Clinical and pharmacological group: & nbsp

Antifungal means

Included in the formulation
  • Vero-Fluconazole
    capsules inwards 
    VEROPHARM SA     Russia
  • Disorel-Sanovel
    capsules inwards 
  • Diflazon®
    solution d / infusion 
  • Diflucan®
    powder inwards 
    Pfizer Inc.     USA
  • Diflucan®
    capsules inwards 
    Pfizer Inc.     USA
  • Diflucan®
    solution in / in 
    Pfizer Inc.     USA
  • Micon
    solution d / infusion 
  • Medoflucon®
    capsules inwards 
    MEDSERV, LLC     Russia
  • Mycomomax®
    capsules inwards 
    Zentiva c.s.     Czech Republic
  • Mycosyst®
    capsules inwards 
    GEDEON RICHTER, OJSC     Hungary
  • Mycosyst®
    solution d / infusion 
    GEDEON RICHTER, OJSC     Hungary
  • Mycoflucan®
    pills inwards 
  • Mycoflucan®
    solution d / infusion 
  • Nofung®
    capsules inwards 
  • Procanazole
    capsules inwards 
  • Fangifflu
    capsules inwards 
  • Flukozan
    solution d / infusion 
    LENS-PHARM, LLC     Russia
  • Flukoside
    capsules inwards 
  • Flukomabol®
    solution d / infusion 
    PREBAND PFC, LLC     Russia
  • Fluconazole
    capsules inwards 
  • Fluconazole
    capsules inwards 
    PHARMACY 36.6, CJSC     Russia
  • Fluconazole
    solution d / infusion 
  • Fluconazole
    capsules inwards 
  • Fluconazole
    solution d / infusion 
    RUSYUROFARM, LLC     Russia
  • Fluconazole
    capsules inwards 
    VALENTA PHARM, PAO     Russia
  • Fluconazole
    capsules inwards 
    REPLEK FARM Skopje, OOO     Macedonia
  • Fluconazole
    capsules inwards 
    FARMPROJECT, CJSC     Russia
  • Fluconazole
    solution d / infusion 
    EAST-FARM, CJSC     Russia
  • Fluconazole
    capsules inwards 
    OZONE, LLC     Russia
  • Fluconazole
    capsules inwards 
    BIOKOM, CJSC     Russia
  • Fluconazole
    capsules inwards 
    VERTEKS, AO     Russia
  • Fluconazole
    capsules inwards 
  • Fluconazole
    pills inwards 
    TECHNOLOG, JSC     Ukraine
  • Fluconazole
    capsules inwards 
    Hemofarm AD     Serbia
  • Fluconazole
    capsules inwards 
  • Fluconazole
    capsules inwards 
    Astrafarm, CJSC     Russia
  • Fluconazole
    capsules inwards 
    MEDISORB, CJSC     Russia
  • Fluconazole OBL
    capsules inwards 
  • Fluconazole Zentiva
    solution d / infusion 
    Zentiva c.s.     Czech Republic
  • Fluconazole Cabi
    solution d / infusion 
  • Fluconazole STADA
    capsules inwards 
  • Fluconazole-Acti
    solution d / infusion 
    Aktifarm, OOO     Russia
  • Fluconazole-Sandoz®
    capsules inwards 
    Sandoz d.     Slovenia
  • Fluconazole-Teva
    capsules inwards 
  • Flukonorm
    capsules inwards 
  • Flucorus®
    solution d / infusion 
    MS-VITA, LLC     Russia
  • Flukorem
    gel externally 
    REMEDIYA, LLC     Russia
  • Flucostat®
    solution d / infusion 
  • Flucostat®
    capsules inwards 
  • Forkan®
    solution d / infusion 
    Cipla Ltd.     India
  • Forkan®
    capsules inwards 
    Cipla Ltd.     India
  • Ciscan®
    capsules inwards 
  • Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

    VED

    АТХ:

    J.02.A.C   Triazole derivatives

    J.02.A.C.01   Fluconazole

    Pharmacodynamics:

    Antifungal agent. The triazole derivative exhibits an antifungal effect by blocking the biosynthesis of the ergosterol of the fungal cell membrane. "Target" for the action of the drug is the enzyme 14-α-demethylase.

