Active substanceFluconazoleFluconazole
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  • Dosage form: & nbspcapsules
    Composition:
    1 capsule contains:
    Active substance: Fluconazole in terms of dry matter 50 mg or 150 mg. Excipients:
    Capsules of 50 mg:
    lactose, monohydrate 26 mg, starch potato extra 20 mg, magnesium stearate 2.5 mg, silicon dioxide colloid 1.5 mg.
    Capsules of 150 mg:
    Lactose, monohydrate - 52 mg, starch potato extra - 40 mg, magnesium stearate - 5 mg, silicon dioxide colloid - 3 mg.
    Capsule composition:
    Gelatin, titanium dioxide, indigocarmine.
    Description:
    Capsules 50 mg:
    hard gelatin capsules number 2.
    The capsule body is white, capsule caps light-blue. The contents of the capsules are white or almost white, odorless powder.
    Capsules 150 mg:
    hard gelatin capsules №1.
    The capsule body is white, capsule cover is dark blue.
    The contents of the capsules are white or almost white, odorless powder.
    Pharmacotherapeutic group:Antifungal agent.
    ATX: & nbsp

    J.02.A.C   Triazole derivatives

    J.02.A.C.01   Fluconazole

    Pharmacodynamics:
    Fluconazole, a representative of the class of triazole antifungal agents, is a potent selective inhibitor of the synthesis of sterols in the fungal cell.
    The drug is effective in opportunistic fungal infections, incl. The activity of fluconazole in the models of endemic mycoses, including infections caused by Blastomyces dermatitidis, Coccidiodes immitis and Histoplasma capsulatum, has also been shown.
    Pharmacokinetics:
    After oral administration fluconazole it is well absorbed, its bioavailability is 90%. The maximum concentration after ingestion, fasting 150 mg is 90% of the plasma content when administered intravenously at a dose of 2.5 - 3.5 mg / l.Simultaneous food intake does not affect the absorption of the drug taken internally. The concentration in the plasma reaches a peak after 0.5-1.5 hours after administration, the half-life of fluconazole is about 30 hours. The plasma concentrations are in direct proportion to the dose. 90% level of equilibrium concentration is reached by 4-5 days of treatment with the drug (with the administration of 1 time / day).
    The introduction of a shock dose (on the first day), which is 2 times higher than the usual daily dose, allows reaching 90% of the level of equilibrium concentration, by the second day. The apparent volume of distribution approximates the total water content in the body. Binding to plasma proteins is 11-12%.
    Fluconazole well penetrates into all body fluids. Concentrations of the drug in saliva and sputum are similar to those in plasma. In patients with fungal meningitis, the fluconazole content in the cerebrospinal fluid reaches 80% of its plasma level.
    In the stratum corneum, the epidermis, the dermis and the sweat fluid, high concentrations are reached that exceed the serum levels.
    Fluconazole is excreted mainly by the kidneys; approximately 80% of the administered dose is excreted in the urine in unchanged form.The clearance of fluconazole is proportional to the creatinine clearance. Metabolites of fluconazole in peripheral blood were not detected.
    Fluconazole is an inhibitor of the isoenzyme CYP2C9 in the liver.
    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 AIDS patients, organ transplantation ); the drug can be used to prevent 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;
    • -candidosis of mucous membranes, incl. 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, the body, the groin area; pityriasis - lichen, onychomycosis; candidiasis of the skin;
    • Deep endemic mycoses, including coccidiomycosis, paracoccidiomycosis, sporotrichosis and histoplasmosis in patients with normal immunity.
    Contraindications:
    simultaneous reception of terfenadine or astemizole and other drugs that extend the QT interval.
    hypersensitivity to the drug or a similar structure of azole compounds.
    deficiency of lactase, lactose tolerance, glucose-galactose malabsorption.
    children's age (up to 3 years).
    Carefully:
    Hepatic and / or renal failure, concomitant administration of potentially hepatotoxic drugs, alcoholism, potentially pro-rhythmogenic conditions in patients with multiple risk factors (organic heart disease, electrolyte balance disorders, simultaneous use of drugs that cause arrhythmias).
    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 intended benefit, 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:
    Adults with cryptococcal meningitis and cryptococcal infections of other locations on the first day usually prescribed 400 mg (8 capsules 50 mg), and then continue treatment at a dose of 200 mg (4 capsules 50 mg) -400 mg (8 capsules 50 mg) 1 time / day . The duration of treatment for cryptococcal infections depends on the clinical efficacy, confirmed by mycological examination; in cryptococcal meningitis, it usually lasts at least 6-8 weeks.
