UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00036/0307-9
POTASSIUM NITRATE AND SODIUM FLUORIDE 5/0.315%
W/W TOOTHPASTE
PL 00036/0307-9
UKPAR
TABLE OF CONTENTS
Lay Summary
Page 2
Scientific discussion
Page 3
Steps taken for assessment
Page 11
Summary of Product Characteristics
Page 12
Product Information Leaflet/labelling
Page 15
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00036/0307-9
POTASSIUM NITRATE AND SODIUM FLUORIDE 5/0.315%
W/W TOOTHPASTE
PL 00036/0307-9
LAY SUMMARY
On 08 December 2010, the MHRA granted Stafford-Miller Limited Marketing
Authorisations (licences) for the medicinal products Potassium Nitrate and Sodium
Fluoride 5/0.315% w/w Toothpaste (PL 00036/0307-9). These are General Sale
Licence (GSL) medicines.
Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste is formulated to
relieve the pain of sensitive teeth and to protect against the effects of acid erosion. It
also contains fluoride, so it protects against decay like regular toothpaste.
No new or unexpected safety concerns arose from these simple applications and it
was, therefore, judged that the benefits of using Potassium Nitrate and Sodium
Fluoride 5/0.315% w/w Toothpaste outweigh the risks; hence Marketing
Authorisations have been granted.
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00036/0307-9
POTASSIUM NITRATE AND SODIUM FLUORIDE 5/0.315%
W/W TOOTHPASTE
PL 00036/0307-9
SCIENTIFIC DISCUSSION
TABLE OF CONTENTS
Introduction
Page 4
Pharmaceutical assessment
Page 5
Non-clinical assessment
Page 8
Clinical assessment
Page 9
Overall conclusions and risk benefit assessment
Page 10
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00036/0307-9
INTRODUCTION
Based on the review of the data on quality, safety and efficacy, the MHRA granted
Marketing Authorisations for the medicinal products Potassium Nitrate and Sodium
Fluoride 5/0.315% w/w Toothpaste (PL 00036/0307-9) to Stafford-Miller Limited on
the 08 December 2010. The products are available on a General Sales Licence (GSL).
Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste is indicated for the
relief of dentinal hypersensitivity, prevention of dental caries and protection against
the effects of acid erosion of tooth enamel.
This toothpaste contains potassium nitrate and sodium fluoride. Potassium ions are
thought to reduce hypersensitivity by interfering with pulpal nerve conduction.
Sodium fluoride is an established anticaries agent, which prevents dental caries.
Fluoride inhibits caries and acid-erosion of dental enamel and dentine by promoting
tooth remineralisation/rehardening and inhibiting tooth demineralisation/enamel
softening. Fluoride in the oral cavity is incorporated into hydroxyapatite in enamel to
form fluoroapatite. Fluoroapatite is less soluble than hydroxyapatite and more
resistant to acid attack than the original enamel that it replaces. Fluoride also inhibits
the metabolism of acid-producing bacteria that are responsible for caries.
These applications were submitted as simple abridged applications, according to
Article 10c of Directive 2001/83/EC, cross-referring to Sensodyne Pronamel
Toothpaste (PL 00036/0105) also held by Stafford Miller Limited, which was granted
a Marketing Authorisation on 27 November 2007.
No new data were submitted nor were they necessary for these simple applications, as
the data are identical to those of the previously granted cross-reference product.
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00036/0307-9
PHARMACEUTICAL ASSESSMENT
LICENCE NO:
PROPRIETARY NAME:
COMPANY NAME:
E.C. ARTICLE:
LEGAL STATUS:
1
PL 00036/0307-9
Potassium Nitrate and Sodium Fluoride 5/0.315%
w/w Toothpaste
Stafford-Miller Limited
Article 10c of Directive 2001/83/EC
GSL
INTRODUCTION
These are simple, informed consent applications for Potassium Nitrate and Sodium
Fluoride 5/0.315% w/w Toothpaste submitted under Article 10c of Directive
2001/83/EC. The applications cross-refer to Sensodyne Pronamel Toothpaste
(PL 00036/0105), approved on 27 November 2007 to the Marketing Authorisation
Holder Stafford Miller Limited.
