Flavour Tablets
(sodium alginate, sodium hydrogen carbonate, calcium carbonate)
PL 00063/0627
LAY SUMMARY
The Medicines and Healthcare products Regulatory Agency (MHRA) granted Reckitt
Benckiser Healthcare (UK) Limited a Marketing Authorisation (licence) for the
medicinal product, Gaviscon Peppermint Flavour Tablets (PL 00063/0627), on 10th
August 2010. This is a medicine available on the General Sales List (GSL), and can
be purchased at pharmacies, supermarkets and other retail outlets without the
supervision of a pharmacist.
Gaviscon Peppermint Flavour Tablets belong to a group of medicines called ‘reflux
suppressants’, which form a protective layer on top of the stomach contents to prevent
stomach acid escaping from the stomach where it works into the food pipe causing
pain and discomfort.
Gaviscon Peppermint Flavour Tablets are chewable tablets used for the treatment of
symptoms of gastro-oesophageal reflux such as acid regurgitation, heartburn and
indigestion (related to reflux) which may occur, for example, following meals or
during pregnancy, and in patients with symptoms related to oesophagitis.
This application is considered to be identical to a previously granted licence for
Gaviscon Peppermint Tablets (PL 00063/0134), authorised to Reckitt Benckiser
Healthcare (UK) Limited on 7th October 2003. The proposed and reference products
are identical.
No new or unexpected safety concerns arose from this application and it was therefore
judged that the benefits of Gaviscon Peppermint Flavour Tablets outweigh the risk;
hence a Marketing Authorisation has been granted.
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UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
Gaviscon Peppermint Flavour Tablets
(sodium alginate, sodium hydrogen carbonate, calcium carbonate)
PL 00063/0627
SCIENTIFIC DISCUSSION
TABLE OF CONTENTS
Introduction
Page 4
Pharmaceutical assessment
Page 5
Non-clinical assessment
Page 8
Clinical assessment
Page 9
Overall conclusion and risk benefit assessment
Page 10
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UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
INTRODUCTION
Based on the review of the data on quality, safety and efficacy, the MHRA granted
Reckitt Benckiser Healthcare (UK) Limited a Marketing Authorisation for the
medicinal product, Gaviscon Peppermint Flavour Tablets (PL 00063/0627), on 10th
August 2010. The product is available on a General Sales Licence (GSL).
This is a simple, abridged, ‘informed consent’ application submitted according to
Article 10(c) of EC Directive 2001/83 (as amended), cross-referencing the Marketing
Authorisation for Gaviscon Peppermint Tablets (PL 00063/0134), licensed to Reckitt
Benckiser Healthcare (UK) Limited on 7th October 2003.
Gaviscon Peppermint Flavour Tablets are indicated for the treatment of symptoms of
gastro-oesophageal reflux such as acid regurgitation, heartburn and indigestion
(related to reflux), for example, following meals or during pregnancy or in patients
with symptoms related to reflux oesophagitis.
On ingestion the medicinal product reacts rapidly with gastric acid to form a raft of
alginic acid gel having a near neutral pH and which floats on the stomach contents
effectively impeding gastro-oesophageal reflux. In severe cases the raft itself may be
refluxed into the oesophagus, in preference to the stomach contents, and exert a
demulcent effect. The mechanism of action of the medicinal product is physical and
does not depend on absorption into the systemic circulation.
The pharmacovigilance system as described by the Marketing Authorisation Holder
(MAH) fulfils the requirements and provides adequate evidence that the MAH has the
services of a Qualified Person (QP) 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.
The MAH has provided adequate justification for not submitting a Risk Management
Plan (RMP). As the application is for a product that is identical to the reference
product, for which safety concerns requiring additional risk minimisation have not
been identified, a risk minimisation system is not considered necessary. The reference
product has been in use for many years and the safety profiles of the actives are well
established.
