Active substanceFluconazoleFluconazole
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  • Dosage form: & nbspsolution for infusions
    Composition:

    One bottle (100 ml) contains:

    active substance: fluconazole 200 mg;

    Excipients: sodium chloride 900 mg, sodium hydroxide q.s., hydrochloric acid q.s.,

    water for injection up to 100 ml.

    Description:
    A colorless or slightly colored transparent solution.

    Pharmacotherapeutic group:Antifungal agent.
    ATX: & nbsp

    J.02.A.C   Triazole derivatives

    J.02.A.C.01   Fluconazole

    Pharmacodynamics:
    Representative of the class of triazole derivatives. Has a highly specific effect, inhibiting the activity of cytochrome P450 fungi. Blocking the conversion of lanosterol of fungal cells to ergosterol; increases the permeability of the cell membrane.
    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 less inhibits oxidative processes dependent on cytochrome P450 in human liver microsomes). Does not have anti-androgenic 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:
    After intravenous administration fluconazole well penetrates into tissues and body fluids. Distribution
    The concentration in the plasma is in direct proportion to the dose.The concentration of the active substance in breast milk, articular fluid, saliva, sputum and peritoneal fluid is similar to that in plasma.
    In the fluid, epidermis and stratum corneum (selective accumulation), concentrations exceeding serum levels are achieved.
    It penetrates well into the cerebrospinal fluid, with fungal meningitis, the concentration in the cerebrospinal fluid is about 85% of that in the plasma.
    The 90% equilibrium plasma fluconazole concentration (Css) is reached by 4-5 days. The introduction of the "shock" dose (on the first day), which is 2 times higher than the usual daily dose, allows one to achieve a concentration corresponding to 90% Css by day 2.
    The apparent volume of the distribution (Vd) approximates the total content of liquid. organism. The connection with plasma proteins is low -11-12%.
    Metabolism and excretion
    The half-life (T1 / 2) is 30 h: 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 clearance of creatinine.
    The pharmacokinetics of fluconazole significantly depends on the functional state of the kidneys, and there is an inverse relationship between Tmax and creatinine clearance (CK).After hemodialysis, within 3 hours, the concentration of fluconazole in the plasma is reduced by 50%. Pharmacokinetics of fluconazole is similar for intravenous administration and oral administration, which makes it easy to switch from one application to another.

    Indications:
    Cryptococcosis, including cryptococcal meningitis and infections of other localization (eg, lungs, skin), both in patients with normal immune response, and in patients with various forms of immunodepression (including AIDS patients, organ transplantation); maintenance therapy to prevent recurrence of cryptococcosis in AIDS patients.
    Generalized candidiasis, including candidemia, disseminated candidiasis and others. forms of invasive candidiasis infection, such as peritoneal, endocardial, eye, bronchopulmonary and urinary tract infections, including in patients with malignant
    tumors located in intensive care units, patients receiving cytotoxic or immunosuppressive agents, as well as in patients with other factors predisposing to the development of candidiasis.
    Prevention of candidiasis in the presence of a high risk of generalized infection, for example in patients with severe or long-lasting neutropenia.
    Deep endemic mycoses (coccidiomycosis and histoplasmosis) in patients with normal immunity.
    Oropharyngeal candidiasis, candidiasis of the esophagus and mucous membranes in children.

    Contraindications:
    Hypersensitivity to the components of the drug, as well as to other antifungal agents - azole derivatives; simultaneous application of terfenadine (against the background of the continuous use of fluconazole at a dose of 400 mg / day or more) or astemizole; lactation period.

    Carefully:
    Hepatic insufficiency, the appearance of rash against the background of fluconazole in patients with superficial fungal infection, and invasive / systemic fungal infections, simultaneous use of terfenadine and fluconazole at a dose of less than 400 mg / day, potentially pro-rhythmic conditions in patients with multiple risk factors, organic heart disease, disorders electrolyte balance, simultaneous use of drugs that cause arrhythmias, simultaneous reception with rifabutin and other inducers of cytochrome P450, acetylsalicylic acid), pregnancy.

    Pregnancy and lactation:
    Avoid the use of fluconazole in pregnancy, except in cases of severe and potentially life-threatening fungal infections, when the expected benefit of fluconazole for the mother significantly exceeds the possible risk to the fetus. Since the concentration of fluconazole in breast milk and in plasma is the same, it is contraindicated to apply the drug during the period of breastfeeding.

