Fluconazole capsules 50mg, Teva No. 7

• Cryptococcosis, including cryptococcal meningitis and infections at other sites (eg, lungs, skin), incl. in patients with a normal immune response and in AIDS patients, organ transplant recipients and patients with other forms of immunodeficiency; supportive therapy to prevent relapse of cryptococcosis in AIDS patients.

• Generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidiasis, such as infections of the peritoneum, endocardium, eyes, respiratory and urinary tract, incl. in patients with malignant tumors in the ICU and receiving cytotoxic or immunosuppressive drugs, as well as in patients with other factors predisposing to the development of candidiasis.

• Candidiasis of the mucous membranes, including the mucous membranes of the oral cavity and pharynx, esophagus, non-invasive bronchopulmonary infections, candiduria, mucocutaneous and chronic atrophic oral candidiasis (associated with wearing dentures), incl. 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 in order to reduce the frequency of relapses of vaginal candidiasis (3 or more episodes per year); candidal balanitis.

• Mycoses of the skin, including mycoses of the feet, body, groin, pityriasis versicolor, onychomycosis and skin candidal 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.

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.

Individual. It is intended for oral administration and intravenous administration.

Inside, regardless of the meal.
The capsules should be swallowed whole with a glass of water.
The daily dose of fluconazole depends on the nature and severity of the fungal infection.

Adults
Vaginal candidiasis: 150 mg once.
Candidiasis of the mucous membranes of the oral cavity and pharynx: 50 mg 1 time / day for 7-14 days. Normally, treatment should not exceed 14 days, with the exception of patients with severely impaired immunity.
Chronic atrophic oral candidiasis associated with dentures: 50 mg once daily for 14 days in combination with topical antiseptics.
Other candidal infections of the mucous membranes (with the exception of vaginal candidiasis described above), for example, with esophagitis, non-invasive bronchopulmonary infections, mucocutaneous candidiasis, etc .: 50 mg daily for 14-30 days.
In severe cases of candidal infections of the mucous membranes, in particular with relapses, the daily dose may be increased to 100 mg / day.
Mycoses of the skin, including mycoses of the feet, body, groin and skin candidal infections: 150 mg 1 time / week or 50 mg 1 time / 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.
Onychomycosis: 150 mg once a week. Treatment should be continued until the infected nail is replaced (an uninfected nail grows out). Fingernails and toenails usually take 3-6 and 6-12 months to regrow, respectively. However, the growth rate can vary widely from person to person, and also by age. After successful treatment of persistent chronic infections, nail shape changes are sometimes observed.

Pityriasis versicolor: 300 mg once a week for 2 weeks; some patients require a third dose of 300 mg / week, while for some patients a single dose of 300-400 mg is sufficient. An alternative treatment regimen is 50 mg 1 time / day for 2-4 weeks.
Candidemia, disseminated candidiasis and other invasive candidal infections: an average of 400 mg on the first day, and then 200 mg / day. Depending on the severity of the clinical effect, the dose can be increased to 400 mg / day. The duration of therapy depends on the clinical effectiveness.
Cryptococcal meningitis: on the first day on average 400 mg, then 200-400 mg 1 time / day. The duration of treatment for cryptococcal infections depends on the presence of a clinical and mycological effect; treatment is usually continued for at least 6-8 weeks. Prevention of relapse of cryptococcal meningitis in AIDS patients: after completion of the full course of primary treatment, fluconazole therapy at a dose of 200 mg / day can be continued for a very long time.
Prevention of candidiasis: 50-400 mg 1 time / day, depending on the degree of risk of developing a fungal infection. If there is a high risk of generalized infection, for example, in patients with severe or long-term neutropenia after cytotoxic chemotherapy or radiation therapy, the recommended dose is 400 mg 1 time / day. Fluconazole is prescribed a few days before the expected appearance of neutropenia, and after an increase in the number of neutrophils more than 1000 / ?L, treatment is continued for another 7 days.

Children over 16 years of age
Method of administration and dosage - as with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. The maximum daily dose for children is 400 mg. Fluconazole is used daily 1 time / day.

Elderly patents
In the absence of signs of renal failure, the drug is used in a standard dose.