The MAH has provided adequate justification for not submitting an Environmental
Risk Assessment (ERA). They have stated that the medicinal product contains the
well-established ingredient sodium alginate, a low toxicity product of seaweed,
commonly used and currently on the market at the same strength throughout Europe.
On this basis, the marketing of Gaviscon Peppermint Flavour Tablets should not
result in an overall increase in the environmental exposure concentrations of the
active ingredient, sodium alginate. The product does not contain any other
components that would require environmental risk assessment under the European
Medicines Agency guidelines.
No new data were submitted nor was it necessary for this simple application, as the
data are identical to that of the previously granted cross-reference product. As the
cross-reference product was granted prior to the introduction of current legislation, no
PAR was generated for it.
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UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
PHARMACEUTICAL ASSESSMENT
LICENCE NUMBER:
PL 00063/0627
PROPRIETARY NAME:
Gaviscon Peppermint Flavour Tablets
ACTIVE INGREDIENTS:
Sodium alginate, sodium hydrogen carbonate,
calcium carbonate
COMPANY NAME:
Reckitt Benckiser Healthcare (UK) Limited
E.C. ARTICLE:
Article 10c of Directive 2001/83/EC (as amended)
LEGAL STATUS:
GSL
1.
INTRODUCTION
This is a simple abridged application, submitted under Article 10c of Directive
2001/83/EC (as amended) for Gaviscon Peppermint Flavour Tablets. The proposed
Marketing Authorisation Holder (MAH) is Reckitt Benckiser Healthcare (UK)
Limited.
The reference product is Gaviscon Peppermint Tablets (PL 00063/0134), authorised to
Reckitt Benckiser Healthcare (UK) Limited on 7th October 2003. The proposed and
reference products are identical.
2.
MARKETING AUTHORISATION APPLICATION FORM
2.1 Name(s)
The approved name of the product is Gaviscon Peppermint Flavour Tablets. The
product name is accepted.
2.2 Strength, pharmaceutical form, route of administration, container and pack
sizes
Gaviscon Peppermint Flavour Tablets are presented as off-white to cream, circular,
chewable tablets for oral administration. Each tablet contains 250mg of sodium
alginate, 133.5mg of sodium hydrogen carbonate and 80mg of calcium carbonate. The
tablets are licensed for marketing in the following containers (full details are provided
in the SmPC):
i)
Blister packs consisting of polyvinylchloride (PVC) / polyethylene
(PE) / polyvinylidene chloride (PVdC) / aluminium foil blister strips
contained in an outer carton - pack sizes 4, 6, 8, 16, 24, 32, 48 or 64
tablets
ii)
Polypropylene containers containing 8, 12, 16, 18, 20, 22 or 24 tablets.
Multiple packs (2 x 16, 2 x 18, 2 x 20, 2 x 22 or 2 x 24) will be packed
into cartons. Full list of pack sizes is 8, 12, 16, 18, 20, 22, 24, 2 x 16, 2
x 18, 2 x 20, 2 x 22 or 2 x 24 tablets
The MAH has stated that not all pack sizes may be marketed. The container closure
systems and pack sizes are the same as those for the reference product.
The approved shelf-life (2 years) and storage conditions (‘Do not store above 30°C’)
are identical to the details registered for the cross-reference product.
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UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
2.3 Legal status
The product is a GSL licensed medicine, available by supply through pharmacies,
supermarkets and other retail outlets without the need for supervision by a pharmacist.
2.4 Marketing Authorisation Holder / Contact Persons / Company
The proposed Marketing Authorisation Holder is ‘Reckitt Benckiser Healthcare (UK)
Limited, Dansom Lane, Hull, HU8 7DS, United Kingdom’.
The Qualified Person (QP) responsible for pharmacovigilance was stated and their CV
included.
2.5 Manufacturers
The proposed manufacturing sites are consistent with those registered for the crossreference product and evidence of GMP compliance has been provided.
2.6 Qualitative and quantitative composition
The proposed composition is identical to 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 and the maximum batch size is stated.
