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`CURANAIL 5% NAIL LACQUER (AMOROLFINE HYDROCHLORIDE)
`PL 10590/0049
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`UKPAR
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`TABLE OF CONTENTS
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`Page 2
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`Page 3
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`Page 20
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`Page 21
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`Page 22
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`Page 27
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`Page 30
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`Lay Summary
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`Scientific discussion
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`Steps taken for assessment
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`Steps taken after authorisation – summary
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`Summary of Product Characteristics
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`Product Information Leaflet
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`Labelling
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`FlatWing Ex. 1028, p. 1
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`CURANAIL 5% NAIL LACQUER
`PL 10590/0049
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`LAY SUMMARY
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`The MHRA granted Galderma (UK) Limited a Marketing Authorisation (licence) for the
`medicinal product Curanail 5% nail Lacquer (PL 15909/0049) on 7th April 2006. This
`medicine which is available from Pharmacies is used to treat mild fungal infections of the nail
`in up to 2 nails.
`
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`Curanail 5% Nail Lacquer contains the active ingredient amorolfine (as the hydrochloride),
`which is one of a group of medicines known as anti-fungals, which kill a wide variety of fungi
`which can cause infections.
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`This new product is a duplicate of a previously granted application for Loceryl Nail Lacquer
`5% (PL 10590/0042) held by Galderma (UK) Limited which is available on prescription for
`more serious fungal nail infections. Curanail 5% Nail Lacquer is for milder fungal infections
`of the nail and has been granted a different legal supply classification, which means it can be
`sold in pharmacies.
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`No new or unexpected safety concerns arose from these applications. It was, therefore, judged
`that the benefits of Curanail 5% Nail Lacquer being available from a pharmacy outweigh the
`risks. Hence a Marketing Authorisation has been granted.
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`MHRA PAR – Curanail 5% Nail Lacquer PL 10590/0049 - 2 -
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`FlatWing Ex. 1028, p. 2
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`CURANAIL 5% NAIL LACQUER
`PL 10590/0049
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`SCIENTIFIC DISCUSSION
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`TABLE OF CONTENTS
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`Introduction
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`Pharmaceutical assessment
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`Preclinical assessment
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`Clinical assessment
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`Overall conclusions and risk benefit assessment
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`Page 4
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`Page 5
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`Page 6
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`Page 7
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`Page 19
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`MHRA PAR – Curanail 5% Nail Lacquer PL 10590/0049 - 3 -
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`FlatWing Ex. 1028, p. 3
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`INTRODUCTION
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`
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`The UK granted a marketing authorisation for the medicinal product Curanail 5% Nail
`Lacquer (PL 10590/0049) to Galderma (UK) Limited on 7th April 2006. The product is
`available in Pharmacies (P).
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`The application was submitted according to article 10.c [formerly article 10.1(a)(i)] of
`Directive 2001/83/EC, cross-referring to Loceryl Nail Lacquer 5% (PL 10590/0042). The
`cross-reference application was granted on 19th April 1999 as a change of ownership from PL
`00031/0285, held by Roche Products Limited which was itself granted a marketing
`authorisation for on 4th July 1991.
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`No new quality data was submitted nor was it necessary for this simple application, as the
`data is 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 public
`assessment report was generated for it.
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`The product contains the active ingredient amorolfine hydrochloride which is a broad
`spectrum topical antimycotic agent that has both fungistatic and fungicidal activity against all
`pathogens of nail mycosis. The product is indicated for the treatment of mild cases of distal
`and lateral subungual onychomycoses caused by dermatophytes, yeasts and moulds limited up
`to 2 nails.
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`MHRA PAR – Curanail 5% Nail Lacquer PL 10590/0049 - 4 -
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`FlatWing Ex. 1028, p. 4
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`PHARMACEUTICAL ASSESSMENT
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`This abridged simple application is associated with a reclassification application – see
`medical assessment for the joint medical/ pharmaceutical assessment.
