Pevaryl 1% 6 sachets 10 g non-alcoholic cutaneous solution

INDICATIONS

The product is indicated in the therapy of: - skin mycosis caused by dermatophytes, yeasts and moulds; - skin infections caused by Gram-positive bacteria: streptococci and staphylococci; - mycotic otitis externa, ear canal mycosis (limited to the skin emulsion form); - onychomycosis; - Pityriasis Versicolor.

ACTIVE INGREDIENTS

Pevaryl 1% cream 100 g of cream contains: active ingredient: econazole nitrate 1.0 g. Excipients with known effect: This medicinal product contains butylated hydroxyanisole, benzoic acid and linalool as fragrance in the perfume. Pevaryl 1% skin spray, alcoholic solution 100 g of alcoholic skin solution contain: active ingredient: econazole nitrate 1.0 g. Excipients with known effect: This medicinal product contains propylene glycol and linalool as fragrance in the perfume. Pevaryl 1% skin powder 100 g of skin powder contains: active ingredient: econazole nitrate 1.0 g. Excipients with known effect: This medicinal product contains linalool as a fragrance in the perfume. Pevaryl 1% skin emulsion 100 g of skin emulsion contain: active ingredient: econazole nitrate 1.0 g. Excipients with known effect: This medicinal product contains butylated hydroxyanisole, benzoic acid and linalool as fragrance in the perfume. Pevaryl 1% non-alcoholic cutaneous solution 100 g of non-alcoholic cutaneous solution contains: active ingredient: econazole 1.0 g. Excipients with known effect: This medicinal product contains benzyl alcohol. For the full list of excipients, see section 6.1.

EXCIPIENTS

Cream: Excipients: mixture of stearic acid esters with glycols; mixture of fatty acids with polyethylene glycol; Vaseline oil; Butylated hydroxyanisole; perfume n.4074; benzoic acid; purified water. Alcoholic solution skin spray: Excipients: ethyl alcohol; propylene glycol; perfume n.4074; tris(hydroxymethyl)amino methane. Skin dust: Excipients: precipitated silica; perfume n.4074; zinc oxide; talc. Skin emulsion: Excipients: precipitated silica; mixture of stearic acid esters with glycols; mixture of fatty acids with polyethylene glycol; Vaseline oil; butylated hydroxyanisole; benzoic acid; perfume n.4074; purified water. Non-alcoholic skin solution: Excipients: polysorbate 20; benzyl alcohol; sorbitan monolaurate; N-[2-hydroxyethyl]-N-[2-(laurylamino)-ethyl] amino acetic acid sodium salt of 3,6,9-trioxadocosyl sulfate; polyoxyethylene glycol 6000 distearate; purified water.

CONTRAINDICATIONS AND SIDE EFFECTS

PEVARYL is contraindicated in patients with known hypersensitivity to the active substance or to any of the excipients, listed in paragraph 6.1.

DOSAGE

PEVARYL must be applied morning and evening, to the infected skin areas, with a light massage, until the mycosis completely disappears (1-3 weeks). It is advisable to continue the application of PEVARYL for a few days after the disappearance of the mycosis. Intertriginous spaces (e.g. interdigital spaces of the foot, folds of the buttocks) in the wet stage should be cleansed with gauze before applying PEVARYL. In the treatment of onychomycosis, an occlusive bandage is recommended. In the treatment of otomycosis (only if there is no lesion of the eardrum) instill 1-2 drops of PEVARYL skin emulsion 1-2 times a day, or insert a strip of gauze soaked in it into the external auditory canal. PEVARYL cutaneous powder should be used as complementary therapy to PEVARYL cream and alcoholic solution cutaneous spray. In the case of intertrigo, the use of PEVARYL cutaneous powder may be sufficient. PEVARYL non-alcoholic skin solution: sprinkle the entire damp body for three consecutive evenings, placing the product on a sponge; do not rinse. The drug takes effect during the night and must be removed by washing the following morning. If Pityriasis Versicolor has not been eradicated after 15 days from the end of the applications, repeat the treatment. To avoid relapses it is recommended to carry out the treatment again after 1 and 3 months. The regular and prescribed use of PEVARYL is of decisive importance for recovery.

CONSERVATION

Emulsion, skin spray, alcoholic solution and cream: store at a temperature not exceeding 25°C. Cutaneous powder: this medicinal product does not require any special storage conditions. PEVARYL, like any medicine, must be stored out of the reach of children.