    14-α-demethylase is part of a group of enzymes known collectively cytochrome P450. All enzymes of the cytochrome P450 group contain a hematinic iron-containing pigment. Fluconazole binds to the iron atom of the hematinic group and inactivates 14-α-demethylase, which leads to a disruption in the synthesis of ergosterol and the accumulation of lanosterol and other sterols. Their incorporation into the membrane instead of ergosterol significantly disrupts the structure and function of the fungal cell membrane.

    The decrease in the synthesis of ergosterol, as well as the accumulation of 14α-methylsterols, destroys the densely packed acyl chains of the phospholipids of the fungal membranes. Destabilization of the fungal membrane leads to dysfunction of membrane enzymes, including those involved in the electron transport chain, and ultimately to cell death.

    Used in systemic mycosis: candidosis, cryptococcosis, blastomycosis, histoplasmosis, coccidioidomycosis, as well as dermatomycosis. Relatively low toxic profile and a high degree of penetration into the cerebrospinal fluid make fluconazole a drug of choice in systemic candidiasis and cryptococcal meningitis. Due to complications associated with intrathecal administration of amphotericin B, fluconazole - The first-line drug in coccidioid meningitis. Although fluconazole and is active against the causative agents of blastomycosis, histoplasmosis, sporotrichosis, it is inferior in efficacy against pathogens of these infections to itraconazole. Fluconazole Ineffective in aspergillosis.

    Pharmacokinetics:

    The pharmacokinetics of fluconazole is similar for intravenous administration and for oral administration.

    After oral administration fluconazole is well absorbed, its plasma levels (and total bioavailability) exceed 90% of plasma levels of fluconazole in intravenous administration. Simultaneous food intake does not affect absorption during ingestion. The maximum concentration is reached in 0,5-1,5 h after administration of fluconazole on an empty stomach. The concentration in the blood plasma is proportional to the dose.

    90% of the equilibrium concentration is achieved by 4-5 days after the start of therapy (with repeated administration once a day).

    The introduction of a shock dose (on day 1), which is 2 times greater than the average daily dose, makes it possible to achieve 90% equilibrium concentration to the 2nd day. The apparent equilibrium volume approaches the total water content in the body. Binding to blood plasma proteins is low (11-12%).

    Fluconazole well penetrates into all body fluids. The levels of fluconazole in saliva and sputum are similar to those in plasma. In patients with fungal meningitis, fluconazole levels in the cerebrospinal fluid are about 80% of its levels in the blood plasma.

    In the stratum corneum, the epidermis, the dermis and the sweat fluid, high concentrations are reached that exceed the serum levels. Fluconazole accumulates in the stratum corneum. When administered at a dose of 50 mg once a day, the concentration of fluconazole after 12 days was 73 μg / g, and after 7 days after discontinuation of treatment, only 5.8 μg / g. When applied at a dose of 150 mg once a week, the fluconazole concentration in the stratum corneum on the 7th day was 23.4 μg / g, and 7 days after the second dose, 7.1 μg / g.

    The concentration of fluconazole in the nails after 4 months of administration at a dose of 150 mg once a week was 4.05 μg / g in healthy and 1.8 μg / g in the affected nails; in 6 months. after completion of therapy fluconazole was still determined in the nails.

    Fluconazole is excreted mainly by the kidneys; approximately 80% of the administered dose is detected in the urine unchanged. The clearance of fluconazole is proportional to the creatinine clearance.No circulating metabolites were detected.

    A prolonged half-life from plasma allows fluconazole once for vaginal candidiasis and once a day or once a week for other indications.

    Indications:

    Cryptococcosis, including cryptococcal meningitis and other localization infections (eg, lungs, skin), including in patients with normal immune response and in AIDS patients, recipients of transplanted organs and patients with other forms of immunodeficiency; maintenance therapy to prevent recurrence of cryptococcosis in AIDS patients.

    Generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidiasis infection, such as peritoneal, endocardial, eye, respiratory and urinary tract infections, including in patients with malignant tumors in the intensive care unit and receiving cytotoxic or immunosuppressive agents, as well as in patients with other factors predisposing to the development of candidiasis.

    Candidiasis of the mucous membranes, including mucous membranes of the oral cavity and pharynx, esophagus, non-invasive bronchopulmonary infections, candiduria,mucocutaneous and chronic atrophic candidiasis of the oral cavity (associated with the wearing of dentures), including in patients with normal and suppressed immune function; prevention of recurrence of oropharyngeal candidiasis in AIDS patients.

    Genital candidiasis; acute or recurrent vaginal candidiasis; prevention to reduce the frequency of recurrence of vaginal candidiasis (3 or more episodes a year); candidiasis balanitis.

    Mycosis of the skin, including mycosis of the feet, body, inguinal region, pityriasis, onychomycosis and cutaneous candidiasis infections.

    Deep endemic mycoses in patients with normal immunity, coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis.

    Prevention of fungal infections in patients with malignant tumors, predisposed to the development of such infections as a result of cytotoxic chemotherapy or radiation therapy.

    I.B20-B24.B20.5   The disease caused by HIV, with manifestations of other mycoses

    I.B20-B24.B20.4   The disease caused by HIV, with manifestations of candidiasis

    I.B35-B49.B35.4   Mycosis of the trunk

    I.B35-B49.B35.3   Mycosis of the feet

    I.B35-B49.B35.2   Mycosis brushes

    I.B35-B49.B35.1   Mycosis of nails

    I.B35-B49.B35.0   Mycosis of the beard and head

    I.B35-B49.B35.6   Epidermophytosis inguinal

    I.B35-B49.B36.0   Multicolored lichen

    I.B35-B49.B37.0   Candidiasis stomatitis

    I.B35-B49.B37.7   Candida septicemia

    I.B35-B49.B37.6   Candidiasis endocarditis (I39.8 *)

    I.B35-B49.B37.4   Candidiasis of other urogenital localizations

    I.B35-B49.B37.3   Candidiasis of the vulva and vagina (N77.1 *)

    I.B35-B49.B37.2   Candidiasis of skin and nails

    I.B35-B49.B37.1   Pulmonary Candidiasis

    I.B35-B49.B37.8   Candidiasis of other localizations

    I.B35-B49.B38   Coccidioidomycosis

    I.B35-B49.B39   Histoplasmosis

    I.B35-B49.B41   Paracoccidioidomycosis

    I.B35-B49.B42   Sporotrichosis

    I.B35-B49.B45   Cryptococcosis

    I.B35-B49.B45.2   Cutaneous Cryptococcosis

    I.B35-B49.B45.1   Cerebral Cryptococcosis

    I.B35-B49.B45.0   Pulmonary cryptococcosis

    XIV.N40-N51.N51.2 *   Balanitis in diseases classified elsewhere

    XX.Y85-Y89.Y88.0   Consequences of adverse effects of medicinal products, medicines and biological substances used for therapeutic purposes

    XXI.Z40-Z54.Z51.1   Chemotherapy for neoplasm

    XXI.Z40-Z54.Z51.0   Radiotherapy course (supportive)

    Contraindications:Hypersensitivity(including other azoles), concurrent administration of terfenadine or astemizole, pregnancy, breast-feeding, children under 3 years of age. Simultaneous use with drugs that increase the QT interval and metabolizewith the aid of the CYP3A4 isoenzyme, such as cisapride, astemizole, erythromycin, pimozide and quinidine.
    Carefully:Alcoholism, abnormal liver function, IHD, chronic obstructive pulmonary disease, electrolyte balance disorder, heart valve disease, liver cirrhosis, chronic renal failure, rash on fluconazole in persons with superficial fungal infection and invasive (systemic) fungal infections, simultaneous reception Terfenadine and fluconazole at a dose of less than 400 mg per day, potentially proaritmogenic states in individuals with multiple risk factors (organic heart disease, at the same time the reception of funds that cause arrhythmias).
    Pregnancy and lactation:

    When pregnancy is possible only with life-threatening severe infections, if the expected effect of therapy exceeds the potential risk for the fetus (adequate and strictly controlled safety studies in pregnant women have not been conducted). There are reports of various congenital disorders in infants whose mothers for 3 months or more were treated with high fluconazole doses of 400-800 mg / day for coccidioidomycosis, although the cause-and-effect relationship of these cases to fluconazole is unclear.