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`The company has submitted an expert statement confirming that all pharmaceutical aspects
`are the same as the cross reference product. The Marketing Authorisation Application form
`has been updated to reflect the current granted licence. The Drug Substance Specification,
`method of manufacture and Finished Product Specification are consistent with the current
`granted MA and this is satisfactory
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`Conclusion
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`This MA may be approved as a P product.
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`PRECLINICAL ASSESSMENT
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`No new preclinical data have been supplied with this application and none are required for
`applications of this type.
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`CLINICAL ASSESSMENT
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`BACKGROUND
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`INTRODUCTION
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`1.
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`Galderma UK LTD have submitted an abridged application requesting a POM to P
`reclassification for Curanail 5% Lacquer containing amorolfine hydrochloride. It is proposed
`that the product will be used to treat onychomycosis affecting the distal nail plate caused by
`dermatophytes, yeasts and moulds in adults aged 18 years and over with a pack size of 3ml.
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`Treatment should be without interruption until the nail has regenerated and the affected areas
`are finally cured. The required frequency and duration of treatment depends on intensity and
`localisation of the infection. In general, it is 6 months for finger nails and 9-12 months for toe
`nails. A review of treatment is recommended at intervals of 3 months.
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`The abridged application is submitted under Article 10.c [formerly article 10.1 (a) (i)] as a so
`called “informed consent application” cross referring to the previously authorised product
`Loceryl Nail Lacquer 5 % (PL 10590/0042).
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`2.
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`Loceryl Nail Lacquer was initially authorised in 1991 and marketed by Roche UK from that
`year. The product is authorised in about sixty countries worldwide, in four of which it is
`available over-the-counter. In Austria and Singapore it was reclassified in 1993 and in
`Germany and Australia it was made available OTC in 1997.
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`In the UK amorolfine hydrochloride is only available as a prescription medicine. This is the
`first application for pharmacy availability of a product containing this ingredient.
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`Amorolfine is a broad spectrum topical antimycotic agent that has both fungistatic and
`fungicidal activity against all pathogens of nail mycosis. It is a morpholine derivative that
`acts on enzymes involved in ergosterol synthesis in the fungal cell wall leading to changes in
`membrane permeability and disruption of key fungal metabolic processes.
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`In 1998 the House of Lords Select Committee on Science and Technology report on
`resistance to antibiotics and other anti-microbial agents noted the possibility that wider
`availability of anti-fungal agents without prescription might contribute to the development of
`resistance. Following this, the (then) MCA reviewed the issue of resistance related to the
`legal status of anti-fungal medicines in a paper considered by CSM in October 1999. This
`review concluded:
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`“Although the level of fungal drug resistance is currently thought to be below that
`observed with bacteria, increased use of anti-fungal agents would lead to increased
`selective pressure and probably more widespread resistance.”
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`However, it was noted that there was little robust evidence that non-prescription use of topical
`anti-fungal agents had been associated with the emergence of resistance.
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`Other topical antifungal products are already available either as Pharmacy or GSL medicines
`including clotrimazole, miconazole, terbinafine, econazole and sulconazole. These are
`indicated for fungal skin infections due to dermatophytes, yeasts, moulds and other fungi,
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`MHRA PAR – Curanail 5% Nail Lacquer PL 10590/0049 - 7 -
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`PHARMACEUTICAL COMMENT
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`such as ringworm, athlete’s foot, intertrigo, fungal nappy rash, candidal vulvitis and vaginitis.
`Treatment is generally from one to three weeks in duration.
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`3.
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`3.1 Marketing Authorisation Application (MAA)
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`The MAA is being assessed separately and in parallel with this reclassification application.
`There are no issues relating to the abridged application which impinge on the reclassification
`application. The applicant has provided suitable reassurance that there are no differences in
`the chemistry and pharmacy data between this product and the cross reference product.
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`3.2 Pack Size
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`The proposed pack size for the pharmacy product is 3ml. This is smaller than the current,
`marketed POM pack of 5ml.
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`The applicant estimates that the pack would last for three months if used once a week on four
`nails. If only two nails were affected it could last up to six months. The duration of treatment
`is usually six months for finger nails and nine to twelve months for toe nails.
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`It is likely therefore that if toe nails are affected, a repeat supply may be necessary.
