Trade name of the drug: Fludar

Active ingredients (INN): fluconazole

Dosage form: instant tablets

Composition:

one tablet contains:

active substance:  fluconazole – 50 mg;

excipients:  pregelatinized starch, crospovidone, microcrystalline cellulose, sodium saccharin, aspartame, colloidal silicon dioxide, sunset yellow dye, sodium croscarmellose, magnesium stearate, Powderoma Orange flavor.

 

Description: flat-cylindrical tablets of a round shape, orange with white specks, with a dividing line on one side and flat on the other side.

Pharmacotherapeutic group: Antifungal agent.

ATH code:  J02AC01

 

Pharmacological properties

Pharmacodynamics

Antifungal agent of the class of triazole compounds, a potent selective inhibitor of sterol synthesis in fungal cells.

Has a highly specific effect, inhibiting the activity of fungal enzymes dependent on cytochrome P ₄₅₀ . Blocks the conversion of fungal lanosterol into ergosterol; increases the permeability of the cell membrane, disrupts its growth and replication. Fluconazole, being highly selective for cytochrome P _{450 of}  fungi, practically does not inhibit these enzymes in the human body (in comparison with itraconazole, clotrimazole, econazole and ketoconazole, it suppresses cytochrome P ₄₅₀ dependent oxidative processes in human liver microsomes). Does not possess antiadrogenic activity. Active in opportunistic mycoses, including those caused by Candida spp. (including generalized forms of candidiasis against the background of immunosuppression), Cryptococcus Neoformans and Coccidioides immitis (including intracranial infections), Microsporum spp. and Trichophyto N spp; with endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulatum (including immunosuppression).

Fluconazole therapy did not affect plasma testosterone concentrations in men and steroids in women of childbearing age. Fluconazole had no clinically significant effect on endogenous steroid levels and their response to adrenocorticotropic hormone (ACTH) stimulation in men.

 

Pharmacokinetics

Absorption – high (food does not affect the rate of absorption). Bioavailability – 90%. The maximum concentration of the drug after oral administration is achieved in 0.5-1.5 hours.

The connection with blood plasma proteins is 11-12%. Plasma concentration is in direct proportion to the dose. Equilibrium concentration is achieved on 4-5 days of admission (when taking the drug once a day).

Taking a loading dose on the first day, twice the usual daily dose, allows you to reach an equilibrium concentration of 90% on the second day.

It penetrates well into all body fluids. The concentration of the active substance in breast milk, joint fluid, saliva, sputum and peritoneal fluid is similar to those in plasma. Constant values ​​in vaginal secretions are achieved after 8 hours and are kept at this level for at least 24 hours.

In patients with fungal meningitis, the level of fluconazole in the cerebrospinal fluid reaches 80% of its concentration in blood plasma.

In sweat fluid, epidermis and stratum corneum (selective accumulation), concentrations exceeding serum are achieved. Fluconazole accumulates in the stratum corneum. When taking the drug at a dose of 50 mg / day, the concentration of fluconazole in the stratum corneum after 12 days is 73 μg / g, and 7 days after completion of treatment, 5.8 μg / g. When using a dose of 150 mg once a week, the concentration of fluconazole in the stratum corneum on the seventh day reached 23.4 μg / g, and 7 days after taking the second dose, 7.1 μg / g. The concentration of fluconazole in nails after 4 months of use at a dose of 150 mg once a week is 4.05 μg / g in healthy nails and 1.8 μg / g in affected nails. 6 months after the end of therapy, fluconazole was still detectable in the nails.

The drug is completely excreted by the kidneys, and approximately 80% of the administered dose is detected in the urine unchanged. Fluconazole clearance is proportional to creatinine clearance. No circulated metabolites have been identified.

The long plasma half-life (approximately 30 hours) makes it possible to take fluconazole once for vaginal candidiasis and use it once a day or once a week for other diseases caused by susceptible fungi.

 

Indications for use

– cryptococcosis (systemic lesions caused by Cryptococcus fungi), including meningitis, sepsis, lung and skin infections, both in patients with a normal immune response and in patients with various forms of immunosuppression (including AIDS patients, organ transplantation);

– prevention of cryptococcal infection in AIDS patients;

– generalized candidiasis: candidemia, disseminated candidiasis (with damage to the endocardium, abdominal organs, respiratory organs, eyes and urogenital organs), including in patients receiving a course of cytostatic or immunosuppressive therapy, as well as in the presence of other factors predisposing to their development – treatment and prevention;

– candidiasis of the mucous membranes: oral cavity, pharynx, esophagus, candiduria, mucocutaneous and chronic oral atrophic candidiasis (associated with wearing dentures); non-invasive bronchopulmonary candidiasis;

– genital candidiasis, vaginal candidiasis (acute and recurrent), candidal balanitis;

– prevention of fungal infections in patients with malignant tumors during chemotherapy or radiation therapy; prevention of recurrence of oropharyngeal candidiasis in AIDS patients;

– skin mycoses of various localization: feet, groin area, onychomycosis, pityriasis versicolor, lichen, candidal skin infections;

– deep endemic mycoses (coccidioidomycosis, sporotrichosis and histoplasmosis) in patients with normal immunity.

 

Method of administration and dosage

It is taken orally, daily, once a day.

The daily dose depends on the nature and severity of the fungal infection and is determined individually. The duration of treatment depends on the clinical and mycological effect.

Adults.

For  cryptococcal infections  , 400 mg is usually prescribed on the first day, and then treatment is continued at a dose of 200-400 mg once a day. The duration of treatment is usually 6-8 weeks. To prevent recurrence of cryptococcal meningitis in AIDS patients (after completion of the full course of primary treatment), therapy at a dose of 200 mg can be continued for a long time.

