Bulletin 55 | January 2014 | v2.0

Topical antifungal nail treatment review (Amorolfine 5% nail lacquer (Loceryl®, Curanail®, Omicur®); Tioconazole 28% cutaneous solution (Trosyl®); Salicylic acid, tannic acid & boric acid paint (Phytex®)) This is one of a number of bulletins providing further information on medicines contained in the PrescQIPP DROP-List (DRugs Of Low Priority). This bulletin focuses on topical antifungal nail treatment, i.e. amorolfine 5% nail lacquer (Loceryl®, Curanail®, Omicur®), tioconazole 28% cutaneous solution (Trosyl®) and salicylic acid, tannic acid and boric acid paint (Phytex®) which are low priority treatments. Self-care may be appropriate for the majority of asymptomatic patients with fungal infection of the nails. If treatment is deemed necessary, a systemic antifungal is more effective than topical therapy. Further bulletins, including the DROP-List, are available on the PrescQIPP website, available at www.prescqipp.info1

Recommendations •

Unsightly nails due to fungal infection are primarily a cosmetic problem. Self–care measures alone (incorporating good nail hygiene) are recommended if the person has few troublesome symptoms.

•

The patient should be informed that there is no absolute need for treatment. Discuss possible treatment options including side effects and success rate of treatment.

•

Treatment does not always cure the infection. Cure rates range between approximately 60–80%. Treatment that eradicates the infection sometimes does not restore the nail's appearance to normal.

•

Topical antifungal therapy offers very little benefit for the management of fungal nail infections. There is limited evidence for efficacy in dermatophyte infections.

•

Fungal nail infections are rare in children. Children younger than 18 years of age who require antifungal therapy should be referred to dermatology for conformation of diagnosis before any treatment is initiated. It is important that children under 18 are not treated empirically/referred for OTC purchase until they have been assessed by a specialist.

•

If treatment is deemed necessary, it is important to confirm the diagnosis (positive microscopy or positive culture) e.g. if the condition is severe and debilitating, painful or in patients with peripheral vascular disease, diabetes or those who are immune-compromised.

•

If a decision is made to initiate treatment, systemic therapy is almost always more successful than topical treatment in dermatophyte onychomycosis. Systemic terbinafine is the most effective agent, however there is still a 20-30% failure rate. Side effects such as headache, itching, loss of sense of taste, gastrointestinal symptoms, rash, fatigue, and abnormal liver function, can occur. Serious side effects, such as liver failure, are rare.

•

Topical therapy should only be considered if the infection is mild and superficial or where systemic therapy is contra-indicated or not tolerated e.g. hepatic or liver impairment. In these cases, patients should be advised to purchase over the counter (OTC) amorolfine 5% nail lacquer for the treatment of a maximum of 2 nails.

This is an NHS document not to be used for commercial or marketing purposes

1 of 5

PrescQIPP Bulletin 55: Topical antifungal nail treatment review v2.0

Background Topical antifungal nail treatments i.e. amorolfine 5% nail lacquer (Loceryl®, Curanail®, Omicur®), tioconazole 28% cutaneous solution (Trosyl®), salicylic acid, tannic acid & boric acid paint (Phytex®) feature as no.12 in the PrescQIPP DROP-List.1 The DROP-List is an accumulation of medicines that are regarded as low priority, poor value for money or medicines for which there are safer alternatives. In the PrescQIPP membership area (16.2 million patients, August 2013), £1,746,772 was spent on amorolfine, tioconazole and Phytex paint over the course of 12 months. Self-care should be the primary option for the majority of asymptomatic patients with fungal nail infections. If treatment is deemed necessary, oral therapy should be considered. As with all reviews, individual patient circumstances need to be borne in mind, however with assistance from practice nurses, support from your local CCG prescribing teams and the experiences of CCGs/GPs that have already undertaken this work, it is hoped that GPs will participate in realising the cost savings.

Introduction Onychomycosis is an infection of the nail apparatus by fungi that include dermatophytes, non-dermatophyte moulds and yeasts (mainly Candida species). The toenails are affected in 80% of all cases of onychomycosis. Dermatophyte infection, mostly due to Trichophyton rubrum, is the cause in over 90% of cases. Onychomycosis is classified clinically as distal and lateral subungual onychomycosis (DLSO), superficial white onychomycosis (SWO), proximal subungual onychomycosis (PSO), candidal onychomycosis and total dystrophic onychomycosis.2 Mild and superficial infection3 of the nail includes: •

Superficial onychomycosis (small flaky white patches and pits on the top of the nail plate; the nail is roughened and crumbles easily).

•

Mild distal onychomycosis (the nail lifts up and the free edge erodes).

•

Lateral onychomycosis (white or yellow opaque streaks on one side of the nail), although this may be less likely to respond than distal or superficial onychomycosis.

