Active substanceFluconazoleFluconazole
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  • Dosage form: & nbspcapsules
    Composition:

    Composition of contents of capsules

    Capsules 50 mg:

    Active substance:

    Fluconazole 50 mg

    Excipients:

    Colloidal silicon dioxide 0.3 mg Magnesium stearate 1.2 mg Talc 3.3 mg Povidone 3.6 mg Corn Starch 12.1 mg Lactose (anhydrous) 49.5 mg.

    Composition of hard gelatin capsule:

    Bottom part: Titanium dioxide, Cv. I. 77891, E 171 2.0%, Gelatin to 100%

    Top part: Indigokarmin Tsv.I.73015, E 132 0.0086%, Titanium dioxide Cv. I. 77891, E 171 4.0%, Gelatin to 100%.

    Capsules 100 mg:

    Active substance:

    Fluconazole 100 mg

    Excipients:

    Silica colloidal dioxide 0.6 mg, Magnesium stearate 2.4 mg. Talc 6.6 mg, Povidone 7.2 mg, Corn starch 24.2 mg, Lactose (anhydrous) 99.0 mg.

    Composition of hard gelatin capsule:

    Bottom part: Titanium dioxide Cv. I. 77891, E 171 2.0%, Gelatin to 100%

    Top part: Indigokarmin Tsv.I. 73015, E 132 0.0471% ,. Titanium dioxide Cv. I. 77891, E 171 4.0%, Gelatin to 100%.

    Capsules 150 mg:

    Active substance:

    Fluconazole 150 mg

    Excipients:

    Silica colloidal dioxide 0.9 mg, Magnesium stearate 3.6 mg, Talc 9.9 mg, Povidone 10.8 mg, Corn starch 36.3 mg,

    Lactose (anhydrous) 148.5 mg.

    Composition of hard gelatin capsule:

    Bottom part: Titanium dioxide, Cv. I. 77891, E 171 2.0%, Gelatin to 100%.

    Top part: Indigo carmine Tsv.I. 73015, E 132 0.2513%, Titanium dioxide Cv. I. 77891, E 171 1.5%, Gelatin to 100%.

    Description:

    Contents of capsules

    White or almost white powder, or a dense powder mass.

    Capsules 50 mg:

    Hard gelatin capsules with a size of 4 (Coni-Snap). Upper part: light blue, opaque (L 910). Lower part: white, opaque (L 500).

    Capsules 100 mg:

    Hard gelatin capsules with a size of 2 (Coni-Snap). Upper part: turquoise, opaque (L 890).Lower part: white, opaque (L 500).

    Capsules 150 mg:

    Hard gelatin capsules with a size of 1 (Coni-Snap). Upper part: blue, opaque (54.038). Lower part: white, opaque (L 500).

    Pharmacotherapeutic group:Antifungal agent
    ATX: & nbsp

    J.02.A.C   Triazole derivatives

    J.02.A.C.01   Fluconazole

    Pharmacodynamics:

    Fluconazole is a representative of the class of triazole derivatives, it is a selective inhibitor of the synthesis of sterols in the fungal cell. 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 the cytochrome P450 system 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 androgenic activity.

    The drug is active in mycoses caused by Candida spp., Cryptococcus neoformans, Microsporum spp., Trichophyton spp. Blastomyces dermatidis, Coccidioides immitis and Histoplasma capsulatum. i

    Pharmacokinetics:

    After oral administration fluconazole it is well absorbed, its bioavailability is 90%. The maximum concentration (Cmax) after oral administration of 150 mg is achieved through 0.5-1.5 hours and is 90% of the concentration in the plasma with intravenous administration at a dose of 2.5-3.5 mg / kg.Simultaneous food intake does not affect the absorption of the drug taken internally. Concentrations in the plasma are in direct proportion to the dose. 90% equilibrium concentration is achieved by 4-5 days of treatment with the drug (once a day);

    The use on the first day of a dose, which is 2 times greater than the usual daily dose, makes it possible to achieve a fluconazole concentration in plasma equal to 90% of the equilibrium concentration value by the second day. Apparent; volume of distribution. is close to the total water content in the body. Binding to plasma proteins - 11-12%.

    Fluconazole well penetrates into all body fluids.

    In the stratum corneum of the epidermis, the dermis and the sweat fluid, high concentrations are reached that exceed the serum levels. After ingestion of 150 mg on day 7, the concentration in the stratum corneum is 23.4 μg / g, and 1 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.

