Active substanceFluconazoleFluconazole
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  • Dosage form: & nbspcapsules
    Composition:
    Active ingredient: fluconazole 50 mg and 150 mg
    Excipients: Silica colloidal dioxide 0.3 mg and 0.9 mg, magnesium stearate 1.2 mg and 3.6 mg, talc 3.3 mg and 9.9 mg, povidone K-30 3.6 mg and 10, 8 mg, corn starch 12.1 mg and 36.3 mg, lactose monohydrate 49.5 mg and 148.5 mg.
    The gelatin capsule formulation: gelatin 51.0 mg and 80.4 mg, purified water 8.9 mg and 13.8 mg, titanium dioxide 1.1 mg and 1.8 mg.

    Description:
    Capsules 50 mg: Capsules number 2. The capsule body is white, the cap of the capsule is white.
    Capsules 150 mg: Capsules №0. The capsule body is white, the cap of the capsule is white.
    Contents of capsules - a mixture of granules and powder white or white with a slightly yellowish hue of color.

    Pharmacotherapeutic group:Antifungal agent.
    ATX: & nbsp

    J.02.A.C   Triazole derivatives

    J.02.A.C.01   Fluconazole

    Pharmacodynamics:
    Antifungal agent, 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. Active with opportunistic fungal infections, incl. 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 with immunodepression).

    Pharmacokinetics:
    Well absorbed in the gastrointestinal tract (food does not affect the rate of absorption), bioavailability - 90%.
    The time to reach the maximum concentration (Stach) after ingestion, fasting 150 mg - 0.5-1.5 hours. The concentration in the plasma is in direct proportion to the dose.
    Equilibrium concentration is achieved by the 4-5 day of intake. The connection with proteins is 11-12%. 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 held at this level for at least 24 hours. In fungal meningitis, the concentration in the cerebrospinal fluid is about 80% of that in the plasma. In the fluid, epidermis and the stratum corneum (selective accumulation), concentrations exceeding serum levels are achieved.
    After oral administration of 150 mg on day 7, the concentration in the stratum corneum of the dermis is 23.4 μg / g, and a week after the second dose, 7.1 μg / g; concentration in the nails after 4 months of application in a dose of 150 mg once a week - 4.05 μg / g in healthy and 1.8 μg / g - in the affected nails.
    The half-life (T1 / 2) is 30 hours.It is excreted mainly by the kidneys (80% - unchanged, 11% - in the form of metabolites). The clearance of fluconazole is proportional to the clearance of creatinine (CC).
    The pharmacokinetics of fluconazole significantly depends on the functional state of the kidneys, and there is an inverse relationship between T1 / 2 and KK. After hemodialysis for 3 hours, the plasma concentration of fluconazole is reduced by 50%.

    Indications:
    cryptococcosis, including cryptococcal meningitis and other localizations of this infection (including lungs, skin), both in patients with normal immune response, and in patients with various forms of immunosuppression (including those with AIDS, organ transplantation ); the drug can be used in the prevention of cryptococcal infection in AIDS patients;
    generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidiasis infections (peritoneal, endocardial, eye, respiratory and urinary tract infections). Treatment can be performed in patients with malignant neoplasms, in intensive care units, in patients undergoing cytostatic or immunosuppressive therapy, and in the presence of other factors predisposing to the development of candidiasis;
    Candidiasis of mucous membranes, including.oral cavity and pharynx (including atrophic candidiasis of the oral cavity, associated with the wearing of dentures), esophagus, non-invasive bronchopulmonary candidiasis, candiduria, candidiasis of the skin; prevention of recurrence of oropharyngeal candidiasis in AIDS patients;
    genital candidiasis: vaginal candidiasis (acute and chronic recurrent), preventive use to reduce the frequency of recurrences of vaginal candidiasis (3 or more episodes a year); Candidiasis balanitis;
    prevention of fungal infections in patients with malignant neoplasms that are predisposed to such infections as a result of chemotherapy with cytostatics or radiation therapy;
    mycosis of the skin, including mycosis of the feet, trunk, inguinal region; pityriasis lichen, onychomycosis; candidiasis of the skin;
    Deep endemic mycoses, including coccidiomycosis and histoplasmosis, in patients with normal immunity.

    Contraindications:
    Hypersensitivity to fluconazole, other components of the drug or to other azole compounds; simultaneous reception of terfenadine (against the background of a constant intake of fluconazole at a dose of 400 mg per day or more), cisapride or astemizole and other drugs,prolonging the QT interval and increasing the risk of severe rhythm disturbances; lactose intolerance; deficiency of lactase; glucose-galactose malabsorption; lactation period; Children under 3 years old (for this dosage form).

