Active material: Fluconazole
When ATH: J02AC01
CCF: Antifungal agent
ICD-10 codes (testimony): B35.0, B35.1, B35.2, B35.3, B35.4, B35.6, B36.0, B37.0, B37.1, B37.2, B37.3, B37.4, B37.6, B37.7, B37.8, B38, B39, B41, B42, B45, H19.2, Z29.8
When CSF: 08.01.01
Manufacturer: OAO Pharmstandard-Leksredstva (Russia)
Pharmaceutical form, composition and packaging
◊ Capsules opaque, light pink / pinkish-brown, №2; contents of capsules – powder white or nearly white.
Excipients: colloidal silicon dioxide (aэrosyl), corn starch, magnesium stearate, sodium lauryl, lactose.
Ingredients of the capsule shell: gelatin, iron oxide red dye (E172), metilparagidroksiʙenzoat, propilparagidroksibenzoat, Titanium dioxide (E171), acetic acid.
7 PC. – packings Valium planimetric (1) – packs cardboard.
◊ Capsules opaque, white, №0; contents of capsules – powder white or nearly white.
Excipients: colloidal silicon dioxide (aэrosyl), corn starch, magnesium stearate, sodium lauryl, lactose.
Ingredients of the capsule shell: gelatin, metilparagidroksiʙenzoat, propilparagidroksibenzoat, Titanium dioxide (E171), acetic acid.
1 PC. – packings Valium planimetric (1) – packs cardboard.
Antifungal agent. Fluconazole - representative of the class of triazole antifungal agents, It is a potent selective inhibitor of sterol synthesis in the fungal cells.
It is active against agents of opportunistic fungal infections, incl. caused by Candida spp., Cryptococcus neoformans, Microsporum spp., Trichophyton spp. Fluconazole is also shown activity in models of endemic mycoses, including infections, caused by Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum.
After oral administration fluconazole is well absorbed. Bioavailability is 90%. Cmax fluconazole in plasma after administration of a dose fasting 150 mg of 90% of its content in the plasma at / in a dose of 2.5-3.5 mg / l.
Tmax achieved through 0.5-1.5 h after administration. Simultaneous food intake has no effect on absorption when administered.
Plasma concentration is proportional to the dose.
90% Css It is achieved by 4-5 day drug treatment (when receiving 1 time / day).
Bolus (1 day), in 2 times the average daily dose, achieves 90% Level Css for the 2nd day. In Кажущийсяd It is approaching the total water content in the body. Protein binding – 11-12%.
Fluconazole penetrates well into all body fluids. Fluconazole concentration in saliva and sputum are similar plasma concentrations. Patients with fungal meningitis fluconazole concentrations in cerebrospinal fluid are about 80% the levels in plasma.
In the stratum corneum, epidermis, derma and sweat liquid reaches high concentrations, which exceed serum.
T1/2 is about 30 no.
Fluconazole is derived mainly kidneys; about 80% the administered dose found in the urine in unchanged form. The clearance of fluconazole is proportional QC. Fluconazole metabolites in blood has been detected.
- Kryptokokkoz, including cryptococcal meningitis and other localizations of this infection (incl. lungs, skin), both in patients with a normal immune response, and in patients with various forms of immunosuppression (incl. AIDS patients, organ transplantation); drug can be used to prevent cryptococcal infection in AIDS patients;
- Generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive Candida infections (incl. infection of the peritoneum, endokarda, eye, respiratory and urinary tract). The treatment can be carried out in patients with malignant tumors, Patients in intensive care units, patients, receiving cytotoxic or immunosuppressive agents, and the presence of other factors, predisposing to candidiasis;
- Mucosal candidiasis, incl. oral cavity and pharynx (including atrophic oral candidiasis, associated with wearing dentures), esophagus, non-invasive bronchopulmonary infections, kandidurija; prevention of relapse of oropharyngeal candidiasis in patients with AIDS;
- Genital candidiasis: vaginalynogo treating candidiasis (acute and chronic recurrent), prophylactic treatment to reduce the frequency of relapses vaginal candidiasis (3 or more episodes per year); kandidoznыj ʙalanit;
- Prevention of fungal infections in patients with malignant tumors, who are predisposed to such infections as a result of cytotoxic chemotherapy or radiotherapy;
- Fungal infections of the skin, including tinea pedis, body, groin, chromophytosis, onychomycosis and skin candidiasis;
- Deep endemic mycoses, including coccidioidomycosis, Paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immunity.
The drug is taken orally.
Adults at cryptococcal meningitis and cryptococcal infections at other sites administered on the first day 400 mg, and then continue treatment at a dose 200-400 mg 1 time / day. The duration of treatment for cryptococcal infections depends on the clinical effectiveness, confirmed by mycological examination; cryptococcal meningitis treatment is generally continued, at least, 6-8 weeks.