    Concentrations of the drug in saliva, sputum, breast milk, articular and peritoneal fluid are similar to its concentration in the blood plasma. In patients with fungal meningitis, the fluconazole content in the cerebrospinal fluid reaches 80% of its concentration level in the plasma.

    Constant values ​​in vaginal secretions are reached 8 hours after ingestion and are kept at this value for at least 24 hours. It is an inhibitor of the CYP2C9 isoenzyme in the liver. The pharmacokinetics of fluconazole significantly depend on the functional state of the kidneys, and there is an inverse relationship between T1/2 and QC.

    The half-life (T1/2) of fluconazole is about 30 hours. Fluconazole is excreted mainly by the kidneys; approximately: 80% of the administered dose is excreted by the kidneys unchanged, 11% - in the form of metabolites. The clearance of fluconazole is proportional to the creatinine clearance. Metabolites of fluconazole in peripheral blood were not detected.

    After hemodialysis: within 3 hours the concentration of fluconazole in the plasma is reduced by 50%.

    Indications:

    Cryptococcosis: cryptococcal meningitis, cryptococcal infections of lung and skin; cryptococcal sepsis; prevention of recurrences of cryptococcosis in AIDS patients, organ transplantation or other immunodeficiency cases:

    Generalized candidiasis: candidemia, disseminated candidiasis and others

    forms of invasive candidiasis infections (infection of the abdominal cavity, endocardium, eyes, respiratory and urinary tracts),including in patients receiving a course of cytostatic or immunosuppressive therapy, as well as in the presence of other factors predisposing to the development of candidiasis - treatment and prevention.

    Candidiasis of the mucous membranes: the oral cavity, including atrophic candidiasis of the oral cavity, associated with the wearing of dentures, pharynx, esophagus and non-invasive bronchopulmonary infections, candiduria.

    Genital candidiasis: vaginal (acute or chronic recurrent form), candidal 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; prevention of recurrence of oropharyngeal candidiasis in AIDS patients.

    Mycosis of the skin, including mycosis of the feet, trunk, inguinal region; pityriasis lichen, onychomycosis;

    Deep endemic mycoses, including coccidioidosis, paracoccidioidosis and histoplasmosis in patients with normal immunity.

    Contraindications:
    • Hypersensitivity to fluconazole, other components of the drug or other closely related azole compounds:
    • Simultaneous use of terfenadine (against the background of continuous administration of fluconazole at a dose of 400 mg per day and above) and cisapride, since both drugs prolong the QT interval and increase the risk of severe cardiac rhythm disturbances
    • Simultaneous application of astemizole;
    • Lactose intolerance; deficiency of lactase; glucose-galactose malabsorption;
    • Lactation period.
    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, simultaneous administration of fluconazole with rifabutin or other drugs metabolized; system of cytochrome P450, 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, concomitant use of medications that cause arrhythmias); patients with intolerance to acetylsalicylic acid, pregnancy.
    Pregnancy and lactation:

    The use of fluconazole during pregnancy is possible only if the potential benefit to the mother exceeds the risk to the fetus.

    Fluconazole is defined in breast milk in the same concentration as in plasma, so its use during lactation is contraindicated.

    Dosing and Administration:

    The drug is taken orally.

    When transferring from intravenous administration to taking capsules and vice versa, there is no need to change the daily dose.

    Application in adults

    In cryptococcal infections, the usual dose of fluconazole is 400 mg once a day on the first day of treatment, later on - 200-400 mg once a day. The duration of treatment for cryptococcal infections depends on the clinical efficacy, confirmed by mycological examination, and usually ranges from 6 to 8 weeks.

    The recommended duration of treatment for cryptococcal meningitis is 10-12 weeks after a negative result of a microbiological study of a sample of cerebrospinal fluid.

    To prevent the recurrence of cryptococcal meningitis in AIDS patients after completing the full course of primary therapy fluconazole appoint a patient in a dose of at least 200 mg per day for a long period.

    With candidemia, disseminated candidiasis and other invasive candidiasis infections, the daily dose of fluconazole is 400 mg on the first day and 200 mg on subsequent days.If necessary, the dose of the drug can be increased to 400 mg / day. The duration of treatment depends on clinical effectiveness.

    With severe systemic candidiasis - it is possible to increase the dose to 800 mg per day. The duration of therapy depends on clinical effectiveness. Should continue at least 2 weeks after receiving negative blood cultures or after the disappearance of the symptoms of the disease.