2.8 Finished product / shelf-life specification
The proposed finished product specification is consistent 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
There are no materials of human or animal origin contained in, or used in the
manufacturing process for, the proposed product. None of the excipients are sourced
from genetically modified organisms.
3.
EXPERT REPORT
A satisfactory quality overall summary has been prepared by an appropriately
qualified expert. The CV of the expert was provided.
4.
PRODUCT NAME & APPEARANCE
See 2.1 for details of the proposed product name. The appearance of the product (offwhite to cream, slightly mottled, circular, tablets) is identical to that of the crossreference product.
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UKPAR Gaviscon Peppermint Flavour Tablets
5.
PL 00063/0627
SUMMARY OF PRODUCT CHARACTERISTICS (SmPC)
The approved SmPC is consistent with the details registered for the cross-reference
product.
6.
PATIENT INFORMATION LEAFLET (PIL) / CARTON
PIL
The approved PIL is satisfactory and in line with the approved SmPC. It has been
prepared according to the Quality Review of Documents (QRD) template and is
consistent with the details registered for the cross-reference product.
PIL user testing has been accepted, based on a bridging report provided by the
applicant making reference to the successful user-testing of the PIL for the reference
product, Gaviscon Peppermint Tablets (PL 00063/0134). The text, content and layout
of the proposed PIL are essentially identical to the approved PIL for the reference
product. The bridging report is accepted.
The PIL for the polypropylene containers is attached to the container in the form of a
label and should be unfolded to read.
Cartons
Colour mock-ups of the labelling have been provided and are satisfactory. The
approved artwork is comparable to the artwork registered for the cross-reference
product and complies with statutory requirements. In line with current legislation the
applicant has included the name of the product in Braille on the outer packaging.
The MAH has stated that not all licensed pack sizes may be marketed. However, they
have committed to submitting mock-ups for currently unmarketed pack sizes to the
relevant regulatory authorities for approval before those packs are commercially
marketed.
7.
CONCLUSIONS
The grounds for this application are considered adequate. A Marketing Authorisation
was therefore granted.
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UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
NON-CLINICAL ASSESSMENT
This is a simple, abridged, ‘informed consent’ application made under Article 10(c) of
EC Directive 2001/83 (as amended).
No new non-clinical data have been supplied with this application and none are
required for an application of this type. A non-clinical overview has been written by a
suitably qualified person and is satisfactory. The CV of the non-clinical expert has
been supplied.
The Marketing Authorisation Holder has provided adequate justification for not
submitting an Environmental Risk Assessment (ERA).
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UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
CLINICAL ASSESSMENT
This is a simple, abridged, ‘informed consent’ application made under Article 10(c) of
EC Directive 2001/83 (as amended), cross-referring to the Marketing Authorisation
for Gaviscon Peppermint Tablets (PL 00063/0134).
No new clinical data have been supplied with the application, and none are required
for applications of this type. A clinical overview has been written by a suitably
qualified person and is satisfactory. The CV of the clinical expert has been supplied.
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UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
OVERALL CONCLUSION AND BENEFIT-RISK ASSESSMENT
QUALITY
The data for this application are consistent with those previously assessed for the
cross-reference product and as such have been judged to be satisfactory.
NON-CLINICAL
No new non-clinical data were submitted and none are required for an application of
this type.
EFFICACY
This application is considered identical to the previously granted licence for Gaviscon
Peppermint Tablets (PL 00063/0134, Reckitt Benckiser Healthcare (UK) Limited).
No new or unexpected safety concerns arise from this application.
PRODUCT LITERATURE
The approved SmPC, PIL and labelling are satisfactory and consistent with the details
registered for the cross-reference product.
PIL user testing has been accepted, based on a bridging report provided by the
applicant making reference to the successful user-testing of the PIL for the reference
product, Gaviscon Peppermint Tablets (PL 00063/0134). The bridging report is
accepted.
