Active substanceFluconazoleFluconazole
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  • Dosage form: & nbspcapsules
    Composition:
    Active substance: fluconazole 50,100 or 150 mg.
    Excipients: milk sugar, sodium carboxymethyl starch and / or corn starch, polyvinylpyrrolidone or povidone 8000, aerosil, magnesium stearate.
    Description:Hard gelatin capsules No. 1 orange for a dosage of 50 mg, white for a dosage of 100 mg and yellow for a dosage of 150 mg.
    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. caused by Candida spp., Cryptococcus neoformans, Microsporum spp., Trichophyton spp. Also shown is the activity of fluconazole in endemic mycosis models, including infections caused by Blastomyces dermatitidis, Coccidiodes immitis and Histoplasma capsulatum.
    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 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 use of 1 time / day).
    The introduction of a shock dose (on the first day), which is 2 times higher than the usual daily dose,corresponding to 90% of the equilibrium concentration, by the second day. The apparent volume of distribution approximates the total water content in the body. Binding to plasma proteins - 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 unchanged. The clearance of fluconazole is proportional to the creatinine clearance. Metabolites of fluconazole in peripheral blood were not detected.
    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;
    • Candidiasis 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), prophylactic 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 similar in structure to azole compounds;
    • children's age (up to 6 months).
    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 expected effect 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 sites on the first day, 400 mg are usually prescribed, and then continue treatment at a dose of 200-400 mg once / ct. 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 / day. for a long period of time.
    When 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 clinical effectiveness.
    When 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.
    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 agents for the treatment of the prosthesis.
    For 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.
    When 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 month. The duration of therapy is determined individually; it varies from 4 to 12 months. Some patients may need more frequent use.
    When 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 1 time / 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 is continued for another 7 days.
    When mycosis of the skin, including mycosis of the feet, skin of the inguinal region, and candidiasis of the skin the recommended dose is 150 mg once a week or 50 mg 1 time / day.The duration of therapy in usual cases is 2-4 weeks, however, with foot mycoses, longer therapy (up to 6 weeks) may be required.
    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 receive 300-400 mg once; an alternative treatment regimen is to apply 50 mg once a day for 2-4 weeks.
    When onychomycosis the recommended dose is 150 mg once a week. Treatment should continue until the replacement of the infected nail (the growth of the uninfected nail). For the repeated growth of the nails on the fingers and toes normally takes 3-6 months. and 6-12 months. respectively.
    When deep endemic mycoses may require the use of the drug in a dose of 200-400 mg / 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.
    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.
    When candidiasis of mucous membranes 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 generalized candidiasis or cryptococcal infection the recommended dose is 6-12 mg / kg / day. depending on the severity of the disease.
    For prevention of fungal infections in children with reduced immunity, at which 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), in accordance with 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.) Regimendosage should be adjusted as indicated below.
    The 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 SC from 11 to 50 ml / min. a dose of 50% is recommended. Patients regularly on dialysis, one dose of the drug is used after each session of hemodialysis.
    Side effects:
    From the digestive system: nausea, diarrhea, flatulence, abdominal pain, rarely - a violation of liver function (hyperbilirubinemia, increased activity of alanine aminotransferases, aspartate aminotransferate, increased activity of alkaline phosphatase)
    From the nervous system: headache, rarely - convulsions.
    From the hematopoiesis: rarely - leukopenia, thrombocytopenia, neutropenia, agranulocytosis.
    Allergic reactions: skin rash, rarely - malignant exudative erythema (Steve Jas-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), anaphylactoid reactions.
    Other: rarely - 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:
    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 oral hypoglycemic agents - derivatives of sulfonylurea (chloropropanide, glibenclamide, glipizide, tolbutamide) in healthy people. The combined use of fluconazole and oral hypoglycemic agents in diabetic patients is permissible, 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, when 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 drug level 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 receiving fluconazole at a dose of 200 mg / day. It 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 early detection of symptoms of theophylline overdose, as taking fluconazole leads to a decrease in the average clearance rate of theophylline from the plasma.
    With the simultaneous use of fluconazole and cisapride, cases of unwanted reactions from the heart, including paroxysms of ventricular tachycardia (torsades de points), are described.
    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 the side effects of zidovudine should be expected to increase.
    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 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 when 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.
    Care should be taken when taking fluconazole simultaneously with cisapride, rifabutin, or other drugs metabolized by the cytochrome P450 system.
    Form release / dosage:
    Capsules of 50,100 and 150 mg.
    Packaging:
    For 1 or 10 capsules with a dosage of 150 mg; 2 or 10 capsules with a dosage of 100 mg; for 4.7 or 10 capsules with a dosage of 50 mg in a loop cell package. 1 contour pack together with instructions for use in the pack. For 1 or 10 capsules with a dosage of 150 mg; 2 or 10 capsules with a dosage of 100 mg; for 4.7 or 10 capsules with a dosage of 50 mg in a jar of orange glass.On 1 bank together with the instruction on application in a pack.

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

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

    Terms of leave from pharmacies:On prescription
    Registration number:P N001760 / 01
    Date of registration:14.08.2008 / 05.10.2015
    Expiration Date:Unlimited
    The owner of the registration certificate:VEROPHARM SA VEROPHARM SA Russia
    Manufacturer: & nbsp
    Information update date: & nbsp02.02.2017
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