Trade name of the drug: Fludar

Active ingredient (INN): fluconazole

Dosage form: capsules

Composition:

active substance: fluconazole 50 mg and 150 mg;

excipients: anhydrous lactose, corn starch, purified talc, magnesium stearate.

Description:

Capsules 50 mg: hard gelatinous No. 1 cylindrical shape, consisting of a black lid and an orange body.

The contents of the capsules are from white to almost white powder.

Capsules 150 mg: hard gelatinous cylindrical No. 1, consisting of a green lid and a white body.

The contents of the capsules are from white to almost white powder.

Pharmacotherapeutic group: Antifungal agent.

ATX code: J02AC01

 

Pharmacological properties

Antifungal drug derived from triazole. The mechanism of action is associated with a pronounced inhibition of the cytochrome P450-dependent enzyme 14α-demethylase of the fungal cell and, as a result, suppression of the synthesis of the main component of the fungal cell wall – ergosterol. Highly active against Candida spp., Mirosporum spp., Trichoptyton spp., Cryptococcus neoformans, Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum.

Pharmacokinetics

After oral administration, fluconazole is well absorbed, its bioavailability is 90%. The maximum concentration (C _max ) after oral administration, on an empty stomach, 150 mg is 90% of the plasma content.

Simultaneous food intake does not affect the absorption of the drug taken orally. The plasma concentration reaches a peak 0.5-1.5 hours after administration, the half-life (T _1/2 ) of fluconazole is about 30 hours. Plasma concentrations are in direct proportion to the dose. 90% level of equilibrium concentration (Css) is achieved by 4-5 days of drug treatment (when taken 1 time / day).

The introduction on the first day of a loading dose 2 times higher than the usual daily dose, allows you to reach a level corresponding to 90% (Css) by the second day. The apparent volume of distribution (Vd) approaches the total body water content. Plasma protein binding – 11-12%.

Fluconazole penetrates well into all body fluids. Concentrations of the drug in saliva and sputum are similar to those in plasma. In patients with fungal meningitis, the content of fluconazole in the cerebrospinal fluid reaches 80% of its plasma level.

In the stratum corneum, epidermis, dermis and sweat fluid, high concentrations are achieved, which exceed serum concentrations.

Fluconazole is excreted mainly by the kidneys; while approximately 80% of the administered dose is excreted unchanged. Fluconazole clearance is proportional to creatinine clearance (KK). Fluconazole metabolites were not detected in the peripheral blood.

 

 

 

Indications for use

– cryptococcosis, including cryptococcal meningitis and other localizations of this infection (including lungs, skin), both in patients with a normal immune response and in patients with various forms of immunosuppression (including in AIDS patients, during transplantation organs);

– the drug can be used to prevent cryptococcal infection in AIDS patients;

– generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidiasis infection (including infections of the peritoneum, endocardium, eyes, respiratory and urinary tract). Treatment can be carried out in patients with malignant neoplasms, patients in intensive care units, patients receiving cytotoxic or immunosuppressive drugs, as well as in the presence of other factors predisposing to the development of candidiasis;

– candidiasis of the mucous membranes , incl. oral cavity and pharynx (including atrophic candidiasis of the oral cavity associated with wearing dentures), esophagus, non-invasive bronchopulmonary infections, candiduria; prevention of recurrence of oropharyngeal candidiasis in AIDS patients;

– genital candidiasis : treatment of vaginal candidiasis (acute and chronic recurrent), prophylactic use in order to reduce the frequency of relapses of vaginal candidiasis (3 or more episodes per year); candidal balanitis;

– prevention of fungal infections in patients with malignant neoplasms who are predisposed to such infections as a result of cytotoxic chemotherapy or radiation therapy;

– mycoses of the skin , including mycoses of the feet, body, groin, pityriasis versicolor, onychomycosis and candidiasis of the skin;

 

Method of administration and dosage

The daily dose of fluconazole depends on the nature and severity of the fungal infection. A single oral dose is sufficient in most cases to cure vaginal candidiasis. Treatment of other forms of the disease requires repeated use of the drug up to clinically and laboratory confirmed disappearance of the active stage of the fungal infection.

The capsules are taken orally, without chewing, with water or any other liquid.

For adults with cryptococcal meningitis and cryptococcal infections of other localization , 400 mg is prescribed on the first day, and then treatment is continued at a dose of 200-400 mg 1 time / day. The duration of treatment for cryptococcal infections depends on the clinical efficacy confirmed by mycological research; for cryptococcal meningitis, therapy is usually continued for at least 6-8 weeks.

With candidemia, disseminated candidiasis and other invasive candidal infections , the average dose is 400 mg on the first day, and then 200 mg / day. With insufficient clinical efficacy, the dose can be increased to 400 mg / day. The duration of therapy depends on the clinical effectiveness.