    In oropharyngeal candidiasis, including patients with impaired immunity, the usual dose of fluconazole is 50-100 mg once a day for 7-14 days. To prevent the recurrence of oropharyngeal candidiasis in AIDS patients after completing the full course of primary therapy - 150 mg once a week. If necessary, the treatment can be prolonged, especially with severe immunity disorders.

    With 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 antiseptic agents to handle the prosthesis.

    In other candidiasis infections, for example, with esophagitis, noninvasive bronchopulmonary infections, candiduria, candidiasis of the skin and mucous membranes, the daily dose is 50-100 mg for 14-30 days.

    In severe mucosal candidiasis - 100-200 mg per day:

    For the prevention of fungal infections in patients with malignant neoplasms, the dose of fluconazole should be 50 mg once a day until the patient is at a high risk because of cytotoxic or radiation therapy.

    With vaginal candidiasis - 150 mg once. To reduce the frequency - relapses are used once a month for 150 mg for 4-12 months, sometimes you may need more frequent use.

    With balanitis caused by Candida spp., fluconazole appoint a single dose of 150 mg orally.

    For the prevention of candidiasis, the recommended dose of fluconazole is 50-400 mg once a 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 once daily. 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.

    In skin mycoses (including candidiasis), including mycosis of the feet, skin of the inguinal area, the recommended dose is 150 mg once a week or 50 mg once a 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 mg once; 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 is healthy. 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 2 years. The duration of therapy is determined individually; it can be 11-24 months with coccidioidosis; 2-17 months with paracoccidioidosis and 3-17 months with histoplasmosis.

    Use in children

    The duration of treatment depends on the clinical and mycological effect. In children, the drug should not be used in a daily dose exceeding that of adults. Fluconazole apply daily once a 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 given to achieve a more rapid equilibrium concentration.

    For the treatment of generalized candidiasis and 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, in whom the risk of infection is associated with neutropenia developing in; as a result of cytotoxic chemotherapy or radiotherapy, the drug is prescribed at 3-12 mg / kg per day, depending on the severity and duration of preservation of induced neutropenia.

    In newborns fluconazole is output more slowly, therefore in the first 2 weeks of life the drug is prescribed in the same dose (in mg / kg) as in older children, but at an interval of 72 hours. Children aged 3-4 weeks of life are given the same dose at intervals of 48 hours.

    Application in elderly patients

    In the absence of violations of the kidneys should follow the usual recommendations for dosing the drug. For patients with impaired renal function (creatinine clearance <50 mL / min), the dosage regimen should be adjusted as indicated below.

    Use in patients with renal insufficiency

    Fluconazole is excreted mainly by the kidneys in unchanged form. With a single application of fluconazole, no dose changes are required. If a course of treatment is necessary in patients (including children) with impaired renal function, a "shock" dose of 50 mg to 400 mg should be initially administered. In the future, the daily dose (depending on the indication) is determined according to the following table:

    Creatinine clearance (ml / min)

    % of recommended dose

    > 50

    100%, once a day

    <50 (without dialysis)

    50%, once a day

    Patients on continuous dialysis

    100%, after each dialysis session

    Side effects:

    From the digestive system: nausea, vomiting, diarrhea, flatulence, abdominal pain, taste change, liver function disorder (hyperbilirubinemia, increased activity of "liver" transaminases, alkaline phosphatase, jaundice, hepatitis, hepatocellular necrosis, including fatal).

    From the nervous system: headache, dizziness, convulsions.

    On the part of the organs of 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, urticaria, skin itching), bronchial asthma (more often with intolerance to acetylsalicylic acid).

    From the side of the cardiovascular system: increase in the duration of the QT interval on an electrocardiogram, fibrillation / flutter of the ventricles.

    Other: a violation of kidney 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). After a three-hour hemodialysis session, the concentration of fluconazole in the blood plasma is reduced by approximately 50%.

    Interaction:

    Anticoagulants: In patients receiving fluconazole and indirect anticoagulants of the coumarin series, careful monitoring of prothrombin time is necessary, since it may increase.

    Sulfonylurea preparations: fluconazole with the simultaneous administration may extend the half-life of sulfonylurea derivatives, therefore, when combined, the possibility of developing i hypoglycemia should be taken into account.

