CLOTRIMAZOLE

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CLOTRIMAZOLE (CLOTRIMAZOLUM)

Composition:

Active substance: clotrimazole;

1 g of cream contains 10 mg of clotrimazole;

Excipients: cetylstearyl alcohol, octyldodecanol, polysorbate 60, sorbitan monostearate, cetil wax, benzyl alcohol, purified water.

Pharmaceutical form. Cream.

Main physicochemical properties: white homogeneous cream.

Pharmacotherapeutic group. Topical antifungal agents. Imidazole and triazole derivatives. Clotrimazole. ATC code D01AC01.

Pharmacological properties.

Pharmacodynamics.

The antifungal mechanism of action of clotrimazole is associated with inhibition of ergosterol synthesis, leading to structural and functional damage of the fungal cytoplasmic membrane.

Clotrimazole has a broad spectrum of antifungal activity in vitro and in vivo, acting against dermatophytes, yeasts, molds, and others.

Under appropriate testing conditions, minimal inhibitory concentrations for these fungal types range from approximately 0.062 to 8.0 µg/ml of substrate.

The mechanism of action of clotrimazole involves primarily fungistatic or fungicidal activity, depending on the concentration of clotrimazole at the site of infection.

In vitro, activity is limited to proliferating fungal elements; fungal spores exhibit only minimal sensitivity.

In addition to its antifungal activity, clotrimazole also acts against Gram-positive microorganisms (streptococci, staphylococci, Gardnerella vaginalis) and Gram-negative microorganisms (Bacteroides).

In vitro, clotrimazole inhibits the growth of Corynebacteria and Gram-positive cocci (except Enterococci) at concentrations of 0.5–10 µg/ml of substrate.

Primary resistant strains among susceptible fungal species are rarely encountered. Development of secondary resistance in susceptible fungi has so far been observed only in very rare instances under therapeutic conditions.

Preclinical studies using repeated toxic doses have not revealed any harmful, genotoxic, or carcinogenic effects on the human body.

Clotrimazole showed no teratogenic effects in reproductive toxicity studies in mice, rats, and rabbits. In rat studies, high oral doses produced maternal toxicity and embryotoxicity, resulting in reduced fetal weight and decreased offspring survival. Studies in rats demonstrated that clotrimazole and/or its metabolites are excreted into milk, reaching concentrations 10–20 times higher than those in plasma within 4 hours after administration, followed by a decline to a ratio of 0.4 within 24 hours.

Pharmacokinetics.

Pharmacokinetic studies have shown that when the cream is applied topically to the skin, clotrimazole is minimally absorbed through intact or inflamed skin into the human systemic circulation. Peak serum concentrations of clotrimazole were below the limit of detection (0.001 µg/ml), indicating that systemic side effects or effects are unlikely to occur following topical application of clotrimazole cream.

Clinical characteristics.

Indications.

Dermatomycoses caused by mold fungi and other fungi (e.g., Trichophyton species).

Dermatomycoses caused by yeasts (Candida species).

Skin conditions associated with secondary fungal infections.

Candidal vulvitis and candidal balanitis.

Contraindications.

Hypersensitivity to the active ingredient or to any of the excipients of the product.

Do not use the cream for treatment of nail infections or scalp skin infections.

Interaction with other medicinal products and other forms of interaction.

Laboratory studies have shown that concomitant use of the cream with latex contraceptives may reduce the functional integrity of the latter, which could consequently affect the efficacy of these products. This effect is temporary and occurs only during the period of application of the product. Patients are advised to use alternative contraceptive methods for at least 5 days after application of this product.

Special precautions for use

Due to the presence of cetyl stearyl alcohol in the medicinal product, local skin reactions (e.g., contact dermatitis) may occur during use.

Use during pregnancy or breastfeeding

Clinical studies on the effect of clotrimazole on female fertility have not been conducted; however, animal studies have shown no effect of clotrimazole on fertility.

The number of studies on the use of clotrimazole during pregnancy is limited. Animal studies with clotrimazole have shown reproductive toxicity when high oral doses were administered (see section "Pharmacodynamics"). Topical treatment with clotrimazole results in low systemic exposure; therefore, harmful effects on reproductive function are not expected.

Clotrimazole may be used during pregnancy, but only under medical supervision.

There are no data on the excretion of clotrimazole into breast milk. However, systemic absorption following topical application is minimal and is unlikely to result in systemic effects. Clotrimazole may be used during breastfeeding. When applied topically to the nipple area, the breasts should be washed before breastfeeding.

Ability to influence the reaction rate while driving or operating machinery

Clotrimazole cream does not affect or has only a negligible effect on the ability to drive or operate machinery.

Method of Administration and Dosage

The product is intended for topical use.

Apply a thin layer of cream to the affected area of skin 2–3 times daily and gently rub in. A ½ cm strip of cream is sufficient to treat an area the size of a palm. Treatment for dermatophytosis should last at least one month, and for candidiasis at least two weeks.

Before applying the cream to infected feet, they should be washed and dried thoroughly, especially between the toes.

Children

Experience of use is lacking.

Overdose

There is no risk of acute intoxication, as overdose is unlikely following topical application (even over large skin areas under conditions favoring increased absorption) or after accidental oral ingestion. There is no specific antidote. After accidental oral ingestion, gastric lavage may rarely be considered if a life-threatening dose has been ingested within the previous hour or if there are visible symptoms of overdose (e.g., dizziness, nausea, vomiting). Gastric lavage should only be performed if appropriate conditions for the procedure are available.

Adverse Reactions

Since data on the adverse effects listed below are based on spontaneous reports, it is not possible to determine their exact frequency.

Immune system disorders: anaphylactic reaction, angioneurotic edema, hypersensitivity.

Vascular disorders: syncope, arterial hypotension.

Respiratory, thoracic and mediastinal disorders: dyspnea.

Skin and subcutaneous tissue disorders: blisters, contact dermatitis, erythema, paresthesia, skin peeling, pruritus, rash, urticaria, skin irritation/burning sensation.

General disorders and administration site conditions: irritation at application site, reaction at application site, swelling, pain.

Allergic reactions on the skin or mucous membranes may occur in patients hypersensitive to cetyl stearyl alcohol.

Shelf life. 3 years.

Storage conditions. Keep out of reach of children. Store below 25 °C. Do not freeze.

Packaging. 20 g of cream in an aluminum tube, 1 tube per cardboard box.

Supply category. Over-the-counter.

Manufacturer.

Delpharm Poznan S.A., Poland.

Manufacturer's address.

189 Grunwaldzka Str., 60-322 Poznan, Poland.