Colour mock-ups of the labelling have been provided and are satisfactory. The
approved labelling artwork complies with statutory requirements. The MAH has
stated that not all licensed pack sizes may be marketed. However, they have
committed to submitting mock-ups for currently unmarketed pack sizes to the relevant
regulatory authorities for approval before those packs are commercially marketed.
BENEFIT-RISK ASSESSMENT
The quality of the product is acceptable and no new non-clinical or clinical safety
concerns have been identified. The applicant’s product is identical to the crossreference product. The benefit: risk ratio is considered to be positive.
10
UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
Gaviscon Peppermint Flavour Tablets
(sodium alginate, sodium hydrogen carbonate, calcium carbonate)
PL 00063/0627
STEPS TAKEN FOR ASSESSMENT
1
The MHRA received the Marketing Authorisation application on 9th March
2010
2
Following standard checks and communication with the applicant the MHRA
considered the application valid on 11th March 2010
3
Following assessment of the application the MHRA requested further
information relating to the quality dossier on 2nd June 2010, 21st June 2010 and
20th July 2010
4
The applicant responded to the MHRA’s requests, providing further information
for the quality sections on 17th June 2010, 23rd June 2010 and 24th July 2010
respectively
5
The application was determined on 10th August 2010
11
UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
Gaviscon Peppermint Flavour Tablets
(sodium alginate, sodium hydrogen carbonate, calcium carbonate)
PL 00063/0627
STEPS TAKEN AFTER AUTHORISATION
Not applicable
12
UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
SUMMARY OF PRODUCT CHARACTERISTICS
The UK Summary of Product Characteristics (SmPC) for Gaviscon Peppermint
Flavour Tablets is as follows:
1
NAME OF THE MEDICINAL PRODUCT
Gaviscon Peppermint Flavour Tablets.
2
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains sodium alginate 250 mg, sodium hydrogen carbonate 133.5 mg and
calcium carbonate 80 mg.
Excipients: Aspartame (E951) 3.75 mg per tablet.
For excipients, see Section 6.1.
3
PHARMACEUTICAL FORM
Chewable tablet.
An off-white to cream, slightly mottled tablet.
4
CLINICAL PARTICULARS
4.1
Therapeutic indications
Treatment of symptoms of gastro-oesophageal reflux such as acid regurgitation, heartburn and
indigestion (related to reflux), for example, following meals or during pregnancy or in patients
with symptoms related to reflux oesophagitis.
4.2
Posology and method of administration
For oral use, after being thoroughly chewed.
Adults and children 12 years and over: Two to four tablets after meals and at bedtime.
Elderly: No dose modifications necessary for this age group.
4.3
Contraindications
This medicinal product is contraindicated in patients with known or suspected hypersensitivity
to the active substances or to any of the excipients.
4.4
Special warnings and precautions for use
The sodium content of a four-tablet dose is 246 mg (10.6 mmol). This should be taken into
account when a highly restricted salt diet is recommended, e.g. in some cases of congestive
cardiac failure and renal impairment.
Each four-tablet dose contains 320 mg (3.2 mmol) of calcium carbonate. Care needs to be
taken in treating patients with hypercalcaemia, nephrocalcinosis and recurrent calcium
containing renal calculi.
Due to its aspartame content this medicinal product should not be given to patients with
phenylketonuria.
There is a possibility of reduced efficacy in patients with very low levels of gastric acid.
If symptoms do not improve after seven days, the clinical situation should be reviewed.
Treatment of children younger than 12 years of age is not generally recommended, except on
medical advice.
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UKPAR Gaviscon Peppermint Flavour Tablets
4.5
PL 00063/0627
Interaction with other medicinal products and other forms of interaction
Due to the presence of calcium carbonate which acts as an antacid, a time-interval of 2 hours
should be considered between Gaviscon intake and the administration of other medicinal
products, especially H2-antihistaminics, tetracyclines, digoxine, fluoroquinolone, iron salt,
ketoconazole, neuroleptics, thyroxine, penicilamine, beta-blockers (atenolol, metoprolol,
propanolol), glucocorticoid, chloroquine and diphosphonates.