To prevention of relapse of cryptococcal meningitis in patients with AIDS, after completing a full course of primary treatment, therapy fluconazole 200 mg / day may be continued for a long time.
At kandidemii, disseminated candidiasis and other invasive Candida infections dose averages 400 mg on the first day, and then 200 mg / day. When insufficient clinical efficacy dose may be increased to 400 mg / day. The duration of therapy depends on the clinical effectiveness.
At orofaringealьnom kandidoze the drug is prescribed an average of 50-100 mg 1 time / day; duration of therapy – 7-14 days. If necessary in patients with severe depression of immunity, treatment may be longer.
At atrophic oral candidiasis, associated with wearing dentures, the drug is prescribed in high doses 50 mg 1 times / day for 14 days in combination with local antiseptic agents for treatment of prosthesis.
At Others lokalizatsiyah candidiasis (for isklyucheniem genitalynogo candidiasis), eg, эzofagite, non-invasive bronchopulmonary lesions, kandidurii, candidiasis of the skin and mucous membranes, effective dose averages 50-100 mg / day when the duration of treatment 14-30 days.
To prevention of relapse of oropharyngeal candidiasis in patients with AIDS after completing a full course of primary therapy, fluconazole may be appointed by 150 mg 1 times / week.
At vaginal candidiasis fluconazole take a single oral dose 150 mg. To reduce the frequency of recurrent vaginal candidiasis preparation can be applied at a dose 150 mg 1 times / month. The duration of therapy is determined individually; it ranges from 4 to 12 Months. Some patients may require more frequent use of.
At ʙalanite, вызванном Candida spp., Fluconazole prescribe a single dose 150 mg orally.
To preventions candidiasis The recommended dose of fluconazole 50-400 mg 1 times / day depending on the degree of risk of fungal infection. If you have a high risk of generalized infection, eg, in patients with severe or long-anticipated persistent neutropenia, The recommended dose is 400 mg 1 time / day. Fluconazole administered a few days before the expected occurrence of neutropenia; after increasing the number of neutrophils more than 1000 / ml treatment was continued for 7 d.
At mycosis of the skin, including tinea pedis, smooth skin, groin and skin candidosis The recommended dose is 150 mg 1 times / week. or 50 mg 1 time / day. Duration of therapy in conventional cases is 2-4 Sun., however athlete's foot may require longer therapy (to 6 Sun.).
At pityriasis versicolor The recommended dose is 300 mg 1 times / week. during 2 weeks; some patients required a third dose 300 mg / Sun., while in some cases it is sufficient a single dose of the drug in 300-400 mg. Alternative treatment is the use of the drug 50 mg 1 times / day for 2-4 Sun.
At onixomikoze The recommended dose is 150 mg 1 times / week. Treatment should be continued until infected nail replacement (sprouting uninfected nail). For the re-growth of the fingernails and feet normally required 3-6 months and 6-12 months, respectively.
At Deep endemic mycoses may be required drug dose 200-400 mg / day for up to 2 years. The duration of therapy is determined individually and is at coccidioidomycosis 11-24 Months, when paracoccidioidomycosis – 2-17 Months, when sporotrichosis – 1-16 Months, if histoplasmosis – 3-17 Months.
In children, as in the similar infections in adults, the duration of treatment depends on the clinical and mycological effect. In children, the drug should not be administered in a daily dose of, greater than that of adults. Flucostat used daily 1 time / day.
At mucosal candidiasis The recommended dose of fluconazole 3 mg / kg / day. The first day can be assigned to the loading dose 6 mg / kg in order to more quickly achieve permanent equilibrium concentrations.
For the treatment of generalizovannogo candidiasis infections and kriptokokkovoy The recommended dose is 6-12 mg / kg / day, depending on the severity of the disease.
To prevention of fungal infections in immunocompromised children, in which the risk of infection associated with neutropenia, developing as a result of cytotoxic chemotherapy or radiotherapy, the drug is prescribed for 3-12 mg / kg / day, depending on the severity and duration of neutropenia induced by conservation.
In children with impaired renal function the daily dose should be reduced (in the same proportion, in adults) in accordance with the severity of renal insufficiency.
In elderly patients in the absence of renal dysfunction drug is used in accordance with the usual dosing regimen.
In patients impaired renal function in single dose change the dose is not required. Repeated use of the drug with CC more 50 ml / min the drug is prescribed in high doses. In the resort of 11 to 50 ml / min you must first assign a loading dose of 50 mg 400 mg, then – dose, component 50% Recommended by. Patients, who regularly dialysis, administered one dose of the drug after each hemodialysis.
From the digestive system: change in taste, nausea, flatulence, vomiting, stomach ache, diarrhea; rarely – abnormal liver function (jaundice, hepatitis, gepatonekroz, giperʙiliruʙinemija, increased ALT, IS, Alkaline phosphatase).
CNS: headache, dizziness; rarely – convulsions.
