Clotrimazole

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

Composition:

Active ingredient: clotrimazole;

1 g of ointment contains 10 mg of clotrimazole;

Excipients: propylene glycol, polyethylene glycol (macrogol) 400, polyethylene glycol (macrogol) 1500, polyethylene glycol (macrogol) 4000, poloxamer 338, disodium edetate (Trilon B), cetostearyl alcohol, cetostearyl alcohol ether of polyethylene glycol (macrogol), purified water.

Pharmaceutical form. 1% ointment.

Main physicochemical properties: white-colored ointment.

Pharmacotherapeutic group.

Antifungal agents for topical use.

ATC code D01A C01.

Pharmacological Properties.

Pharmacodynamics.

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

Clotrimazole has a broad spectrum of antifungal activity in vitro and in vivo and acts against dermatophytes, yeasts, molds, and dimorphic fungi.

Under appropriate testing conditions, minimal inhibitory concentrations for these fungal types are approximately < 0.062–8.0 mcg/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 proliferation of Corynebacteria and gram-positive cocci (except Enterococci) at concentrations of 0.5–10 mcg/mL of substrate.

Primarily resistant strains of otherwise susceptible fungal species are rarely encountered. Development of secondary resistance during treatment in susceptible fungi has so far been observed very rarely. Preclinical studies conducted in volunteers using single and repeated toxic doses did not reveal any damaging toxic, genotoxic, or effects on reproductive function.

Pharmacokinetics.

Pharmacokinetic studies have shown that absorption of clotrimazole is negligible—less than 2% and 3–10% of the applied dose—with peak plasma concentrations of the active substance below 10 ng/mL. Therefore, the occurrence of adverse reactions or systemic effects is unlikely.

Clinical characteristics.

Indications.

Fungal skin infections caused by dermatophytes, yeasts, molds, and other pathogens sensitive to clotrimazole.

Skin infections caused by Malassezia furfur (pityriasis versicolor) and Corynebacterium minutissimum (erythrasma).

Infections of the vulva and adjacent areas in women (candidal vulvitis), as well as inflammation of the glans penis and foreskin in the sexual partner caused by yeast fungi (candidal balanitis).

Contraindications.

The drug should not be used in cases of hypersensitivity to clotrimazole, cetostearyl alcohol, or any other components of the drug.

Do not use for treatment of nails or scalp skin infections.

Interaction with other medicinal products and other forms of interaction.

Clotrimazole may inhibit the action of other topical antifungal agents, particularly polyene antibiotics (amphotericin B, nystatin, natamycin). The antifungal effect of clotrimazole is suppressed by high doses of dexamethasone and enhanced by topical application of hydroxybenzoic acid (its propyl ester).

Special precautions for use

Cetylstearyl alcohol may cause local skin irritation (e.g., contact dermatitis). Propylene glycol may also cause skin irritation. In such cases, it is recommended to use alternative dosage forms of the drug that do not contain these components.

The cream is intended for topical application to the skin only.

Avoid contact of the cream with the eyes. Do not swallow.

If no clinical improvement is observed within 4 weeks after initiation of treatment, the patient should consult a physician to confirm the diagnosis microbiologically and to rule out other causes of the disease.

When used concomitantly with latex products (e.g., condoms and diaphragms) in the genital area, the functional integrity of these products may be reduced due to the excipients contained in the cream, which may consequently affect the safety and efficacy of such contraceptive methods.

This effect is temporary and occurs only during treatment.

Sexual intercourse should be avoided during treatment with this medication, as the infection may be transmitted to the partner.

The patient should consult a physician if hypersensitivity to any antifungal agents or imidazole derivatives is known; if there is a history of sexually transmitted infections in the patient or their sexual partner; or if the patient develops high body temperature (≥38°C), lower abdominal pain, dysuria, back pain, purulent vaginal discharge with unpleasant odor, vulvar or vaginal ulcers, erythema, diarrhea, nausea, vomiting, painful vaginal bleeding, or other systemic symptoms.

Warning regarding treatment of candidal vulvitis in women.
Treatment should not be performed during menstruation. Treatment should be completed before the onset of menstruation.

Do not use tampons, intravaginal douches, spermicides, or other vaginal products during treatment with this medication.

Use during pregnancy or breastfeeding.

Clinical studies on the effect of clotrimazole on female fertility have not been conducted; however, animal studies have not shown any adverse effect of clotrimazole on fertility.

The number of clinical studies on the use of clotrimazole during pregnancy is limited. Animal studies have not revealed any direct or indirect harmful effects in terms of reproductive toxicity. As a precautionary measure, it is advisable to avoid using clotrimazole during the first trimester of pregnancy.

Breastfeeding should be discontinued during treatment with clotrimazole. The cream should not be applied to the area of the mammary glands throughout the entire breastfeeding period.

Ability to affect reaction speed when driving or operating machinery. No effect.

Method of Administration and Dosage

Apply the ointment to adults. Before application, thoroughly clean and dry the affected areas. Apply the ointment 1–3 times daily in a thin layer (a 0.5 cm strip) to the affected skin area and surrounding regions, and gently rub in.

For candidal vulvitis or candidal balanitis in adults, apply a 0.5 cm strip of cream 2–3 times daily in a thin layer to the affected areas (external genitalia and perineum in women, or glans penis and foreskin in men), and gently rub in.

Treatment of candidal vulvitis or candidal balanitis requires simultaneous treatment of both sexual partners.

Duration of therapy:

• Erythrasma – 2–4 weeks
• Dermatomycoses – 3–4 weeks
• Pityriasis versicolor – 1–3 weeks
• Candidal vulvitis and candidal balanitis – 1–2 weeks

Depending on the nature and severity of the condition, the physician may prescribe an individual dosing regimen, method of administration, and duration of treatment.

Before applying the medication, wash feet with warm soapy water and thoroughly rub in the ointment, especially between the toes. To ensure effective treatment, continue using the ointment for an additional 2 weeks after subjective symptoms have disappeared, depending on the condition.

The patient must inform the physician if there is no improvement after 4 weeks of treatment.

Children

There is no experience with the use of this medication in children.

Overdose

There is no risk of acute intoxication, as overdose is unlikely following a single vaginal dose or topical application to the skin (even over large skin areas under conditions favoring increased absorption), or after accidental oral ingestion. No specific antidote exists.

In case of accidental oral ingestion, gastric lavage may rarely be required if a life-threatening dose has been ingested within the previous hour or if visible symptoms of overdose are present (e.g., dizziness, nausea, or vomiting). Gastric lavage should only be performed if adequate airway protection is ensured.

Side effects.

During the use of the medication the following adverse reactions may occur:

• Immune system: allergic reactions, including fainting, arterial hypotension, dyspnea, urticaria;
• Skin and subcutaneous tissue: redness (erythema), blisters, malaise, discomfort/pain, swelling, irritation, peeling, itching, rash, prickling, burning/feeling of heat.

In case of hypersensitivity to cetearyl alcohol, allergic reactions on the skin or mucous membranes may occur.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25°C. Do not freeze.

Keep out of reach of children.

Packaging.

15 g or 25 g in tubes; 1 tube per pack.

Supply category.

Over-the-counter.

Manufacturer. JSC "FITOPHARM".

Manufacturer's address and location of its business activity.

Ukraine, 84500, Donetsk region, Bakhmut, Sybirtseva St., 2.

Marketing authorization holder. JSC "FITOPHARM".

Address of the marketing authorization holder.

Ukraine, 02092, Kyiv, Almatynska St., 12.