Clotrimazole

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CLOTRIMAZOLE

Composition:

Active ingredient: clotrimazole;

1 tablet contains clotrimazole (calculated as 100 % dry substance) – 100 mg;

Excipients: lactose monohydrate, corn starch, microcrystalline cellulose, colloidal anhydrous silicon dioxide, adipic acid, calcium stearate.

Pharmaceutical form. Vaginal tablets.

Main physicochemical properties: white or almost white, oval-shaped tablets with a biconvex surface.

Pharmacotherapeutic group. Antimicrobial and antiseptic agents used in gynecology. Imidazole derivatives. ATC Code G01AF02.

Pharmacological properties.

Pharmacodynamics.

The antifungal mechanism of action of imidazole 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, acting against dermatophytes, yeasts, and molds.

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 primary 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 and exerts a trichomonacidal effect at a concentration of 100 µg/ml.

Primarily resistant strains of susceptible fungal species are rarely encountered. Development of secondary resistance in susceptible fungi during treatment has so far been observed very rarely.

Pharmacokinetics.

Only a small amount of clotrimazole (3–10%) is absorbed. Absorbed clotrimazole is rapidly metabolized in the liver into inactive metabolites. Therefore, the peak plasma concentration of clotrimazole after vaginal administration of a 500 mg dose was less than 10 ng/ml. This indicates that the occurrence of measurable systemic adverse effects following intravaginal administration of clotrimazole is unlikely.

Clinical characteristics.

Indications.

Genital infections (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 other components of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

When clotrimazole vaginal tablets are used concomitantly with oral tacrolimus (FK-506; immunosuppressant) or sirolimus, plasma levels of tacrolimus/sirolimus may increase. Patients should be carefully monitored for symptoms of tacrolimus or sirolimus overdose, and plasma concentrations should be checked if necessary.

When clotrimazole is used concomitantly with nystatin, amphotericin B, and other polyene antibiotics, the activity of clotrimazole may be reduced.

High-dose dexamethasone reduces the antifungal activity of clotrimazole.

The antimicrobial activity of clotrimazole is enhanced by high local concentrations of propyl p-hydroxybenzoate.

Special precautions.

The tablets are contraindicated for oral administration. Contact with eyes should be avoided.

Patients should consult a physician in the following cases:

• persistence of symptoms for more than 7 days;
• recurrence of symptoms within 2 months;
• known hypersensitivity to any antifungal agents or imidazole derivatives;
• history of sexually transmitted infections in the patient or her sexual partner;
• more than two episodes of candidal vaginitis within the past 6 months;
• high body temperature (38 °C or higher), lower abdominal pain, dysuria, back pain, purulent vaginal discharge with unpleasant odor, vulvar or vaginal ulcers, erythema, nausea or vomiting, diarrhea, vaginal bleeding or passage of blood clots accompanied by shoulder pain.

During treatment with this medicinal product, vaginal sexual intercourse should be avoided, as the infection may be transmitted to the sexual partner. The product may reduce the effectiveness of latex-based contraceptives (e.g. condoms, diaphragms). This effect is temporary and occurs only during the treatment period. Patients are advised to use alternative contraceptive methods for at least 5 days after administration of the product.

Upon physician's prescription, simultaneous topical treatment of external genital organs with 1% clotrimazole cream or 1% clotrimazole solution may be performed; if necessary, the physician may prescribe additional systemic medicinal products (e.g. oral metronidazole).

Medical consultation is also recommended before use if the patient is pregnant or suspects pregnancy; or if the patient is under 12 or over 60 years of age.

Treatment should not be performed during menstruation. The treatment course should be completed before the onset of menstruation.

Do not use tampons, intravaginal douches, spermicides, or other vaginal products during use of this medicinal product.

In patients with impaired liver function, periodic monitoring of liver function is recommended.

If no therapeutic effect is observed, microbiological testing should be performed to confirm the diagnosis and rule out other causes of the condition. Simultaneous treatment of both sexual partners is recommended.

The product should be used for the full duration of the prescribed treatment course, even if symptoms resolve earlier. Adherence to these recommendations helps prevent reinfection.

Use during pregnancy or breastfeeding.

Animal studies with the active substance have not revealed any effects of clotrimazole on fertility or direct or indirect harmful effects from the standpoint of reproductive toxicity. Clinical data on the use of clotrimazole during pregnancy are limited; therefore, use of vaginal tablets Clotrimazole is not recommended during the first trimester of pregnancy.