    Action category for the fetus by FDA - C.

    At the time of treatment, breastfeeding should be discontinued (fluconazole concentrations in breast milk are comparable to plasma ones).

    Dosing and Administration:

    Inside, intravenously. The dose, route of administration, duration of the course of treatment are determined individually depending on the indications, the patient's condition, clinical and mycological effect. The daily dose depends on the nature and severity of the infection. In children, the daily dose should not exceed the maximum daily dose for adults. When transferring a patient from intravenous administration of fluconazole to oral administration and vice versa, there is no need to change the daily dose.

    Adults with cryptococcosis and generalized candidiasis - intravenously, by mouth, 400 mg on the first day, then 200-400 mg per day; with oropharyngeal candidiasis - inside, 50-100 mg per day for 7-14 days; with vaginal candidiasis - inside, 150 mg once, in chronic form - once a month for 150 mg for 4-12 months; with mycosis - 150 mg once a week. Duration of therapy is determined individually, it varies from 4 to 12 months. Some patients may need more frequent use.

    To prevent the recurrence of oropharyngeal candidiasis in AIDS patients after completing the full course of primary therapy - 150 mg once a week.

    With atrophic oral candidiasis associated with the wearing of dentures, 50 mg once a day for 14 days in combination with local antiseptic agents for prosthesis treatment.

    With other localizations of candidiasis (with the exception of the genital), for example, with esophagitis, non-invasive bronchopulmonary disease, candiduria, candidiasis of the skin and mucous membranes, and so on, the effective dose is usually 150 mg per day with a treatment duration of 14-30 days.

    With balanitis caused by Candida, fluconazole is administered orally once a day at a dose of 150 mg per day.

    For the prevention of candidiasis, the recommended dose is 50-400 mg once a day, depending on the degree of risk of fungal infection. For the prevention of candidiasis in patients with malignant neoplasms the recommended dose of fluconazole is 150-400 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 per day. Fluconazole appoint a few days before the expected appearance of neutropenia; after an increase in the number of neutrophils more than 1 thousand / μl, treatment is continued for another 7 days.

    With mycosis of the skin, including mycosis of the feet, skin of the inguinal region, and skin candidiasis, the recommended dose is 150 mg once a week or 50 mg once a day, the dosage regimen depends on the clinical and mycological effect. 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 (2 capsules of 150 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 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). For the repeated growth of 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 coccidioidomycosis, 2-17 months with paracoccidioidomycosis, 1-16 months with sporotrichosis and 3-17 months with histoplasmosis.

    Children with generalized candidiasis - 6-12 mg / kg per day, with candidiasis of the mucous membranes - 3-6 mg / kg per day, for the prevention of fungal infections - 3-12 mg / kg per day.

    Side effects:

    From the side immune system: hypersensitivity (cross with all azoles), other anaphylactic, anaphylactoid and allergic reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria).

    From the side nervous system: headache, dizziness, peripheral neuropathy, paresthesia, excessive fatigue, rarely - convulsions.

    From the side digestive system: loss of appetite, dryness of the oral mucosa, changes in taste, abdominal pain, vomiting, nausea, diarrhea, flatulence, rarely - impaired liver function (jaundice, hepatitis, hepatonecrosis, hyperbilirubinemia, increased activity of alanine aminotransferase, aspartate aminotransferase, increased alkaline phosphatase activity, hepatocellular necrosis), including severe.

    From the side hemopoiesis: rarely - leukopenia, thrombocytopenia (bleeding, petechiae), neutropenia, agranulocytosis.

