Public Assessment Report
Acidex Advance Oral Suspension (Aniseed Flavour)
Acidex Advance Oral Suspension (Peppermint
Flavour)
(Sodium alginate and potassium hydrogen carbonate)
UK Licence No.: PL 04917/0143-0144
Pinewood Laboratories Limited
Acidex Advance Oral Suspension (Aniseed Flavour/Peppermint Flavour)
PL 04917/0143-0144
Lay Summary
Acidex Advance Oral Suspension (Aniseed Flavour)
Acidex Advance Oral Suspension (Peppermint Flavour)
(Sodium alginate and potassium hydrogen carbonate)
This is a summary of the Public Assessment Report (PAR) for Acidex Advance Oral
Suspension (Aniseed Flavour) (PL 04917/0143) and Acidex Advance Oral Suspension
(Peppermint Flavour) (PL 04917/0144). These medicinal products will be referred to
as Acidex Oral Suspension in this lay summary for ease of reading.
This summary explains how Acidex Oral Suspension was assessed and its
authorisation recommended, as well as its conditions of use. It is not intended to
provide practical advice on how to use Acidex Oral Suspension.
For practical information about using Acidex Oral Suspension, patients should read the
package leaflet or contact their doctor or pharmacist.
What is Acidex Oral Suspension and what is it used for?
These products are extension applications of the previously authorised products,
Acidex Max Strength Heartburn Relief Oral Suspension (Aniseed Flavour) and Acidex
Max Strength Heartburn Relief Oral Suspension (Peppermint Flavour) (PL
04917/0113-0114; Pinewood Laboratories Limited).
The reference products for Acidex Oral Suspension are Gaviscon Advance Aniseed
Suspension (PL 00063/0108) and Gaviscon Advance Peppermint Flavour Oral
Suspension (PL 00063/0612).
Acidex Oral Suspension is used to prevent and relieve the symptoms of acid reflux,
including during pregnancy and relieve the symptoms of conditions such as hiatus
hernia (protrusion of muscle though a muscle wall), reflux oesophagitis (inflamed
foodpipe) and symptoms of hoarseness and other voice disorders, sore throat and
cough associated with reflux. It can also be used to control heartburn symptoms which
may occur when taking, or following withdrawal of medication to reduce stomach acid
such as proton pump inhibitors (PPIs) or H2 antagonists.
How does Acidex Oral Suspension work?
Acidex Oral Suspension contains the active ingredients sodium alginate and potassium
hydrogen carbonate which belong to a group of medicines called ‘reflux suppressants’.
This medicine stops reflux (when the acid stomach contents flow back up the gullet
(oesophagus) and causes pain and discomfort known as heartburn or acid indigestion)
from happening by keeping the stomach contents away from the lining of the food pipe
to relieve the symptoms of heartburn and acid indigestion.
How is Acidex Oral Suspension used?
Acidex Oral Suspension is taken by mouth after meals and at bed time. The bottle
should be shaken well before use. Patients should leave 1-2 hours between taking this
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medicine and other medicines. Patients must check with their doctor or pharmacist if
they are not sure.
The recommended dose for adults, children over 12 years and the elderly is 5-10 ml
after meals and at bedtime. Acidex Oral Suspension should be used only under medical
supervision in children under 12 years.
Please read section 3 of the package leaflet for detailed information on dosing
recommendations, the route of administration, and the duration of treatment.
Acidex Oral Suspension can be obtained from a pharmacy.
What benefits of Acidex Oral Suspension have been shown in studies?
No additional studies were needed as Acidex Oral Suspension acts in a physical way
forming a raft on the stomach contents and is pharmaceutically equivalent to the
reference products.
What are the possible side effects of Acidex Oral Suspension?
Like all medicines, Acidex Oral Suspension can cause side effects, although not
everybody gets them.
For the full list of all side effects reported with Acidex Oral Suspension, see section 4
of the package leaflet available on the MHRA website.
For the full list of restrictions, see the package leaflet.
Why was Acidex Oral Suspension approved?
The MHRA decided that the benefits of Acidex Oral Suspension outweigh the
identified risks and it was recommended that it be approved for use.
What measures are being taken to ensure the safe and effective use of Acidex Oral
Suspension?