With oropharyngeal candidiasis , the drug is prescribed on average 50-100 mg 1 time / day; the duration of therapy is 7-14 days. If necessary, in patients with a pronounced decrease in immunity, treatment may be longer.

In case of atrophic candidiasis of the oral cavity associated with wearing dentures, the drug is prescribed in an average dose of 50 mg 1 time / day for 14 days in combination with local antiseptic agents for processing the prosthesis.

 

 

 

 

With other localizations of candidiasis (with the exception of genital candidiasis), for example, esophagitis, non-invasive bronchopulmonary lesions, candiduria, candidiasis of the skin and mucous membranes , the effective dose is on average 50-100 mg / day with a treatment duration of 14-30 days.

For the prevention of recurrence of oropharyngeal candidiasis in AIDS patients, after the completion of the full course of primary therapy, fluconazole can be prescribed 150 mg 1 time / week.

For vaginal candidiasis, fluconazole is taken once orally at a dose of 150 mg. To reduce the frequency of relapses of vaginal candidiasis, the drug can be used at a dose of 150 mg 1 time / month. The duration of therapy is determined individually; it varies from 4 to 12 months. Some patients may require more frequent use.

For balanitis caused by Candida spp., Fluconazole is administered as a single oral dose of 150 mg.

For the prevention of candidiasis, the recommended dose of fluconazole is 50-400 mg 1 time / day, depending on the degree of risk of developing a fungal infection. In the presence of a high risk of generalized infection, for example, in patients with expected severe or long-term neutropenia, the recommended dose is 400 mg 1 time / day. Fluconazole is prescribed several days before the expected appearance of neutropenia; after an increase in the number of neutrophils more than 1000 / μl, treatment is continued for another 7 days.

For mycoses of the skin, including mycoses of the feet, smooth skin, inguinal region and candidiasis of the skin, the recommended dose is 150 mg 1 time / week. or 50 mg once a day. The duration of therapy in normal cases is 2-4 weeks, however, with mycoses of the feet, longer therapy (up to 6 weeks) may be required.

With pityriasis versicolor, the recommended dose is 300 mg once a week. within 2 weeks; some patients require a third dose of 300 mg / week, while in some cases a single dose of 300-400 mg is sufficient.

An alternative treatment regimen is the use of the drug at a dose of 50 mg 1 time / day for 2-4 weeks.

With onychomycosis, the recommended dose is 150 mg 1 time / week. Treatment should be continued until the infected nail is replaced (an uninfected nail grows out). For the re-growth of nails on the fingers and toes, it normally takes 3-6 months. and 6-12 months. respectively.

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 exceeding that in adults. Fluconazole is used daily 1 time / day.

For candidiasis of the mucous membranes, the recommended dose of fluconazole is 3 mg / kg / day. On the first day, a loading dose of 6 mg / kg may be prescribed in order to more rapidly achieve constant equilibrium concentrations.

For the treatment of generalized candidiasis and 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 whom the risk of developing an infection is associated with neutropenia, which develops as a result of cytotoxic chemotherapy or radiation therapy, the drug is prescribed at 3-12 mg / kg / day, depending on the severity and duration of the persistence of induced neutropenia.

In children with impaired renal function, the daily dose of the drug should be reduced (in the same proportional relationship as in adults) in accordance with the severity of renal failure.

 

 

In elderly patients in the absence of impaired renal function, the drug is used in accordance with the usual dosage regimen.

In patients with impaired renal function with a single dose, a change in the dose of the drug is not required. With repeated use of the drug with CC more than 50 ml / min, the drug is prescribed in an average dose. With CC from 11 to 50 ml / min, you should first prescribe a loading dose of 50 mg to 400 mg, then a dose of 50% of the recommended dose. Patients undergoing regular dialysis are given one dose of the drug after each hemodialysis session.

 

Side effects

From the digestive system: taste changes, vomiting, nausea, diarrhea, flatulence, abdominal pain, rarely – liver dysfunction (jaundice, hepatitis, hepatonecrosis, hyperbilirubinemia, increased activity of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase).

From the nervous system: headache, dizziness, rarely – convulsions.

From the side of hematopoiesis: rarely – leukopenia, thrombocytopenia, neutropenia, agranulocytosis.

From the side of the cardiovascular system: an increase in the duration of the Q-T interval; fibrillation, flutter of the ventricles.

Allergic reactions: skin rash, rarely – malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), anaphylactoid reactions.

Others: rarely – impaired renal function, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

 

Contraindications

Simultaneous reception of terfenadine (against the background of constant intake of fluconazole at a dose of 400 mg / day or more) or astemizole and other drugs that prolong the QT interval. Hypersensitivity to the drug or structurally related azole compounds.

Children up to age 1 year.

Pregnancy, lactation.

