MYCONAIL 80 mg/g Medicated nail lacquer Bottle/3,3ml

Medicated nail lacquer (clear, colourless to slightly yellowish solution).
Bottle containing 3,3 ml, with screw cap fitted with an applicator brush. Box of 1.

One gram of medicated nail lacquer contains 80 mg of ciclopirox.

Excipients with known effect :

One gram of medicated nail lacquer solution contains 10 mg of cetostearyl alcohol and 730 mg of ethanol.

Excipients:

Mild to moderate onychomycoses caused by dermatophytes, yeasts and moulds, without involvement of the nail matrix/lunula.

MYCONAIL is indicated in adults.

Dosage

Paediatric population

The safety and efficacy of MYCONAIL 80 mg/g medicated nail lacquer in children and adolescents under 18 years of age have not yet been established. No data are available.

Method of administration

Cutaneous use.

Topical use on the nails of the fingers and toes and on the immediately adjacent skin (periungual area, hyponychium).

Unless otherwise specified, MYCONAIL 80 mg/g medicated nail lacquer is applied as a thin layer once daily to the affected nail(s), after the nails have been washed and thoroughly dried. The medicated nail lacquer should be applied to the entire nail plate, over 5 mm of surrounding skin and, if possible, under the free edge of the nail. Approximately thirty seconds are needed for MYCONAIL 80 mg/g medicated nail lacquer to dry. Treated nails must not be washed for at least six hours, so application in the evening, before going to bed, is recommended. After this period, usual hygiene practices may be resumed.

It is not necessary to remove MYCONAIL 80 mg/g medicated nail lacquer using a solvent or abrasive (i.e. a nail file); washing the nails is sufficient. If the lacquer is unintentionally removed by washing, MYCONAIL 80 mg/g medicated nail lacquer may be applied again.

It is recommended to regularly remove the free edge of the nail and any onycholytic material using nail clippers.

Treatment must be continued until complete clinical and mycological cure and until a healthy nail has regrown. The treatment duration for fingernails is normally achieved in approximately 6 months, whereas it is approximately 9 to 12 months for toenails.

A control fungal culture should be performed 4 weeks after the end of treatment in order to avoid any disturbance of culture results by possible residues of the active substance.

As this is a topical treatment, no dose adjustment is necessary in special patient populations.

If the condition is refractory to treatment with MYCONAIL 80 mg/g medicated nail lacquer and/or if there is extensive involvement of one or more fingernails and toenails, complementary oral treatment should be considered.

Hypersensitivity to the active substance or to any of the excipients listed in section Composition.

Children and adolescents under 18 years of age, due to the lack of experience in this age group.

Mild to moderate onychomycosis is defined as a fungal infection affecting up to 75 % of the nail surface, with involvement of up to 5 nails, without involvement of the nail matrix/lunula.

In cases of severe onychomycosis and predisposing factors, such as diabetes and immune disorders, oral treatment should be considered.

The duration of the disease, the extent of infection (involvement of the nail plate) and the thickness of the nail (if > 2 mm, this may indicate matrix involvement, with keratinised debris) may influence the outcome of treatment.

In case of sensitisation, treatment must be discontinued and appropriate measures taken.

Patients with a history of diabetes, immune dysfunction, peripheral vascular disease, injury, painful or severely damaged nails, skin diseases such as psoriasis or any other chronic skin condition, oedema, or respiratory disorders (yellow nail syndrome) should undergo a medical examination before starting treatment.

The risk that the healthcare professional removes the non-adherent nail or that the patient tears it off while washing must be seriously considered in patients with a history of insulin-dependent diabetes or diabetic neuropathy.

Contact with the eyes and mucous membranes must be avoided.

The medicated nail lacquer is intended for external use only.

Nail varnishes or other cosmetic nail products must not be used on treated nails.

MYCONAIL 80 mg/g medicated nail lacquer contains cetostearyl alcohol which may cause local skin reactions (for example: contact dermatitis).

The bottle must be closed again after use.

This medicine contains 730 mg of alcohol (ethanol) per gram of solution. This may cause a burning sensation on damaged skin.

This product is flammable. Keep away from heat sources or naked flames.

No drug interaction studies have been performed. However, after use as recommended, the systemic bioavailability of ciclopirox is less than 2 %, which is considered a negligible amount, so that no systemic interaction is anticipated.

Pregnancy

There are no data on exposure of pregnant women to ciclopirox. Studies in animals have not revealed any direct or indirect harmful effect on gestation, embryonic development, fetal development and/or delivery. However, there are no relevant data on possible long-term effects on postnatal development (see section Preclinical safety). As systemic exposure to ciclopirox is negligible, the use of MYCONAIL 80 mg/g medicated nail lacquer may be considered during pregnancy if necessary.