`Individuals seeking a repeat purchase will be asked about duration of treatment so far and if
`necessary the pharmacist will recommend a treatment review.
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` A
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` review of treatment after 3 months is recommended. If, however, there is sufficient product
`remaining in the pack after 3 months, it is possible that users may not return to discuss
`progress with their pharmacist.
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`Assessor’s comment
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`The proposed pack size of 3ml is considered acceptable. The patient information
`leaflet should include information about the importance of a 3 monthly review with the
`pharmacist, and what to do it the condition does not improve.
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`4. MEDICAL ASSESSMENT OF SUITABILITY FOR PHARMACY AVAILABILITY
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`The expert report in support of the pharmacy availability of amorolfine nail lacquer was
`signed by an independent pharmaceutical and clinical physician. Further information has been
`supplied on the subject of resistance and is considered acceptable.
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`4.1 Rationale for treatment
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`Onychomycosis is sometimes misunderstood to be a trivial cosmetic problem that does not
`merit treatment. However, the condition has high prevalence as a result of heavy
`contamination of communal bathing places by infected users. The applicant claims that the
`high prevalence of the disease justifies the rationale of treatment to reduce the number of
`infections. Onychomycosis should not therefore be considered a trivial disease, and there is a
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`sound case for treatment on the grounds of public health considerations and effect on quality
`of life.
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`Assessor’s comment
`This is acceptable.
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`4.2 Management of onychomycosis
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`Onychomycosis can be treated with oral and topical agents. Systemically active agents can
`achieve more thorough penetration of the nail, thus leading to better cure rates. However, oral
`treatment can cause side effects such as gastrointestinal disturbances and increases in liver
`enzymes. The risk of systemic side effects and the lengthy duration of treatment required for
`optimum efficacy mean that systemic therapy is often reserved for severe or relapsing cases,
`for difficult to treat infections and for patients with immunologic disorders or debilitating
`diseases.
`
`The advantage of topical anti-mycotic agents is that the potential for undesirable systemic
`effects and drug interactions are very limited.
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`Assessor’s comment
`Systemic therapy is almost always more successful than topical treatment, which should
`only be used in mild cases of onychomycosis where nail dystrophy and complete nail plate
`destruction do not occur. However, among topical treatments amorolfine nail lacquer is the
`most effective preparation. It has been shown to be effective in 50% of cases of both
`fingernail and toenail infections.
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`4.3 Indication
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`The applicant is proposing that Curanail Lacquer be sold for the indication “onychomycosis
`affecting the distal nail plate caused by dermatophytes, yeast and moulds”. The approved
`indication for the POM product is “onychomycosis caused by dermatophytes, yeast and
`moulds”. Thus, the applicant is proposing to restrict the indication to distal onychomycosis.
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`There are four clinical types of onychomycosis. The most common form is disto-lateral
`subungual onychomycosis (DLSO), when the nail bed is affected. DLSO is usually caused by
`Trichophyton rubrum. The second form is superficial white onychomycosis (SWO), which
`accounts for 10% of cases. This infection is caused by Trichophyton mentagrophytes, which
`directly invades the superficial layers of the nail plate. Proximal subungual onychomycosis is
`the least common type in otherwise healthy individuals. It is more common in
`immunocompromised patients and is a clinical marker for HIV infection. Vascular disease
`and diabetes also may present in this way. The fourth form is candidal onychomycosis.
`Candida species may invade nails previously damaged by infection or trauma.
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`All these varieties of onychomycosis may eventually progress to total nail dystrophy where
`the nail plate is almost completely destroyed.
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`Assessor’s comment
`According to BNF, PRODIGY and Guidelines for Treatment of Onychomycosis by the
`British Association of Dermatologist topical antifungal therapy is recommended for the
`treatment of mild cases of DLSO where the infection is confined to the distal edge of the
`MHRA PAR – Curanail 5% Nail Lacquer PL 10590/0049 - 9 -
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`FlatWing Ex. 1028, p. 9
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`nail. BNF suggests topical treatment with amorolfine in cases when up to two nails are
`affected.
