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Dosage form: & nbspcapsules
Composition:
1 capsule contains:
Active substance: fluconazole 50 mg, 100 mg, 150 mg and 200 mg (respectively).Excipients: lactose monohydrate, corn starch, silicon dioxide colloid, anhydrous, sodium lauryl sulfate, magnesium stearate.
Capsule shell composition:
The capsule body is 50 mg, 100 mg and 200 mg: titanium dioxide E171, gelatin
Capsule capsule of 150 mg: titanium dioxide E171, dye blue patented E131, gelatin
Capsule capsules of 50 mg, 100 mg and 150 mg: titanium dioxide E171, dye blue patented E131, gelatin.
Capsule capsule 200 mg: titanium dioxide E171, indigo carmine dye FD & C blue E132, dye azorubin E122, gelatin.

Description:
Capsules 50 mg: hard gelatin capsules number 4. The cap of the capsule is light-blue, the capsule body is white. The contents of the capsule are white or almost white powder.
Capsules 100 mg: hard gelatin capsules number 2. The cap of the capsule is blue, the capsule body is white. The contents of the capsule are white or almost white powder.
Capsules 150 mg: hard gelatin capsules number 1. The cap and the capsule body are light blue. The contents of the capsule are white or almost white powder.
Capsules 200 mg: Hard gelatin capsules №0. Capsule cap is dark purple, capsule body is white. The contents of the capsule are white or almost white powder.

Pharmacotherapeutic group:Antifungal agent.
Pharmacodynamics:
Fluconazole, a representative of the class of triazole antifungal agents, is a potent selective inhibitor of the fungal enzyme 14-a-demethylase. The drug prevents the transition of lanosterol to ergosterol, the main component of cell membranes of fungi.
The drug is effective in opportunistic fungal infections, in t.p. caused by Candida spp. (Candida albicans, Candida tropicalis), Cryptococcus neoformans, Microsporum spp., Trichophyton spp. Also shown is the activity of fluconazole on models of endemic mycoses, including infections caused by Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum.

Pharmacokinetics:
After oral administration fluconazole it is well absorbed, its bioavailability is 90%. The maximum concentration (Cmax) after ingestion, fasting 150 mg is 90% of the plasma content when given intravenously at a dose of 2.5 to 3.5 mg / kg. Simultaneous food intake does not affect the absorption of the drug taken internally. The concentration in the plasma reaches a peak after 0.5-1.5 h (TCam) after administration. Concentrations in the plasma 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 administration of 1 time / day).
The use on the first day of a dose, which is 2 times higher than the usual daily dose, makes it possible to achieve a drug level in plasma equal to 90% of the equilibrium concentration value by the second day. The apparent volume of distribution approximates the total volume of water in the body. Binding to plasma proteins is small - 11-12%.
Fluconazole well penetrates into all body fluids, including cerebrospinal fluid. 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.
Less than 5% of fluconazole is metabolized on first passage through the liver. The half-life (T1 / 2) of fluconazole is about 30 hours. Prolonged T1 \ 2 allows the use of a single dose of the drug for the treatment of vaginal candidiasis and ensures the drug is taken once a day for other indications. Fluconazole is excreted mainly by the kidneys; approximately 80% of the administered dose is excreted by the kidneys 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 and chronic
  • relapsing), prophylactic use to reduce the frequency of recurrences of vaginal candidiasis (3 or more episodes per 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:
Hypersensitivity to fluconazole, other components of the drug or other azole compounds; simultaneous reception of terfenadine (against the background of the continuous use of fluconazole at a dose of 400 mg / day or more), cisapride or astemizole and other drugs that extend the QT interval and increase the risk of severe rhythm disturbances; lactation period; Children under 3 years old (for this dosage form).