From the hematopoietic system: rarely – leukopenia, thrombocytopenia, agranulocytosis.
Cardio-vascular system: prolongation of the QT interval, flicker, ventricular flutter.
Allergic reactions: skin rash; rarely - malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), anaphylactoid reactions.
Metabolism: rarely – hypercholesterolemia, hypertriglyceridemia, kaliopenia.
Other: rarely – renal dysfunction, alopecia.
- Concomitant use of drugs, prolonging the QT interval (incl. terfenadine or astemizole);
- Children up to age 3 years;
- Hypersensitivity to the drug or similar in structure azole compounds.
FROM caution use in patients with hepatic and / or renal insufficiency, simultaneously with the reception of potentially hepatotoxic drugs, alcoholism, if proaritmogennoe states in patients with multiple risk factors (organic heart disease, electrolyte imbalance, concomitant use of drugs, arhythmogenic).
Pregnancy and lactation
Application fljukostat® during pregnancy is possible only in case of severe and potentially life-threatening fungal infections, when the expected benefit of treatment exceeds potential risk for the fetus.
As fluconazole is excreted in breast milk in concentrations, close to the concentration in plasma, during breastfeeding is not recommended for the drug.
In rare cases, fluconazole was accompanied by toxic changes in the liver, incl. fatal, mainly in patients with severe concomitant diseases. There was no explicit dependence of the frequency of hepatotoxic effects of fluconazole of the total daily dose, duration of therapy, sex and age of the patient. Fluconazole hepatotoxicity is usually reversible; its signs disappeared after cessation of therapy. When clinical signs of liver damage, that may be associated with fluconazole, the drug should be discontinued.
AIDS patients are more prone to the development of severe skin reactions in the application of many drugs. When the patient, receiving treatment for superficial fungal infections, rash, which can be associated with administration of fluconazole, the drug should be discontinued. If a rash in patients with invasive / systemic fungal infections should be carefully monitored and cancel fluconazole when a bullous lesions or erythema multiforme.
Care must be taken while the application of fluconazole with cisapride, astemizolom, rifaʙutinom, tacrolimus or other drugs, metabolized by cytochrome P450 isoenzymes.
Symptoms: hallucinations, paranoidalynoe behavior.
Treatment: recommended gastric lavage and symptomatic therapy. As fluconazole is excreted in the urine, forced diuresis enhances its excretion. Hemodialysis for 3 h decreases the plasma concentration of fluconazole approximately 50%.
When using fluconazole and warfarin there was an increase in prothrombin time 12%. In this connection, it is recommended to monitor the prothrombin time in patients, receiving Flucostat® in combination with the anti kumarinovyh.
With simultaneous use of fluconazole increases T1/2 oral hypoglycemic drugs – sulfonylureas (hlorpropamyda, glibenclamide, tolbutamide and glipizide). Co-administration of fluconazole and oral hypoglycemic agents may be, but should take into account the possibility of hypoglycemia.
Concomitant use of fluconazole and phenytoin may cause a higher concentration of phenytoin to a clinically significant degree. Therefore, if necessary, a combined use of these drugs should be monitoring the concentration of phenytoin with the dose adjusted to ensure that the therapeutic plasma concentration.
Simultaneous administration of fluconazole and rifampicin reduces the AUC by 25% and shortening T1/2 Fluconazole from plasma on 20%. Therefore patients, receiving both rifampicin, dose of fluconazole is recommended to increase.
It is recommended to control the concentration of cyclosporine in the blood of patients, receiving fluconazole, tk. when using Fluconazole and cyclosporine in patients with renal transplant acceptance fluconazole 200 mg / day results in a slow increase in the concentration of cyclosporine in the blood plasma.
Patients, receiving high doses of theophylline, or who have a chance of developing theophylline intoxication, must be supervised for early detection of the symptoms of an overdose of theophylline, tk. simultaneous administration of fluconazole reduces the average rate of clearance from the plasma theophylline.
With simultaneous use of fluconazole and terfenadine, cisapride or described cases of adverse reactions from the heart, including paroxysms of ventricular tachycardia (the type of arrhythmia “pirouette”).
There are reports about the interaction of fluconazole and rifabutin, accompanied by an increase in serum levels of the last. With simultaneous use of fluconazole and rifabutin described cases of uveitis. It is necessary to carefully monitor patients, while receiving rifabutin and fluconazole.
With simultaneous use of fluconazole and zidovudine there is an increase in the plasma concentration of zidovudine, which is caused by a decrease in the conversion of the latter into its metabolite.
With simultaneous use of fluconazole with midazolam increased risk of psychomotor effects, with tacrolimus – increased risk of nephrotoxicity.
Conditions of supply of pharmacies
The drug is resolved to application as an agent Valium holidays.
Conditions and terms
The drug should be stored out of reach of children at temperature from 15 ° to 25 ° C. Shelf life – 2 year.