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`The indication of the P product should be restricted to patients with early onychomycosis
`when involvement is limited to mild distal disease in up to 2 nails.
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`4.4 Posology
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`The posology for the approved POM product is once weekly. The SPC states that “twice
`weekly application may prove beneficial in some cases”. For the proposed P product the
`posology is once weekly. Thus the applicant is proposing to delete the sentence “Twice
`weekly application may prove beneficial in some cases” and retain only the once weekly
`administration in section 4.2. in the SPC.
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`In an open, randomized study 456 patients with onychomycosis were treated once or twice
`weekly for up to 6 months with amorolfine. Overall cure rates for those treated twice weekly
`compare to those treated once weekly were 54.2% vs. 46.0% (p=0.4). Clinical cure or
`improvement was achieved 74 and 68% of patients receiving twice- and once-weekly
`treatment, respectively. The mycological cure rate was 76.1% for twice-weekly treatment and
`70.6% for once-weekly treatment.
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`Assessor’s comment
`Based on these clinical data once weekly administration of amorolfine 5% lacquer in mild
`cases of DLSO seems to be justified.
`
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`It should be noted that patients with severe impairment of peripheral circulation were
`excluded from this study. There are several underlying conditions, which predispose for
`fungal
`nail
`infection
`including
`impaired
`circulation,
`diabetes mellitus,
`immunosuppression. Since these patients need regular supervision of their underlying
`condition from a doctor, they should be excluded from the P supply of amorolfine.
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`4.5 Safety
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`4.5.1 First POM criterion:
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`• A direct or indirect danger exists to human health, even when used correctly, if
`utilised without medical supervision
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`4.5.1.1 Safety related to misdiagnosis
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`Onychomycotic changes to the nail usually have specific characteristics that can be easily
`recognised. DLSO can be quickly and simply recognised by individuals by the very
`characteristic progress of the infection. According to PRODIGY fungal infections of the nail
`is characterised by nail thickening and discoloration. The texture of the nail changes and the
`nail may be soft and easily broken.
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`Pharmacists will be given comprehensive training and educational materials to assist
`diagnosis in those individuals who present to a pharmacy. The pharmacy protocol gives
`guidance on how to recognise and distinguish the most commonly found nail disorders. If
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`there is any doubt on diagnosis, pharmacists will be advised to refer individuals to their GP
`for a full consultation and diagnostic screen.
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`The leaflet contains pictures of infected nails, which also help patients in the identification of
`the condition.
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`All individuals receiving Curanail Lacquer are advised to return for regular 3 monthly
`treatment reviews. One of the purposes of the review is to ensure that the treatment is
`appropriate for the condition.
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`Approximately 50% of nail abnormalities are caused by fungus. The remaining 50% are
`caused by a variety of disorders. These include inflammatory skin disease such as psoriasis,
`eczema and trauma. Often these conditions are associated with other symptoms involving the
`skin and or nail that can distinguish them from fungal infections.
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`Assessor's comment
`PRODIGY and Guidelines for Treatment of Onychomycosis by the British Association of
`Dermatologist state that the diagnosis of onychomycosis should be confirmed by mycology
`before the treatment is commenced. However, in current general practice the diagnosis is
`based on the clinical picture alone. Other conditions similar to nail infection are
`accompanied by skin symptoms, which can help in the differential diagnosis.
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`is used
`is misdiagnosed and Curanail Lacquer
`if onychomycosis
`Moreover,
`inappropriately, the risk to health is negligible, either directly through use of treatment, or
`indirectly through lack of treatment of the disorders mistaken for onychomycosis.
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`4.5.1.2 Resistance
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`Amorolfine is a broad spectrum antimycotic agent with both fungistatic and fungicidal
`activity against all pathogens of nail mycosis.
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`Little specific data are available which demonstrate either an issue of acquired resistance with
`amorolfine, or similar products treating this indication.
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`Fungal resistance can be one of the reasons of treatment failure of antifungal drugs. However,
`currently there is very little data to suggest that resistance to antifungal agents is a problem.