    From the side of cardio-vascular system: increase in the duration of the QT interval, fibrillation / flutter of the ventricles, pirouette tachycardia (torsade de pointes).

    From the side metabolism: hypercholesterolemia, hypertriglyceridemia, hypokalemia, hyperglycemia.

    From the side musculoskeletal system: myalgia.

    Other: weakness, asthenia, peripheral edema, neutropenia, skin itching, pulmonary edema, fever, excessive sweating, vertigo.

    In the place of application: itching, burning sensation in the vagina, skin rash in the area of ​​the external genitalia;

    Overdose:

    Symptoms: nausea, vomiting, diarrhea, in severe cases - convulsions, hallucinations, paranoid behavior.

    Treatment: gastric lavage, forced diuresis, hemodialysis (three-hour hemodialysis reduces the concentration of the drug in the plasma by approximately 50%), symptomatic therapy.

    Interaction:

    Alprazolam, diazepam, midazolam, triazolam - increase of their concentration in the blood, strengthening and lengthening of their sedative and hypnotic action.

    Alfentanil, eletriptan - decrease in their clearance, because fluconazole is a potent inhibitor of the CYP2C9 isoenzyme cytochrome P450 and a moderate inhibitor of the isoenzyme CYP3A4.

    Amitriptyline, nortriptyline - increase the effect.

    Astemizole, pimozide, terfenadine, cisapride, quinidine, erythromycin - increasing their concentration in the blood, unwanted reactions from the heart, including paroxysms of ventricular tachycardia (torsades de points), prolongation of the QT interval (sudden death due to arrhythmia is possible); concomitant use is contraindicated.

    Buspirone - a significant increase in the concentration of buspirone in the blood.

    Warfarin - strengthening of anticoagulant action. 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.

    Hydrochlorothiazide - decreased kidney elimination, increased blood concentrations (by 40%) and fluconazole toxicity.

    Hypoglycemic agents (sulfonylurea preparations, for example glibenclamide) - increasing their concentration in the blood, the development of hypoglycemia.

    Carbamazepine, phenytoin, phenobarbital - a decrease in the concentration of fluconazole in the blood, therapeutic inefficiency or exacerbation of the infection.

    Macrolide antibiotics (clarithromycin, erythromycin) - Increased concentration and toxicity of fluconazole, simultaneous use is undesirable.

    Polyene antifungal agents (including amphotericin B) - decreased activity of polyene antibiotics.

    Combination with rifampicin leads to a 25% decrease in AUC and a 20% decrease in the half-life of fluconazole from the plasma, inefficiency, exacerbation of infection. Therefore, patients receiving concomitantly rifampicin, it is advisable to increase the dose of fluconazole.

    There have been reports of an interaction between fluconazole and rifabutin, accompanied by an increase in the 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.

    Tacrolimus, ciclosporin - increase of their toxicity.

    Exposition tofacitinib Increases when it is used together with drugs that are both moderate inhibitors of the CYP3A4 isoenzyme and potent inhibitors of the CYP2C19 isoenzyme (for example fluconazole).

    Special instructions:

    Synthetic triazole, less toxic than itraconazole and amphotericin B, penetrates well into the cerebrospinal fluid. Maximum bioavailability when ingestion. Applied for the treatment of fungal meningitis.

    Treatment with fluconazole can begin before the results of sowing and other laboratory tests, but after receiving the results of these studies, therapy must be changed accordingly.

    In the course of treatment, it is necessary to monitor blood counts, kidney and liver function. If there are violations of the kidneys and the liver should stop taking the drug.

    Treatment should continue until clinical and hematologic remission (except for acute vaginal candidiasis). Premature termination of treatment leads to relapse.

    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.

    In rare cases, the use of fluconazole was accompanied by toxic changes in the liver, including fatalities, 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.

    Impact on the ability to drive vehicles and manage mechanisms.

    Be careful. During the treatment period, it is necessary to refrain from driving and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions, since dizziness and convulsions may occur during treatment with fluconazole.

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