Active substanceFluconazoleFluconazole
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  • Dosage form: & nbspcapsules
    Composition:

    Active substance: fluconazole -50.00mg.

    Excipients: lactose monohydrate (milk sugar) - 81.72 mg, starch pregelatinized - 26.52 mg, silicon dioxide colloid - 0.16 mg, magnesium stearate - 1.44 mg, sodium lauryl sulfate - 0.16 mg.

    Capsule composition 50 mg: capsule body: dye crimson - 0.0153%, dye quinoline yellow - 0.0134%, titanium dioxide - 2.0000%, gelatin - up to 100%;

    capsule cap: dye azorubin - 0.6483%, colorant

    diamond black - 0.0192%, dye crimson - 0.0336%, dye blue patented - 0.0088%, dye quinoline yellow - 0.1912%, titanium dioxide - 0.8000%, gelatin - up to 100%.

    Active substance: fluconazole -150.00 mg.

    Auxiliaryth substances: lactose monohydrate (sugar milk) - 58.49 mg, starch pregelatinization - 18.98 mg, silicon dioxide colloid - 0.23 mg, magnesium stearate - 2.07 mg, sodium lauryl sulfate - 0.23 mg.

    Capsule composition: 150 mg: capsule body: titanium dioxide -0.8000 %, iron oxide oxide yellow 0.1%, gelatin - up to 100%; capsule cap: titanium dioxide 2.0%, iron oxide oxide yellow 0,1%, gelatin - up to 100%

    Description:

    Capsules hard gelatin № 2. Capsules 50 mg - capsule case light brown, with pink shade of color, cap capsule brownish red color, opaque.

    Capsules 150 mg - body and cap of light yellow color, opaque. The contents of the capsules are a powder or a mixture of powder and granules white or white with a slightly yellowish hue of color. It is allowed to compact the contents of the capsule according to the shape of the capsule, disintegrating upon pressing.

    Pharmacotherapeutic group:Antifungal agent.
    ATX: & nbsp

    J.02.A.C   Triazole derivatives

    J.02.A.C.01   Fluconazole

    Pharmacodynamics:
    Fluconazole, a representative of a new class of triazole antifungal agents. Has a highly specific effect, inhibiting the activity of enzymes of fungi, dependent on cytochrome P450. Blocking the conversion of lanosterol of fungal cells to ergosterol; increases the permeability of the cell membrane, disrupts its growth and replication. Fluconazole, being highly selective for cytochrome P450 fungi, practically does not inhibit these enzymes in the human body (in comparison with itraconazole, clotrimazole, econazole and ketoconazole to a lesser extent suppresses oxidative processes dependent on cytochrome P450 in human liver microsomes). Does not have antiadrogenic activity.
    It is active in opportunistic mycoses, including those caused by Candida spp. (including generalized forms of candidiasis on the background of immunodepression), Cryptococcus neoformans and Coccidioides immitis (including intracranial infections), Microsporum spp. and Trichophyton spp .; with endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulatum (including immunosuppression).