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`Resistance can be considered to be more of a problem when it involves clinically important
`microbes. Fungal infections of the toe nails are mainly due to dermatophytes, which are not
`associated with clinically serious infections. Resistance in moulds is not common and
`generally, if resistance is found it is intrinsic and not acquired. Infections of the finger nails
`can be caused by yeasts such as Candida species. There has not been any increase noted in
`resistance despite many OTC antifungal being available to treat Candida infections.
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`Assessor's comment
`Despite the lack of specific data on resistance to topically administered amorolfine, since
`amorolfine is not used for systemic treatment of fungal infections, resistance is not
`considered be a major issue.
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`4.5.1.3 Safety profile of amorolfine
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`FlatWing Ex. 1028, p. 11
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`Amorolfine has a good safety profile with very few side effects reported in clinical studies or
`in use as a POM medicine. The most frequently reported adverse events are nail disorders and
`skin irritations.
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`The absorption of amorolfine to the systemic circulation through nail is negligible. The
`plasma concentration of amorolfine in patients receiving twice weekly applications of
`amorolfine nail lacquer for up to 12 months was measured in two studies. At the end of
`treatment, the majority of patients had no detectable plasma concentrations of amorolfine and
`others had concentrations of only between 0.1 and 0.3 ng/ml.
`
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`Assessor's comment
`Between 1991 and 2004 there are 26 reports dealing with 38 reactions for amorolfine on
`the ADROIT database.
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`The clinical pharmacology of the product assumes negligible systemic side effects of
`amorolfine lacquer.
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`
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`4.5.2 Second POM criterion:
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`• There is frequent incorrect use which could lead to a direct or indirect danger to
`human health.
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`The product information clearly describes the method of administration. Therefore, it is
`unlikely that the product will be used incorrectly.
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`To avoid reoccurrence the treatment should be continued until the infected section of the nail
`has fully grown out. This may take up to 12 months for toenails and individuals may not
`experience improvement in their conditions before 3 months. With such a long duration of
`treatment, it is important to maintain patient compliance. Review of the treatment at 3
`monthly intervals serves as an opportunity to help with this.
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`4.5.2.1 Safety related to misuse or abuse
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`Amorolfine is not considered to be a drug of abuse.
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`4.5.2.2 Overdosing - accidental or deliberate
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`There have been isolated reports of individuals applying amorolfine nail lacquer more
`frequently than it is recommended. Moreover, it is unlikely that this kind of overdosing can
`lead any serious consequences.
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`4.5.3 Third POM criterion:
`
`
`•
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`It is a substance the activity and/or side effects of which require further investigation
`
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`Amorolfine is not a substance which requires further investigation. No concerns arise in
`regard to this criterion.
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`PHARMACY PROTOCOL AND TRAINING
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` 5
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`FlatWing Ex. 1028, p. 12
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`The Pharmacy Protocol and Training proposals have been prepared by a suitably qualified
`person. The aim is to provide suitable background and educational material for pharmacists
`and medicines counter assistants.
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`The material includes background information on onychomycosis, amorolfine and the SPC
`for Curanail, together with more detailed information on:
`
`
`• Whether the condition is suitable for treatment with Curanail
`• Whether the product is suitable for the customer
`• Advice on initial supply of the product
`• Advice while using the product
`• Other strategies to combat or prevent onychomycosis
`
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`Assessor’s comment
`The proposals are acceptable.
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`PRODUCT INFORMATION
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` 6
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`Certain changes were made to the product information (SPC, PIL and labelling) to reflect the
`non-prescription use of the product.
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`DISCUSSION
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` 7
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`
`
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`The high prevalence of onychomycosis justifies the rationale of the treatment of the condition.
`Onychomycosis should not therefore be considered a trivial disease, and should be treated to
`reduce the number of the condition and increase quality of life.
`
`Although systemic therapy is almost always more successful than topical treatment in the
`management of onychomycosis, topical treatment has proved to be effective in the mild cases
`of onychomycosis. Among topical treatments amorolfine nail lacquer is the most effective
`preparation.
`
`Amorolfine has a good safety profile with very few side effects reported in clinical studies or
`in use as a POM medicine. The clinical pharmacology of the product assumes minimal
`systemic side effects of amorolfine lacquer. The most frequently reported adverse events are
`nail disorders and skin irritations.