The current applications are considered valid.
2
MARKETING AUTHORISATION APPLICATION (MAA)
2.1 Name(s)
The proposed name of the product applications is Potassium Nitrate and Sodium
Fluoride 5/0.315% w/w Toothpaste. The products have been named in-line with
current requirements.
2.2 Strength, pharmaceutical form, route of administration, container and pack
sizes
Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste is presented as a
smooth, glossy slightly milky/transluscent white to cream paste at pH 7.1. It contains
potassium nitrate 5.0% w/w and sodium fluoride 0.315% w/w, and is packaged into
decorated polyethylene barrier laminate tubes with a tamper evident foil seal and a
colour cap in pack sizes of 45, 75 and 100ml.
Not all pack sizes may be marketed. However, the Marketing Authorisation Holder
has committed to submitting mock-ups of the packaging for any pack size to the
relevant regulatory authorities for approval before marketing
The proposed shelf life is 2 years (unopened) with the storage conditions ‘Store below
30°C’. Once opened the product must be used within 6 months. The shelf-life and
storage conditions are identical to those for the reference product and are satisfactory.
2.3 Legal status
The products are General Sale Licence (GSL) medicines.
2.4 Marketing authorisation holder/Contact Persons/Company
The proposed Marketing Authorisation holder is Stafford Miller Limited, 980 Great
West Road, Brentford, Middlesex, TW8 9GS, UK (trading as GlaxoSmithKline
Consumer Healthcare, Brentford, TW8 9GS, UK).
The Qualified Person (QP) responsible for pharmacovigilance is stated and their
Curriculum Vitae (CV) is included.
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00036/0307-9
2.5 Manufacturers
The proposed manufacturing sites are consistent with those registered for the
reference product and evidence of Good Manufacturing Practice compliance has been
provided.
2.6 Qualitative and quantitative composition
The proposed composition is consistent with the details registered for the
cross-reference product.
2.7 Manufacturing process
The proposed manufacturing process is consistent with the details registered for the
cross-reference product and the maximum batch size is stated.
2.8 Finished product/shelf-life specifications
The proposed finished product specifications are in-line with the details registered for
the cross-reference product.
2.9 Drug substance specification
The proposed drug substance specifications are consistent with the details registered
for the cross-reference product.
2.10 TSE Compliance
No materials of human or animal origin have been used in the manufacture of these
products. This is consistent with the reference product.
2.11 Bioequivalence
No bioequivalence data are required to support these informed consent applications, as the
proposed products are manufactured to the same formula utilising the same process as the
cross-reference product, Sensodyne Pronamel Toothpaste (PL 00036/0105).
3
EXPERT REPORT
The applicant has included a detailed pharmaceutical expert report, written by an
appropriately qualified person.
4.
PRODUCT NAME & APPEARANCE
See 2.1 for details of the proposed product names. The appearance of the products is
identical to that of the cross-reference product.
5.
SUMMARY OF PRODUCT CHARACTERISTICS (SmPC)
The proposed SmPCs are consistent with the details registered for the cross-reference
product.
6.
PATIENT INFORMATION LEAFLET (PIL)/LABELLING
PIL
No PIL has been provided. There is no package leaflet for this medicinal product as
all relevant information has been included on the labelling.
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00036/0307-9
Labelling
The labelling texts are satisfactory. The patient information supplied in the labelling is
identical to that for the reference product, Sensodyne Pronamel Toothpaste, apart
from the name. The patient information for Sensodyne Pronamel Toothpaste has been
prepared in accordance with the requirements of Articles 59(3) and 61(1) of Directive
2001/83/EC, as amended, and has undergone user testing. No further user testing is
therefore required in support of the labelling text supplied with this application.
The MAH has submitted text versions only and has committed to submitting mock-up
packaging to the relevant regulatory authorities for approval before packs are
marketed.
7.