Carefully:: hepatic and / or renal insufficiency, the appearance of a rash against the background of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections, concurrent administration of terfenadine and fluconazole at a dose of less than 400 mg / day, potentially pro-rhythmogenic states in patients with multiple risk factors organic heart diseases, electrolyte balance disorders, simultaneous intake of drugs that cause arrhythmias); patients with intolerance to acetylsalicylic acid, pregnancy.
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:
Inside. The daily dose depends on the nature and severity of the fungal infection.
Adults with cryptococcal meningitis and cryptococcal infections of other sites on the first day usually prescribed 400 mg, and then continue treatment at a dose of 200-400 mg once / day.The duration of treatment for cryptococcal infections depends on the clinical efficacy, confirmed by mycological examination; in cryptococcal meningitis, it is usually continued for at least 6-8 weeks.
To prevent the recurrence of cryptococcal meningitis in AIDS patients, after completing the full course of primary treatment, fluconazole prescribe at a dose of 200 mg / day for a long period of time.
With candidemia, disseminated candidiasis and other invasive candidiasis infections, the dose is usually 400 mg on the first day, and then on 200 mg. With insufficient clinical efficacy, the dose of the drug can be increased to 400 mg / day; 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 culture shsh after the disappearance of the symptoms of the disease.
With 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 (3 weeks).
With atrophic candidiasis of the oral cavity, associated with the wearing of dentures, fluconazole usually prescribed 50 mg 1 time / day for 14 days in combination with local antiseptic agents for prosthesis treatment.
For other candidiasis localizations (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; with severe mucous candidiasis - 100-200 mg / day. 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.
With 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.
With balanitis caused by Candida, fluconazole appoint a single dose of 150 mg orally.
For the prevention of candidiasis, the recommended dose 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 increasing the number of neutrophils more than 1000 / mm, treatment is continued for another 7 days.
With mycosis of the skin, including mycosis of the feet, skin of the inguinal area, and skin candidiasis, the recommended dose is 150 mg once a week or 50 mg 1 time / 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 300-400 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 200-400 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.
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 that would exceed that of adults. The drug is used daily 1 time / day.
In mucosal candidiasis, 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 of generalized candidiasis or cryptococcal infection, the recommended dose is 6-12 mg / kg / day, depending on the severity of the disease.
For the prevention of fungal infections in children with reduced immunity,in which the infection risk associated with neutropenia that develops as a result of cytotoxic chemotherapy or radiation therapy, the drug is prescribed for 3-12 mg / kg / day, depending on the severity and duration of preservation-induced neutropenia.
The maximum daily dose for children is 12 mg / kg.
Dosing for patients with renal insufficiency
Fluconazole is excreted mainly by the kidneys in unchanged form. With a single admission, a dose change is not required.
Adult patients with impaired renal function with a repeated prescription of the drug should first be prescribed 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 equal to 50% of the recommended dose or a usual dose of 1 every 2 days is applied. Patients regularly on dialysis, one dose of the drug is used after each session of hemodialysis.
In children with impaired renal function, the daily dose of the drug should be reduced (in the same proportional relationship as in adults), according to the degree of renal insufficiency.
In elderly patients in the absence of violations of kidney function should follow the usual dosage regimen.

Side effects:
On the part of the digestive system: nausea, diarrhea, flatulence, vomiting, abdominal pain, taste change, rarely - increased activity of liver enzymes and impaired liver function (jaundice, hyperbilirubinemia, increased activity of alanine aminotransferase (ALT), aspartic aminotransferase (ACT) and alkaline phosphatase (APF), hepatitis, hepatocellular necrosis), incl. with a lethal outcome.
From the side of the nervous system: headache, dizziness; rarely convulsions.
On the part of the organs of hematopoiesis: rarely - agranulocytosis, neutropenia. Patients with severe fungal infections may have hematologic changes (leukopenia and thrombocytopenia).
From the cardiovascular system: an increase in the duration of the Q-T interval on an electrocardiogram (ECG), flicker / flutter of the ventricles.
Allergic reactions: skin rash, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome),bronchial asthma (more often with intolerance to acetylsalicylic acid), anaphylactoid reactions (including angioedema, facial edema, urticaria, cutaneous
itching).
Other: rarely - renal dysfunction, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Overdose:
Symptoms: nausea, vomiting, diarrhea, in severe cases, convulsions, hallucinations, paranoid behavior may occur.
Treatment: symptomatic, gastric lavage; since fluconazole excreted by the kidneys it is recommended forced diuresis. Hemodialysis within 3 hours reduces the concentration in the plasma by 2 times.

