CICLOPIROX OLAMINE BIOGARAN 1 % Cream Tube/30g

Ciclopirox olamine.............................................................................................................................................. 1 g

For 100 g of cream.

Excipients with known effect : each gram of cream contains 65,6 mg of cetyl alcohol, 70,8 mg of stearyl alcohol and 10 mg of benzyl alcohol.

Dermatoses superinfected or not by bacteria:

• trichophyton dermatophytoses,

• epidermophyton, microsporum outside of tinea capitis,

• cutaneous candidiasis,

• pityriasis versicolor,

Dermatophyte onychomycoses.

Mild to moderate seborrheic dermatitis of the face.

Dosage

• Cutaneous mycoses: 2 daily applications for 21 days on average.

• Dermatophyte onychomycoses: application of CICLOPIROX OLAMINE BIOGARAN alone or in combination with another treatment for several months.

• Mild to moderate seborrheic dermatitis of the face:

• initial treatment (2 to 4 weeks): 2 applications per day,
• beyond that, as maintenance treatment: 1 application per day for 28 days.

Method of administration

The areas to be treated must be clean and dry.

Hands must be washed thoroughly before and after each application.

CICLOPIROX OLAMINE BIOGARAN must be applied to the areas of skin to be treated by massaging gently.

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

Avoid contact with the eyes and mucous membranes.

CICLOPIROX OLAMINE BIOGARAN must not be applied to open wounds.

Candidiasis: use of an acidic pH soap, which promotes the multiplication of Candida, is not recommended.

In case of local or systemic sensitization, the applied product must be immediately withdrawn, treatment with CICLOPIROX OLAMINE BIOGARAN discontinued, and appropriate treatment initiated.

This medicine contains:

• cetyl alcohol and stearyl alcohol, which may cause local skin reactions (for example: contact dermatitis);

• benzyl alcohol, which may cause allergic reactions and, with topical application, slight local irritation.

No interaction studies have been performed.

Pregnancy

There are limited data (fewer than 300 pregnancies with known outcome) on the use of ciclopirox olamine in pregnant women.

However, no effect is expected during pregnancy, since systemic exposure to ciclopirox olamine is negligible (see section Pharmacokinetics) and no embryotoxic or teratogenic effect has been observed following oral, topical or subcutaneous administration of ciclopirox olamine in animals (see section Preclinical safety).

As a precaution, it is preferable to avoid the use of CICLOPIROX OLAMINE BIOGARAN during pregnancy.

Breast-feeding

There are insufficient data on the excretion of ciclopirox olamine and its potential metabolites in human milk. As a precaution, it is preferable to avoid the use of CICLOPIROX OLAMINE BIOGARAN during breast-feeding.

Fertility

No effect on male or female fertility has been demonstrated in rats following oral administration of ciclopirox olamine up to 5 mg/kg/day (see section Preclinical safety).

CICLOPIROX OLAMINE BIOGARAN has no effect on the ability to drive vehicles or use machines.

The following table presents adverse effects by MedDRA system organ class.

Frequencies are defined as: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10 000, < 1/1000), very rare (< 1/10 000), not known (cannot be estimated from the available data).

* requires interruption of treatment

** cases of contact dermatitis have been reported since marketing

*** does not require discontinuation of treatment

The possibility of systemic effects must be considered in case of prolonged treatment over a large area, on damaged skin, a mucous membrane, or under an occlusive dressing.

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 Centres of Pharmacovigilance - Website: https://signalement.social-sante.gouv.fr/

No cases of overdose have been reported.

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

Ciclopirox olamine is an active antifungal (pyridone family) in vitro on:

• Candida and yeasts: MIC 1 to 4 micrograms/mL,

• dermatophytes (Trichophyton and Epidermophyton, Microsporum): MIC 1 to 4 micrograms/mL,

• various fungi: MIC 0,5 to 8 micrograms/mL.

It furthermore has antibacterial properties against Gram-positive (staphylococci, streptococci) and Gram-negative (Escherichia coli, Proteus, Pseudomonas).

Percutaneous absorption is very low: 1,1 to 1,6 % of the applied dose is detected in urine. Maximum plasma concentrations are negligible (0.2 to 0.3 micrograms/mL).

After cutaneous application of CICLOPIROX OLAMINE BIOGARAN, ciclopirox olamine diffuses into the epidermis and pilosebaceous follicles, with impregnation of the superficial layers of the stratum corneum being particularly significant, with antifungal concentrations obtained. The risk of systemic passage of ciclopirox olamine is negligible.

Ciclopirox olamine has the particularity of penetrating and crossing the nail keratin.

Acute toxicity studies performed with ciclopirox and/or ciclopirox olamine in rats and mice after oral or subcutaneous administration show similar and moderate toxicities (LD50 between 1740 mg/kg and 2500 mg/kg).

Repeated-dose toxicity studies with ciclopirox olamine demonstrated good systemic tolerance with a chronic oral NOAEL (No Observable Adverse Effect Level : No observable adverse effect dose) chronic oral dose of 10 mg/kg/day in rats and dogs.

A set of genotoxicity studies did not demonstrate genotoxic potential of ciclopirox olamine. An equivocal clastogenic activity was observed in the HPRT/V79 test with a significant increase in mutations preferentially affecting small colonies.

 Ciclopirox olamine also significantly inhibited DNA repair activity in the UDS test (Unscheduled DNA Synthesis : unscheduled DNA synthesis), but without any genotoxic effect in this test. However, the hypothesis is that the clastogenic activity in vitro of ciclopirox olamine is directly related to its potential to chelate calcium present in the culture medium.

No carcinogenicity study has been performed with ciclopirox and/or ciclopirox olamine.

Ciclopirox olamine administered orally to rats (up to 5 mg/kg/day) induced no adverse effect on male or female fertility.

No embryotoxic or teratogenic effect was observed after oral, topical or cutaneous administration of ciclopirox olamine.‑Studies were conducted in several animal species: mouse, rat, rabbit and monkey.

Ciclopirox olamine administered orally to female rats up to 5 mg/kg/day from day 15th of gestation until weaning of the pups induced no adverse effect on peri- or postnatal development.

Local tolerance studies conducted in rabbits showed that the cream was slightly irritating to the skin and eyes. The product having been judged sensitising in guinea pigs (0,1 mL per application), its photosensitising potential (in humans) cannot be ruled out, as the latter could not be evaluated. The product is not photo-irritant. In the LLNA test (Local Lymph Node Assay : Local lymph node stimulation test) in mice, the product was judged not sensitising.

2 years.

Store at a temperature not exceeding 25°C.

No special requirements.