    To prevent the recurrence of cryptococcal meningitis in AIDS patients, after completing the full course of primary treatment, fluconazole appoint a dose of 200 mg (4 capsules of 50 mg) per day for a long period of time.
    With candidemia, disseminated candidiasis and other invasive candidiasis infections, the dose is usually 4,00 mg (8 capsules 50 mg) on ​​the first day, and then 200 mg (4 capsules 50 mg each). With insufficient clinical efficacy, the dose of the drug can be increased to 400 mg (8 capsules 50 mg) per day. The duration of therapy depends on clinical effectiveness.
    With oropharyngeal candidiasis, the drug is usually prescribed at 50-100 mg 1 time / day; the duration of treatment is 7-14 days. If necessary, in patients with a marked decrease in immunity, treatment may be longer.
    With atrophic candidiasis of the oral cavity, associated with the wearing of dentures, fluconazole usually prescribed 50 mg 1 time / day for 14 days in combination with local antiseptic agents for prosthesis treatment.
    In other localizations of candidiasis (with the exception of genital candidiasis), for example, with esophagitis, noninvasive bronchopulmonary disease, candiduria, candidiasis of the skin and mucous membranes, etc., the effective dose is usually 50-100 mg / day with a treatment duration of 14-30 days.To prevent the recurrence of oropharyngeal candidiasis in AIDS patients after completing the full course of primary therapy, the drug can be prescribed 150 mg once a week.
    With vaginal candidiasis fluconazole taken once inside the 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 week. The duration of antirecurrent therapy is determined individually and, as a rule, is 6 months. The use of a single dose to children under 18 years of age and patients older than 60 years without a doctor's recommendation is not recommended.
    With balanitis caused by Candida, fluconazole appoint a single dose of 150 mg orally.
    For the prevention of candidiasis, the recommended dose of fluconazole is 50-400 mg 1 time / day, depending on the degree of risk of fungal infection. If there is a high risk of generalized infection, for example, in patients with expected severe or persistent neutropenia, the recommended dose is 400 mg (8 capsules 50 mg) 1 time / day. Fluconazole appoint a few days before the expected appearance of neutropenia; after increasing the number of neutrophils more than 1000 / mm3 treatment is continued for another 7 days.
    With mycosis of the skin, including mycosis of the feet, skin of the inguinal region, and skin drops, the recommended dose is 150 mg once a week or 50 mg 1 time / day. Duration of therapy in usual cases is 2-4 weeks, however, with foot mycoses, longer therapy (up to 6 weeks) may be required.
    With 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 receive 300-400 mg once; an alternative treatment regimen is to apply 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 mg (4 capsules of 50 mg) -400 mg (8 capsules 50 mg) per day for up to 2 years. The duration of therapy is determined individually; it can be 11-24 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. 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 / day.
    In mucosal candidiasis, the recommended dose of fluconazole is 3 mg / kg / day. On the first day, a shock dose of 6 mg / kg may be prescribed to achieve a more rapid equilibrium equilibrium concentration.
    For treatment of generalized candidiasis or cryptococcal infection, the recommended dose is 6-12 mg / kg / day, depending on the severity of the disease.
    For the treatment of fungal infections in children with reduced immunity, the risk of infection is associated with neutropenia, which develops as a result of cytotoxic chemotherapy or radiation therapy, the drug is prescribed at 3-12 mg / kg / day, depending on the severity and duration of preservation of induced neutropenia.
    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. Patients with renal insufficiency (creatinine clearance less than 50 ml / min) dosage regimen should be adjusted as indicated below.
    Use of the drug in patients with impaired renal function.
    Fluconazole is excreted mainly with urine in unchanged form. With a single admission, a dose change is not 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 creatinine clearance (CK) is more than 50 ml / min, the usual dose of the drug (100% of the recommended dose) is used. With KK from 11'to 50 ml / min apply a dose equal to 50% of the recommended. Patients regularly on dialysis, one dose of the drug is used after each session of hemodialysis.
    Side effects:
    On the part of the digestive system: changes in taste, vomiting, nausea, diarrhea, flatulence, abdominal pain, impaired liver function (jaundice, hepatitis, hepatonecrosis, hyperbilirubinemia, increased activity of alanine aminotransferases, aspartate aminotransferase, increased alkaline phosphatase activity), incl. with a lethal outcome.
