Micetal Dermal Cream
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Micetal Dermal Cream
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Each gram of cream contains: Flutrimazole (INN)
10mg
3. PHARMACEUTICAL FORM
Cream (O/W emulsion)
4 CLINICAL PARTICULARS
4.1. Therapeutic Indications
MICETAL Dermal Cream is indicated for the topical treatment of tinea pedis, tinea corporis, tinea cruris, cutaneous candidiasis, and pityriasis versicolor.
4.2. Posology and Method of Administration
Adult
MICETAL Dermal Cream is applied topically once or twice daily. The cream should be applied sparingly and rubbed gently into the cleansed, affected skin and surrounding area. Application to intertriginous lesions should be performed with small quantities to avoid skin maceration.
The recommended duration of therapy is four weeks, with the exception of pityriasis for which 1 to 3 weeks may suffice. Patients should be advised to continue applications should there be early resolution of lesions (unless otherwise instructed). Failure to respond after four weeks of therapy should prompt a re-evaluation of the diagnosis.
Children
The safety and efficacy of MICETAL Dermal Cream has not been established in children under the age of 10.
Elderly
Same posology and method of administration as for adults.
4.3. Contra-Indications
MICETAL Dermal Cream is contra-indicated in individuals who have shown hypersensitivity to antifungals of the imidazole type or to any of the components of the pharmaceutical form (see section 6.1. List of excipients).
4.4. Special Warnings and Special Precautions for Use
MICETAL Dermal Cream is for external use only.
MICETAL Dermal Cream should be applied only to the affected area(s) and a narrow border of unaffected peri-lesional skin (about 0.5 cm).
The possible systemic absorption and local toxicity of MICETAL Dermal Cream following application to exposed subepidermal layers has not been studied. Therefore, the product should not be applied to lesions where disruption of the epidermal layer is evident (eg. as in ulcerated areas).
MICETAL Dermal Cream must not be applied to the eyes, to skin in close proximity to the eyes, to any mucous membranes or to skin adjacent to mucous membranes.
If irritation or sensitivity develop during the use of MICETAL Dermal Cream, treatment should be discontinued and appropriate therapy instituted.
4.5. Interaction with other Medicinal Products and other Forms of Interaction
None known.
4.6. Pregnancy and Lactation
From animal studies no teratogenic effects due to flutrimazole could be inferred. To date, there is no clinical experience from controlled studies using MICETAL Dermal Cream in pregnant women. During the first trimester of pregnancy MICETAL Dermal Cream should be used only when the drug is considered essential to the welfare of the patient.
Since it is not known whether flutrimazole is excreted in human milk, caution should be exercised when the drug is administered to a nursing woman.
MICETAL Dermal Cream should not be applied to the breasts during lactation.
4.7. Effects on Ability to Drive and Use Machines
None.
4.8. Undesirable Effects
The incidence of adverse reactions associated with the administration of MICETAL Dermal Cream was 8% in clinicals trials, the most common ones being slight burning, irritation, itching and erythema in the application area.
Hypersensitivity reactions are possible and may occur as a worsening of the rash in the first instance.
4.9. Overdose
Acute overdosage with topical application of flutrimazole is unlikely and would not be expected to lead to a life-threatening situation. However, in case of accidental ingestion a symptomatic treatment should be followed.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Flutrimazole is a topical antifungal of the imidazole type. Like other imidazole derivatives, flutrimazole exerts its activity by altering the fungal cell membrane because of its interference with the ergosterol synthesis by inhibition of the enzyme lanosterol-14a-demethylase.
Microbiology
In-vitro studies have demonstrated that flutrimazole is active against several species of the genera Candida, Microsporum, and Trichophyton, as well as Epidermophyton floccosum and Malassezia furfur (Pityrosporum orbiculare).
The following fungal species, which are relevant to the approved indications have been shown to be susceptible to flutrimazole in vitro and clinical efficacy in infections due to one or more of these organisms has been satisfactorily demonstrated in clinical trials:
Epidermophyton floccosum Malasseziafurfur (Pityrosporum orbiculare)
Microsporum can is Microsporum gypseum Trichophyton mentagrophytes Trichophyton rubrum
5.2 Pharmacokinetic Properties
The percutaneous absorption of flutrimazole in intact or scarified skin of animals was very low. Skin distribution studies in animals revealed that flutrimazole is retained mainly in the stratum spinosum, stratum granulosum and the basal layer of the epidermis, the latter acting as a barrier preventing the penetration of the drug.
The poor percutaneous absorption was confirmed by the results of a study in humans: Following the application of 0.6 g of a cream containing 1% (14C)-flutrimazole applied to normal or scarified skin of a surface area of 250 cm2, no radioactivity was observed in plasma and faeces, while in urine only 0.65% of the dose administered could be recovered.
In vitro metabolism studies performed suggest that flutrimazole is not metabolised by cytochrome P-450 from human skin microsomes, but with both dog and human hepatic microsomes one metabolite was formed suggesting the involvement of cytocbrome P-450.
5.3 Pre-clinical Safety Data
The poor percutaneous absorption of flutrimazole indicates a minimal risk of systemic toxic effects. However, toxicity trials performed after systemic application of flutrimazole revealed a very low acute toxicity, and the only effects observed in repeat dose and reproduction studies were attributed to effects on the biosynthesis of steroids known for all imidazole antifungals. There is no evidence of genotoxicity or teratogenicity, and the nature of the compound as well as its route and duration of administration in humans suggest absence of carcinogenic potential.
The topical application of flutrimazole in animals did not produce sensitization or reactions of phototoxicity.
6
PHARMACEUTICAL PARTICULARS
List of Excipients
6.1
Benzyl alcohol 1%, macrogol cetostearyl ether, cetostearyl alcohol, glyceryl monostearate 40-50, diisopropyl adipate, anhydrous disodium hydrogen phosphate, sodium dihydrogen phosphate dihydrate, macrogol 400 and purified water.
6.2 Incompatibilities
None known.
6.3 Shelf-Life
5 years.
6.4 Special Precautions for Storage
MICETAL Dermal Cream should be stored below 250C.
6.5 Nature and Content of Container
30 g aluminium tube with screw cap.
6.6 Special precautions for disposal
None.
ADMINISTRATIVE DATA
7. MARKETING AUTHORISATION HOLDER
J. Uriach & Cia S.A.
Poligon Industrial Riera de Caldes
Avinguda Cam! Reial 51-57
08184 Palau-solita Plegamans (Barcelona)
SPAIN
MARKETING AUTHORISATION NUMBER(S)
8.
PL 11906/0002
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
06/01/2003
10 DATE OF REVISION OF THE TEXT
15/07/2009