Active ingredient: fluconazole - 50 mg

Excipients: lactose monohydrate - 47 mg, corn starch - 16.65 mg, colloidal silicon dioxide - 0.1125 mg, sodium lauryl sulfate - 0.1125 mg, magnesium stearate - 1.125 mg

• Simultaneous use of terfenadine during repeated use of fluconazole at a dose of 400 mg / day or more;

• simultaneous use with drugs that increase the QT interval and are metabolized by the CYP3A4 isoenzyme, such as cisapride, astemizole, erythromycin, pimozide and quinidine;

• hypersensitivity to fluconazole or azole substances with a structure similar to fluconazole;

• hereditary galactose intolerance;

• lactase deficiency and glucose-galactose malabsorption syndrome;

• period of pregnancy;

• lactation period;

• children under 16 years of age.

Carefully

Liver failure; renal failure; the appearance of a rash during the use of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections; simultaneous use of terfenadine and fluconazole at a dose of less than 400 mg / day; potentially proarrhythmic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance and concomitant therapy that promotes the development of such disorders).

pharmachologic effect

The antifungal agent, a triazole derivative, is a potent selective inhibitor of sterol synthesis in the fungal cell.

Fluconazo is active in vitro and in clinical infections against most of the following microorganisms: Candida albicans, Candida glabrata (many strains are moderately sensitive), Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans.

Fluconazole has been shown to be active against the following microorganisms in vitro, but the clinical significance of this is unknown: Candida dubliniensis, Candida guilliermondii, Candida kefyr, Candida lusitaniae.

When taken orally, fluconazole has been shown to be active in various animal models of fungal infections. Demonstrated the activity of the drug in opportunistic mycoses, incl. caused by Candida spp. (including generalized candidiasis in immunosuppressed animals); Cryptococcus neoformans (including intracranial infections); Microsporum spp. and Trichophyton spp. The activity of fluconazole was also established in models of endemic mycoses in animals, including infections caused by Blastomyces dermatitides, Coccidioides immitis (including intracranial infections) and Histoplasma capsulatum in animals with normal and suppressed immunity.

Fluconazole is highly specific for cytochrome P450 dependent fungal enzymes. Fluconazole therapy at a dose of 50 mg / day for up to 28 days does not affect the concentration of testosterone in the blood plasma in men or the concentration of steroids in women of childbearing age. Fluconazole at a dose of 200-400 mg / day has no clinically significant effect on endogenous steroid levels and their response to ACTH stimulation in healthy male volunteers.

Pharmacokinetics

The pharmacokinetics of fluconazole are similar when administered intravenously and when taken orally.

After oral administration, fluconazole is well absorbed, its plasma levels (and overall bioavailability) exceed 90% of the plasma levels of fluconazole when administered intravenously. Concomitant food intake does not affect oral absorption. Cmax is reached within 0.5-1.5 hours after taking fluconazole on an empty stomach. Plasma concentration is proportional to the dose.

90% Css is reached by the 4th-5th day after the start of therapy (with repeated administration 1 time / day).

The introduction of a loading dose (on the 1st day), 2 times higher than the average daily dose, makes it possible to achieve Css 90% by the 2nd day. The apparent Vd approaches the total body water content. Plasma protein binding is low (11-12%).

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

In the stratum corneum, epidermis-dermis and sweat fluid, high concentrations are achieved, which exceed serum concentrations. Fluconazole accumulates in the stratum corneum. When taken in a dose of 50 mg 1 time / day, the concentration of fluconazole after 12 days was 73 ?g / g, and 7 days after stopping treatment - only 5.8 ?g / g. When used in a dose of 150 mg 1 time / week. the concentration of fluconazole in the stratum corneum on the 7th day was 23.4 ?g / g, and 7 days after taking the second dose - 7.1 ?g / g.

Concentration of fluconazole in nails after 4 months of use at a dose of 150 mg 1 time / week. was 4.05 ?g / g in healthy and 1.8 ?g / g in affected nails; 6 months after completion of therapy, fluconazole was still detectable in the nails.

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

Prolonged T1 / 2 from blood plasma allows you to take fluconazole once for vaginal candidiasis and 1 time / day or 1 time / week. with other indications.

Side effect

From the nervous system: headache, dizziness, convulsions, change in taste, paresthesia, insomnia, drowsiness, tremors.

From the digestive system: abdominal pain, diarrhea, flatulence, nausea, dyspepsia, vomiting, dryness of the oral mucosa, constipation.

From the hepatobiliary system: hepatotoxicity, in some cases with a fatal outcome, an increase in the concentration of bilirubin, serum aminotransferase activity (ALT and AST), alkaline phosphatase, liver dysfunction, hepatitis, hepatocellular necrosis, jaundice, cholestasis, hepatocellular damage.