Fungal nail infection is more common in people who already have fungal skin infections and psoriasis. Patients with diabetes mellitus, peripheral vascular disease, and immunocompromised patients are more at risk of secondary infection and it is important to assess the effects and symptoms of the fungal nail infection in these patients.3 Environmental factors e.g. occlusive footwear, warm, damp conditions and trauma to the nail, predispose to fungal and Candida nail infection.3 Although fungal nail infections can have negative effects on the patient’s emotional, social, and work life, they will not tend to lead to complications that could be of detriment to the patient’s health. The British Association of Dermatologists (BAD)2 state that only 50% of cases of nail dystrophy are fungal, and it is not easy to identify these clinically. The length of treatment needed (6-12 months) is too long for a trial of therapy and mycology confirmation is necessary. This opinion is endorsed by the Health Protection Agency (HPA)4 with recommendations that many nail problems can look like a fungal infection e.g. psoriasis or injury. As only 45% of dermatology samples received are positive for fungal infection, recommendations are to always send samples before starting lengthy treatment.

Clinical evidence Topical amorolfine has evidence of limited effectiveness for dermatophyte infections.5 Also there is no good evidence of effectiveness from randomised controlled trials (RCT) for other topical treatments for dermatophyte nail infections, including topical tioconazole, topical salicylic acid and topical undecanoates.3 Combined topical treatment and oral drug treatment are not recommended because there is only weak evidence for oral terbinafine combined with topical treatments, and weaker evidence for oral itraconazole combined with topical treatments.3

This is an NHS document not to be used for commercial or marketing purposes

2 of 5

PrescQIPP Bulletin 55: Topical antifungal nail treatment review v2.0 •

A Cochrane review5 evaluated the management of fungal nail infections and found limited good quality evidence to support the efficacy of topical amorolfine, although it identified that of the topical agents, amorolfine may be the most effective. Further research on the effectiveness of topical amorolfine was recommended.

•

Amorolfine nail lacquer has been shown to be effective in around 50% of cases of both fingernail and toenail infection in a large study where only cases with infections of the distal portion of the nail were treated.6 While it is clearly possible to achieve clinical and mycological cure with topical nail preparations, these cure rates do not compare favourably with those obtained with systemic drugs. Currently, topical therapy can only be recommended for the treatment of SWO and in very early cases of DLSO where the infection is confined to the distal edge of the nail.

•

There is limited evidence that topical treatment alone is effective in the treatment of Candida onychomycosis. In a small open-label trial, 32 people with Candida onychomycosis applied topical amorolfine 5% nail lacquer twice weekly for 40 weeks. At 40 weeks, 90% of infected nails were either clinically cured or showed only minor signs of residual dystrophy.7

•

Dosing regimens of amorolfine were compared in one RCT (n = 456) without a placebo control and found that 46% of those randomized to amorolfine applied once a week for 6 months achieved mycological cure of dermatophyte infection compared with 54% of those who applied topical amorolfine twice a week.8

•

Application with amorolfine should be once weekly to the affected finger or toe nails. Treatment duration is for 6 months for fingernail infections and 9–12 months for toenail infections9, 10 The SPC also recommends a review of the treatment at intervals of approximately three months9, 10 Tioconazole solution11 should be applied to the affected nails and immediately surrounding skin every twelve hours. The duration of treatment is up to six months but may be extended to twelve months.

NICE Clinical Knowledge summaries (CKS)3 recommend that self-care may be appropriate for people who are not bothered by the infected nail or who wish to avoid the possible adverse effects of drug treatment. The British Association of Dermatologists (BAD)2 have produced guidelines on the management of nail infections. These are included in the NICE CKS on fungal nail infections.5 Recommendations include: •

Topical treatment can only be recommended for treating superficial white onychomycosis (SWO), very early distal and lateral subungal onychomycosis (DLSO) or where systemic therapy is contraindicated e.g. liver or renal impairment. Topical treatment is inferior to systemic therapy in all but a small number of cases of very distal infection or in SWO.

•

Amorolfine (Loceryl or Curanail) nail lacquer is effective only in around 50% of fingernail and toenail dermatophyte infections.

•

Terbinafine is superior to itraconazole in dermatophyte onychomycosis, and should be considered as first-line treatment, with itraconazole as the next best alternative. Cure rates of 80–90% for fingernail infection and 70–80% for toenail infection can be expected. The most common adverse effects12 (mild and transient) associated with terbinafine are nausea, mild abdominal pain, diarrhoea, and dyspepsia. These normally resolve on stopping treatment. Hepatotoxicity may occur in people with and without pre-existing liver disease. Rare cases of cholestasis, hepatitis, jaundice, and liver failure have been reported. Serious skin reactions, such as Stevens-Johnson syndrome and lupus erythematosus-like rash have been reported. In cases of treatment failure the reasons for such failure should be carefully considered. In such cases either an alternative drug or nail removal in combination with a further course of therapy to cover the period of regrowth should be considered.

•

The NICE CKS3 states further that specialist advice is needed for children as fungal nail infection is rare in children, and the preferred treatments are not licensed for use in children.