A risk management plan (RMP) has been developed to ensure that Acidex Oral
Suspension is used as safely as possible. Based on this plan, safety information has
been included in the Summaries of Product Characteristics and the package leaflet for
Acidex Oral Suspension 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 Acidex Oral Suspension
Marketing Authorisations were granted in the UK on 28 September 2016.
For more information about taking Acidex Oral Suspension, read the package leaflet,
or contact your doctor or pharmacist. The full PAR for Acidex Oral Suspension
follows this summary.
This summary was last updated in November 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
Steps taken after authorisation - Summary
Annex 1
Page 5
Page 7
Page 9
Page 10
Page 11
Page 12
Page 17
Page 18
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Acidex Advance Oral Suspension (Aniseed Flavour/Peppermint Flavour)
I
PL 04917/0143-0144
Introduction
The Medicines and Healthcare products Regulatory Agency (MHRA) granted
Pinewood Laboratories Limited Marketing Authorisations for the medicinal products
Acidex Advance Oral Suspension (Aniseed Flavour) (PL 04917/0143) and Acidex
Advance Oral Suspension (Peppermint Flavour) (PL 04917/0144) on 28 September
2016. These products are available from a pharmacy.
Acidex Oral Suspension is used for the treatment of symptoms resulting from the
reflux of acid, bile and pepsin into the oesophagus such as acid regurgitation,
heartburn, indigestion (occurring due to the reflux of stomach contents), for instance,
after gastric surgery, as a result of hiatus hernia, during pregnancy, accompanying
reflux oesophagitis, including symptoms of laryngopharyngeal reflux such as
hoarseness and other voice disorders, sore throats and cough. It can also be used to
treat the symptoms of gastro-oesophageal reflux during concomitant treatment with or
following withdrawal of acid suppressing therapy.
These applications were submitted under Article 10(3) of Directive 2001/83/EC, as
amended, as hybrid applications given that these are locally-acting products. The
applicant has cross referred to Gaviscon Advance Aniseed Suspension, which was
originally authorised to Reckitt Benckiser Healthcare (UK) Limited (PL 00063/0108)
on 29 April 2002, and Gaviscon Advance Peppermint Flavour Oral Suspension (PL
00063/0612), authorised on 11 October 2010. The present applications have been
submitted as extension applications to the applicant’s Marketing Authorisations for
previously granted licences for Acidex Max Strength Heartburn Relief Oral
Suspension (Aniseed Flavour) (PL 04917/0113) and Acidex Max Strength Heartburn
Relief Oral Suspension (Peppermint Flavour) (PL 04917/0114).
These medicinal products act in a physical way. On ingestion the suspension reacts
with gastric acid to rapidly form a raft of alginic acid gel having a near-neutral pH
which floats on the stomach contents effectively impeding gastro-oesophageal reflux
for up to 4 hours, and protecting the oesophagus from acid, pepsin and bile. In severe
cases the raft itself may be refluxed into the oesophagus in preference to the stomach
contents and exert a demulcent effect. In addition in vitro evidence has shown that the
raft has a secondary action and is able to entrap bile and pepsin within it structure,
further protecting the oesophagus from these gastric components.
No new non-clinical or clinical studies were conducted, which is acceptable. The
products are locally-acting oral suspensions containing the same active substances in
the same concentration as the currently authorised reference products. Thus, in
accordance with the Note for Guidance on the Investigation of Bioequivalence
(CPMP/EWP/QWP/1401/98 Rev 1**), the applicant was not required to submit
bioequivalence studies for these applications.
A summary of the pharmacovigilance system and a detailed risk management plan
have been provided with these applications and these are satisfactory.
No new or unexpected safety concerns arose during the review of information provided
by the Marketing Authorisation Holder and it was, therefore, judged that the benefits of
taking Acidex Advance Oral Suspension (Aniseed Flavour) and Acidex Advance Oral
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Suspension (Peppermint Flavour) outweigh the risks and Marketing Authorisations
were granted.
The umbrella name Acidex was accepted as these products contain the same type of
active substances as other Acidex products which have been shown to be equivalent to
Gaviscon products, and this product has the same advantage as Gaviscon Advance in
fact a smaller dose is required, therefore, the name Acidex Advanced oral suspension is
deemed to be acceptable.