    From the nervous system: headache, dizziness, convulsions.
    From the hematopoiesis: leukopenia, thrombocytopenia,
    neutropenia, agranulocytosis.
    On the part of the cardiovascular system: an increase in the duration of the Q-T interval, fibrillation / flutter of the ventricles.
    Allergic reactions: skin rash, malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), anaphylactoid reactions (including angioedema, face swelling, hives, itching of the skin).
    Other: impaired renal function, 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:
    When using fluconazole with warfarin, prothrombin time increases (on average by 12%). In this regard, it is recommended to carefully monitor the prothrombin time in patients receiving the drug in combination with coumarin anticoagulants.
    Fluconazole increases the half-life of plasma from oral hypoglycemic agents - derivatives of sulfonylurea (chloropropanide, glibenclamide, glipizide, tolbutamide) in healthy people. Joint use of fluconazole and oral hypoglycemic agents in diabetic patients is allowed, but the doctor should keep in mind the possibility of developing hypoglycemia.
    The simultaneous use of fluconazole and phenytoin can lead to an increase in the concentration of phenytoin in the plasma to a clinically significant degree. Therefore, if it is necessary to jointly use these drugs, it is necessary to monitor the concentrations of phenytoin with correction of its dose in order to maintain the concentration of phenytoin within the therapeutic interval.
    The combination with rifampicin leads to a 25% reduction in AUC and a 20% decrease in the half-life of fluconazole from the plasma.
    Therefore, patients receiving concomitantly rifampicin, it is advisable to increase the dose of fluconazole.
    It is recommended to monitor the concentration of cyclosporine in the blood in patients receiving fluconazole, since the use of fluconazole and cyclosporine in patients with kidney transplantation of fluconazole at a dose of 200 mg / day leads to a slow increase in the concentration of cyclosporine in the plasma.
    Patients who receive high doses of theophylline or who are likely to develop theophylline intoxication,
    should be monitored for the purpose of early detection of symptoms of overdose and correction of the dose of theophylline, as taking fluconazole leads to a decrease in the average clearance rate of theophylline from the plasma.
    With simultaneous application fluconazole and terfenadine, cisapride, cases of unwanted reactions from the heart, including paroxysms of ventricular tachycardia (torsades de points), have been described.
    The simultaneous use of fluconazole and hydrochlorothiazide can lead to an increase in the concentration of fluconazole in plasma by 40%.
    There have been reports of an interaction between fluconazole and rifabutin, accompanied by an increase in serum levels of the latter. With the simultaneous use of fluconazole and rifabutin, cases of uveitis are described. It is necessary to carefully observe patients who simultaneously receive rifabutin and fluconazole.
    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 an increase in the side effects of zidovudine should be expected.
    Fluconazole increases the concentration of midazolam - increases the risk of psychomotor effects (more pronounced when fluconazole is administered orally); tacrolimus - risk of nephrotoxicity.
    Special instructions:
    In rare cases, the use of fluconazole was accompanied by toxic changes in the liver, incl. with a fatal outcome, mainly in patients with serious concomitant diseases. 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 was 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 when using many drugs. In those cases where the rash and it develop in patients with superficial fungal infection. is regarded as definitely associated with fluconazole, the drug should be withdrawn. 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.
    Caution should be exercised while taking fluconazole with cisapride, rifabutin or other drugs metabolized by the cytochrome P 450 system.
    Treatment should be continued until the appearance, clinicohematological remission. Premature termination of treatment leads to relapse. 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.
    Effect on the ability to drive transp. cf. and fur:
    The effect of fluconazole on the ability to drive vehicles or work with other mechanisms is not revealed.
    Form release / dosage:Capsules 150 mg, 50 mg.
    Packaging:
    Capsules of 150 mg - 1 capsule in a contour mesh box made of PVC and aluminum foil. One contour cell packaging together with instructions for use in a pack of cardboard. Let go without a prescription.
    Capsules of 50 mg - 7 capsules in a contour mesh box made of PVC and aluminum foil. One contour cell packaging together with instructions for use in a pack of cardboard. Let go on prescription.
    Storage conditions:
    At a temperature of no higher than 25 ° C, in a dry, dark place.
    Keep out of the reach of children.
    Shelf life:
    2 years. Do not use after the expiration date.
    Terms of leave from pharmacies:On prescription
    Registration number:LS-002325
    Date of registration:28.02.2012
    The owner of the registration certificate:Astrafarm, CJSCAstrafarm, CJSC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp19.10.2015
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