4.6
Pregnancy and lactation
Open controlled studies in 281 pregnant women did not demonstrate any significant adverse
effects of Gaviscon on the course of pregnancy or on the health of the foetus/new-born child.
Based on this and previous experience the medicinal product may be used during pregnancy
and lactation. Nevertheless, taking into account the presence of calcium carbonate (see
Section 5.3) it is recommended to limit the treatment duration as much as possible.
4.7
Effects on ability to drive and use machines
Not relevant.
4.8
Undesirable effects
Very rarely (=1/10,000) patients may develop allergic manifestations such as urticaria or
bronchospasm, anaphylactic and anaphylactoid reactions.
4.9
Overdose
In the event of overdose symptomatic treatment should be given. The patient may notice
abdominal distension.
5
PHARMACOLOGICAL PROPERTIES
5.1
Pharmacodynamic properties
Pharmacotherapeutic group: Other drugs for peptic ulcer and gastro-oesophageal reflux
disease (GORD) ATC code: A02BX.
On ingestion the medicinal product reacts rapidly with gastric acid to form a raft of alginic
acid gel having a near neutral pH and which floats on the stomach contents effectively
impeding gastro-oesophageal reflux. In severe cases the raft itself may be refluxed into the
oesophagus, in preference to the stomach contents, and exert a demulcent effect.
5.2
Pharmacokinetic properties
The mechanism of action of the medicinal product is physical and does not depend on
absorption into the systemic circulation.
5.3
Preclinical safety data
There is limited evidence in some reports in animals of delay in calcification of foetal
skeleton/bone abnormalities relating to calcium carbonate.
6
PHARMACEUTICAL PARTICULARS
6.1
List of excipients
Peppermint flavour
Macrogol 20,000
Mannitol (E421)
Copovidone
Aspartame (E951)
Acesulfame potassium (E950)
Magnesium stearate
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UKPAR Gaviscon Peppermint Flavour Tablets
6.2
PL 00063/0627
Incompatibilities
Not applicable.
6.3
Shelf life
2 years.
6.4
Special precautions for storage
Do not store above 30°C.
6.5
Nature and contents of container
Unprinted, glass-clear, thermoformable laminate of uPVC/PE/PVdC with aluminium foil
lidding blisters packed into cartons.
Blister pack containing 4, 6 or 8 individually sealed tablets.
Larger packs (16, 24, 32, 48 and 64) will be made up of multiples of the above units and
packed into cartons.
Pack sizes 4, 6, 8, 16, 24, 32, 48 or 64 tablets
Polypropylene container containing 8, 12, 16, 18, 20, 22 or 24 tablets.
Multiple packs (2 x 16, 2 x 18, 2 x 20, 2 x 22 or 2 x 24) will be packed into cartons.
Pack sizes 8, 12, 16, 18, 20, 22, 24, 2 x 16, 2 x 18, 2 x 20, 2 x 22 or 2 x 24 tablets.
Not all pack sizes may be marketed.
6.6
Special precautions for disposal
No special requirements.
7
MARKETING AUTHORISATION HOLDER
Reckitt Benckiser Healthcare (UK) Limited,
Dansom Lane,
Hull,
HU8 7DS,
United Kingdom.
8
MARKETING AUTHORISATION NUMBER(S)
PL 00063/0627
9
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
10/08/2010
10
DATE OF REVISION OF THE TEXT
10/08/2010
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UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
PATIENT INFORMATION LEAFLET
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UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
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UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
PIL (in the form of a label) for polypropylene containers
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UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
LABELLING
Blister carton, with Braille – pack size 8
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UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
Blister carton, with Braille – pack size 16
20
UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
Blister carton, with Braille – pack size 32
21
UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
Braille translation
Blister foil
22
UKPAR Gaviscon Peppermint Flavour Tablets
PL 00063/0627
Label for polypropylene container
23