Clotrimazole

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

Composition:

Active substance: clotrimazole;

1 tablet contains 100 mg of clotrimazole;

Excipients: maize starch, lactose, povidone (K-30), magnesium stearate, colloidal anhydrous silicon dioxide, sodium starch glycolate (type A).

Pharmaceutical form. Vaginal tablets.

Main physico-chemical properties: vaginal tablets are elongated in shape with a biconvex surface, one end rounded, the other flat, white in colour.

Pharmacotherapeutic group.

Antibacterial and antiseptic agents used in gynecology, excluding combination products containing corticosteroids. Imidazole derivatives.

ATC code G01AF02.

Pharmacological properties.

Pharmacodynamics.

The mechanism of antifungal action of imidazole derivatives 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 less than 0.062–8.0 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 Trichomonas vaginalis, gram-positive microorganisms (streptococci, staphylococci), and gram-negative microorganisms (Bacteroides, Gardnerella vaginalis).

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 of 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 reproductive effects.

Pharmacokinetics.

Pharmacokinetic studies following vaginal administration have shown that only a small amount of clotrimazole (3–10%) is absorbed. Absorbed clotrimazole is rapidly metabolized in the liver to inactive metabolites. Therefore, the peak plasma concentration of clotrimazole after vaginal administration of a 500 mg dose is less than 10 ng/mL. This indicates that measurable systemic effects or adverse reactions following vaginal administration of clotrimazole are unlikely.

Clinical characteristics.

Indications.

Infections of the genital area (vaginitis) caused by fungi (usually of the genus Candida) and superinfections caused by bacteria sensitive to clotrimazole.

Contraindications.

Hypersensitivity to clotrimazole or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

The following interactions may occur when used concomitantly with other medicinal products:

with oral tacrolimus (FK-506; immunosuppressant) or sirolimus – increased plasma levels of these drugs; when used concomitantly with clotrimazole, careful monitoring of the patient should be performed to detect symptoms of tacrolimus or sirolimus overdose, and, if necessary, by measuring their plasma concentrations;

with nystatin – reduced activity of clotrimazole;

with amphotericin B and other polyene antibiotics – reduced activity of the latter.

Concomitant use of clotrimazole with latex contraceptives may damage the latter; therefore, the effectiveness of such contraceptives may be reduced. Patients are advised to use alternative contraceptive methods for at least 5 days after administration of this medicinal product.

Special precautions for use.

Avoid contact with the eyes. Do not swallow.

The patient is advised to consult a physician:

• at the first signs of the disease;
• if symptoms persist for more than 7 days;
• if symptoms recur within 2 months or occur more than 4 times during the past 12 months;
• if there is a history of sexually transmitted infections or a partner with a significant history of sexually transmitted infections;
• if there have been more than 2 episodes of candidal vaginitis within the past 6 months;
• during pregnancy or suspected pregnancy;
• if the patient is over 60 years of age;
• if the patient has a high body temperature (38 °C or higher), lower abdominal pain, dysuria, back pain, purulent vaginal discharge with unpleasant odor, vulvar or vaginal ulcers, redness, diarrhea, nausea, vomiting, vaginal bleeding accompanied by shoulder pain;
• if hypersensitivity to any antifungal agents or imidazole derivatives has been diagnosed.

It is not recommended to use Clotrimazole without prior medical consultation in the following cases:

• irregular, abnormal, or clotted vaginal bleeding;
• vulvar or vaginal ulcers, or wound formation;
• purulent vaginal discharge with unpleasant odor;
• lower abdominal or back pain, or dysuria;
• any adverse reactions such as redness, irritation, or swelling associated with treatment;
• elevated body temperature (38 °C or higher);
• nausea or vomiting;
• diarrhea.

Treatment should not be carried out during menstruation. Therapy should be completed before the onset of menstruation.

Since both the vagina and external genital organs (labia and adjacent areas) are typically affected, combined treatment of both areas is recommended, including topical application of cream for external use.

During treatment with Clotrimazole, it is recommended that both partners receive treatment using appropriate dosage forms.

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

The efficacy and safety of latex products (such as condoms and diaphragms) may be reduced.

Do not use tampons, vaginal douches, spermicides, or other vaginal products during treatment with Clotrimazole.

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 effect of clotrimazole on fertility.

Animal studies have not revealed any direct or indirect harmful effects in terms of reproductive toxicity. The number of studies on clotrimazole use during pregnancy is limited; therefore, it is recommended to avoid using Clotrimazole during the first trimester of pregnancy.

During pregnancy, vaginal tablets should be used without an applicator.

If Clotrimazole is used, breastfeeding should be discontinued.

Ability to affect reaction speed while driving or operating machinery.

Clotrimazole vaginal tablets do not affect the ability to drive a vehicle or operate machinery, or have only a negligible effect.

Method of Administration and Dosage

One vaginal tablet should be administered in the evening. The treatment course with 100 mg vaginal tablets lasts 6 days.

For children aged 12 years and older, the medicinal product Clotrimazole should be used only after consultation with a physician.

Vaginal tablets should be inserted as deeply as possible into the vagina in the evening. The most convenient way is to lie on the back with slightly bent knees, using an applicator. For children aged 12 years and older, Clotrimazole medicinal product should be applied without an applicator.

Clotrimazole vaginal tablets must completely dissolve within the vagina; otherwise, undissolved fragments of the vaginal tablet may exit the vagina. To prevent this, it is important to insert the medicinal product as deeply as possible into the vagina before going to sleep. If vaginal tablets do not dissolve completely during one night, consider switching to another dosage form.

Children.

The medicinal product Clotrimazole is not indicated before the onset of menarche.

Do not use in children under 12 years of age.

For children aged 12 years and older, use Clotrimazole medicinal product only after consultation with a physician; do not use an applicator.

Overdose.

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

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

Adverse reactions.

Immune system disorders: allergic reactions, including loss of consciousness, arterial hypotension, dyspnea, urticaria.

Reproductive system and breast disorders: skin desquamation in the genital area, pruritus, rash, swelling, erythema, discomfort, burning sensation, irritation, pelvic pain, vaginal bleeding.

Gastrointestinal disorders: abdominal pain.

Reporting of adverse reactions after drug registration is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua

Shelf life. 4 years.

Storage conditions.

Store in the original packaging, protected from light, in a place inaccessible to children, at a temperature not exceeding 30 °C.

Packaging.

6 vaginal tablets in a strip, 1 strip with an applicator in a cardboard box.

6 vaginal tablets in a blister, 1 blister with an applicator in a cardboard box.

Availability category. Over-the-counter (without prescription).

Manufacturer.

Evertogen Life Sciences Limited.

Manufacturer's address.

Plot No: S-8, S-9, S-13/P & S-14/P TSIIC, Pharma SEZ, Green Industrial Park, Polepally (V), Jadcherla (M), Mahabubnagar, Telangana, IN-509 301, India.