On the part of the skin: rash, alopecia, exfoliative skin lesions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, acute generalized exanthematous pustulosis, increased sweating, drug rash.

On the part of the hematopoietic and lymphatic system * leukopenia, including neutropenia and agranulocytosis, thrombocytopenia, anemia.

From the immune system: anaphylaxis (including angioedema, facial edema, urticaria, itching).

From the side of the cardiovascular system: an increase in the QT interval on the ECG, ventricular tachysystolic arrhythmia of the 'pirouette' type, arrhythmia.

From the side of metabolism: increased concentration of cholesterol and triglycerides in blood plasma, hypokalemia.

From the musculoskeletal system: myalgia.

Others: weakness, asthenia, fatigue, fever, vertigo.

Application during pregnancy and lactation

There have been no adequate and well-controlled studies of the safety of fluconazole in pregnant women. The use of fluconazole during pregnancy should be avoided, except in cases of severe and potentially life-threatening fungal infections, when the expected benefit of treatment outweighs the possible risk to the fetus. Women of childbearing age should use reliable contraception during treatment. Fluconazole is determined in breast milk at concentrations close to plasma concentrations, therefore, use during lactation (breastfeeding) is not recommended.

Application for violations of liver function

Fluconazole should be used with caution in patients with severe hepatic impairment.

Application for impaired renal function

In patients with renal insufficiency (CC <50 ml / min), dosage adjustment is required.

Application in children

It is used in children in special dosage forms.

Use in elderly patients

In elderly patients in the absence of signs of renal failure, fluconazole is used in the usual dose. If a single dose is necessary, a doctor's consultation is required.

special instructions

It is used with caution in case of violations of liver function indicators against the background of the use of fluconazole, with the appearance of a rash against the background of the use of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections, with the simultaneous use of terfenadine and fluconazole at a dose of less than 400 mg / day, with potentially proarrhythmic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance and concomitant therapy that contributes to the development of such disorders).

The hepatotoxic effect of fluconazole was usually reversible; its signs disappeared after discontinuation of therapy. It is necessary to monitor the condition of patients whose liver function indicators are impaired during treatment with fluconazole in order to identify signs of more serious liver damage. If clinical signs or symptoms of liver damage appear, which may be associated with fluconazole, it should be discontinued.

AIDS patients are more likely to develop severe skin reactions with many drugs. If a patient receiving treatment for a superficial fungal infection develops a rash that can be associated with the use of fluconazole, it should be discontinued. If a rash occurs in patients with invasive / systemic fungal infections, they should be closely monitored and fluconazole should be discontinued if bullous lesions or erythema multiforme appear.

Concomitant use of fluconazole at doses less than 400 mg / day and terfenadine should be closely monitored.

With the use of fluconazole, an increase in the QT interval and ventricular fibrillation / flutter have been observed very rarely in patients with multiple risk factors, such as organic heart disease, electrolyte imbalance, and concomitant therapy that contributes to the development of such disorders.

Therapy can be started pending culture and other laboratory test results. However, anti-infective therapy needs to be adjusted accordingly when the results of these studies become known.

There have been reports of cases of superinfection caused by strains of Candida other than Candida albicans, which are often not sensitive to fluconazole (for example, Candida krusei). In such cases, alternative antifungal therapy may be required.

Drug interactions

With simultaneous use with warfarin, fluconazole increases prothrombin time (by 12%), and therefore may develop bleeding (hematoma, bleeding from the nose and gastrointestinal tract, hematuria, melena). In patients receiving coumarin anticoagulants, it is necessary to constantly monitor the prothrombin time.

After oral administration of midazolam, fluconazole significantly increases the concentration of midazolam and psychomotor effects, and this effect is more pronounced after taking fluconazole orally than when using it intravenously. If concomitant therapy with benzodiazepines is necessary, patients taking fluconazole should be monitored to reduce the dose of benzodiazepine accordingly.

With the simultaneous use of fluconazole and cisapride, adverse reactions from the heart are possible, incl. fibrillation / flutter of the ventricles (arrhythmia of the 'pirouette' type). The use of fluconazole at a dose of 200 mg 1 time / day and cisapride at a dose of 20 mg 4 times / day leads to a pronounced increase in plasma concentrations of cisapride and an increase in the QT interval on the ECG. Concomitant use of cisapride and fluconazole is contraindicated.