`
`According to BNF, PRODIGY and Guidelines for Treatment of Onychomycosis by the British
`Association of Dermatologist topical antifungal therapy is recommended for the treatment of
`mild cases of DLSO when up to two nails are affected. Based on this, the indication of the P
`product should be restricted to patients with early onychomycosis when involvement is limited
`to mild distal disease in up to 2 nails.
`
`There are several underlying conditions, which predispose for fungal nail infections including
`impaired circulation, diabetes mellitus, and immunosuppression. Since these patients need
`
`MHRA PAR – Curanail 5% Nail Lacquer PL 10590/0049 - 13 -
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`FlatWing Ex. 1028, p. 13
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`regular supervision of their underlying condition from a doctor, they should be excluded from
`the P supply of amorolfine.
`
`Although according to guidelines the diagnosis of onychomycosis should be confirmed by
`mycology before antifungal treatment is commenced, this does not reflect current general
`practice where diagnosis is established based on the clinical picture alone. Furthermore, if
`onychomycosis is misdiagnosed and Curanail Lacquer is used inappropriately, the risk to
`health is negligible, either directly through use of treatment, or indirectly through lack of
`treatment of the disorders mistaken for onychomycosis.
`
`There is little specific data available on resistance to topically administered amorolfine.
`Available resistance data to antifungals used for nail infections do not raise any concern over
`the issue of resistance. Furthermore, the fact that amorolfine is not used for systemic
`treatment of fungal infections, gives further reassurance.
`
`The treatment should be continued without interruption until the nail is regenerated and the
`affected areas are finally cured. In general, it is six months in case of finger nails and nine to
`twelve months for toe nails. Re-occurrence of onychomycosis can only be avoided when both
`the fungi and the spores are eliminated, which will only occur once the infected section of the
`nail has fully grown out. With such a long duration of treatment, it is important to warn
`patients to use the product correctly. Treatment review at 3 monthly intervals serves as an
`opportunity to maintain patient compliance.
`
` 8
`
`
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`CONCLUSION
`
`
`The advice of the Committee is sought on whether amorolfine nail lacquer for the treatment of
`mild cases of disto-lateral subungual onychomycosis caused by dermatophytes, yeasts and
`moulds limited up to 2 nails may safely be supplied without prescription.
`
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`MHRA PAR – Curanail 5% Nail Lacquer PL 10590/0049 - 14 -
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`FlatWing Ex. 1028, p. 14
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`COMMITTEE ON SAFETY OF MEDICINES RECOMMENDATION –
`14th April 2005
`
`
`
`The UK Advisory Committee considered whether Curanail 5% Lacquer containing
`amorolfine 5% falls within a description or class specified for the purpose of Section 58 of the
`Medicines Act 1968 by Order made under Section 58(1) as being appropriate for supply on a
`Prescription Only basis in accordance with Section 58(A)(2) of that Act, and advised that the
`product could be available for non-prescription supply, under the following conditions:
`
`
`• Treatment of onychomycosis affecting the distal nail plate of not more than 2 nails,
`caused by dermatophytes, yeasts and moulds in adults aged 18 years and over
`• Maximum strength 5%
`• Maximum pack size 3ml of product.
`
`
`Additionally, a number of points relating to the Summary of Product Characteristics, Product
`Information Leaflet and labelling were raised. The applicant agreed to the changes.
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`EXTERNAL CONSULTATION PROCESS
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`ARM 31 proposing pharmacy availability of Curanail Lacquer was issued on 18 July 2005
`with a deadline for comments of 30 August 2005.
`
`There were 20 responses, of which 15 were in favour, 1 against the proposal, 1 neither for
`nor against and 3 with no comment.
`
`Those organisations in favour included the Royal College of General Practitioners, Royal
`College of Physicians, Royal Pharmaceutical Society of Great Britain, National Pharmacy
`Association and other pharmacy organisations, together with the Royal College of Nursing
`and the Skin Care Campaign.
`
`The British Association of Dermatologists did not express a preference and an individual
`pharmacist was not in favour.
