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SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml medicated nail lacquer contains 55.74 mg amorolfine hydrochloride equivalent to 50 mg amorolfine. For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Medicated nail lacquer Clear, colourless solution with a characteristic odour.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Treatment of onychomycosis without involvement of the matrix (particularly in the distal region, affecting less than 80% of the nail surface), caused by dermatophytes and yeasts.
4.2 Posology and method of administration
Posology
The nail lacquer should be applied once weekly to the affected finger- or toenails.
Elderly: There are no specific dosage recommendations for use in elderly patients. Paediatric population:
Method of administration The medicinal product is intended for application to the nails. Instructions on use:
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The patient should apply
Warning: Nail files used for treatment must no longer be used for the care of healthy nails.
1. Before using the lacquer for the first time, diseased sections of nail surfaces should be filed down as much as possible. When using the lacquer again in future, it should be filed again as required (e.g. if the nails have grown thicker). The pack contains disposable files.
2. For cleansing the nail surface, always one of the alcohol swabs supplied should be used. This will also remove any remnants of lacquer.
3. The medicated nail lacquer should be applied with one of the enclosed reusable spatulas. The pack contains a spatula holder in order to facilitate the application of the medicated nail lacquer. The reusable spatulas should be put into the spatula holder.
4. The nail lacquer should be removed by using one of the reusable spatulas sup- plied. The spatula should be re-dipped for each nail to be treated (with the surface perforated), without wiping it off on the bottle neck (risk of screw top sticking to the bottle).
5. Using the spatula,
6. Due to the special shape of the spatula holder a contact of the spatula with the surface/shelf space is avoided (fungal spores remain on the spatula). Intermedi- ately the spatula can be put aside without worrying that fungal spores could be transmitted.
7. The bottle should be tightly closed immediately after each use, to prevent the solution from drying out. The treated nails should be allowed to dry for 10 minutes.
8. For reuse, the spatula should be cleaned after use with an alcohol swab. After application of
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4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
4.4 Special warnings and precautions for use
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed. For simultaneous use with cosmetic nail polish refer to section 4.2.
4.6 Fertility, pregnancy and lactation
Experience with amorolfine use during pregnancy and/or lactation is limited. Only a few cases of exposure to topical amorolfine use in pregnant women have been reported in the post-authorisation setting, therefore the potential risk is unknown. Studies in animals have shown reproductive toxicity at high oral doses (see section 5.3); it is unknown whether amorolfine is excreted in human milk. Amorolfine should not be used during pregnancy and/or lactation unless clearly necessary. Pregnancy No effects during pregnancy are anticipated, since systemic exposure to amo- rolfine is negligible.
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4.7 Effects on ability to drive and use machines
4.8 Undesirable effects
Rare cases of nail changes (e.g. discolouration, brittle or broken nails) have been reported with the use of amorolfine containing nail lacquer. These reactions can also be attributed to the onychomycosis itself.
System Organ Class Frequency Adverse reactions
Immune system disor- Not known Hypersensitivity reac- ders tions (also outside the (cannot be estimated site of application, which from the available data)* may be associated with a swelling of the face, lips, tongue or throat, respira- tory problems and/or se- vere rash)*
Skin and subcutaneous Rare Nail disorder, nail discol- tissue disorders oration, onychoclasis (≥ 1/10000, < 1/1000) (broken nails), onychor- rhexis (brittle nails)
Very rare ( < 1/10000) Skin burning sensation
Not known Erythema*, pruritus*, contact dermatitis* (irrita- (cannot be estimated tive or allergic) (including from the available data)* allergic contact dermati- tis with spreading reac- tion), urticaria*, blister*
*Experience from post-marketing period 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 me- dicinal product. Healthcare professionals are asked to report any suspected ad- verse reactions via the national reporting system listed in Appendix V.
4.9 Overdose
No case of overdose has been reported. Amorolfine is intended for topical use. In case of accidental oral ingestion appropriate measure for gastric emptying can be taken.
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5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antifungals for dermatological use; other antifungals for topical use ATC code: D01AE16 Amorolfine hydrochloride is a morpholine derivative. As such, it belongs to a new substance class of antifungal agents and possesses a broad spectrum of activity. Amorolfine intervenes in ergosterol biosynthesis in the fungal cell membrane and thereby develops both fungistatic and fungicidal efficacy.