    Phenytoin: simultaneous application of fluconazole and phenytoin may be accompanied by an increase in the concentration of phenytoin in a clinically significant degree, which requires a reduction in its dose.

    Rifampicin: with simultaneous administration of rifampicin and fluconazole, the maximum concentration and the half-life of the latter decrease, so if the combined use is necessary, the dose of fluconazole should be increased.

    Rifabutin: The combined use of fluconazole and rifabutin is accompanied by increased serum concentration of the latter, it is possible to develop uveitis.

    Cyclosporine: when combined with fluconazole and cyclosporine, it is recommended to monitor the concentration of the latter in the blood, as it may increase.

    Terfenadine: taking into account the emergence of serious, life-threatening, arrhythmias in patients taking antifungal agents - azole derivatives in combination with terfenadine, their joint intake is contraindicated.

    Cisapride: with simultaneous administration of fluconazole and cisapride, cases of adverse cardiac reactions, including paroxysms of ventricular tachycardia, have been described. Simultaneous reception is contraindicated.

    Zidovudine: when combined with fluconazole may increase zidovudine concentration in blood plasma. Patients taking this combination should be observed to identify side effects of zidovudine.

    Theophylline: taking fluconazole leads to a decrease in the average clearance rate: theophylline from the blood plasma, therefore, the risk of toxic theophylline and its overdose increases.

    Midazolam: simultaneous application of fluconazole and midazolam leads to: a significant increase in the concentration of the latter in blood plasma and the risk of developing psychomotor reactions.

    Hydrochlorothiazide: with the simultaneous administration of fluconazole and hydrochlorothiazide, the concentration of fluconazole in the blood plasma increases by 40%.

    Tacrolimus: with the simultaneous administration of fluconazole and tacrolimus, the concentration of the latter in the serum increases, which leads to an increased risk of nephrotoxicity.
    Care should be taken when using fluconazole in patients who are simultaneously receiving other drugs metabolized by the cytochrome P450 system.

    Special instructions:

    Treatment with fluconazole must be continued until the appearance of clinical-hematologic remission; Premature termination of treatment leads to relapse.

    Because the fluconazole is excreted mainly by the kidneys, caution should be exercised in patients with renal insufficiency. With long-term treatment fluconazole om dosing should be carried out taking into account the clearance of creatinine.

    In rare cases, the use of fluconazole was accompanied by a toxic effect on the liver, including fatal, mainly in patients with serious concomitant diseases. It is necessary to monitor liver function. If there are signs of liver damage that may be associated with the use of fluconazole, the drug should be discontinued.

    Against the background of taking the drug in patients, there were rare cases of development of exfoliative skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.Patients with AIDS and malignant neoplasms are more likely to develop severe skin reactions with many drugs. If the patient develops a superficial fungal infection of the rash during treatment, which can be associated with the use of fluconazole, the drug should be discontinued. When rashes appear in patients with invasive / systemic fungal infections, they should be carefully monitored and canceled fluconazole with the appearance of bullous lesions or erythema multiforme.

    Caution should be exercised while taking fluconazole with rifabutin or: other drugs, the metabolic system of cytochrome P450.

    It is necessary to monitor prothrombin time in patients simultaneously receiving fluconazole and indirect anticoagulants of the coumarin series.

    Effect on the ability to drive transp. cf. and fur:

    Patients should be careful when driving vehicles or when working with machinery, since dizziness may occur during fluconazole treatment.

    Form release / dosage:Capsules, 50 mg, 100 mg and 150 mg.
    Packaging:

    Capsules 50 mg: 7 capsules in a blister of PVC and aluminum foil.For 1 blister in a cardboard box with instructions for use.

    Capsules 100 mg: 7 capsules in a blister of PVC and aluminum foil. For 4 blisters in a cardboard box with instructions for use.

    Capsules 150 mg: 1 capsule in a blister of PVC and aluminum foil. For 1.2 or 4 blisters in a cardboard box with instructions for use.

    Storage conditions:

    At a temperature of no higher than 30 ° C.

    Keep out of the reach of children!

    Shelf life:

    5 years.

    Do not use after the expiry date printed on the package.

    Terms of leave from pharmacies:Without recipe
    Registration number:П N012167 / 01
    Date of registration:02.06.2010 / 28.07.2014
    Expiration Date:Unlimited
    The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary
    Manufacturer: & nbsp
    Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary
    Information update date: & nbsp07.06.2018
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