During pregnancy, vaginal tablets should be administered without using an applicator.

Breastfeeding should be discontinued during treatment with Clotrimazole vaginal tablets.

Ability to affect reaction rate while driving or operating machinery.

No effect.

Method of administration and dosage.

The drug should be administered to adults as 1 tablet twice daily for 3 days or 1 tablet once daily for 6 days.

Vaginal tablets should be inserted as deeply as possible into the vagina, preferably in the evening. The most convenient way is to lie on the back with slightly bent knees.

Clotrimazole vaginal tablets must dissolve completely within the vagina. If not sufficiently moistened, undissolved fragments of the vaginal tablet may be expelled from 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 the vaginal tablets do not dissolve completely during one night, consider using a vaginal cream instead.

Children.

Do not use in children under 12 years of age. For children aged 12 years and older, use only after consultation with a physician.

Overdose.

There is no risk of acute intoxication, as overdose is unlikely following a single vaginal dose or after accidental oral ingestion. There is no specific antidote.

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

Side effects.

Immune system: allergic reactions, including erythema, skin rash, swelling, fainting, arterial hypotension, dyspnea, urticaria, itching. If these symptoms occur, treatment with clotrimazole should be discontinued.

Reproductive system and mammary glands: peeling of the skin in the genital area; burning sensation, redness, discomfort, pain and swelling of the mucous membrane at the vaginal entrance; irritation, pelvic pain, vaginal bleeding.

Gastrointestinal tract: abdominal pain, gastrointestinal disturbances.

Shelf life. 3 years.

Storage conditions. In the original packaging at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Packaging. 10 tablets per blister, 1 blister per carton.

Prescription status. Over-the-counter.

Manufacturer. Public Joint-Stock Company “Scientific and Production Center “Borshchahivskiy Chemical and Pharmaceutical Plant”.

Manufacturer’s location and address of its business activity.

17 Myru Street, Kyiv, 03134, Ukraine.

INSTRUCTION

for medical use of medicinal product

CLOTRIMAZOLE

(CLOTRIMAZOLE)

Composition:

Active ingredient: clotrimazole;

1 tablet contains clotrimazole (calculated as 100% dry substance) – 100 mg;

Excipients: lactose monohydrate, corn starch, microcrystalline cellulose, colloidal anhydrous silicon dioxide, adipic acid, calcium stearate.

Pharmaceutical form. Vaginal tablets.

Main physicochemical properties: white or almost white, oval-shaped, biconvex tablets.

Pharmacotherapeutic group. Antimicrobial and antiseptic agents used in gynecology. Imidazole derivatives. ATC code G01AF02.

Pharmacological properties.

Pharmacodynamics.

The antifungal mechanism of action of imidazole 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, acting against dermatophytes, yeasts, and molds.

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

The mechanism of action of clotrimazole is related to primary 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 antifungal activity, clotrimazole is also active 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 and exerts trichomonacidal effects at a concentration of 100 µg/mL.

Initially resistant strains of susceptible fungal species are rare. Secondary resistance development in susceptible fungi during treatment has been observed very rarely to date.

Pharmacokinetics.

Only a small amount of clotrimazole (3–10%) is absorbed. Absorbed clotrimazole is rapidly metabolized in the liver into inactive metabolites. Therefore, the peak plasma concentration of clotrimazole after a single 500 mg vaginal dose was less than 10 ng/mL. This indicates that measurable systemic side effects following intravaginal administration of clotrimazole are unlikely.

Clinical characteristics.

Indications.

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

Contraindications.

Hypersensitivity to clotrimazole or to any other component of the medicinal product.

Interaction with other medicinal products and other types of interactions.

Concomitant use of clotrimazole vaginal tablets with oral tacrolimus (FK-506; immunosuppressant) or sirolimus may increase plasma levels of tacrolimus/sirolimus. Patients should be closely monitored for symptoms of tacrolimus or sirolimus overdose, and plasma concentrations should be checked if necessary.

Concomitant use of clotrimazole with nystatin, amphotericin B, or other polyene antibiotics may reduce the activity of clotrimazole.

Dexamethasone, when used in high doses, reduces the antifungal effect of clotrimazole.