`
`DISCUSSION OF RESPONSES TO CONSULTATION
`
`
`The majority of responders were in favour of the proposal. The main issue raised was
`concern over the efficacy of the product. Additional issues were related to the posology
`and misdiagnosis.
`
`Efficacy and posology
`
`Five responses were received on the issues of efficacy and posology. The Royal College of
`Physicians do not object the proposal and think that it is reasonable to make this product
`available for the general public. However, the College expressed concern that the product
`would be ineffective. The British Association of Dermatologists considers that the patient
`information leaflet patients should inform patients that the cure rate with Curanail lacquer
`might be quite low. A pharmacist disagreed with the proposal and commented that topical
`antifungal nail lacquers were not effective preparations.
`
`The Royal Pharmaceutical Society of Great Britain (RPSGB) pointed out that further
`information was needed whether efficacy was likely to be affected by administering the
`product once weekly as opposed to the approved 1-2 times weekly administration.
`
`The Dispensing Doctor’s Association commented that the P product should be used twice a
`week as it was indicated for the POM product.
`
`The British Association of Dermatologists commented that since onychomycosis was
`improving slowly, it could be expected that patients terminate the treatment early. The
`Royal Pharmaceutical Society of Great Britain think that it should be emphasised in the
`PIL that patients should return to the pharmacy at 3-month intervals for further assessment.
`
`
`Assessor’s comment:
`
`The issues of efficacy and the posology have been discussed in the previous paper.
`
` It has been acknowledged that systemic therapy is more successful than topical
`
`MHRA PAR – Curanail 5% Nail Lacquer PL 10590/0049 - 16 -
`
`FlatWing Ex. 1028, p. 16
`
`
`
`treatment. The BNF, PRODIGY and Guidelines for Treatment of Onychomycosis
`by the British Association of Dermatologist recommend topical antifungal therapy
`only in mild cases of onychomycosis. BNF suggests topical treatment in cases
`when up to two nails are affected. Based on this guidance the indication of
`amorolfine will be restricted for the treatment of mild cases of disto-lateral
`subungual onychomycosis limited up to 2 nails.
`
`The posology for the POM product is once weekly. The POM SPC also states that
`twice weekly application may prove beneficial in some cases. The applicant
`provided additional evidence to show that in mild cases once weekly administration
`of amorolfine is similarly effective to the twice weekly application.
`
`The PIL should emphasise the need to review progress with the pharmacist 3
`monthly intervals.
`
`
`
`5.1 Misdiagnosis
`
`The British Association of Dermatologists expressed concern over the appropriateness of
`the diagnosis without laboratory test. Additionally, it is thought that a large number of
`patients with onychomycosis from other causes would be getting treatment inappropriately.
`
`Others commented that the pharmacy training will ensure that the product is supplied for
`appropriate patients. The RPSGB has emphasised the importance of the role of the
`pharmacist in appropriate diagnosis and have raised a query on the plans to cascade
`training material to pharmacists.
`
`
`ASSESSOR’S COMMENT:
`
`The issue of misdiagnosis have been discussed in the previous paper. In current
`general practice the diagnosis of onychomycosis is based on the clinical picture
`alone. Other conditions similar to nail infection are accompanied by skin
`symptoms, which help in the differential diagnosis. In addition, patients with
`underlying conditions, which predispose for fungal nail infection (impaired
`circulation, diabetes mellitus, immunosuppression) will be excluded from the P
`supply of amorolfine and will be referred to their GP.
`
`The role of the pharmacist is important with the initial diagnosis and ensuring
`correct use. It is important that the applicant liaises with the RPSGB to ensure
`suitable training material is supplied to all pharmacists.
`
`
`CONCLUSION
`
`
`6.
`
`No new issues have been identified during consultation. Fifteen of the responders were in
`favour; one was not in favour of the proposal. One responder expressed concerns and three
`did not provided comment. The applicant should liaise with the RPSGB in relation to the
`content and distribution of the training material.
`
`
`MHRA PAR – Curanail 5% Nail Lacquer PL 10590/0049 - 17 -
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`FlatWi