Clotrimazole - instructions for use, dose, side effects, contraindications

Name of components	Amount, mg
Active substance
Clotrimazole¹	100,0
Excipients
Lactose Monohydrate	1122,2
Potato starch'¹	180,0
Adipic acid	140,0
Sodium bicarbonate	110,0
Magnesium stearate	31,3
Silica colloidal dioxide	12,3
Sodium lauryl sulfate	4,2
Total mass of the dosing unit	1700,0

Notes:

1. This amount of clotrimazole refers to an anhydrous substance with a clotrimazole content of 100%, so the amount to be loaded is calculated based on the actual content of the active substance and water in the original substance. The difference between the tabulated and calculated amount of clotrimazole is compensated for by the amount of lactose monohydrate being loaded.

2. This amount refers to anhydrous potato starch, so the charge is calculated taking into account the water content of the starting material.

Description:

White biconvex tablets, with a smooth surface, oblong, rounded at one end and flattened from the other.

Pharmacotherapeutic group:Antifungal agent.

ATX: & nbsp

G.01.A.F.02 Clotrimazole

Pharmacodynamics:

Mechanism of action

Clotrimazole inhibits the growth and division of microorganisms and, depending on the concentration, may exert a fungistatic or fungicidal action. The mechanism of action of clotrimazole is associated with a change in the permeability of cell membranes due to the effect on the synthesis of ergosterol and binding to the phospholipids of the fungal cell wall. Clotrimazole suppresses the synthesis of proteins, fats, DNA, polysaccharides, damages nucleic acids in mushroom cells and accelerates the excretion of potassium. It can also suppress the activity of oxidative and peroxidant enzymes and the biosynthesis of triglycerides and phospholipids in fungal cells. In higher concentrations clotrimazole causes damage to cell membranes by mechanisms that do not depend on the synthesis of sterols. Clotrimazole prevents the transformation of blastospore Candida albicans in invasive forms of mycelium. Changing the activity of the cell membrane leads to cell death, and this process depends on the contact of the drug with the microbes.

Activity spectrum

Clotrimazole is characterized by a wide range of antifungal and antibacterial activity. It is active against:

- dermatophytes (Epidermophyton floccosum, Microsporum canis, Trichophyton mentagrophytes, Trichophyton rubrum);

- yeast (Candida sp., Cryptococcus neoformans);

- dimorphic fungi (Coccidioides immitis, Histoplasma capsulatum. Paracoccidioides brasiliensis);

- protozoa (Trichomonas vaginalis).

Clotrimazole is also active against certain gram-positive bacteria.

In vitro Clotrimazole is characterized by a wide spectrum of fungistatic and fungicidal activity. It affects the mycelium of dermatophytes (Trichophyton, Microsporum, Epidermophyton) is similar to griseofulvin, its effect on budding yeast-like fungi (Candida) is similar to the action of polyenes (amphotericin B and nystatin).

In concentrations below 1 μg / mlClotrimazole inhibits the development of most strains Trichophyton rubrum, Trichophyton mentcigrophytes, Epidermophyton floccosum, Microsporum canis.

In concentration 3 mcg / ml clotrimazole suppress the development of most other microorganisms: Pityrosporum orbiculare, Aspergillus fumigatus, kind Candida, including Candida albicans, some strains Staphylococcus aureus, Streptococcus pyogenes, a also some strains Proteus vulgaris and Salmonella. Clotrimazole is active against fungi of genera: Sporothrix, Cryptococcus, Cephalosporium, Fusarium. In concentrations above 100 μg / ml, it is effective against Trichomonas vaginalis.

Mushrooms that are resistant to clotrimazole are extremely rare; only single resistant strains are described Candida guilliermondii.

There was no reported development of resistance to fungi sensitive to clotrimazole after passage Candida albicans and Trichophyton mentagrophytes. Cases of development of resistance to clotrimazole strains Candida albicans, resistant to polyene antibiotics due to a chemical mutation, is not described.

Pharmacokinetics:

Suction and distribution

Pharmacokinetic studies of clotrimazole with intravaginal application have shown that the absorption is 3-10% of the administered dose. In the liver clotrimazole is metabolized to pharmacologically inactive metabolites, therefore its plasma concentration in intravaginal administration at a dosage of 500 mg is less than 10 ng / ml, confirming the fact that clotrimazole when intravaginal introduction does not lead to significant systemic effects or side effects.

Metabolism

Clotrimazole is mainly metabolized in the liver to metabolites that are excreted through the kidneys and intestines.

Indications:

- Vaginitis caused by fungi of the genus Candida;

- infections of genital organs caused by fungi of the genus Candida, including infections caused by strains resistant to nystatin;

- superinfections of the genital organs caused by other pathogens that are sensitive to clotrimazole;

- sanation of the birth canal before delivery.

Contraindications:

- Hypersensitivity to clotrimazole or other components of the drug;

- age up to 12 years;

- the period of menstruation.

Carefully:

In the first case of candidal vaginitis, it is necessary to consult a doctor.

If any of the factors listed below are identified before the appointment of vaginal tablets Clotrimazole you should consult your doctor:

- more than two episodes of candidal vaginitis in the previous six months;

- the presence of a history of sexually transmitted diseases, or contact with a partner who has a sexually transmitted disease;

- proven or suspected pregnancy;

- age over 60 years;

- a history of hypersensitivity to imidazoles or other antifungal drugs for vaginal use.

