GYNOPURA 1 % Cr T/30g

For 100 g of cream :

Econazole nitrate: 1,000 g

Excipients with known effect: benzoic acid, butylhydroxyanisole (E320).

Candidiasis

Cutaneous candidiasis encountered in human clinical practice is usually due to Candida albicans. However, the demonstration of a Candida on the skin cannot in itself constitute an indication.

• Treatment of non-macerated fold mycoses: genital, submammary, interdigital intertrigo, etc.
• Treatment of nail mycoses: onychomycosis and perionychia. A concomitant systemic antifungal treatment is necessary.

Antifungal treatment of a possible digestive and/or vaginal focus is required in candidiasis of the inguinal and intergluteal folds to prevent recurrences.

Dermatophytoses

• Treatment
  • dermatophytoses of glabrous skin,
  • Non-macerated genital and crural intertrigo.
• Treatment of tinea. Concomitant systemic antifungal treatment is necessary.

Erythrasma

Dosage

Apply GYNOPURA to the skin 2 to 3 times a day, without exceeding 3 applications per day. Treatment should be continued for 2 to 4 weeks.

Method of administration

Cutaneous use.

Apply the cream to the lesions to be treated with the tips of the fingers, a few drops having been placed in the hollow of the hand or directly on the lesions. Massage gently and regularly until complete penetration.

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

For external use only.

• Candidiasis: use of an acidic pH soap (pH favouring the multiplication of Candida) is not recommended.
• The risk of systemic passage must be taken into account in situations where the phenomenon of local occlusion may recur (for example elderly subjects, pressure sores, submammary intertrigo).
• Do not apply in the eye, nose or generally on mucous membranes.
• Drug interaction with vitamin K antagonists: the INR must be monitored more frequently and the dosage of the vitamin K antagonist adjusted during treatment with GYNOPURA and after its discontinuation (see section Interactions).
• This medicine contains 0,2 g of benzoic acid per 100 g of cream. Benzoic acid may cause local irritation. Benzoic acid may increase the risk of jaundice (yellowing of the skin and eyes) in newborns (up to 4 weeks).
• This medicine contains butylhydroxyanisole (E320) and butylhydroxytoluene, which may cause local skin reactions (for example contact dermatitis) or irritation of the eyes and mucous membranes.
• This medicine contains a fragrance containing citronellol. Citronellol may cause allergic reactions.
• If a hypersensitivity (allergic) or irritation reaction occurs, treatment must be discontinued.

Associations requiring precautions for use

Econazole is a known inhibitor of CYP3A4/2C9.

+ Vitamin K antagonists (acenocoumarol, fluindione, warfarin)

Increased effect of the vitamin K antagonist and increased risk of bleeding.

More frequent monitoring of the INR. Possible adjustment of the vitamin K antagonist dosage during treatment with econazole and after its discontinuation.

Pregnancy

Preclinical studies have shown reproductive toxicity (see section Preclinical safety).

The systemic absorption of econazole is low (< 10 %) after application to healthy skin in humans. There are no adequate and well-controlled studies on the harmful effects of using GYNOPURA in pregnant women, nor relevant epidemiological data.

Consequently, GYNOPURA should not be used during the first trimester of pregnancy, unless the physician considers it essential for the mother. GYNOPURA may be used during the second and third trimesters if the potential benefit to the mother outweighs the possible risks to the fetus.

Breast-feeding

After oral administration of econazole nitrate to lactating rats, econazole and/or its metabolites were excreted into the milk and were found in the pups.

It is not known whether cutaneous application of GYNOPURA can result in sufficient systemic absorption of econazole to produce detectable amounts in breast milk. Caution should be exercised when GYNOPURA is used by breastfeeding mothers. Do not apply to the breasts during breastfeeding.

The safety of GYNOPURA, all forms combined, was evaluated in 470 patients who participated in 12 clinical trials treated either with the cream form (8 clinical trials) or the emulsion form (4 clinical trials). The most frequently reported adverse effects were: pruritus (1,3 %), burning sensation (1,3 %), pain (1,1 %).

Adverse effects reported during clinical trials and since the marketing of GYNOPURA, all forms combined, are classified by System Organ Class and by frequency using the following categories: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100), rare (≥ 1/10 000 to < 1/1 000), very rare (< 1/10 000), frequency not known (cannot be estimated from the available data).

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: www.signalement-sante.gouv.fr.

No cases of overdose have been reported to date.

Treatment:

GYNOPURA must be used only by the cutaneous route. In case of accidental ingestion, treatment will be symptomatic.

If this medicine is accidentally applied to the eyes, rinse with clear water or a saline solution and consult a doctor if symptoms persist.

Pharmacotherapeutic classification: ANTIFUNGAL FOR TOPICAL USE - IMIDAZOLE AND TRIAZOLE DERIVATIVES, ATC code: D01AC03.

Mechanism of action

Econazole nitrate is an imidazole derivative with antifungal and antibacterial activity.

The antifungal activity has been demonstrated in vitro and acts on the agents responsible for cutaneous and mucosal mycoses:

• Dermatophytes (Trichophyton, Epidermophyton, Microsporum),
• Candida and other yeasts,
• Malassezzia furfur (agent of Pityriasis Capitis and of Pityriasis Versicolor),
• Moulds and other fungi.

The antibacterial activity has been demonstrated in vitro against Gram-positive bacteria.

Its mechanism of action, which differs from that of antibiotics, operates at several levels: membrane (increase in permeability), cytoplasmic (inhibition of oxidative processes at the level of the mitochondria), and nuclear (inhibition of RNA synthesis).

• Activity on Corynebacterium minutissimum (erythrasma),
• Actinomycetes.

In vivo experiments performed in healthy volunteers (with or without occlusive dressing) showed that econazole nitrate penetrated the deepest dermal cell layers. In the upper layers of the dermis and in the epidermis, econazole nitrate reaches fungicidal concentrations.

Econazole nitrate accumulates in large quantities in the stratum corneum and remains there for 5 to 16 hours. The stratum corneum thus acts as a reservoir.

The rate of systemic absorption is approximately between 0,5 % and 2 % of the applied dose.

Transcutaneous passage may be increased on damaged skin.

A low neonatal survival rate and foetal toxicity have been reported only in cases of maternal toxicity. In animal studies, econazole nitrate showed no teratogenic effect but was foetotoxic in rodents at maternal doses of 20 mg/kg/day subcutaneously and 10 mg/kg/day orally. The transferability of these observations to humans is unknown.

3 years.

Store at a temperature not exceeding 25 °C.

No special requirements.