Universal reference book for medicines

Active substance: fluconazole

Type: Antifungal medication for external use

Manufacturer: Remedy (Russia) manufactured by ENCUBE ETHICALS (India)
Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..

Antifungal agent, a derivative of triazole.
It is a selective inhibitor of the synthesis of sterols in the fungal cell. Fluconazole is highly specific for fungal enzymes that are dependent on cytochrome P450.
When administered orally and with iv administration, fluconazole was active in various models of fungal infections in animals.

Fluconazole is active in opportunistic mycoses, incl.
caused by Candida spp., including generalized candidiasis in animals with reduced immunity; Cryptococcus neoformans, including intracranial infections; Microsporum spp. and Trychoptyton spp. It is active in models of endemic mycoses in animals, including infections caused by Blastomyces dermatitidis, Coccidioides immitis, including intracranial infections, and Histoplasma capsulatum in animals with normal and reduced immunity.
The pharmacokinetics of fluconazole is similar for intravenous administration and for oral administration.

After oral administration, fluconazole is well absorbed, its plasma levels (and total bioavailability) exceed 90% of fluconazole levels in blood plasma when administered iv.
Simultaneous food intake does not affect absorption during ingestion. C max is achieved in 0.5-1.5 hours after taking fluconazole on an empty stomach.The concentration in the blood plasma is proportional to the dose.
90% C ss is reached by the 4th-5th day after the start of therapy (with repeated intake 1 time / day).

The introduction of a shock dose (on the 1st day), 2 times higher than the average daily dose, makes it possible to achieve C ss 90% by the 2nd day.
Apparent V dapproximates the total water content in the body. Binding to blood plasma proteins is low (11-12%).
Fluconazole well penetrates into all body fluids.
The levels of fluconazole in saliva and sputum are similar to those in plasma. In patients with fungal meningitis, fluconazole levels in the cerebrospinal fluid are about 80% of its levels in the blood plasma.
In the stratum corneum, the epidermis-dermis and the sweat fluid, high concentrations are reached that exceed the serum levels.
Fluconazole accumulates in the stratum corneum. When administered at a dose of 50 mg once a day, the fluconazole concentration was 73 μg / g after 12 days, and only 5.8 μg / g 7 days after discontinuation of treatment. When applied at a dose of 150 mg 1 time / week. the fluconazole concentration in the stratum corneum on the 7th day was 23.4 μg / g, and 7 μg / g 7 days after the second dose.
The concentration of fluconazole in the nails after a 4-month application in a dose of 150 mg 1 time / week.
was 4.05 μg / g in healthy and 1.8 μg / g in the affected nails; 6 months after the end of therapy, fluconazole was still detected in the nails.
Fluconazole is excreted mainly by the kidneys;
approximately 80% of the administered dose is detected in the urine unchanged. The clearance of fluconazole is proportional to QC. No circulating metabolites were detected.
Prolonged T 1/2 from the blood plasma allows to take fluconazole once for vaginal candidiasis and 1 time / day or 1 time / week.
with other indications.
Cryptococcosis, including cryptococcal meningitis and infections of other localization (eg, lungs, skin), incl.
in patients with normal immune response and in AIDS patients, recipients of transplanted organs and patients with other forms of immunodeficiency; Supportive therapy for the prevention of recurrences of cryptococcosis in AIDS patients.
Generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidiasis infection, such as peritoneal, endocardial, eye, respiratory and urinary tract infections, incl.
in patients with malignant tumors who are in the ICU and receiving cytotoxic or immunosuppressive agents, as well as in patients with other factors predisposing to the development of candidiasis.
Candidiasis of mucous membranes, including mucous membranes of the oral cavity and pharynx, esophagus, non-invasive bronchopulmonary infections, candiduria, mucocutaneous and chronic atrophic candidiasis of the oral cavity (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 to reduce the frequency of recurrence of vaginal candidiasis (3 or more episodes a year);candidiasis balanitis.
Mycosis of the skin, including mycosis of the feet, body, inguinal region, pityriasis, onychomycosis and cutaneous candidiasis 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.