    Pharmacokinetics:
    Suction
    After oral administration fluconazole well absorbed. Simultaneous food intake does not affect the absorption rate (absorption) of the drug when ingested.The time to reach the maximum concentration (TChax) after ingesting 150 mg of fluconazole 0.5-1.5 hours later is 90% of the plasma concentration when administered intravenously at a dose of 2.5-3.5 mg / l.
    Distribution
    The concentration in the plasma is in direct proportion to the dose. The equilibrium concentration of the drug in plasma (Css) is reached by the 4-5 day of intake (once taken once a day). The introduction of a "shock" dose (on the first day), which is 2 times greater than the usual daily dose, allows one to achieve a concentration corresponding to 90% Css by day 2. Well penetrates into all body fluids. The concentration of the active substance in breast milk, articular fluid, saliva, sputum and peritoneal fluid is similar to that in plasma. Constant values ​​in vaginal secretions are reached 8 hours after ingestion and are maintained at this level for at least 24 hours. It penetrates well into the cerebrospinal fluid (CSF); in fungal meningitis, the concentration in the CSF is about 85% of that in the plasma. In the liquid of the sweat, the dermis and the stratum corneum (selective accumulation), high concentrations are reached that exceed the serum levels. When administered at a dose of 50 mg once a day, the concentration of fluconazole after 12 days was 73 μg / g, and after 7 days after discontinuation of treatment it was 5.8 μg / l. After ingestion 150 mg 1 time per week.- On day 7, the fluconazole concentration in the stratum corneum was 23.4 μg / g, and 7 days after the second dose, 7.1 μg / g.
    Concentration in the nails after 4 months of use in a dose of 150 mg once a week: in healthy nails - 4.05 μg / g, in the affected - 1.8 μg / g. After 6 months. after completion of therapy, fluconazole was still determined in the nails.
    The apparent volume of distribution (Vd) approaches the total content of extracellular fluid in the body. The connection with plasma proteins is low -11-12%. Metabolism and excretion
    The half-life (T1 / 2) is 30 hours. It is an inhibitor of the CYP2C9 isoenzyme in the liver. It is excreted mainly by the kidneys (80% - unchanged, 11% - in the form of metabolites). The clearance of fluconazole is proportional to the creatinine clearance. The pharmacokinetics of fluconazole significantly depends on the functional state of the kidneys, and there is an inverse relationship between T1 / 2 and creatinine clearance (CC). After hemodialysis, within 3 hours, the concentration of fluconazole in the plasma is reduced by 50%.
    The pharmacokinetics of fluconazole is similar for intravenous administration and oral administration, which makes it easy to switch from one type of reception to another.

    Indications:
    • Systemic damage caused by Cryptococcus fungi, including meningitis, sepsis, lung and skin infections, both in patients with normal immune response, and in patients with various forms of immunosuppression (including AIDS patients, transplant recipients); Supportive therapy for the prevention of cryptococcal infection in AIDS patients.
    • The generalized candida of the lake: Candidemia, disseminated candidiasis (with
    • damage to the eyes, endocardium, abdominal organs, respiratory organs and urogenital organs). Treatment can be conducted in patients with malignant neoplasms and receiving a course of cytostatic or immunosuppressive therapy, as well as in the presence of other factors predisposing to their development - treatment and prevention.
    • Candidiasis of mucous membranes: oral cavity, pharynx, esophagus, non-invasive bronchopulmonary candidiasis, candiduria, mucocutaneous and chronic oral atrophic candidiasis (associated with wearing dentures).
    • Genital candidiasis: vaginal (acute and recurrent). Candidiasis balanitis. Prophylactic use to reduce the frequency of recurrence of vaginal candidiasis (three or more episodes per year).
    • Prevention of fungal infections in patients with malignant tumors on the background of chemo- or radiation therapy; prevention of recurrence of oropharyngeal candidiasis in AIDS patients.
    • Mycosis of the skin: stop, body, inguinal area, onychomycosis, pityriasis, skin candidiasis infections.
    • Deep endemic mycoses (coccidiomycosis, paracoccidiomycosis, sporotrichosis and histoplasmosis) in patients with normal immunity.

    Contraindications:
    - simultaneous reception of terfenadine (against the background of a constant intake of fluconazole in a dose
    400 mg / day and more), astemizole and other drugs that extend the QT interval.
    - simultaneous administration of cisapride.
    - hypersensitivity to the drug or a close structure of azole
    connections.
    - lactose intolerance, lactase deficiency or glucose-galactase malabsorption.
    - children's age up to 3 years (for this dosage form).

    Carefully:
    Hepatic and / or renal failure, the appearance of a rash against the background of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections, potentially pro-rhythmic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance,simultaneous reception of drugs that cause arrhythmias), simultaneous reception of potentially hepatotoxic drugs, alcoholism. Simultaneous reception of terfenadine and fluconazole in a dose of less than 400 mg / day.

    Pregnancy and lactation:
    The use of the drug in pregnant women is not advisable, except for severe or life-threatening forms of fungal infections, if the intended use of the drug for the mother exceeds the possible risk to the fetus.
    Fluconazole is found in breast milk in the same concentration as in plasma, so its use during lactation is not recommended.

    Dosing and Administration:

    Inside.

    Adults with cryptococcal meningitis and cryptococcal infections of other localizations the first day is usually prescribed 400 mg, and then continue treatment at a dose of 200 mg - 400 mg 1 time / day. The duration of treatment for cryptococcal infections depends on the clinical efficacy, confirmed by mycological examination; with cryptococcal meningitis, it usually lasts a minimum of 6-8 weeks.