Breast-feeding

It is not known whether ciclopirox or its metabolites are excreted in human milk, but at the therapeutic doses of MYCONAIL 80 mg/g medicated nail lacquer, no effect on the newborn/infant is expected.

Fertility

No fertility studies have been performed in humans. A reduced fertility index was observed in rats after oral administration (see section Preclinical safety). These animal data are of negligible clinical relevance due to the low systemic exposure to ciclopirox after therapeutic treatment with MYCONAIL 80 mg/g medicated nail lacquer.

MYCONAIL 80 mg/g medicated nail lacquer has no or negligible influence on the ability to drive and use machines.

The frequencies of occurrence of adverse effects are as follows: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1 000, < 1/100), rare (≥ 1/10 000, < 1/1 000), very rare (< 1/10 000), frequency not known (cannot be estimated from the available data).

General disorders and administration site conditions :

Very rare: erythema, scaling, burning and itching at the application site.

Frequency not known: skin rash, eczema, allergic dermatitis, also beyond the application site.

Discolouration (transient) of the nail (this reaction may also be due to the onychomycosis itself).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr.

MYCONAIL 80 mg/g medicated nail lacquer is indicated for topical administration. No cases of overdose have been reported with this product. In case of accidental oral ingestion, an appropriate method of gastric lavage may be used.

Pharmacotherapeutic class: Antifungals for topical use - Other antifungals for topical use, ATC code: D01AE14

MYCONAIL 80 mg/g medicated nail lacquer is an original patented formulation of ciclopirox, based on hydroxypropyl chitosan, adapted to the delivery of the active substance to the nail.

MYCONAIL 80 mg/g medicated nail lacquer exerts a topical antimycotic action. The active substance is ciclopirox (a pyridone derivative). In vitro, ciclopirox has been shown to be fungicidal and fungistatic, and also has sporicidal activity. Ciclopirox is active against a broad spectrum of dermatophytes, yeasts, moulds and other fungi. For most dermatophytes (Trichophyton species, Microsporum species, Epidermophyton species) and yeasts (Candida albicans, other Candida species), the MIC is in the range of 0,9 to 3,9 μg/ml.

Sensitivity table (strains involved in the disease)

Dermatophytes	Trichophyton rubrum Trichophyton mentagrophytes Trichophyton spp Microsporum canis Epidermophyton floccosum
Yeasts	Candida albicans Candida parapsilosis
Moulds	Scopulariopsis brevicaulis Aspergillus spp Fusarium solani

Clinical efficacy and safety

MYCONAIL 80 mg/g medicated nail lacquer was evaluated in a long-term clinical study conducted in 467 patients with onychomycosis. It was a three-arm study, controlled versus placebo and versus a commercial ciclopirox 8 % nail lacquer formulation. All treatments were applied every day for 48 weeks to the infected nails. Patients were then followed for a further period of 12 weeks. All clinical assessment was made on one target: the nail of the big toe.

Table of results at end of follow-up (week 60):

Judgement criterion	MYCONAIL nail lacquer	Placebo	Reference product in Europe
Complete "cure"*	12,7 %	1,3 %	5,8 %
"Responder#" patients	28,7 %	14,7 %	17,3 %
"Improvement"§	46,5 %	34,7 %	39,7 %
Reduction of affected nails$	36,3 %	16,2 %	21,8 %

* : Negativisation observed by KOH microscopy and fungal culture, and the target nail appearing 100 % healthy

# : Negativisation observed by KOH microscopy and fungal culture, and reduction of the surface area affected to ≤ 10 % (including zero) of the total surface area of the target nail, as measured by the blinded evaluator

§ : Patients with a decrease of at least 20 % of the surface area assessed blindly by the evaluator, at the end of treatment compared with baseline, and negativisation of KOH microscopy and fungal culture

$ : Reduction of the surface area affected to ≤ 10 % of the total surface area of the target nail, as measured blindly by the evaluator

MYCONAIL showed better efficacy than placebo and than the reference ciclopirox. A better effect was demonstrated both for the rate of "cure", which is the primary criterion, and for the rate of "responders", which is the most important secondary criterion. Indeed, the cure rate is higher by 119 % (statistically significant, p < 0,05) and the responder rate is higher by 66 % (statistically significant, p < 0,05) compared with the reference product.

During the clinical study, no systemic adverse effect related to the medicine was recorded.