For  candidal infections, the  dose is 400 mg on the first day, then 200 mg per day, if necessary, the dose can be increased to 400 mg per day. The duration of therapy depends on the clinical effectiveness.

With  oropharyngeal candidiasis  – 50-100 mg once a day for 7-14 days or, if necessary, for a longer time. In atrophic candidiasis of the oral mucosa, it is usually prescribed in a dose of 50 mg once a day for 14 days; in other candidal infections of the mucous membranes (with the exception of vaginal candidiasis), the effective dose is usually 50-100 mg with a treatment duration of 14-30 days.

For  vaginal candidiasis and balanitis,  take a single dose of 150 mg.

For  skin infections, including mycoses of the feet and groin skin  , the recommended dose is 150 mg once a week or 50 mg once a day. The duration of therapy is usually 2-4 weeks, however, with mycoses of the feet, longer therapy (up to 6 weeks) may be required. For pityriasis versicolor, the recommended dose is 50 mg once a day for 2-4 weeks.

For  onychomycosis, the  recommended dose is 150 mg once a week.

Treatment should be continued until the infected nail is replaced (growth of an uninfected nail).

For the  prevention of fungal infections  in patients with reduced immune function, the dose is 50 mg once a day, while the patient is at risk.

Children from 6 years old.

With  candidiasis of the  mucous  membranes  – 3-6 mg per 1 kg of body weight per day, not less than 3 weeks;

With  systemic candidiasis  – 6-12 mg per 1 kg of body weight per day, for 10-12 weeks (until laboratory confirmation of the absence of the pathogen in the cerebrospinal fluid).

The daily dose for children should not exceed the dose for adults.

For elderly patients with renal insufficiency with a single dose, a dose change is not required. With repeated administration, the drug is prescribed in an initial dose of 50 to 400 mg. After that, the daily dose (depending on the creatinine clearance indicators) is determined according to the table:

Doses and duration of treatment are determined individually.

 

Side effects

Often

– decreased appetite, nausea, diarrhea, constipation, flatulence, abdominal pain, toothache;

– headache, dizziness, fatigue

– skin rash

Seldom

– dysfunction of the liver (icterus of the sclera, jaundice, hyperbilirubinemia, increased activity of alanine aminotransferase, asparagine aminotransferase and alkaline phosphatase);

– hepatotoxicity, including isolated cases with a fatal outcome in persons with severe concomitant diseases (AIDS, cancer);

– convulsions;

– exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), anaphylactoid reactions;

– leukopenia, thrombocytopenia (bleeding, petechiae), neutropenia, agranulocytosis, hypercholesterolemia, hypertriglyceridemia, hypokalemia;

– impaired renal function;

– alopecia;

– an increase in the QT interval on the ECG, fibrillation / flutter of the ventricles.

 

Contraindications

– increased individual sensitivity to fluconazole or triazole compounds and other components of the drug;

– simultaneous use with terfenadine and astemizole, cisapride;

– pregnancy and lactation period;

– children under 6 years of age.

 

Drug interactions

With the simultaneous use of fluconazole with coumarin anticoagulants, prothrombin time should be monitored, since the effectiveness of the latter increases.

With hypoglycemic agents, hypoglycemia may develop.

With rifampicin, the dose of fluconazole should be increased, since there is a decrease in absorption by 25% and the half-life of fluconazole by 20%.

With zidovudine, an increase in their concentrations in the blood is possible.

With terfenadine or cisapride, the risk of arrhythmias, including paroxysms of ventricular tachycardia, increases.

With theophylline, it is necessary to observe the symptoms of an overdose of the latter, since its half-life is lengthened.

With rifabutin and cyclosporine, the development of uveitis is possible.

With tacrolimus – increases serum concentrations of the latter.

With phenytoin, it is necessary to monitor the concentration of the latter in the blood plasma, so its effectiveness increases to a large extent.

With hydrochlorothiazide – can lead to an increase in plasma concentration of fluconazole up to 40%.

 

special instructions

Treatment should be continued until the onset of clinical and hematological remission of the disease. Premature discontinuation of treatment leads to relapses. Treatment can begin before the results of sowing or other laboratory tests are obtained, followed by correction of fungicidal therapy according to the results of the research.

During treatment, it is necessary to monitor blood counts, kidney and liver function.

If you experience impaired renal and liver function, you should stop taking the drug. The hepatotoxic effect of fluconazole is usually reversible, symptoms disappear after discontinuation of therapy.

If skin rashes occur in immunosuppressed patients, careful observation is necessary, and if the skin reaction progresses, treatment should be discontinued (risk of developing Stevens-Johnson syndrome, Lyell’s syndrome).

It is necessary to control the prothrombin index while using it with coumarin anticoagulants.

It is recommended to monitor the blood concentration of cyclosporine in renal transplant patients receiving fluconazole.

Features of the influence of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

It is prescribed with caution to transport drivers and persons whose work requires precise coordination of movements.

The drug should not be used after the expiration date and should be kept out of the reach of children.

 

Overdose

Symptoms : nausea, abdominal pain, diarrhea, flatulence, headache, dizziness, hallucinations, skin rash, anaphylactic reactions.

Treatment : symptomatic therapy (gastric lavage, supportive therapy); forced diuresis can accelerate the elimination of the drug.

 

Release form

7 tablets of 50 mg are placed in a blister strip packaging, which, together with the instructions for medical use, are placed in a cardboard box.

 

Storage conditions

Store in a dry, dark place at a temperature not exceeding 25 ^° C.

Keep out of the reach of children.

 

Shelf life

3 years.

Do not use after the expiration date.

 

Conditions of dispensing from pharmacies

Without recipe.