It is intended for oral and intravenous administration.
For adults, depending on the indications, treatment regimens and the clinical situation, the daily dose is 50-400 mg, the frequency of application is 1 time / day.

For children, the dose is 3-12 mg / kg / day, the frequency of application is 1 time / day.

In patients with impaired renal function, the dose of fluconazole is reduced depending on the CK.

The duration of treatment depends on the clinical and mycological effect.

From the side of the nervous system: headache, dizziness, convulsions, change in taste.

From the side of the digestive system: abdominal pain, diarrhea, flatulence, nausea, dyspepsia, vomiting, hepatotoxicity (including rare cases with fatal outcome), increased level of alkaline phosphatase, bilirubin, serum level of aminotransferases (ALT and AST), liver dysfunction, hepatitis, hepatocellular necrosis, jaundice.

On the part of the cardiovascular system: an increase in the QT interval on the ECG, flicker / flutter of the ventricles.

Dermatological reactions: rash, alopecia, exfoliative skin diseases, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

On the part of the hematopoiesis system: leukopenia, including neutropenia and agranulocytosis, thrombocytopenia.

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

Allergic reactions: anaphylactic reactions (including angioedema, edema of the face, urticaria, pruritus).

Simultaneous use of terfenadine during multiple use of fluconazole at a dose of 400 mg / day or more;
simultaneous application of cisapride; hypersensitivity to fluconazole; hypersensitivity to azole derivatives with a fluconazole-like structure.
Adequate and controlled studies of the safety of fluconazole in pregnant women have not been conducted.
Avoid the use of fluconazole in pregnancy, except in cases of severe and potentially life-threatening fungal infections, when the expected benefit of treatment exceeds the possible risk to the fetus.
Women of childbearing age in the period of treatment should use reliable contraception.

Fluconazole is determined in breast milk in concentrations close to plasma, so the use during lactation (breastfeeding) is not recommended.

Fluconazole should be used with caution in patients with severe renal dysfunction.
If the renal function is impaired, the dose of fluconazole should be reduced.
Fluconazole should be used with caution in patients with severe impairment of liver function.

Contraindicated in children under 1 year.

With caution apply when violations of liver function indicators against the background of fluconazole, with the appearance of a rash against the background of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections, while using terfenadine and fluconazole at a dose of less than 400 mg / day, with potentially proarrhythmic states in patients with multiple risk factors (organic heart disease, electrolyte balance disorders and contributing to the development of such disorders concomitantly
The hepatotoxic effect of fluconazole was usually reversible;
signs of it disappeared after discontinuation of therapy. It is necessary to monitor the condition of patients who, during treatment with fluconazole, are disturbed by liver function tests, in order to identify signs of more serious liver damage. If there are clinical signs or symptoms of liver damage that may be associated with fluconazole, it should be discarded.
Patients with AIDS are more likely to develop severe skin reactions with many drugs.
When a patient who is treated for a superficial fungal infection has a rash that can be associated with fluconazole, it should be discarded. If rashes appear in patients with invasive / systemic fungal infections, fluconazole should be carefully monitored and discarded when bullous lesions or erythema multiforme occur.
Simultaneous use of fluconazole in doses less than 400 mg / day and terfenadine should be carefully monitored.

With fluconazole, an increase in the QT interval and fibrillation / flutter of the ventricles were very rare in patients with multiple risk factors, such as organic heart disease, electrolyte imbalance, and concomitant therapy that promoted the development of such disorders.