CONCLUSIONS
The data submitted with the applications are acceptable. The grant of Marketing
Authorisations is recommended.
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00036/0307-9
NON-CLINICAL ASSESSMENT
As these applications are identical to the cross-reference product Sensodyne Pronamel
Toothpaste (PL 00036/0105), no new non-clinical data have been supplied with these
applications and none are required. A non-clinical expert report has been written by a
suitably qualified person and is satisfactory.
A suitable justification has been provided for non-submission of an environmental
risk assessment. As these applications are for products that are identical to products
already marketed, no increase in environmental burden is anticipated from the
marketing of these products.
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00036/0307-9
CLINICAL ASSESSMENT
As these applications are identical to the cross-reference product Sensodyne Pronamel
Toothpaste (PL 00036/0105), no new clinical data have been supplied with these
applications and none are required. A clinical expert report has been written by a
suitably qualified person and is satisfactory.
The Marketing Authorisation Holder has provided a suitable pharmacovigilance
system that fulfils the requirements and provides adequate evidence that the
Marketing Authorisation Holder has the services of a qualified person responsible for
pharmacovigilance, and has the necessary means for the notification of any adverse
reaction suspected of occurring either in the Community or in a third country.
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00036/0307-9
OVERALL CONCLUSION AND BENEFIT/RISK ASSESSMENT
QUALITY
The data for these applications 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 applications of
this type.
EFFICACY
These applications are identical to the previously granted application for Sensodyne
Pronamel Toothpaste (PL 00036/0105), granted to Stafford Miller Limited on
27 November 2007.
SAFETY
No new or unexpected safety concerns arose from these applications.
PRODUCT LITERATURE
The approved SmPC is satisfactory and consistent with the details registered for the
cross-reference product.
No Patient Information Leaflet has been provided as the labelling text includes all the
relevant information that would be presented in the PIL. The information stated in the
labelling text is satisfactory and consistent with the SmPC.
The user-testing of the labelling text has been accepted based on bridging to the
successful user-testing of the patient information for ‘Sensodyne Pronamel
Toothpaste’ (PL 00036/0105). The bridging is accepted.
BENEFIT/RISK ASSESSMENT
The quality of the products is acceptable and no new non-clinical or clinical safety
concerns have been identified. The applicant’s products are identical to the reference
product. Extensive clinical experience with potassium nitrate and sodium fluoride is
considered to have demonstrated the therapeutic value of the compounds. The
benefit/risk is, therefore, considered to be positive.
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00036/0307-9
POTASSIUM NITRATE AND SODIUM FLUORIDE 5/0.315%
W/W TOOTHPASTE
PL 00036/0307-9
STEPS TAKEN FOR ASSESSMENT
1
The MHRA received the marketing authorisation applications on 19 October
2009
2
Following standard checks and communication with the applicant the MHRA
considered the applications valid on 06 November 2009 (PL 00036/0307-8) and
09 November 2009 (PL 00036/0039)
3
Following assessment of the applications the MHRA requested further
information on 05 February 2010 (PL 0036/00309 only) and 03 March 2010 (PL
00036/00307-8)
4
The applicant responded to the MHRA’s request, providing further information
on 31 July 2010.
5
The applications were determined on 08 December 2010
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00036/0307-9
SUMMARY OF PRODUCT CHARACTERISTICS
1
NAME OF THE MEDICINAL PRODUCT
Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
2
QUALITATIVE AND QUANTITATIVE COMPOSITION
Potassium Nitrate 5.0% w/w
Sodium Fluoride 0.315% w/w (1450 ppm fluoride)
For full list of excipients, see section 6.1
3
PHARMACEUTICAL FORM
Toothpaste
Smooth, glossy slightly milky/translucent white to cream paste at pH 7.1
4
4.1
CLINICAL PARTICULARS
Therapeutic indications
Relief of dentinal hypersensitivity
Prevention of dental caries
Protection against the effects of acid erosion of tooth enamel
4.2
Posology and method of administration
For dental use
Use 2-4 times a day, in place of ordinary toothpaste
4.3
Contraindications
Known allergic reactions to any of the active ingredients or excipients.