    For the prevention of recurrence cryptococcal meningitis in AIDS patients, after completing the full course of primary treatment, fluconazole prescribe at a dose of 200 mg / day for a long period of time.

    With candidemia, disseminated candidiasis and other invasive candidiasis infections The dose is usually 400 mg on the first day, and then 200 mg. With insufficient clinical effectiveness, the dose of the drug can be increased to 400 mg / day. The duration of therapy depends on the clinical effectiveness.

    With oropharyngeal candidiasis the drug is usually prescribed 50-100 mg once a day; the duration of treatment is 7-14 days. When necessity, in patients with a pronounced decrease in immunity treatment can be longer. To prevent the recurrence of oropharyngeal candidiasis in AIDS patients after completing a full course of primary therapy the drug can be prescribed 150 mg once a week.

    When atrophic candidiasis of the oral cavity, associated with the wearing of dentures, fluconazole usually appoint 50 mg once a day for 14 days in combination with local antiseptic

    means for processing the prosthesis. When other localizations of candidiasis (with the exception of genital candidiasis), for example, with esophagitis, nonsynvaginal bronchopulmonary

    defeat, candiduria, skin candidiasis and mucous membranes, etc., the effective dose is usually 50-100 mg / day with a treatment duration of 14-30 days.

    When vaginal candidiasis fluconazole is taken single-handedly at a dose of 150 mg. To reduce the frequency of recurrences of vaginal candidiasis, the drug can be used at a dose of 150 mg once a month. The duration of therapy is determined individually; it varies from 4 to 12 months. Some patients may need more frequent use.

    When balaity caused by Candida spp., fluconazole is prescribed once in a dose of 150 mg orally.

    For the prevention of candidiasis recommended dose of fluconazole is 50-400 mg once a day in depending on the degree of risk development of fungal infection. When high risk generalized infection, for example in patients with the expected expressed or prolonged persistent neutropenia, the recommended dose is 400 mg once a day. Fluconazole appoint a few days before the expected appearance of neutropenia; after an increase in the number of neutrophils more than 1000 / mm3 treatment continues for another 7 days.

    When mycoses of rut, including mycosis Stop, groin groove, and kaididosis of rut the recommended the dose is 150 mg once a week or 50 mg once a day. Duration therapy in ordinary cases is 2-4 weeks, but with mycoses stop may be required longer therapy (up to 6 weeks).

    When pityriasis 300 mg

    Once a week for 2 weeks, some patients require a third dose of 300 mg per week, while in some cases it is sufficient to take a single dose of 300 mg to 400 mg; An alternative treatment regimen is to administer 50 mg once daily for 4 weeks.

    When onychomycosis the recommended dose is 150 mg once a week. Treatment should continue until the replacement of the infected nail (growth of uninfected nail). To re-grow the nails on the fingers and toes is required 6 months and 6-12 months, respectively. However, the growth rate can vary widely among different people, and also depending on age.

    When deep endemic mycoses may require the use of the drug at a dose of 200 - 400 mg / day for up to 2 years. The duration of therapy is determined individually; it can be 1 1-24 months with coccidiomycosis; 2-17 months with paracoccidiosis; 1-16 months with sporotrichosis and 3-17 months with histoplasmosis.

    In children, as with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. Have children the drug should not be used in a daily dose that would exceed that of adults, that is, not more than 400 mg per day. The drug is used daily 1 time / day.

    When esophageal candidiasis in children fluconazole is prescribed once in a daily dose of 3 mg / kg, in the following average doses: at the age of 3-6 years (body weight 15-20 kg) - 50 mg; at the age of 7-9 years (body weight 21-29 kg) - 50-100 mg; at the age of 10-12 years (body weight 30-40 kg) - 100-150 mg; at the age of 12-15 years (body weight 40-50 kg) - 100-150 mg. The duration of therapy is at least 3 weeks and 2 weeks after regression of the symptoms.