WARNINGS

All pharmaceutical forms of PEVARYL are indicated for external use only. PEVARYL is not for ophthalmic or oral use. In case of sensitization or irritation reaction, discontinue use of the product. Econazole nitrate powder contains talc. Avoid inhalation to prevent irritation of the airways, especially in children and infants. The application of the spray forms must be done avoiding inhaling the product and making excessive or improper use of it. Important information about some excipients. PEVARYL1% cream contains butylated hydroxyanisole, benzoic acid and linalool: This medicine contains butylated hydroxyanisole. May cause local skin reactions (e.g. contact dermatitis) or irritation of the eyes and mucous membranes. This medicine contains 60 mg of benzoic acid in each 30 g tube which is equivalent to 2 mg/g of cream. Benzoic acid may cause local irritation. Benzoic acid may increase jaundice (yellowing of the skin and eyes) in newborns up to 4 weeks of age. This medicine contains a fragrance with linalool. Linalool can cause allergic reactions. PEVARYL 1% skin spray, alcoholic solution contains propylene glycol and linalool: This medicinal product contains 983.0 mg of propylene glycol per unit dose, which is equivalent to 491.5 mg/g. Propylene glycol may cause local irritation. This medicine contains a fragrance with linalool. Linalool can cause allergic reactions. PEVARYL 1% skin powder contains linalool: This medicine contains a fragrance with linalool. Linalool can cause allergic reactions PEVARYL 1% skin emulsion contains butylated hydroxyanisole, benzoic acid and linalool: This medicinal product contains butylated hydroxyanisole. May cause local skin reactions (e.g. contact dermatitis) or irritation of the eyes and mucous membranes. This medicine contains 60 mg of benzoic acid in each 30 g bottle which is equivalent to 2 mg/g of cream. Benzoic acid may cause local irritation. Benzoic acid may increase jaundice (yellowing of the skin and eyes) in newborns up to 4 weeks of age. This medicine contains a fragrance with linalool. Linalool can cause allergic reactions. PEVARYL 1% non-alcoholic cutaneous solution contains benzyl alcohol: This medicine contains 10 mg of benzyl alcohol in each sachet (10 mg), which is equivalent to 1 mg/g. Benzyl alcohol may cause allergic reactions. Benzyl alcohol may cause mild local irritation.

INTERACTIONS

Econazole is a known inhibitor of cytochromes CYP3A4 and CYP2C9. Despite the limited systemic availability after cutaneous application, clinically relevant interactions with other medicinal products may occur and some have been reported in patients treated with oral anticoagulants, such as warfarin and acenocoumarol. In patients receiving oral anticoagulants, caution should be used and the INR should be monitored more frequently. A dosage adjustment of the oral anticoagulant drug may be necessary during treatment with econazole and after its discontinuation.

SIDE EFFECTS

Data from clinical studies: The safety of econazole nitrate cream (1%) and econazole nitrate emulsion (1%) was evaluated in 12 clinical studies involving 470 subjects, who received administration of at least one of the formulations. Based on the safety data collected from these clinical studies, the most commonly reported adverse drug reactions (ADRs) (incidence ≥ 1%) were (with incidence%): pruritus (1.3%), burning sensation of the skin (1.3%) and pain (1.1%). The ADRs reported with the use of PEVARYL dermatological formulations both in clinical studies, including the adverse reactions reported above, and in post-marketing experience are reported below. Frequencies are reported according to the following convention: Very common ( ≥ 1/10); Municipality ( ≥ 1/100, <1/10); Uncommon ( ≥ 1/1,000, <1/100); Rare ( ≥ 1/10,000, <1/1,000); Very rare (<1/10,000), Not known (frequency cannot be estimated from the available data). In the table below, which shows the adverse reactions of the dermatological formulations of Pevaryl, all ADRs with a known incidence (common or uncommon) come from clinical trial data and all adverse reactions with an unknown incidence come from post-marketing data. Table 1: Adverse Drug Reactions

System organ class - Adverse drug reactions: Frequency.

System Organ Class - Adverse drug reactions: Common (≥ 1/100, < 1/10). Uncommon (≥ 1/1,000, < 1/100). Not Known.

Immune system disorders - Hypersensitivity

Skin and subcutaneous tissue disorders - Adverse drug reactions: Itching, burning sensation of the skin. Erythema. Angioedema, contact dermatitis, rash, urticaria, vesiculation, skin exfoliation.

Systemic disorders and conditions relating to the administration site - Adverse drug reactions: Pain. Malaise Swelling.

The use of products for topical use, especially if prolonged, can give rise to sensitization phenomena. In case of hypersensitivity reactions it is necessary to interrupt treatment and institute appropriate therapy. Reporting of suspected adverse reactions. Reporting suspected adverse reactions that occur after authorization of the medicine is important, as it allows continuous monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system at www.agenziafarmaco.gov.it/it/responsabili.

OVERDOSE

The available pharmaceutical forms are intended exclusively for topical application. In case of accidental ingestion, nausea, vomiting and diarrhea may occur and must be treated with symptomatic therapy. If the product accidentally comes into contact with the eyes, wash with clean water or saline and contact a doctor if symptoms persist. Pevaryl 1% skin powder The powder formulation contains talc: accidental massive aspiration of the dust can cause blockage of the airways, particularly in infants and children. Respiratory arrest should be treated with supportive therapy and oxygen. If breathing is compromised, the following measures should be considered: endotracheal intubation, removal of material and assisted ventilation.

PREGNANCY AND BREASTFEEDING

Pregnancy: Animal studies have shown reproductive toxicity. The risk in humans is unknown. (see section 5.3) In humans, after topical application to intact skin, the systemic absorption of econazole is poor (< 10%). There are no adequate and controlled studies, nor epidemiological data, on the side effects resulting from the use of PEVARYL during pregnancy. Due to systemic absorption, PEVARYL should not be used during the first trimester of pregnancy unless the doctor considers it necessary for the patient's health. PEVARYL can be used during the second and third trimesters of pregnancy if the potential benefit to the mother outweighs the possible risks to the fetus. Breastfeeding: After oral administration of econazole nitrate to lactating rats, econazole and/or its metabolites were excreted in maternal milk and detected in the pups. It is not known whether cutaneous administration of PEVARYL can result in sufficient systemic absorption of econazole to produce detectable concentrations of econazole in human breast milk. Caution should be used when PEVARYL is administered to women during breastfeeding. Fertility: Results from reproduction studies conducted in animals showed no effects on fertility (see section 5.3)

EFFECTS ON DRIVING ABILITY

Not known.