    Dosing and Administration:
    Solution for infusion is administered intravenously drip at a rate of no more than 200 mg / hour.
    The daily dose of fluconazole depends on the nature and severity of the fungal infection. When transferring from an intravenous injection. The use of the drug in the form intended for oral administration, and vice versa, there is no need to change the daily dose.
    The infusion solution is compatible with 20% dextrose solution, Ringer's solution, Hartmann's solution, 5% dextrose solution and 0.9% potassium chloride solution, 4.2% sodium bicarbonate solution, 0.9% sodium chloride solution. Infusions can be performed with conventional transfusion kits using one of the above solvents.
    Adults
    In cryptococcal meningitis and cryptococcal infection of other localizations on the first day, an average of 400 mg of fluconazole is prescribed, 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; with cryptococcal meningitis, it usually lasts a minimum of 6-8 weeks.
    To prevent the recurrence of cryptococcal meningitis in AIDS patients after completion of the full course of primary treatment, fluconazole therapy at a dose of 200 mg / day can be continued for a very long time (transition to an oral form is possible).
    With candidemia, disseminated candidiasis and other invasive candidiasis infections, the dose is, on average, 400 mg on the first day, and then at 200 mg per day. With insufficient clinical efficacy, the dose of fluconazole can be increased to 400 mg / day. The duration of therapy depends on clinical effectiveness.
    For the prevention of candidiasis in the presence of a high risk of generalized infection, for example in patients with severe or long-lasting neutropenia, the recommended dose is 400 mg 1 time / day. Fluconazole appoint a few days before the expected appearance of neutropenia and after an increase in the number of neutrophils more than 1000 / μL treatment is continued for another 7 days.
    With deep endemic mycoses, it may be necessary to use the drug at a dose of 200-400 mg / day for up to 2 years. The duration of therapy is determined individually; it is 11 - 24 months with coccidioidomycosis, with histoplasmosis 3-17 months (transition to an oral form is possible).
    Children
    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, which would exceed that of adults, that is, not more than 400 mg per day. The drug is used daily 1 time / day. If it is necessary to carry out long-term therapy, it is possible to switch to the oral form of fluconazole.
    In cryptococcal meningitis and cryptococcal infections of other localizations, as well as with generalized candidiasis in children, the recommended dose is 6-12 mg / kg / day, depending on the severity of the disease. The duration of therapy is 10-12 weeks (before - laboratory confirmation of the absence of pathogens in the CSF).
    To prevent the recurrence of cryptococcal meningitis in children with AIDS, after the completion of the full course of primary treatment with fluconazole at a dose of 6 mg / kg / day can continue for a long time.
    With oropharyngeal candidiasis in children, the recommended dose is 6 mg / kg / day on the first day, then daily at 3 mg / kg / day, once. Duration of therapy - for at least 2 weeks.
    When candidiasis of mucous membranes in children 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. The duration of therapy is at least 3 weeks.
    When candidiasis of the esophagus in children fluconazole is prescribed once in a dose of 3 mg / kg / day. On the first day, a shock dose of 6 mg / kg / day can be prescribed. Depending on the severity of the disease, the dose can be increased to 6-12 mg / kg / day. The duration of the therapy is at least 3 weeks and 2 weeks after the regression of the symptoms.
    For the prevention of fungal infections in children with reduced immunity, in which the risk of infection is associated with neutropenia, resulting from cytotoxic chemotherapy or radiation therapy, fluconazole is given once in a dose of 3-12 mg / kg / day. The duration of therapy is until elimination of induced neutropenia. - The use of nvenavama in children under 4 weeks of age -
    It should be borne in mind that in newborns fluconazole output slowly. The first 2 weeks of life the drug is prescribed in the same dose (in mg / kg) as for older children, but at an interval of 72 hours. Children at the age of 3 and 4 weeks the same dose is administered at an interval of 48 hours. Elderly people
    In the absence of violations of the kidneys should follow the usual dosage regimen.
    Patients with impaired renal function
    At QC less than 50 ml / min, the dosage regimen is required.
    Fluconazole is excreted mainly with urine in unchanged form. With a single application, a dose change is not required. In patients with impaired renal function with repeated use of the drug, a shock dose of 50 mg to 400 mg should be initially administered, after which the daily dose (depending on the indications) is determined according to the following table:

    Creatinine clearance (ml / min)

    Percent recommended dose

    >50

    100%

    <50 (without dialysis)

    ,50%

    Patients on continuous dialysis

    100% after each dialysis session


    Patients on continuous dialysis 100% after each dialysis session
    In children with impaired renal function, the daily dose of the drug should be reduced (in the same proportion as in adults), in accordance with the degree of renal insufficiency.
    The drug solution contains 0.9% sodium chloride; in each vial of 100 ml contains 15 mM Na + (sodium ions) and Cl (chloride ions), therefore, in patients who require a restriction of sodium or liquid intake, the rate of fluid administration must be considered.