    Carefully:
    Hepatic and / or renal insufficiency, the appearance of rash against the background of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections, concurrent administration of terfenadine and fluconazole at a dose of less than 400 mg per day, potentially pro-rhythmogenic states in patients with multiple risk factors (organic heart disease, electrolyte balance disorders, simultaneous administration of medications, causing arrhythmias); patients with intolerance to acetylsalicylic acid, pregnancy.

    Pregnancy and lactation:
    The use of the drug in pregnant women is inappropriate, except for severe or life-threatening forms of fungal infections, if the expected effect 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 purpose during lactation is not recommended.

    Dosing and Administration:

    Inside. The daily dose depends on the nature and severity of the fungal infection.
    Adults, with cryptococcal meningitis and cryptococcal infections of other locations on the first day, usually prescribed 400 mg, and then continue treatment at a dose of 200-400 mg once a day. The duration of treatment for cryptococcal infections depends on the clinical efficacy, confirmed by mycological examination. The recommended duration of treatment for the initial treatment of cryptococcal meningitis is 10-12 weeks after a negative result of microbiological examination of a sample of cerebrospinal fluid. To prevent the recurrence of cryptococcal meningitis in AIDS patients, after completion of the full course of primary therapy, fluconazole prescribe a dose of 200 mg per day for a long period of time.
    When candidemia, disseminated candidiasis and other invasive candidiasis infections in the first day, the dose is usually 400 mg, and then - 200 mg per day. With insufficient clinical efficacy, the dose of the drug can be increased to 400 mg per day; with severe systemic candidiasis - it is possible to increase the dose to 800 mg per day.The duration of therapy depends on clinical effectiveness; a course of treatment sufficient for a single dose of 300-400 mg; an alternative treatment regimen is to administer 50 mg once a day for 2-4 weeks.
    With 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, it normally takes 3-6 months and 6-12 months, respectively.
    With deep endemic mycoses, it may be necessary to use the drug at a dose of 200-400 mg per day for up to 2 years. The duration of therapy is determined individually; it can be 11-24 months with coccidioidosis and 3-17 months with histoplasmosis.
    Use in children, as with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. In children, the drug should not be used in a daily dose that would exceed that of adults. The drug is used daily 1 time per day.
    In candidiasis of mucous membranes, the recommended dose of fluconazole is 3 mg / kg per day. On the first day, a shock dose of 6 mg / kg can be administered in order to achieve a more rapid equilibrium of concentrations.
    For the treatment of generalized candidiasis or cryptococcal infection, the recommended dose is 6-12 mg / kg per day, depending on the severity of the disease.
    For the prevention of fungal infections in children with reduced immunity, where the risk of infection is associated with neutropenia, resulting from cytotoxic chemotherapy or radiation therapy, the drug is prescribed at 3-12 mg / kg per day, depending on the severity and duration of preservation of induced neutropenia. The maximum daily dose for children is 12 mg / kg.
    Dosing for patients with renal insufficiency
    Fluconazole is excreted mainly by the kidneys in unchanged form. With a single application, dose adjustment is not required.
    Adult patients with impaired renal function in the course of the drug should first be prescribed a "shock dose" of 50 mg to 400 mg. If the creatinine clearance (CK) is> 50 ml / min, the usual dose of the drug (100% of the recommended dose) is used. At CC <50 ml / min, a dose equal to 50% of the recommended dose or a usual dose of 1 every 2 days is applied. Patients regularly on dialysis, a single dose of the drug is used after each session of hemodialysis.
    In children with impaired renal function, the daily dose of the drug should be reduced (in the same proportional relationship as in adults), according to the degree of renal insufficiency.
    In elderly patients in the absence of violations of kidney function should follow the usual dosage regimen.

    Side effects:
    On the part of the digestive system: decreased appetite, changes in taste, nausea, vomiting, diarrhea, flatulence, abdominal pain, increased activity of liver enzymes and impaired liver function (jaundice, hyperbilirubinemia, increased activity of alanine aminotransferase (ALT), aspartate aminotransferase (ACT) and alkaline phosphatase (AF), hepatitis, hepatocellular necrosis), including fatal outcome.
    From the nervous system: headache, dizziness, convulsions.
    On the part of the organs of hematopoiesis: agranulocytosis, neutropenia. Patients with severe fungal infections may have hematologic changes (leukopenia and thrombocytopenia).
    From the cardiovascular system: an increase in the duration of the QT interval on an electrocardiogram (ECG), flicker / flutter of the ventricles.
    Allergic reactions: skin rash, multiforme exudative erythema (incl.Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell syndrome), bronchial asthma (more often with acetylsalicylic acid intolerance) anaphylactoid reactions (including angioedema, facial edema, hives, skin itching).
    Other: impaired renal function, alopecia, hypercholesterolemia,
    hypertriglyceridemia, hypokalemia.