4.4
Special warnings and precautions for use
Sensitive teeth may indicate an underlying problem which needs prompt care by a dentist. See
your dentist as soon as possible for advice.
For children under 6, use a pea-sized amount and supervise brushing to minimise swallowing.
If using fluoride supplements consult your dentist.
4.5
Interaction with other medicinal products and other forms of interaction
None known
4.6
Pregnancy and lactation
No adverse effects known
4.7
Effects on ability to drive and use machines
None known
4.8
Undesirable effects
Very rarely, isolated cases of hypersensitivity type reactions such as angioedema, oral and
facial swelling have been reported in patients using potassium nitrate containing toothpastes,
particularly in patients who are predisposed to hypersensitivity type reactions.
4.9
Overdose
No symptoms of overdose are known
5
5.1
PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties
ATC Code Sodium Fluoride: A01AA01
ATC Code Potassium Nitrate: Not assigned
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00036/0307-9
Potassium ions are thought to reduce hypersensitivity by interfering with pulpal nerve
conduction.
Sodium fluoride is an established anticaries agent, which prevents dental caries. Fluoride
inhibits caries and acid-erosion of dental enamel and dentine by promoting tooth
remineralisation/rehardening and inhibiting tooth demineralisation/enamel softening. Fluoride
in the oral cavity is incorporated into hydroxyapatite in enamel to form fluoroapatite.
Fluoroapatite is less soluble than hydroxyapatite and more resistant to acid attack than the
original enamel that it replaces. Fluoride also inhibits the metabolism of acid-producing
bacteria which are responsible for caries.
Dental type silicas act as polishing and cleaning agents to assist in the removal of food
remnants from the teeth. The grade of silica in the product provides an abrasivity level which
is low relative to most other toothpastes, but is within that recommended in the International
Standard ISO 11609 for dentifrice products.
5.2
Pharmacokinetic properties
The product is applied topically and so the pharmacokinetics of the active ingredients are not
relevant to its efficacy.
5.3
Preclinical safety data
The active ingredients in the product are commonly used and well established. Their safety is
supported by numerous published studies. Many years of clinical experience with the use of
these substances in man supports the opinion that they have a favourable safety profile.
6
6.1
PHARMACEUTICAL PARTICULARS
List of excipients
Purified Water
Sorbitol, Liquid (non-crystallising)
Silica, Dental Type
Glycerol
Macrogols
Xanthan Gum
Titanium Dioxide (E171)
Cocamidopropyl Betaine
Saccharin Sodium
Sodium Hydroxide
Mint Flavour 10926
6.2
Incompatibilities
Not applicable
6.3
Shelf life
2 years.
After opening: 6 months
6.4
Special precautions for storage
Store below 30°C
6.5
Nature and contents of container
The product will be packaged in the following containers and pack sizes:
Pack Type
Pack Size (ml)
Decorated polyethylene barrier laminate tube
45, 75, 100
with a tamper evident foil seal and a colour cap
Not all pack sizes may be marketed
6.6
Special precautions for disposal
No special precautions.
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
7
PL 00036/0307-9
MARKETING AUTHORISATION HOLDER
Stafford Miller Limited
980 Great West Road
Brentford
Middlesex
TW8 9GS
United Kingdom
Trading as: GlaxoSmithkline Consumer Healthcare, Brentford, TW8 9GS, U.K.
8
MARKETING AUTHORISATION NUMBER(S)
PL 00036/0307
PL 00036/0308
PL 00036/0309
9
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
08/12/2010
10
DATE OF REVISION OF THE TEXT
08/12/2010
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00063/0307-9
PATIENT INFORMATION LEAFLET AND LABELLING
The following label/leaflet for PL 00036/0307 is included as a representative example label/leaflet. The text proposed
for PL 00036/0308-9 is consistent with this label/leaflet:
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00063/0307-9
Label/leaflet:
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UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste
PL 00063/0307-9
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