The antimicrobial effect of clotrimazole is enhanced by high local concentrations of propyl ester of p-hydroxybenzoic acid.

Special precautions.

Oral administration of the tablets is prohibited. Contact with eyes should be avoided.

Patients should consult a physician if:

• symptoms persist for more than 7 days;
• symptoms recur within 2 months;
• hypersensitivity to any antifungal agents or imidazole derivatives is known;
• the patient or her sexual partner has a history of sexually transmitted infections;
• there have been more than two episodes of candidal vaginitis within the last 6 months;
• high body temperature (38 °C or higher), lower abdominal pain, dysuria, back pain, purulent vaginal discharge with unpleasant odor, vulvar ulcers, vaginal ulcers, redness, nausea or vomiting, diarrhea, vaginal bleeding or passage of blood clots accompanied by shoulder pain occur.

During treatment with this medicinal product, vaginal intercourse should be avoided, as the infection may be transmitted to the sexual partner. The product may reduce the effectiveness of latex-based contraceptives (condoms, diaphragms). This effect is temporary and occurs only during treatment. Patients are advised to use alternative contraceptive methods for at least 5 days after completing treatment.

Upon physician's prescription, simultaneous treatment of external genitalia with 1% clotrimazole cream or 1% clotrimazole solution may be performed; if necessary, the physician may prescribe additional systemic medicinal products (e.g., oral metronidazole).

Patients should also consult a physician before use if pregnant or suspecting pregnancy; if under 12 or over 60 years of age.

Treatment should not be performed during menstruation. Treatment should be completed before the onset of menstruation.

Tampons, intravaginal douches, spermicides, or other vaginal products should not be used during treatment.

In patients with impaired liver function, periodic monitoring of liver function is recommended.

If no therapeutic effect is observed, microbiological testing should be performed to confirm the diagnosis and rule out other causes of disease. Simultaneous treatment of both sexual partners is recommended.

The product should be used for the full duration of treatment, even if symptoms resolve earlier. Adherence to these recommendations helps prevent reinfection.

Use during pregnancy or breastfeeding.

Animal studies with the active substance did not reveal any effect of clotrimazole on fertility or direct or indirect harmful effects in terms of reproductive toxicity. Clinical data on the use of clotrimazole during pregnancy are limited; therefore, use of clotrimazole vaginal tablets is not recommended during the first trimester of pregnancy.

During pregnancy, vaginal tablets should be administered without using an applicator.

Breastfeeding should be discontinued during treatment with clotrimazole vaginal tablets.

Ability to affect reaction rate when driving or operating machinery.

No effect.

Administration and dosage.

For adults: 1 tablet twice daily for 3 days or 1 tablet once daily for 6 days.

Vaginal tablets should be inserted as deeply as possible into the vagina, preferably in the evening, while lying on the back with slightly bent knees.

Clotrimazole vaginal tablets must dissolve completely in the vaginal environment; otherwise, undissolved fragments may be expelled from the vagina. To prevent this, it is important to insert the tablet as deeply as possible before bedtime. If the vaginal tablets do not dissolve completely overnight, consideration should be given to switching to a vaginal cream.

Children.

Not recommended for children under 12 years of age. For children aged 12 years and older, use only after consultation with a physician.

Overdose.

There is no risk of acute intoxication, as overdose is unlikely after a single vaginal dose or accidental oral ingestion. No specific antidote exists.

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

Side effects.

Immune system: allergic reactions, including erythema, skin rash, swelling, fainting, arterial hypotension, dyspnea, urticaria, itching. If these symptoms occur, treatment with clotrimazole should be discontinued.

Reproductive system and mammary glands: peeling of the skin in the genital area; burning sensation, redness, discomfort, pain and swelling of the mucous membrane at the vaginal entrance; irritation, pelvic pain, vaginal bleeding.

Gastrointestinal tract: abdominal pain, gastrointestinal disturbances.

Shelf life. 3 years.

Storage conditions. In the original packaging at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Packaging. 10 tablets per blister, 1 blister per carton.

Prescription status. Over-the-counter.

Manufacturer.

Public Joint-Stock Company “Scientific and Production Center “Borshchahivskiy Chemical and Pharmaceutical Plant”.

Manufacturer’s location and address of its business activity.

17 Myru Street, Kyiv, 03134, Ukraine.