Interaction:
  • One-time administration of fluconazole in the treatment of vaginal candidiasis is not accompanied by significant interactions. However, when several or more doses of the drug are used simultaneously with other drugs, the following drug interactions are possible:
  • The interaction of fluconazole with terfenadine, cisapride and astemizole can lead to an increase in the concentration of these drugs in the plasma, which in turn can cause prolongation of the QT interval and lead to serious disturbances of the heart rhythm. Fluconazole inhibits the enzymes of the P450 system in the liver, thereby reducing the metabolism of terfenadine, cisapride and astemizole. The simultaneous administration of fluconazole and these drugs is contraindicated.
  • When co-administration of warfarin and fluconazole, prolonged prothrombin time is noted. In this regard, it is necessary to monitor prothrombin time in patients simultaneously receiving fluconazole and anticoagulants of the coumarin series.
  • Fluconazole prolongs T 1/2 oral hypoglycemic drugs (sulfonylurea derivatives). Patients with diabetes mellitus can simultaneously be prescribed, fluconazole and derivatives of sulfonylureas, however, it is necessary to take into account the possible risk of developing hypoglycemia.
  • It must be taken into account that when the simultaneous administration of hydrochlorothiazide and fluconazole is repeated, the concentration of fluconazole in the plasma is increased.
  • Rifampicin accelerates the metabolism of fluconazole. It is necessary to increase the dosage of fluconazole accordingly during their simultaneous use.
  • In patients who underwent renal transplantation, fluconazole can increase the concentration of cyclosporine in plasma.In this regard, it is recommended to monitor the concentration of cyclosporine in patients simultaneously receiving ciclosporin and fluconazole.
  • Fluconazole increases the concentration of theophylline in plasma. In this regard, it is recommended to monitor the concentration of theophylline in patients simultaneously receiving theophylline and fluconazole.
  • Fluconazole may increase plasma concentrations of indinavir and midazolam. With the simultaneous administration of these drugs with fluconazole, their dosage should be appropriately reduced.
  • Clinical studies have shown that as a result of slowing metabolism of zidovudine, its concentration in lasma can increase with simultaneous administration with fluconazole. It is necessary to monitor patients who are simultaneously receiving both of these drugs, since in this case, the incidence of side effects of zidovudine may increase.
  • Fluconazole increases serum concentrations of phenytoin. With a simultaneous appointment, it is necessary to monitor the doses of phenytoin and, accordingly, to correct them.
  • Increases the effectiveness of rifabutin (with simultaneous application described cases of uveitis) and phenytoin in a clinically significant degree (when combinedit is necessary to control the concentration of phenytoin in the plasma).
  • Increases the concentration of tacrolimus - the risk of nephrotoxicity.

Special instructions:
Treatment can be started in the absence of seeding results or other laboratory tests, but if appropriate, a suitable correction of fungicidal therapy is recommended.
Because the fluconazole is excreted mainly by the kidneys, caution should be exercised in patients with renal insufficiency. When treated with multiple doses of fluconazole, dosing should be done taking into account CK.
Caution should be exercised when administering fluconazole to patients with impaired liver function. During treatment, it is necessary to regularly monitor the level of "liver" enzymes and monitor the patient in order to identify possible toxic effects. When the level of "liver" enzymes is raised, the doctor should weigh the benefits of the therapy and the risk of developing severe liver damage. The hepatotoxic effect of fluconazole is usually reversible; symptoms disappear after discontinuation of therapy.
Patients with AIDS are more likely to develop severe skin reactions with many drugs.In those cases where 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.
It is necessary to monitor prothrombin time in patients simultaneously receiving fluconazole and anticoagulants kumarinovoy rad Treatment should continue until the appearance of clinical-hematologic remission. Premature termination of treatment leads to relapse.
Included in the capsules Diflazon® 200 mg azo dye E122 can cause an allergic reaction, including. bronchial asthma. Allergic reactions are more common in patients with intolerance to acetylsalicylic acid.

Effect on the ability to drive transp. cf. and fur:It is not known about the negative impact on the ability to drive and work with other mechanisms
Form release / dosage:
Capsules of 50 mg, 100 mg, 150 mg and 200 mg.

Packaging:
Capsules of 50 mg: 7 capsules per blister.For 1 blister is placed in a pack of cardboard along with instructions for use
Capsules of 100 mg: 7 capsules per blister. For 4 blisters are placed in a pack of cardboard along with instructions for use.
Capsules of 150 mg: 1,2 or 4 capsules per blister. One blister (1 blister each, or 2 capsules, or 4 capsules) is placed in a cardboard box together with instructions for use.
Capsules of 200 mg: 7 or 10 capsules per blister. One blister (a blister pack of 7 capsules) or two blisters (a blister pack of 10 capsules) is placed in a cardboard box together with instructions for use.

Storage conditions:
Store at a temperature not exceeding 25 ° C.
Keep out of the reach of children.

Shelf life:
5 years.
Do not use after expiry date.

Terms of leave from pharmacies:Without recipe
Registration number:П N013210 / 02
Date of registration:23.03.2009
The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO
Manufacturer: & nbsp
Information update date: & nbsp15.10.2015
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