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Acidex Advance Oral Suspension (Aniseed Flavour/Peppermint Flavour)
II
PL 04917/0143-0144
QUALITY ASPECTS
II.1 Introduction
The products consist of a white or cream-coloured oral suspension with aniseed or
peppermint flavour. Each 10 ml solution contains 1000 mg sodium alginate and 200
mg potassium hydrogen carbonate, as active ingredients.
Other ingredients consist of the pharmaceutical excipients calcium carbonate,
carbomer, sodium hydroxide, saccharin sodium, ethyl parahydroxybenzoate (E214),
propyl parahydroxybenzoate (E216), butyl parahydroxybenzoate, isopropyl alcohol,
purified water, star anise oil (aniseed flavour) and peppermint oil (peppermint flavour).
All excipients comply with their respective European Pharmacopoeia monographs
and/or in-house specifications. Satisfactory Certificates of Analysis have been
provided for all excipients. Suitable batch analysis data have been provided for each
excipient.
None of the excipients contain materials of animal or human origin.
No genetically modified organisms (GMO) have been used in the preparation of these
products.
The finished products are packaged in amber glass (type III) bottles with white
polypropylene (PP) caps that have a low density polyethylene (LDPE) liner. The pack
sizes are 150 ml, 200 ml, 250 ml, 300 ml (only aniseed flavour) and 500 ml. Not all
pack sizes may be marketed.
Satisfactory specifications and Certificates of Analysis have been provided for all
packaging components.
II.2. Drug Substance
INN:
Sodium alginate
Structural formula:
Molecular formula:
Molecular mass:
Appearance:
Solubility:
(NaC6H7O6)n
216 g/mol
White or pale yellowish-brown coloured powder.
Sodium alginate slowly dissolves in water to form a viscous,
colloidal solution. It is practically insoluble in alcohol.
Synthesis of the active substance from the designated starting materials has been
adequately described.
An appropriate specification is provided for the active substance. Analytical methods
have been appropriately validated and these are satisfactory for ensuring compliance
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with the relevant specifications. Batch analysis data are provided that comply with the
proposed specifications.
Satisfactory Certificates of Analysis have been provided for all working standards.
Suitable specifications have been provided for all packaging used. The primary
packaging has been shown to comply with current guidelines concerning contact with
food.
Appropriate stability data have been provided supporting a suitable retest period when
stored in the proposed packaging.
INN:
Structural formula:
Potassium hydrogen carbonate
Molecular formula: KHCO3
Molecular mass:
100.1 g/mol
Appearance: White or almost white, crystalline powder or colourless crystals.
Solubility:
Potassium hydrogen carbonate is practically in insoluble in ethanol and
freely soluble in water.
Synthesis of the active substance from the designated starting materials has been
adequately described.
Appropriate proof-of-structure data have been supplied for the active substance. All
potential impurities have been identified and monitored appropriately.
An appropriate specification is provided for the active substance. Analytical methods
have been appropriately validated and they are satisfactory for ensuring compliance
with the relevant specifications. Batch analysis data are provided that comply with the
proposed specification.
Satisfactory Certificates of Analysis have been provided for all working standards.
Suitable specifications have been provided for all packaging used. The primary
packaging has been shown to comply with current guidelines concerning contact with
food.
Appropriate stability data have been provided supporting a suitable retest period when
stored in the proposed packaging.
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II.3. Medicinal Product
Pharmaceutical Development
The objective of the development programme was to produce oral suspensions
containing sodium alginate and potassium hydrogen carbonate that could be considered
as a hybrid products of Gaviscon reference products.
A satisfactory account of the pharmaceutical development has been provided.
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 at pilot-scale batch size and shown satisfactory results.
The Marketing Authorisation holder has committed to perform process validation
studies on consecutive full-scale production batches.
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 product in the packaging proposed for marketing. The
data from these studies support a shelf-life of 24 months with storage conditions “Do
not store above 25◦C” and “Do not refrigerate or freeze”. Once the bottle is opened the
product must be used within 3 months.
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.
III
NON-CLINICAL ASPECTS
III.1 Introduction
As the pharmacodynamic, pharmacokinetic and toxicological properties of sodium
alginate and potassium hydrogen carbonate 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 Marketing Authorisation Holder’s (MAH’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.
