public assessment report ukpar canesten combi … · this is a summary of the public assessment...

PAR Canesten Combi Pessary & External Cream 500mg / 2% w/w pessary & cream

PL 00010/0653

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Public Assessment Report

UKPAR

Canesten Combi Pessary & External Cream 500mg / 2% w/w pessary & cream

(clotrimazole).

UK Licence No: PL 00010/0653

Bayer plc.


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LAY SUMMARY

Canesten Combi Pessary & External Cream 500mg / 2% w/w pessary & cream

(clotrimazole, pessary 500 mg, cream 2% w/w).

This is a summary of the Public Assessment Report (PAR) for Canesten Combi Pessary & External Cream 500mg / 2% w/w pessary & cream (PL 00010/0653). It explains how Canesten Combi Pessary & External Cream 500mg / 2% w/w pessary & cream 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 Canesten Combi Pessary & External Cream 500mg / 2% w/w pessary & cream. The product will be referred to as Canesten Combi throughout the remainder of this public assessment report. For practical information about using Canesten Combi patients should read the package leaflet or contact their doctor or pharmacist. What is Canesten Combi and what is it used for? Canesten Combi is a full course of treatment for vaginal thrush (candidiasis) because it treats both the internal cause and external symptoms. Some women suffer from recurrent attacks of thrush. To reduce the frequency of these attacks, the sexual partner’s penis can be treated with this cream to prevent re-infection, even if they have no symptoms of thrush. Canesten Combi is a combination pack that contains two co-packaged medicines that are identical to Canesten Thrush Cream (PL 00010/0077) and Canesten 500 mg Pessary (PL 00010/0258). Canesten Combi is identical to Canesten Combi 500mg Pessary and 2% Cream, which was added by variation application to the Marketing Authorisations granted to Bayer plc for the two individual products, Canesten Thrush Cream (PL 00010/0077) and Canesten 500 mg Pessary (PL 00010/0258) on 13 October 2000. How is Canesten Combi used? This combination pack contains a pessary and a cream. The route of administration of the pessary is vaginal and the cream is cutaneous (on the skin). How to use the pessary: Unless directed otherwise by the patient’s doctor, the pessary should be inserted as high as pos sible into the vagina, preferably before going to sleep at night for convenient and comfortable treatment. Since the pessary dissolves in the vagina, it may be helpful to wear a panty liner because it is quite common to notice a white chalky residue after using the pessary. This does not mean that the treatment has not worked. However, if the patient notices pieces of undissolved pessary, they should speak to their doctor or a pharmacist, as the treatment may not have worked properly. How to use the cream: Women: Before use, pierce the tube seal by inverting the cap over the end of the tube and pressing.


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To treat the itching and soreness of the vulva, the cream should be thinly and evenly applied to the area around the entrance of the vagina, 2 or 3 times a day and smoothed in gently. The symptoms of thrush should disappear within three days of treatment. If no improvement is seen after seven days the patient must tell their doctor. Treating the patient’s sexual partner: If the patient’s sexual partner is treated with this cream, the cream should be applied to the end of the penis 2 or 3 times a day for up to two weeks. Please refer to section 3 of the package leaflet for information on how to use this medicine, including diagrams on how to insert the pessary. Canesten Combi can be obtained only with a prescription. For further information on how Canesten Combi is used, refer to the package leaflet and Summaries of Product Characteristics available on the Medicines and Healthcare products Regulatory Agency (MHRA) website. How does Canesten Combi work? The active substance in Canesten Combi is clotrimazole. Clotrimazole belongs to a group of medicines called azoles and is an antifungal agent which fights the cause of infections such as vaginal thrush. What benefits of Canesten Combi have been shown in studies? The application for Canesten Combi is considered to be identical to the previously authorised medicinal product for Canesten Combi 500mg Pessary and 2% Cream which contains the two products Canesten Thrush Cream (PL 00010/0077) and Canesten 500 mg Pessary (PL 00010/0258), with the same benefits and risks, so, no new studies have been provided for Canesten Combi. However, reference is made to the studies for Canesten Combi 500mg Pessary and 2% Cream. The company (Bayer plc) referred to the data provided for the medicinal product Canesten Combi 500mg Pessary and 2% Cream (which contains the two products PL 00010/0258 and PL 00010/0077) as a basis for the grant of an identical licence for Canesten Combi (PL 00010/0653). What are the possible side effects from Canesten Combi? Like all medicines, this medicine can cause side effects, although not everybody gets them. Canesten Combi (PL 00010/0653) is considered to be identical to the previously authorised medicinal product Canesten Combi 500mg Pessary and 2% Cream [which contains the two products Canesten Thrush Cream (PL 00010/0077) and Canesten 500 mg Pessary (PL 00010/0258)] with the same benefits and risks. For a full list of all the side effects reported with Canesten Combi see section 4 of the package leaflet, available on the Medicines and Healthcare products Regulatory Agency (MHRA) website.