Tolerance at the application site was regularly monitored throughout the treatment period. The signs and symptoms recorded were 2,8 % and 7,8 % respectively in the MYCONAIL treatment group; 8,6 % signs and 16 % symptoms were recorded in the reference group and 7,2 % signs and 12,4 % symptoms in the placebo group. The sign most frequently recorded was erythema (2,8 % in the MYCONAIL group and 8,6 % in the reference group). The most frequent symptom was a burning sensation (2,8 % in the MYCONAIL group and 10,7 % in the reference group).

A second randomised, long-term clinical study was conducted in 137 patients with onychomycosis. It was a randomised, two-arm study lasting 48 weeks, comparing MYCONAIL nail lacquer applied daily with commercially available acrylate-based nail lacquer containing amorolfine 5 %, applied twice weekly.

All efficacy variables (study endpoints) were assessed on the nail of the big toe.

The study met its primary objective, namely that MYCONAIL nail lacquer, after 12 weeks of treatment, was non-inferior to amorolfine 5 % in terms of negative culture: negative culture in 78,3 % for MYCONAIL nail lacquer versus 64,7 % for amorolfine 5 % nail lacquer, i.e. a difference of 13,6 % between treatments (95 % confidence interval [-1,4 ; 28,5]).

At week 48, the percentages of patients showing a complete cure rate, a treatment success/response rate and mycological cure in the MYCONAIL group were consistently higher than in the reference group:

Table: results obtained at the end of treatment (week 48):

Parameters measured	MYCONAIL nail lacquer	Amorolfine 5 % nail lacquer	Difference (in %)	95 % confidence interval for the difference
Complete cure rate*	35,0 %	11,7 %	23,3**	8,8 ; 37,9
Treatment success rate#	58,3 %	26,7 %	31,7**	14,9 ; 48,4
Mycological cure$	100 %	81,7 %	18,3**	8,5 ; 28,1

* Negative result observed by KOH microscopy and fungal culture, and healthy big toenail at 100 %, as measured by the blinded evaluator

# Negative result observed by KOH microscopy and fungal culture, and reduction of the area of the nail affected by the disease ≤ 10 % of the whole, as measured by the blinded evaluator

$ Negative result observed by KOH microscopy and fungal culture

** p < 0,001

No drug-related systemic adverse effects were recorded in this clinical study.

MYCONAIL 80 mg/g medicated nail lacquer was well tolerated in terms of local and general adverse effects. Signs of irritation were detected in only 2,06 % of patients in the MYCONAIL group, on the skin surrounding the treated nails.

MYCONAIL nail lacquer demonstrated good penetration properties into keratin. On reaching a fungicidal concentration at the site of infection, the active substance binds irreversibly to the fungal cell wall, thereby inhibiting the binding of elements essential for cell synthesis as well as for the respiratory chain.

A very small amount of ciclopirox enters the systemic circulation (< 2 % of the applied dose), and blood concentrations measured in a long-term study were 0,904 ng/ml (n = 163) and 1,144 ng/ml (n = 149) respectively after 6 and 12 months of treatment. This shows that the drug exerts its activity particularly locally and that the risk of any interference with normal bodily functions is negligible.

Non-clinical data from conventional safety pharmacology, repeated-dose toxicology, genotoxicity, carcinogenesis, and reproductive and developmental function studies revealed no particular risk to humans at daily oral doses up to 10 mg of ciclopirox/kg. No embryo-foetal or teratogenic toxicity was noted in reproductive function studies in rats and rabbits. At the oral dose of 5 mg/kg, a decrease in the fertility index in rats was observed. There is no evidence of peri- or postnatal toxicity; however, possible long-term effects on offspring have not been studied. MYCONAIL 80 mg/g medicated nail lacquer did not cause irritation in local tolerance studies in rabbits and guinea pigs.

The chitosan derivative contained in the formulation is free of tropomyosin and did not show allergenic potential in patients with shellfish allergy.

3 years

After first opening of the bottle: 6 months.

Store the bottle in the outer packaging, protected from light. Do not refrigerate or freeze.

After first opening of the bottle: keep the bottle tightly closed to prevent evaporation of the contents.

For storage conditions of the medicinal product after first opening, see section Shelf life.

The product is flammable. Keep away from heat and naked flames.

At temperatures below 15 °C, the medicated nail lacquer may gel. Slight flocculation or the formation of a clear precipitate may also occur, which may disappear when the product is returned to room temperature (25 °C) by rolling the bottle between the hands until the solution is clear again (about one minute). This has no effect on the quality or performance of the product.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Marketing authorisation (AMM)

CIP 3400922285696 (Fl/3,3ml).

Not reimbursed by Social Security.

 

Marketing authorisation holder: Laboratoires Bailleul S.A., 14-16 avenue Pasteur, L-2310 Luxembourg, Luxembourg.