Pharmacological properties
Fluconazole (α-(2,4-difluorophenyl)-α-(1n-1,2,4-triazol-1-ylmethyl)-1-n-1,2,4-triazole-1-ethanol) is a selective inhibitor of sterol synthesis in fungal cells. The drug is active in mycoses caused by Candida spp., Cryptococcus neoformans, Microsporum spp., Trichoptyton spp., Blastomyces dermatitides, Coccidioides immitis, Histoplasma capsulatum.
After oral administration, fluconazole is well absorbed. Bioavailability exceeds 90%. The concentration in blood plasma reaches its maximum value 0.5-1.5 hours after taking the drug on an empty stomach. The half-life is about 30 hours. Fluconazole penetrates well into all body fluids. In the stratum corneum, epidermis, dermis and sweat fluid, concentrations exceeding serum levels are achieved; fluconazole accumulates in the stratum corneum, 6 months after the end of therapy, the drug is detected in the nails. It is excreted mainly by the kidneys; approximately 80% of the administered dose is found in the urine in unchanged form. The clearance of the drug is proportional to creatinine clearance.
Indication
Cryptococcosis, systemic candidiasis, mucosal candidiasis, vaginal candidiasis, prevention of fungal infections in immunocompromised patients, skin mycoses, including mycoses of the feet, body, and groin, tinea versicolor, onychomycosis.
Application
The daily dose of fluconazole depends on the nature and severity of the fungal infection and is determined individually.
adults
In cryptococcal infections, 400 mg is usually prescribed on the 1st day, and then treatment is continued at a dose of 200-400 mg 1 time per day. The duration of treatment is usually 6-8 weeks. For the prevention of relapse of cryptococcal meningitis in AIDS patients after completing the full course of primary treatment, fluconazole therapy at a dose of 200 mg can be continued for a very long period.
In candidiasis, the dose is 400 mg on the 1st day, then 200 mg/day, if necessary, the dose can be increased to 400 mg/day. The duration of therapy depends on clinical effectiveness.
For oropharyngeal candidiasis - 50-100 mg 1 time per day for 7-14 days or, if necessary, for a longer period. For atrophic candidiasis of the oral cavity, it is usually prescribed at a dose of 50 mg 1 time per day for 14 days, for other candidal infections of the mucous membranes (except vaginal candidiasis) the effective dose is usually 50-100 mg with a duration of treatment of 14-30 days.
For vaginal candidiasis and balanitis, Fluconazole is taken once in a dose of 150 mg.
For the prevention of fungal infections in patients with reduced immunity, the dose is 50 mg once a day while the patient is in the risk group.
For skin infections, including athlete's foot, inguinal area, and candidal infections, the recommended dose is 150 mg once a week or 50 mg once a day. The duration of therapy is usually 2-4 weeks, but for athlete's foot, longer therapy may be required (up to 6 weeks). For lichen, 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 a non-infected nail).
children
Children aged 1 to 16 years are prescribed the drug only in cases of extreme necessity: for superficial candidiasis - 1-2 mg/kg of body weight per day, for systemic candidiasis and cryptococcosis - 3-6 mg/kg of body weight per day.
Elderly patients
In the absence of signs of renal failure, the drug is prescribed in the usual dose. With a single dose, dose changes in patients with renal failure are not required. With repeated administration, the drug is prescribed in an initial dose of 50-400 mg, after which the daily dose (depending on creatinine clearance) is determined according to the table:
Creatinine clearance, ml/min Percentage of usual dose
| 50 | 100 |
| 11-50 | 50 |
| Patients undergoing regular dialysis treatment | One dose after each dialysis |
|
Contraindication
Hypersensitivity to the drug or triazole compounds, pregnancy and breastfeeding, age up to 1 year.
Side effects
Hepatotoxic effects and allergic reactions are possible, requiring discontinuation of the drug.
Special instructions
It is prescribed with caution to patients with severe liver dysfunction.
Interactions
When used simultaneously with coumarin anticoagulants, prothrombin time should be monitored; with hypoglycemic agents, hypoglycemia may develop; when combined with rifampicin, the dose of Fluconazole should be increased; when used simultaneously with cyclosporine, zidovudine, an increase in blood concentrations is possible. Simultaneous administration of Fluconazole with food, cimetidine, antacids does not affect its absorption.
Overdose
Gastric lavage, supportive and symptomatic therapy are indicated; forced diuresis can be used to accelerate drug elimination.
Storage conditions
In a dry place, protected from light, at a temperature of 8-15 °C.