Why is Canesten Combi approve d? No new or unexpected safety concerns arose from this application. The MHRA, therefore, considered that the benefits of Canesten Combi outweigh their risks; and the grant of a Marketing Authorisation (licence) was recommended.


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What measures are being taken to ensure the safe and effective use of Canesten Combi? A Risk Management Plan has been developed to ensure that Canesten Combi is used as safely as possible. Based on this plan, safety information has been included in the Summary of Product Characteristics and the package leaflet for Canesten Combi including the appropriate precautions to be followed by healthcare professionals and patients. Known side effects are continuously monitored. Furthermore new safety signals repor ted by patients/healthcare professionals will be monitored/reviewed continuously. Other information about Canesten Combi A Marketing Authorisation was granted in the UK on 23 October 2015. The full PAR for Canesten Combi follows this summary. For more information about treatment with Canesten Combi read the package leaflet, or contact your doctor or pharmacist. This summary was last updated in January 2016 .


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TABLE OF CONTENTS

I Introduction Page 6 II Quality aspects Page 7 III Non-clinical aspects Page 9 IV Clinical aspects Page 9 V User consultation Page 9 VI Overall conclusion, benefit/risk assessment and

recommendation Page 9


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I INTRODUCTION The Medicines and Healthcare products Regulatory Agency (MHRA) granted Bayer plc a Marketing Authorisation for the medicinal product Canesten Combi (PL 00010/0653) on 23 October 2015. The combination product is a prescription-only medicine (POM) for the following use:

• Canesten 500mg Pessary is indicated for the treatment of candidal vaginitis • Canesten External Cream is indicated for the treatment of candidal vulvitis. It should be used as

an adjunct to treatment of candidal vaginitis. The cream can also be used for treatment of the sexual partner’s penis to prevent re-infection.

The application was submitted as an informed consent application according to Article 10c of Directive 2001/83/EC, as amended. The application cross-refers to Canesten Combi 500mg Pessary and 2% Cream which contains Canesten Thrush Cream (PL 00010/0077) and Canesten 500 mg Pessary (PL 00010/0258). This combination pack was added by variation application to the individual Marketing Authorisations for Canesten Thrush Cream (PL 00010/0077) and Canesten 500 mg Pessary (PL 00010/0258) on 13 October 2000. Clotrimazole acts against fungi by inhibiting ergosterol synthesis. Inhibition of ergosterol synthesis leads to structural and functional impairment of the fungal cytoplasmic membrane. Clotrimazole has a broad antimycotic spectrum of action in-vitro and in-vivo, which includes dermatophytes, yeasts, moulds, etc. No new data were submitted nor were necessary to be submitted for this application, as the data are identical to that of the previously granted cross-reference product.


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II QUALITY ASPECTS II.1 Introduction This is an informed consent application for Canesten Combi (PL 00010/0653) submitted under Article 10c of Directive 2001/83/EC, as amended. The application cross-refers to Canesten Combi 500mg Pessary and 2% Cream, which was originally granted a Marketing Authorisation to Bayer plc and which is a combination pack that contains the two individual products, Canesten Thrush Cream (PL 00010/0077) and Canesten 500 mg Pessary (PL 00010/0258) as added by variation application on 13 October 2000. The application is considered valid. II.2. Drug Substance Drug substance specification The proposed drug substance specification is consistent with the details registered for the cross-reference product.