It is highly effective against:
Yeasts: Candida, Malassezia or Pityrosporum, Cryptococcus
Dermatophytes: Trichophyton, Microsporum, Epidermophyton
Moulds: Alternaria, Hendersonula, Scopulariopsis
Dematiaceae: Cladosporium, Fonsecaea, Wangiella
Dimorphic fungi: Coccidioides, Histoplasma, Sporothrix
5.2 Pharmacokinetic properties
Amorolfine from nail lacquer penetrates into and diffuses through the nail plate and is thus able to eradicate poorly accessible fungi in the nail bed. Systemic absorp- tion of the active ingredient is very low with this type of application. Following pro- longed use of
5.3 Preclinical safety data
Acute toxicity:
Species Application LD50 mg amorolfine hydrochlo- ride/kg body weight Mouse intravenous 130 Mouse intraperitoneal 200 Mouse oral 2500
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Rat intraperitoneal 450 Rat oral 1900 Rat dermal more than 2000 Dog oral more than 1000*
* isolated finding: vomiting
Mild skin irritation was observed in the acute skin tests.
Subacute and chronic toxicity: In order to determine subacute and chronic toxicity, studies with a 13-week dura- tion and up to 60 mg amorolfine hydrochloride/kg BW/day or 26-week studies with a dosage up to 40 mg amorolfine hydrochloride/kg BW/day were conducted in rats and dogs. In these studies, no direct relationship was established between drug administration and death of the animals. Just one of the four dogs in the 26-week study receiving 40 mg amorolfine hydrochloride/kg BW/day died on Day 119, sub- sequent to deterioration in its general state of health. Toxic manifestations were mainly observed in each of the highest dose groups, which manifested as keratosis and dermatitis-like skin lesions, dyskeratosis/ parakeratosis of the mucous mem- branes and the mucocutaneous transition area. Only in the highest dose group were cataracts found in rats and dogs. Furthermore, a dose-dependent effect on the liver was observed in dogs (mainly bile duct proliferation and occasional con- gestion or fibrosis of the liver). This effect did not occur in animals at low doses.
Toxicity to reproduction: Fertility: In a fertility study with oral administration in male and female rats, no effect on mating behaviour or fertility was observed at any of the doses tested. A dose of 35 mg amorolfine hydrochloride/kg BW/day resulted in delayed foetal development in rats.
Teratogenicity: In rats, no embryotoxic or teratogenic effects were observed up to the highest ad- ministered doses of 80 mg amorolfine hydrochloride/kg BW/day orally or 36 mg amorolfine hydrochloride/kg BW/day via the vaginal route. In rabbits, a dose of 10 mg amorolfine hydrochloride/kg BW/day (oral) and 8 mg amorolfine hydrochlo- ride/kg bw/day (vaginal) was embryotoxic. However, no teratogenic effect was seen at these doses. In humans, there is no experience with administration during pregnancy and lacta- tion.
Peri- and postnatal toxicity: With regard to peri- and postnatal toxicity, no effect was found in rats at doses up to 3 mg amorolfine hydrochloride/kg BW/day, orally administered. The high dose of 10 mg amorolfine hydrochloride/kg BW/day was shown to be maternally toxic and resulted in higher neonatal mortality during the first days of lactation. The highest dose of 30 mg amorolfine hydrochloride/kg BW/day led to neonatal death in all cases.
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Mutagenicity/carcinogenicity: Amorolfine hydrochloride has been tested up to toxic doses both in vitro and in vivo. No mutagenic potential was found in any of these tests. There have been no long-term carcinogenic studies.
Local tolerability: Animal experiments with topical use of amorolfine hydrochloride showed mild to moderate skin irritation, especially when used under occlusive conditions. How- ever, as occlusive dressings are not recommended for the treatment of topical fun- gal infections in humans, the relevance of increased local irritation under these extreme conditions is deemed to be minor. There was no evidence of any photo- toxic, allergic or photoallergic potential for amorolfine hydrochloride in any of the respective animal experiments performed. Repeated administration of vaginal tab- lets was tolerated by dogs without undesirable effects.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Ethanol Ethyl acetate Ammonio methacrylate copolymer (type A) Butyl acetate Triacetin
6.2 Incompatibilities
Not applicable
6.3 Shelf life
3 years After first opening the bottle: 6 months
6.4 Special precautions for storage
Do not store above 30 °C.
6.5 Nature and contents of container
Brown glass bottles with a white HDPE screw cap in pack sizes of 3 ml and 6 ml (2x 3 ml) medicated nail lacquer (including the fol- lowing medical devices: 10 plastic spatulas in display and spatula holder as appli- cation device, 30 nail files and 30 swabs). Not all pack sizes may be marketed.
6.6 Special precautions for disposal
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No special requirements.
7. MARKETING AUTHORISATION HOLDER
[To be completed nationally]
8. MARKETING AUTHORISATION NUMBER
[To be completed nationally]
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: {DD month YYYY} Date of latest renewal: {DD month YYYY}
[To be completed nationally]
10. DATE OF REVISION OF THE TEXT
{Month/YYYY} [To be completed nationally]