POTASSIUM NITRATE AND SODIUM FLUORIDE 5/0.315% W/W TOOTHPASTE PL 00036/ UKPAR TABLE OF CONTENTS

Transcription

1 POTASSIUM NITRATE AND SODIUM FLUORIDE 5/0.315% W/W TOOTHPASTE PL 00036/ 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 1

2 POTASSIUM NITRATE AND SODIUM FLUORIDE 5/0.315% W/W TOOTHPASTE PL 00036/ 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. 2

3 POTASSIUM NITRATE AND SODIUM FLUORIDE 5/0.315% W/W TOOTHPASTE PL 00036/ 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 3

4 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 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 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. 4

5 PHARMACEUTICAL ASSESSMENT LICENCE NO: PL 00036/ PROPRIETARY NAME: Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste COMPANY NAME: Stafford-Miller Limited E.C. ARTICLE: Article 10c of Directive 2001/83/EC LEGAL STATUS: GSL 1 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. 5

6 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 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 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. 6

7 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. 7

8 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. 8

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. 9

10 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 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. 10

11 POTASSIUM NITRATE AND SODIUM FLUORIDE 5/0.315% W/W TOOTHPASTE PL 00036/ STEPS TAKEN FOR ASSESSMENT 1 The MHRA received the marketing authorisation applications on 19 October 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/ ) 4 The applicant responded to the MHRA s request, providing further information on 31 July The applications were determined on 08 December

12 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 PHARMACEUTICAL FORM Toothpaste Smooth, glossy slightly milky/translucent white to cream paste at ph CLINICAL PARTICULARS 4.1 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 PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties ATC Code Sodium Fluoride: A01AA01 ATC Code Potassium Nitrate: Not assigned 12

13 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 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 PHARMACEUTICAL PARTICULARS 6.1 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 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. 13

14 7 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/ DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 08/12/ DATE OF REVISION OF THE TEXT 08/12/

15 UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste PL 00063/ 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/ is consistent with this label/leaflet: 15

16 UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste PL 00063/ Label/leaflet: 16

17 UKPAR Potassium Nitrate and Sodium Fluoride 5/0.315% w/w Toothpaste PL 00063/