With caution: hepatic or renal failure, concomitant use of potentially hepatotoxic drugs, alcoholism, proarrhythmogenic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance, concomitant use of drugs that cause arrhythmias)

The use of the drug in pregnant women is inappropriate, with the exception of severe or life-threatening forms of fungal infections, if the intended effect outweighs the possible risk to the fetus. Fluconazole is found in breast milk at the same concentration as in plasma, so its administration during lactation is not recommended.

 

Drug interactions

When using fluconazole with warfarin, an increase in prothrombin time was noted by 12%. In this regard, it is recommended to control the prothrombin time in patients receiving the drug in combination with coumarin anticoagulants. With the simultaneous use of fluconazole increases the T _{1/2 of} oral hypoglycemic drugs – sulfonylurea derivatives (chlorpropamide, glibenclamide, glipizide and tolbutamide). The joint appointment of fluconazole and oral hypoglycemic drugs is allowed, but the possibility of hypoglycemia should be taken into account.

 

The simultaneous use of fluconazole and phenytoin may be accompanied by an increase in the concentration of phenytoin in a clinically significant degree. Therefore, if the combined use of these drugs is necessary, it is necessary to monitor the concentration of phenytoin with adjusting its dose in order to ensure a therapeutic concentration in the blood plasma.

The simultaneous use of fluconazole and rifampicin leads to a decrease in the area under the concentration-time curve (AUC) by 25% and a shortening of T _{1/2 of} fluconazole from plasma by 20%. Therefore, in patients receiving rifampicin at the same time, it is recommended to increase the dose of fluconazole. It is recommended to control the concentration of cyclosporine in the blood in patients receiving fluconazole, because when using fluconazole and cyclosporine in patients with a transplanted kidney, taking fluconazole at a dose of 200 mg / day leads to a slow increase in the concentration of cyclosporine in the blood plasma.

Patients receiving high doses of theophylline, or who are likely to develop theophylline intoxication, should be monitored for early detection of symptoms of theophylline overdose. simultaneous administration of fluconazole leads to a decrease in the average rate of clearance of theophylline from plasma.

With the simultaneous use of fluconazole and terfenadine or cisapride, cases of adverse reactions from the heart have been described, including paroxysms of ventricular tachycardia (arrhythmias of the “pirouette” type).

There are reports of the interaction of fluconazole and rifabutin, accompanied by an increase in serum levels of the latter. With the simultaneous use of fluconazole and rifabutin, cases of uveitis have been described. Patients receiving rifabutin and fluconazole should be closely monitored.

With the simultaneous use of fluconazole and zidovudine, there is an increase in the concentration of zidovudine in plasma, which is caused by a decrease in the conversion of the latter into its metabolite.

With the simultaneous use of fluconazole with midazolam, the risk of psychomotor effects increases, with tacrolimus – the risk of nephrotoxicity increases.

 

special instructions

In rare cases, the use of fluconazole was accompanied by toxic changes in the liver, incl. with a lethal outcome, mainly in patients with serious concomitant diseases. In the case of hepatotoxic effects associated with fluconazole, there was no clear dependence of them on the total daily dose, duration of therapy, gender, and age of the patient. The hepatotoxic effect of fluconazole was usually reversible; its signs disappeared after discontinuation of therapy. If clinical signs of liver damage appear, which may be associated with fluconazole, the drug should be discontinued. AIDS patients are more likely to develop severe skin reactions with many drugs. In cases where a rash develops in patients with superficial fungal infection and it is regarded as definitely associated with fluconazole, the drug should be discontinued.

In patients with impaired renal function with a single use of the drug, dose adjustment is not required. When re-applied, they are guided by QC. If CC is more than 50 ml / min, dose adjustment is not required, with CC from 11 to 20 ml / min, 33% of the usual dose is taken with an interval of 72 hours. With CC from 21 to 40 ml / min, half the usual dose is taken with an interval of 48 hours. For patients regularly on dialysis, one dose is taken after each hemodialysis session.

 

Care must be taken when taking fluconazole with cisapride, rifabutin or other drugs metabolized by the cytochrome P450 system. Treatment should be continued until clinical and hematological remission appears, since its premature termination leads to relapses.

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

 

Overdose

In case of overdose, the stomach should be flushed, forced diuresis should be provided and symptomatic treatment should be carried out.

 

Release form

Capsules 50 mg; 150 mg; 150 mg – No. 1; 50 mg – No. 7

 

Storage conditions

In a dry, dark place at a temperature not exceeding 25 ° C.

The drug should be kept out of the reach of children.

 

Shelf life

3 years.

Do not use after the expiration date.

 

Conditions of dispensing from pharmacies

Fludar 50 mg No. 7 – by prescription.

Fludar 150 mg No. 1 – without a prescription.