Patient information leaflets on fungal nail infections can be found at; http://www.bad.org.uk/site/820/Default.aspx and http://www.patient.co.uk/health/fungal-nail-infections-leaflet

This is an NHS document not to be used for commercial or marketing purposes

3 of 5

PrescQIPP Bulletin 55: Topical antifungal nail treatment review v2.0

Costs There is a significant difference in cost between topical antifungal treatments and terbinafine tablets. Table 1 below illustrates the cost differences. Table 1: Product and price comparison – Drug Tariff,13 MIMS,14 Chemist and Druggist15 November 2013 Product

Cost

Terbinafine 250mg od for 28 days

£3.40

Salicylic acid paint (Phytex )

£5.34

Amorolofine 5% w/v nail lacquer (Loceryl) 5ml

£11.35

Amorolofine 5% w/v nail lacquer (Curanail) 3ml (Available to puchase from pharmacies, P medicine)

£19.99 (should last 3 months)

Tioconazole 283 mg/ml Nail Solution (Trosyl)

£27.38

Savings In the PrescQIPP membership area of 16.2 million patients (August 2013) £1,746,772 has been spent on spent on amorolfine® nail lacquer, tioconazole® nail solution and Phytex® paint over the course of 12 months. Reviewing the appropriateness of treatment and discontinuing therapy as appropriate could reduce this spend. This equates to total annual savings across the PrescQIPP membership area per 100,000 patients of £10,873. 50% discontinuation of amorolfine nail lacquer, tioconazole nail solution and salicylic acid paint could reduce the spend by £873,386. This then equates to total annual savings across the PrescQIPP membership area per 100,000 patients of £5,391.

References 1.

PrescQIPP DROP-List. Bulletin available at: http://www.prescqipp.info/resources/viewcategory/171-drop-list

2.

Roberts DT. Taylor WD, Boyle J and British Association of Dermatologists. Guidelines for treatment of onychomycosis. British Journal of Dermatology 2003; 148: 402–410. http://www.bad.org.uk/Portals/_Bad/Guidelines/Clinical%20Guidelines/Onychomycosis. pdf

3.

NICE Clinical Knowledge Summary. Fungal nail infection (onychomycosis) Accessed 10/11/13 via http://www.cks.nhs.uk/fungal_nail_infection

4.

Health Protection Agency/RCGP. Fungal Skin & Nail Infections: Diagnosis & Laboratory Investigation. Quick Reference Guide for Primary Care. Produced April 2009, reviewed April 2011. Accessed 10/11/13 via http://www.hpa.org.uk/webc/hpawebfile/hpaweb_c/1240294785726

5.

Crawford F, Hollis S. Topical treatments for fungal infections of the skin and nails of the foot. Cochrane Database of Systematic Reviews 2007, Issue 3. Art. No.: CD001434. Accessed 10/11/13 via http://www.thecochranelibrary.com/userfiles/ccoch/file/Water%20safety/CD001434.pdf

6.

Zaug M, Bergstraesser M. Amorolfine in onychomycosis and dermatomycosis. Clin Exp Dermatol 1992; 17 (Suppl. 1): 61–70.

7.

Lestringant, G.G., Nsanze, H., Nada, M. et al. Effectiveness of amorolfine 5% nail lacquer in the treatment of long-duration Candida onychomycosis with chronic paronychia. Journal of Dermatological Treatment 1996; 7(2): 89-92.

This is an NHS document not to be used for commercial or marketing purposes

4 of 5

PrescQIPP Bulletin 55: Topical antifungal nail treatment review v2.0 8.

Reinel, D. Topical treatment of onychomycosis with amorolfine 5% nail lacquer: comparative efficacy and tolerability of once and twice weekly use. Dermatology 1992; 184(Suppl 1): 21-24.

9.

Summary of Product Characteristics - Loceryl. Galderma UK Limited. Last updated 18/10/11, accessed 11/11/13 via http://www.medicines.org.uk/emc/medicine

10. Summary of Product characteristics - Curanail. Galderma UK Limited. Last updated 11/12/12, accessed 11/11/13 via http://www.medicines.org.uk/emc/medicine 11. Summary of Product Characteristics - Trosyl. Pfizer Ltd. Last updated 25/7/13, accessed 29/11//13 via http://www.medicines.org.uk/emc/medicine 12. Summary of Product Characteristics - Terbinafine. Actavis. Last updated 10/6/13, accessed 29/11/13 via http://www.medicines.org.uk/emc/medicine 13. Drug Tariff, November 2013. 14. MIMs November 2013. Available at www.mims.co.uk accessed 17.11.13. 15. Chemist and Druggist. November 2013, accessed 17.11.13.

Additional PrescQIPP resources:



Briefing

Data pack

Audit tool and patient letters

Available for download here: http://www.prescqipp.info/-amorolfine-5-nail-lacquer/viewcategory/184 Information prepared by Anita Hunjan, NHS PrescQIPP Programme, November 2013 and reviewed by Katie Smith, East Anglia Medicines Information Service, December 2013. Non-subscriber publication May 2014.

This is an NHS document not to be used for commercial or marketing purposes

5 of 5