    Overdose:
    Symptoms: nausea, vomiting, diarrhea, in severe cases, convulsions, hallucinations, paranoid behavior may occur.
    Treatment: symptomatic, gastric lavage, forced diuresis. Hemodialysis within 3 hours reduces the concentration in the plasma by 2 times.

    Interaction:
    One-time administration of fluconazole in the treatment of vaginal candidiasis is not accompanied by significant interactions.
    When several and higher doses of the drug are used simultaneously with other drugs, the following drug interactions are possible:
    the interaction of fluconazole with terfenadine, cisapride and astemizole can lead to an increase in the concentration of these drugs in the plasma, which in turn can cause prolongation of the QT interval and lead to serious heart rhythm disturbances, including paroxysms of ventricular tachycardia (torsades de pointes). Fluconazole inhibits the enzymes of the P450 system in the liver, thereby reducing the metabolism of terfenadine, cisapride and astemizole. The simultaneous administration of fluconazole and these drugs is contraindicated.
    With the combined use of warfarin and fluconazole, prolonged prothrombin time is noted. In connection with these, it is necessary to control prothrombin time in patients simultaneously receiving fluconazole and indirect anticoagulants of the coumarin series.
    Fluconazole prolongs T1 / 2operoral hypoglycemic drugs (sulfonylurea derivatives). Patients with diabetes mellitus can simultaneously be prescribed fluconazole and derivatives of sulfonylureas, however, it is necessary to take into account the possible risk of developing hypoglycemia.
    It should be taken into account that with repeated simultaneous use of hydrochlorothiazide and fluconazole, the concentration of fluconazole in the plasma is increased.
    Rifampicin accelerates the metabolism of fluconazole. It is necessary to increase the dose of fluconazole accordingly during their simultaneous use.
    In patients who underwent renal transplantation, fluconazole can increase the concentration of cyclosporine in plasma.In this regard, it is recommended to monitor the concentration of cyclosporine in patients simultaneously receiving ciclosporin and fluconazole.
    Fluconazole increases the concentration of theophylline in plasma. In this regard, it is recommended to monitor the concentration of theophylline in patients simultaneously receiving theophylline and fluconazole.
    Fluconazole may increase plasma concentrations of indinavir and midazolam. With the simultaneous use of these drugs with fluconazole, their dose should be appropriately reduced.
    Clinical studies have shown that as a result of slowing the metabolism of zidovudine, its plasma concentration can be increased with simultaneous application with fluconazole. It is necessary to observe patients who simultaneously receive both
    these drugs, since in this case, the incidence of side effects of zidovudine may increase.
    Strengthens the pharmacological effects of rifabusna (with simultaneous application described cases of uveitis) and phenytoin in a clinically significant degree (with combined use requires monitoring of the concentration of phenytoin in the plasma). Fluconazole increases serum concentrations of phenytoin.At simultaneous application it is necessary to control doses of phenytoin and accordingly to correct them.
    Increases the concentration of tacrolimus - the risk of nephrotoxicity.
    Doctors need to take into account that interaction with other drugs has not been specifically studied, but it is possible.

    Special instructions:
    Treatment can be started in the absence of seeding results or other laboratory tests, but if appropriate, a correction of fungicidal therapy is recommended. Because the fluconazole is excreted mainly by the kidneys, caution should be exercised in patients with renal insufficiency. With long-term treatment with fluconazole, dosing should be done taking into account KK.
    Caution should be exercised when administering fluconazole to patients with impaired liver function. During treatment, it is necessary to regularly monitor the activity of "liver" enzymes and monitor the patient in order to identify possible toxic effects. When the activity of "liver" enzymes is increased, the doctor must weigh the benefits of the therapy and the risk of developing severe liver damage.The hepatotoxic effect of fluconazole is usually reversible: symptoms disappear after discontinuation of therapy.
    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.
    It is necessary to monitor prothrombin time in patients who are simultaneously receiving fluconazole and indirect anticoagulants of the coumarin series.
    Treatment should continue until the appearance of clinical and microbiological remission. Premature termination of treatment leads to relapse.
    Effect on the ability to drive transp. cf. and fur:
    The experience with fluconazole indicates that a disruption to the ability to drive and drive the drug is unlikely.
    However, given that the drug may cause dizziness and convulsions,caution should be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions.

    Form release / dosage:Capsules 50 mg and 100 mg.
    Packaging:
    1 (for a dosage of 150 mg) or 7 (for a dosage of 50 mg) capsules in a contour mesh box made of a polyvinylchloride film and aluminum foil. On 1 contour acrylic packing place in a pack a cardboard together with the instruction on application.
    Storage conditions:
    In a dry, dark 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:Without recipe
    Registration number:LP-000771
    Date of registration:29.09.2011
    The owner of the registration certificate:PRODUCTION OF MEDICINES, LTD. PRODUCTION OF MEDICINES, LTD. Russia
    Manufacturer: & nbsp
    Information update date: & nbsp28.09.2015
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