Therapy can begin before the results of sowing and other laboratory tests.
However, anti-infective therapy must be corrected appropriately when the results of these studies become known.
There have been reports of cases of superinfection caused by Candida strains other than Candida albicans, which often do not show sensitivity to fluconazole (for example, Candida krusei).
In such cases, alternative antifungal therapy may be required.
With simultaneous use with warfarin, fluconazole increases prothrombin time (by 12%), which is why bleeding can develop (hematomas, nosebleeds and digestive tract, hematuria, melena).
Patients receiving coumarin anticoagulants should constantly monitor 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 with its use iv.
If concomitant therapy with benzodiazepines is required, patients taking fluconazole should be monitored to appropriately reduce the dose of benzodiazepine.
With the simultaneous use of fluconazole and cisapride, unwanted 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 marked increase in plasma concentrations of cisapride and an increase in the QT interval on the ECG. Simultaneous administration 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 cyclosporin in bone marrow recipients were not observed. With the simultaneous use of fluconazole and cyclosporine, it is recommended to monitor the concentration of cyclosporine in the blood.
Multiple application of hydrochlorothiazide simultaneously with fluconazole leads to an increase in the concentration of fluconazole in plasma by 40%.
The effect of this degree of expression does not require a change in the dosage regimen of fluconazole in patients receiving diuretics at the same time, but this should be taken into account.
With simultaneous application of combined oral contraceptive with fluconazole at a dose of 50 mg, there is no significant effect on the level of hormones, whereas with the daily intake of 200 mg of fluconazole, the AUC of ethinylestradiol and levonorgestrel increase by 40% and 24% respectively, and 300 mg of fluconazole 1 time week - AUC of ethinylestradiol and norethindrone increase by 24% and 13%, respectively.
Thus, the repeated use of fluconazole at these doses is unlikely to affect the effectiveness of combined oral contraceptives.
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 to ensure therapeutic serum concentrations.
The simultaneous use of fluconazole and rifabutin may lead to an increase in serum concentrations of the latter.
With the simultaneous use of fluconazole and rifabutin, cases of uveitis are described. Patients who are simultaneously receiving rifabutin and fluconazole should be carefully monitored.
Simultaneous application of fluconazole and rifampicin results in a 25% decrease in AUC and a 20% decrease in T 1/2 of fluconazole.
In patients taking rifampicin simultaneously, it is necessary to consider the advisability of increasing the dose of fluconazole.
Fluconazole with simultaneous administration leads to an increase in T 1/2 oral oral sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide).
Patients with diabetes can be co-administered fluconazole and oral sulfonylureas, but the possibility of developing hypoglycemia should be considered.
Simultaneous application of fluconazole and tacrolimus leads to an increase in plasma concentrations of the latter.
Cases of nephrotoxicity are described. With this combination, patients should be closely monitored.
With the simultaneous use of azole antifungal agents and terfenadine, serious arrhythmias can occur as a result of an increase in the QT interval.
When fluconazole was taken at a dose of 200 mg / day, there was no increase in the QT interval, however, the use of fluconazole at doses of 400 mg / day and above caused a significant increase in the concentration of terfenadine in plasma. Simultaneous administration of fluconazole in doses of 400 mg / day or more with terfenadine is contraindicated. Treatment with fluconazole in doses less than 400 mg / day in combination with terfenadine should be carefully monitored.
With simultaneous application with fluconazole at a dose of 200 mg for 14 days, the average plasma clearance rate of theophylline is reduced by 18%.
In the administration of fluconazole, patients receiving high-dose theophylline or patients at increased risk of developing the toxic effect of theophylline should be monitored for symptoms of theophylline overdose and, if necessary, adjust the therapy accordingly.
With simultaneous use with fluconazole, there is an increase in zidovudine concentrations, which is probably due to a decrease in the metabolism of the latter to its main metabolite.
Before and after treatment with fluconazole at a dose of 200 mg / day for 15 days, AIDS patients and ARC (AIDS-related complex) had a significant increase in AZOD (20%).
When zidovudine was used in HIV-infected patients at a dose of 200 mg every 8 hours for 7 days with or without fluconazole at a dose of 400 mg / day at intervals of 21 days between the two schemes, a significant increase in zidovudine AUC (74%) was observed with simultaneous application with fluconazole.
Patients receiving this combination should be observed to identify side effects of zidovudine.
The simultaneous use of fluconazole with astemizole or other drugs metabolized by isoenzymes of the cytochrome P450 system may be accompanied by an increase in the serum concentrations of these agents.
With such combinations, patients should be closely monitored.
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