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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, their use 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
There are no objections to the approval of these applications from a non-clinical
viewpoint.
IV
CLINICAL ASPECTS
IV.1 Introduction
These products act in a physical way forming a raft on the stomach contents and
equivalence to the reference product was demonstrated by pharmaceutical testing.
No new efficacy or safety studies have been performed and none are required for
applications of this type. A comprehensive review of the published literature has been
provided by the applicant, citing the well-established clinical pharmacology, efficacy
and safety of sodium alginate and potassium hydrogen carbonate.
IV.2 Pharmacokinetics
These locally-acting products are to be administered as an aqueous oral suspension
containing the same active substances as the currently approved products. No
bioequivalence study has been submitted with these applications and none is required.
IV.3 Pharmacodynamics
No new pharmacodynamic data were submitted and none were required for
applications of this type.
IV.4 Clinical efficacy
No new efficacy data were submitted and none were required for applications of this
type.
IV.5 Clinical safety
No new safety data were submitted and none were required for these applications.
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IV.6 Risk Management Plan (RMP)
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 Acidex Advance Oral Suspension
(Aniseed Flavour) and Acidex Advance Oral Suspension (Peppermint Flavour).
A summary of safety concerns and planned risk minimisation activities, as
approved in the RMP, is listed below:
Routine pharmacovigilance and routine risk minimisation measures are proposed for
all safety concerns.
IV.7 Discussion on the clinical aspects
There are no objections to the approval of these applications from a clinical viewpoint.
The grant of Marketing Authorisations is recommended for these applications.
V
User consultation
A user consultation with target patient groups on the patient information leaflet (PIL)
has been performed on the basis of a bridging report making reference to Acidex Max
Strength Heartburn Relief Oral Suspension (Aniseed Flavour) and Acidex Max
Strength Heartburn Relief Oral Suspension (Peppermint Flavour) (PL 04917/0113 and
PL 04917/0114). The bridging report submitted by the applicant is acceptable.
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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 sodium alginate and potassium
hydrogen carbonate is considered to have demonstrated the therapeutic value of the
compounds. The benefit-risk 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 Acidex Advance Oral Suspension (Aniseed Flavour) and
Acidex Advance Oral Suspension (Peppermint Flavour) are presented below:
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Acidex Advance Oral Suspension (Aniseed Flavour/Peppermint Flavour)
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STEPS TAKEN AFTER INITIAL PROCEDURE – SUMMARY
The following table lists a non-urgent safety update to the Marketing Authorisation for this product that has been approved by the MHRA since
the product was first licensed. The table lists an update that has been added as an annex to this PAR. This is not a complete list of the postauthorisation changes that have been made to this Marketing Authorisation.
Date submitted
Application type
02/02/2017
Type IB
Scope
To update section 5.1 of the Summaries of Product
Characteristic (SmPC) in line with the reference
products (Gaviscon Advance Aniseed and
Peppermint Flavour
Outcome
Approve
24/02/2017
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Annex 1
Our Reference:
Product (s):
PL 04917/0143, Application 0004
PL 04917/0144, Application 0004
Acidex Advance Relief Oral Suspension (Aniseed Flavour)
Acidex Advance Relief Oral Suspension (Peppermint
Flavour)
Marketing Authorisation Holder:
Active Ingredient(s):
Pinewood Laboratories Limited
Sodium alginate and potassium hydrogen carbonate
Type of Procedure:
Submission Type:
Submission Category:
Submission Complexity:
EU Procedure Number (if applicable):
National
Variation
Type IB
Standard
Not applicable
Reason:
To update Section 5.1 of the Summaries of Product Characteristic (SmPCs) in line with the reference
products (Gaviscon Advance Aniseed and Peppermint Flavour).
Supporting Evidence
Revised SmPCs fragments
Evaluation
The proposed changes to the SmPCs are considered satisfactory.
Conclusion
The proposed changes to the SmPCs are considered acceptable and there are no objections to approval.
In accordance with Directive 2010/84/EU, the SmPCs and PILs for products granted Marketing
Authorisations at a national level are available on the MHRA website.
Decision
Approved on 24 February 2017
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