In patients after kidney transplantation, the use of fluconazole at a dose of 200 mg / day leads to a slow increase in the concentration of cyclosporine. However, with repeated administration of fluconazole at a dose of 100 mg / day, changes in the concentration of cyclosporine were not observed in bone marrow recipients. With the simultaneous use of fluconazole and cyclosporine, it is recommended to monitor the concentration of cyclosporine in the blood.

Repeated use of hydrochlorothiazide simultaneously with fluconazole leads to an increase in plasma concentration of fluconazole by 40%. The effect of this degree of severity does not require a change in the dosage regimen of fluconazole in patients receiving concomitant diuretics, but this should be taken into account.

With the simultaneous use of a combined oral contraceptive with fluconazole at a dose of 50 mg, a significant effect on the level of hormones has not been established, while with a daily intake of 200 mg of fluconazole, the AUC of ethinyl estradiol and levonorgestrel increase by 40% and 24%, respectively, and when taking 300 mg of fluconazole 1 time per week - AUC of ethinylestradiol and norethindrone increase by 24% and 13%, respectively. Thus, repeated use of fluconazole at the indicated doses is unlikely to affect the effectiveness of the combined oral contraceptive.

The simultaneous use of fluconazole and phenytoin may be accompanied by a clinically significant increase in the concentration of phenytoin. With this combination, the concentration of phenytoin should be monitored and its dose adjusted accordingly in order to ensure a therapeutic concentration in the blood serum.

The simultaneous use of fluconazole and rifabutin can lead to an increase in serum concentrations of the latter. With the simultaneous use of fluconazole and rifabutin, cases of uveitis have been described. Patients receiving rifabutin and fluconazole concomitantly should be closely monitored.

The simultaneous use of fluconazole and rifampicin leads to a decrease in AUC by 25% and the duration of T1 / 2 of fluconazole by 20%. In patients taking rifampicin at the same time, it is necessary to consider the advisability of increasing the dose of fluconazole.

Fluconazole, when taken simultaneously, leads to an increase in T1 / 2 of oral sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide). Patients with diabetes mellitus can be co-administered with fluconazole and oral sulfonylureas, but the possibility of hypoglycemia should be taken into account.

The simultaneous use of fluconazole and tacrolimus leads to an increase in plasma concentrations of the latter. Cases of nephrotoxicity have been reported. With this combination, the patient's condition should be carefully monitored.

With the simultaneous use of azole antifungal agents and terfenadine, serious arrhythmias may occur as a result of an increase in the QT interval. When taking fluconazole at a dose of 200 mg / day, an increase in the QT interval has not been established, however, the use of fluconazole at doses of 400 mg / day and above causes a significant increase in the plasma concentration of terfenadine. Simultaneous administration of fluconazole at doses of 400 mg / day or more with terfenadine is contraindicated. Treatment with fluconazole at doses less than 400 mg / day in combination with terfenadine should be closely monitored.

ѕри одновременном применении с флуконазолом в дозе 200 мг в течение 14 дней средн¤¤ скорость плазменного клиренса теофиллина снижаетс¤ на 18%. ѕри назначении флуконазола больным, принимающим теофиллин в высоких дозах, или больным с повышенным риском развити¤ токсического действи¤ теофиллина следует наблюдать за по¤влением симптомов передозировки теофиллина и, при необходимости, скорректировать терапию соответствующим образом.

ѕри одновременном применении с флуконазолом отмечаетс¤ повышение концентраций зидовудина, которое, веро¤тно, обусловлено снижением метаболизма последнего до его главного метаболита. ?о и после терапии с применением флуконазола в дозе 200 мг/сут в течение 15 дней больным —ѕ»? и ARC (комплекс, св¤занный со —ѕ»?) установлено значительное увеличение AUC зидовудина (20%).

When used in HIV-infected patients, zidovudine at a dose of 200 mg every 8 hours for 7 days in combination with fluconazole at a dose of 400 mg / day or without it with an interval of 21 days between the two regimens, a significant increase in the AUC of zidovudine was found (74%) with simultaneous use with fluconazole. Patients receiving this combination should be monitored for side effects of zidovudine.

The simultaneous use of fluconazole with astemizole or other drugs, the metabolism of which is carried out by isoenzymes of the cytochrome P450 system, may be accompanied by an increase in serum concentrations of these drugs. With such combinations, the patient's condition should be carefully monitored.