II.3. Medicinal Product Name The proposed product name for this application is Canesten Combi Pessary & External Cream 500mg / 2% w/w pessary & cream (PL 00010/0653). The product has been named in line with current requirements. Strength, pharmaceutical form, route of administrat ion, container and pack sizes Canesten 500mg Pessary contains Clotrimazole 500mg. Canesten External Cream contains Clotrimazole 2% w/w. Each pessary is packed into a blister consisting of 25µm polyamide (PA) / 45µm soft aluminium / 60µm polyvinyl chloride (PVC) and 20µm hard aluminium / 7 grams per square metre heat seal lacquer. The blister and an applicator are enclosed in a cardboard carton. The 10g cream is packed in aluminium tubes with internal lacquer coating, latex stopper and high density polyethylene (HDPE) screw top. The proposed shelf life of the unopened product (pessary and cream) is 36 months with no special storage conditions for the pessary and the storage conditions ‘ Do not store above 25°C’ for the cream. The proposed packaging, shelf-life and storage conditions are consistent with the details registered for the cross-reference product. Legal status On approval, the product will be available as a Prescription Only Medicine (POM). Marketing Authorisation Holder/Contact Persons/Company Bayer plc, Bayer House, Strawberry Hill, Newbury, Berkshire, RG14 1JA, United Kingdom. The Qualified Person (QP) responsible for pharmacovigilance is stated and a satisfactory CV has been provided.


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Manufacturers The proposed manufacturing sites are consistent with those registered for the cross-reference product and evidence of Good Manufacturing Practice (GMP) compliance has been provided. Qualitative and quantitative composition The proposed composition is consistent with the details registered for the cross-reference product. Manufacturing process The proposed manufacturing processes are consistent with the details registered for the cross-reference product and the maximum batch size is stated. Finished product/shelf-life specification The proposed finished product specifications for the cream and pessary are in line with the details registered for the cross-reference product. TSE Compliance With the exception of lactose monohydrate none of the excipients used contain material of animal or human origin. The supplier of lactose monohydrate has confirmed that it is sourced from healthy animals under the same conditions as milk for human consumption. This is consistent with the cross-reference product. Bioequivalence No bioequivalence data are required to support this informed consent application because the proposed product is manufactured to the same formula utilising the same processes as the cross-reference product, Canesten Combi Pessary and 2% Cream. Expert Report The applicant cross-refers to the data for Canesten Combi Pessary and 2% Cream. This is acceptable. Product Name and Appearance See Section II.3 ‘Medicinal Product; Name’ for details of the proposed product name. The appearance of the product is identical to that of the cross-reference product. II.4 Discussion on chemical, pharmaceutical and biological aspects The data submitted with the application is acceptable. The grant of a Marketing Authorisation is recommended.


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III NON-CLINICAL ASPECTS Introduction As this is an informed consent application submitted under Article 10c of Directive 2001/83/EC, as amended, no new non-clinical data have been supplied and none are required. Ecotoxicity/environmental risk assessment (ERA) Suitable justification has been provided for non-submission of an Environmental Risk Assessment. As the application is an identical version of an already authorised product, it is not expected that environmental exposure will increase following approval of the Marketing Authorisation for the proposed product. Discussion on the non-clinical aspects The grant of a Marketing Authorisation is recommended. IV CLINICAL ASPECTS Introduction As this is an informed consent application submitted under Article 10c of Directive 2001/83/EC, as amended, no new clinical data have been supplied and none are required. 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 Canesten Combi. A summary of safety concerns and planned risk minimisation activities, as approved in the RMP, are listed below: Summary table of safety concerns:

Routine pharmacovigilance and routine risk minimisation are proposed for all safety concerns. Discussion on the clinical aspects The grant of a Marketing Authorisation is recommended. V User consultation User-testing of the PIL for Canesten Combi has been accepted based on the bridging report provided by the applicant making reference to the successful user-testing of the PIL for Canesten Pessary and Cream (PL 00010/0300) as the ‘parent PIL’. VI Overall conclusion, benefit/risk assessment and recommendation 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 cross-reference product. Extensive clinical


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experience with clotrimazole is considered to have demonstrated the therapeutic value of the compound. The benefit/risk balance is, therefore, considered to be positive.


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Summaries of Product Characteristics (SmPC), Patient Information Leaflets (PIL) and Labels The Summaries of Product Characteristics and Patient Information Leaflet (PIL) are consistent with the details registered for the cross-reference products. In accordance with Directive 2010/84/EU the Summaries of Product Characteristics (SmPCs) and Patient Information Leaflets (PILs) for products granted Marketing Authorisations at a national level are available on the MHRA website. The approved labelling for Canesten Combi is presented below:


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public assessment report ukpar canesten combi … · this is a summary of the public assessment...

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