    When candidiasis of mucous membranes in children fluconazole is given once in a daily dose of 3 mg / kg, in following average doses: at the age of

    3-6 years (body weight 15-20 kg) - in the first day 100-150 mg, then - 50 mg; at the age of 7-9 years (body weight 21-29 kg) - on the first day 100-200 mg, then - 100 mg; at the age of 10-12 years (body weight 30-40 kg) - on the first day 100-150 mg, then - 50-100 mg; at the age of 12-15 years (body weight 40-50 kg) - on the first day 250-300 mg, then - for 100-150 mg. The duration of therapy is at least 3 weeks.

    When generalized candidiasis and cryptococcal infection (including meningitis) in children fluconazole is prescribed once in a daily dose of 6-12 mg / kg, in the following medium doses: at the age of 3-6 years (body weight 15-20 kg) - 100-250 mg; at the age of 7-9 years (body weight 21-29 kg) - 100-300 mg; at the age of 10-12 years (body weight 30-40 kg) - 200-350 mg; at the age of 12-15 years (body weight 40-50 kg) - 250-400 mg. Duration of therapy - within 10-12 weeks (before laboratory confirmation

    absence of pathogens in CSF). For prevention of fungal infections in children with reduced immunity, in which the risk of infection is associated with neutropenia, developing in result of cytotoxic chemotherapy or radiotherapy, fluconazole is prescribed according to 3-12 mg / kg / day depending on the severity and duration conservation of induced neutropenia, in the following mean doses: at the age of 3-6 years (body weight 15-20 kg) - 50-250 mg; aged 7-9 years (body weight 21-29 kg) - 50-300 mg; at the age of 10-12 bed (weight

    body 30-40 kg) - 100-350 mg; at age 12-15 years (body weight 40- 50 kg) - 100-400 mg. Duration therapy - to eliminate induced neutropenia.

    In children with impaired function nights daily dose of the drug should be reduced (in the same proportional to the dependence that and in adults), in accordance with degree of renal function insufficiency.

    Have elderly patients at There are no violations of kidney function the usual dosage regimen of the drug. Patients with renal insufficiency (clearance

    creatinine less than 50 ml / min) dosing regimens should be

    correct, as indicated below. Use of the drug in patients with impaired renal function. Fluconazole is excreted mainly with urine in an unchanged form. With a single admission, a dose change ns is required. When re-administering the drug, patients with impaired renal function should first introduce a "shock" dose of 50 mg to 400 mg. If the clearance of creatinine (CC) is 50 ml / min, the usual dose of the drug (100% recommended dose) once a day. When KK from 11 to 50 ml / min a dose of 50% recommended. Patients regularly on dialysis, one dose of the drug is used after each session of hemodialysis.

    Side effects:From the digestive system: system: changes in taste, vomiting, nausea, diarrhea, flatulence, abdominal pain, impaired liver function (jaundice, hyperbilirubinemia, increased activity
    alanine aminotransferases, aspartate aminotransferases, alkaline phosphatases, hepatitis,
    hepatocellular necrosis), incl. with a lethal outcome.
    From the nervous system: headache, dizziness, convulsions.
    From the cardiovascular system: enlargement
    duration of the Q-T interval, ventricular fibrillation / flutter.
    From the hematopoiesis: leukopenia, thrombocytopenia,
    neutropenia, agranulocytosis. Allergic reactions', skin rash, multiforme exudative
    erythema (including Stevens-Johnson syndrome), toxic
    epidermal necrolysis (Lyell's syndrome), anaphylactoid reactions (including angioedema, facial edema, hives, itching of the skin).
    Other: renal dysfunction, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.
    Overdose:
    Symptoms: hallucinations, paranoid behavior.
    Treatment: symptomatic, gastric lavage, forced diuresis. Hemodialysis within 3 hours reduces the plasma concentration by approximately 50%.