    Side effects:
    Fluconazole, as a rule, is well tolerated.
    Depending on the frequency of occurrence, the following groups of side effects are distinguished: often more than 1%, infrequently 0.1-1%, rarely -0.01-0.1%; very rarely - less than 0.01%.
    Allergic reactions: infrequent skin rash, rarely - multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), anaphylactoid reactions (including angioedema, face swelling, hives, itching of the skin).
    From the side of the central nervous system: infrequently - headache, dizziness, rarely - convulsions.
    On the part of the gastrointestinal tract: infrequently - nausea, diarrhea, flatulence, abdominal pain, taste change,. Vomiting, rarely - impaired liver function (jaundice, hyperbilirubinemia, increased activity of alanine aminotransferase (ALT), aspartate aminotransferase (ACT) and alkaline phosphatase AF), hepatitis, hepatocellular necrosis), including those with a fatal outcome.
    On the part of the organs of hematopoiesis: rarely - leukopenia, thrombocytopenia, neutropenia, agranulocytosis.
    From the cardiovascular system: rarely - prolongation of the QT interval, very rarely - fibrillation / flutter of the ventricles.
    Other: rarely - renal dysfunction, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

    Overdose:
    Symptoms: hallucinations, paranoid behavior.
    Treatment: symptomatic, forced diuresis. Hemodialysis within 3 hours reduces the concentration in the plasma by approximately 50%.

    Interaction:
    Anticoagulants. Fluconazole increases the prothrombin time of indirect anticoagulants - coumarin derivatives (eg, warfarin) by an average of 12%, therefore careful monitoring of prothrombin time in patients taking fluconazole and indirect anticoagulants - coumarin derivatives.
    Oral hypoglycemic drugs, derivatives of sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide). With their simultaneous use with fluconazole, the half-life of oral hypoglycemic drugs, derivatives of sulfonylureas, lengthens, 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. The simultaneous use 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 concentration of phenytoin and select its dose to provide a therapeutic concentration in the plasma.
    Oral contraceptives. Multiple application of fluconazole (in doses of 50-200 mg) does not affect the effectiveness of combined oral contraceptives. - Rifampicin. Simultaneous application of fluconazole and rifampicin resulted in a 25% decrease in AUC (area under the concentration-time curve) and 20% in the half-life of fluconazole. With the simultaneous use of rifampicin and fluconazole, the dose of fluconazole must be considered.
    Cyclosporine. When treating fluconazole, it is recommended to monitor the concentration of cyclosporine in the blood.
    Theophylline. Fluconazole prolongs the half-life of theophylline and increases the risk of intoxication (it is necessary to correct its dose).
    Terfenadine. The simultaneous use of fluconazole in doses of 400 mg / day or more is contraindicated. Treatment with fluconazole in doses less than 400 mg / ut in combination with terfenadine should be done under close medical supervision.
    Cisapride. With the simultaneous use of fluconazole and cisapride, unwanted reactions from the heart, including paroxysms of ventricular tachycardia (torsade de pointes). Rifabutin. Simultaneous application of fluconazole and rifabutin can lead to an increase in plasma concentrations of the latter. With the simultaneous use of fluconazole and rifabutin, cases of uveitis are described. Patients receiving concurrently rifabutin and fluconazole, must be carefully observed.
    Tacrolimus. Fluconazole increases the plasma 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 plasma 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.
    Midazolam. Fluconazole increases the plasma concentration of midazolam, which increases the risk of developing psychomotor effects (most pronounced when fluconazole is administered orally than intravenously).


    Special instructions:
    Treatment should be continued until the appearance of clinical and hematologic remission. Premature termination of treatment leads to relapse.
    Treatment can be started without the results of sowing or other laboratory tests, but if appropriate, appropriate correction of antifungal therapy is recommended.
    In the course; treatment it is necessary to monitor blood counts (cellular composition, coagulability), kidney and liver function. It is necessary to monitor the prothrombin index when used simultaneously with indirect anticoagulants - coumarin derivatives. If there is a violation of kidney and liver function, stop using the drug. In rare cases, the use of fluconazole was accompanied by toxic, liver changes.
    In the case of hepatotoxic effects associated with fluconazole, their development was not dependent 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 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 systemic fungal infections, patients should be carefully monitored and with the appearance of bullous changes or erythema multiforme fluconazole necessary cancel.
    It is recommended to monitor the concentration of cyclosporine in the blood in patients receiving fluconazole, since in patients with kidney transplantation the use of fluconazole at a dose of 200 mg / day leads to a slow increase in the concentration of cyclosporine in the plasma. Care must be taken when fluconazole is used simultaneously with cisapride, rifabutin, or other drugs metabolized by the cytochrome P450 system.

    Effect on the ability to drive transp. cf. and fur:
    During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

    Form release / dosage:Solution for infusions 2 mg / ml.
    Packaging:
    For 100 ml of solution in a vial of polyethylene, closed with a lid. Each vial is wrapped with a polypropylene BOPP film. For 1 bottle in a cardboard pack together with instructions for use.

    Storage conditions:
    In a dry, the dark place at a temperature of no higher than 30 ° C. Do not freeze. 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:LP-000206
    Date of registration:14.02.2011
    The owner of the registration certificate:Clarice LifeSinceys LimitedClarice LifeSinceys Limited India
    Manufacturer: & nbsp
    Information update date: & nbsp29.09.2015
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