Pregnancy and lactation:

Fertility

Data is not available.

Pregnancy

Use clotrimazole when pregnancy is allowed only if the intended benefit to the mother exceeds the potential risk to the fetus.

In the epidemiological studies that included a retrospective analysis, when applying clotrimazole during pregnancy (even in the first trimester), there was no undesirable effect on the pregnant woman's body,as well as birth defects and unwanted phenomena in the fetus.

Breastfeeding period

The use of clotrimazole in women during breastfeeding is allowed only if the intended benefit to the mother exceeds the potential risk to the child.

Dosing and Administration:

For intravaginal application.

1 tablet 2 times a day. For 3 days or 1 tablet 1 time per day for 6-7 days, preferably at bedtime.

If there is no effect within 3 days, you should confirm the diagnosis.

If symptoms persist for more than 7 days, you need to see a doctor.

Treatment can be repeated if necessary, however, recurrent infections can indicate underlying pathology, including diabetes mellitus or HIV infection.

If symptoms recur within 2 months, the patient should consult a physician.

In case of simultaneous infection of the vulva and adjacent areas, external treatment with cream is necessary.

To completely dissolve vaginal tablets, normal moisture of the vaginal mucosa is required. In women with dry vaginal mucosa, undissolved portions of the tablet may be excretedout. To prevent this, it is necessary to inject the tablet as deep as possible into the vagina before bed.

Treatment during menstruation is not recommended because of the risk of washing the tablet, it must be completed before menstruation.

For sanation of the birth canal, 1 tablet immediately before birth.

Special patient groups

Children

For children over 12 years of age the method of application is the same as for adults.

A drug Clotrimazole Vaginal pills are not recommended for children under 12 years of age.

Repeated course of therapy is possible in accordance with medical indications.

Side effects:The adverse events presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence. Frequency of occurrence is defined as follows: Often (> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1 000 and <1/100), rarely (> 1/10 000 and <1/1 000), rarely (<1/10 000, including individual cases), unknown (can not be estimated from the data available). Frequency categories were formed on the basis of post-registration observation.

Frequency of occurrence of undesirable phenomena

Immune system disorders

Unknown: allergic reactions (urticaria, fainting, arterial hypotension, dyspnea).

Disorders from the gastrointestinal tract

Unknown: abdominal pain.

Violations of the genitals and mammary gland

Unknown: discomfort in the vulva and vagina, congestion and swelling

mucous membrane of the vagina, vaginal discharge, burning, peeling, irritation, itching, pelvic pain, burning sensation in the penis at the sexual partner, pain during intercourse, rash. When these symptoms appear, clotrimazole therapy should be discontinued.

Disturbances from the nervous system

Unknown: headache.

Disorders from the kidneys and urinary tract

Unknown: frequent urination, intercurrent cystitis.

Overdose:

Symptoms

Dizziness, nausea, vomiting.

Treatment

In case of accidental ingestion, symptomatic treatment should be performed.

Interaction:

Contraceptives

The data from laboratory studies indicate that the use of contraceptives containing latex can cause damage to them when combined with the drug Clotrimazole. Consequently, the effectiveness of such contraceptives can be reduced. Patients should be advised to use alternative methods of contraception for at least five days after using the drug Clotrimazole.

Tacrolimus

Concomitant use of clotrimazole vaginally and tacrolimus (FK-506; immunosuppressant) orally may lead to an increase in tacrolimus concentration in the plasma. Patients should be closely monitored in relation to symptoms of an overdose of tacrolimus with the measurement of the concentration of the drug if necessary.

Amphotericin B, nystatin, natamycin reduce the effectiveness of clotrimazole while simultaneously using them.

Special instructions:

Effectiveness of treatment

Avoid contact with eyes and ingestion.

It is recommended to carry out simultaneous treatment of all affected parts of the body. Vaginal tablets Clotrimazole Do not use if any of the following symptoms occur, unless otherwise recommended by your doctor:

- irregular bleeding from the vagina;

- pathological vaginal bleeding, uterine hemorrhage or bloody vaginal discharge;

- ulcers, blisters or open wounds of the vulva or vagina;

- pain in the lower abdomen or dysuria;

- Any undesirable phenomena, for example reddening, irritation, puffiness, associated with treatment;

- fever (temperature 38 ° C or higher) or chills; nausea or vomiting;

- diarrhea;

- separated from the vagina with an unpleasant odor; backache; pain in the shoulder area.

To prevent reinfection, simultaneous treatment of sexual partners is necessary.

Effect on the ability to drive transp. cf. and fur:

Not studied.

Form release / dosage:

Vaginal tablets, 100 mg.

For 6 tablets in a PVC / aluminum foil blister. One blister with instructions for medical use is placed in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:Without recipe

Registration number:П N011413 / 01

Date of registration:07.06.2010

The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia

Manufacturer: & nbsp

GlaxoSmithKline Pharmaceuticals, S.A. Poland

Representation: & nbspGlaxoSmithKline group of companies GlaxoSmithKline group of companies Unknown

Information update date: & nbsp17.05.2013

Illustrated instructions

Instructions

Clotrimazole (Clotrimazole)