    Interaction:
    Anticoagulants. Fluconazole increases the prothrombin time of coumarin anticoagulants (for example, warfarin) by an average of 12%,Therefore, careful monitoring of prothrombin time in patients receiving fluconazole and coumarin anticoagulants.
    Sulfonylurea preparations. With the simultaneous administration of fluconazole and oral preparations of sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide), the half-life of the latter is prolonged, which can lead to the development of hypoglycemia. Periodically monitor the concentration of glucose in the blood and, if necessary, adjust the dose of hypoglycemic drugs.
    Hydrochlorothiazide increases the concentration of fluconazole in plasma by 40%, but this does not require a change in the dosage regimen of fluconazole in patients receiving diuretics at the same time.
    Phenytoin. Simultaneous administration of fluconazole and phenytoin is accompanied by an increase in the concentration of the latter in a clinically significant degree. Therefore, it is necessary to monitor the level of phenytoin and select its dose to provide therapeutic serum concentrations.
    Oral contraceptives. Multiple application of fluconazole (in doses of 50-200 mg) does not affect the effectiveness of the combined contraceptive. Rifampicin. Simultaneous application of fluconazole and rifampicin reduced the area under the concentration-time curve by 25% and the duration of the half-life of fluconazole by 20%. It is necessary to increase the dose of fluconazole at their simultaneous appointment.
    Cyclosporine. In the treatment of fluconazole at a dose of 200 mg / day. the concentration of cyclosporine in the blood increases.
    Theophylline. Fluconazole prolongs the half-life of theophylline and increases the risk of intoxication (it is necessary to correct its dose).
    Terfenadine. Simultaneous reception fluconazole in doses of 400 mg / day. and more with terfenadine is contraindicated. Treatment with fluconazole in doses less than 400 mg / day. In combination with terfenadine should be carried out under the close supervision of a doctor.
    Cisapride. With the simultaneous administration of fluconazole and cisapride, unwanted reactions from the heart, including paroxysms of ventricular tachycardia (torsades de pointes).
    Nifabutin. Cases of uveitis are described.
    Tacrolimus. Increases the concentration of tacrolimus, in connection with which, the risk of nephrotoxic action increases.
    Zidovudine. In patients receiving a combination of fluconazole and zidovudine, an increase in the concentration of zidovudine is observed,which is caused by a decrease in the conversion of the latter into its main metabolite, so we should expect an increase in the side effects of zidovudine.
    Midazolam. Increases the concentration of midazolam, in connection with which the risk of developing psychomotor effects increases (most pronounced when fluconazole is administered orally than intravenously).

    Special instructions:
    Treatment should continue until the appearance of clinical-hematologic remission. Premature termination of treatment leads to relapse.
    Treatment can be started in the absence of seeding results or other laboratory tests, but if appropriate, a correction of fungicidal therapy is recommended.
    In the course of treatment, it is necessary to monitor blood counts, kidney and liver function. If there are violations of kidney and liver function, stop taking the drug. In rare cases, the use of fluconazole was accompanied by toxic changes in the liver. In the case of hepatotoxic effects associated with fluconazole, there was no apparent dependence on the total daily dose, duration of therapy, sex, and age of the patient. The hepatotoxic effect of fluconazole is usually reversible; signs of it disappeared after discontinuation of therapy.If there are clinical signs of liver damage that may be associated with fluconazole, the drug should be discontinued.
    Patients with AIDS are more likely to develop severe skin reactions with many drugs. In those cases where the rash develops in patients with superficial fungal infection and it is regarded as definitely associated with fluconazole, the drug should be discontinued. When rashes appear in patients with invasive / systemic fungal infections, they should be carefully monitored and canceled fluconazole when there are bullous changes or erythema multiforme.

    Effect on the ability to drive transp. cf. and fur:
    In case of adverse reactions from the nervous system, patients are advised to refrain from controlling the car and other mechanisms, as well as to be cautious when engaging in activities that require an increased concentration of attention and speed of psychomotor reactions.

    Form release / dosage:

    Capsules 50 mg and 150 mg.

    Packaging:

    By 1, 2, 3, 4, 5, 6, 7 or 10 capsules in contour cell packaging from polyvinyl chloride and aluminum foil foil lacquered.

    By 1, 2, 7, 10, 14, 28, 50 or 100 capsules in cans of polyethylene terephthalate or cans polymer from polypropylene for medicines.

    One bank or 1, 2, 3, 4, 7 or 10 contour cell packings together with instructions for use placed in a cardboard box (pack).

    Storage conditions:
    In a dry, protected from light place at a temperature of no higher than 25 ° C.
    Keep out of the reach of children.

    Shelf life:
    3 years. Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LS-001728
    Date of registration:27.10.2011
    The owner of the registration certificate:OZONE, LLC OZONE, LLC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp28.09.2015
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