Pharmacological properties
Fluconazole (2-(2,4-difluorophen14l)-1,3-bis(1n-1,2,4-triazol-1-yl)-2-propanol) is an antifungal agent. It specifically acts on fungal enzymes dependent on cytochrome P450, inhibits the synthesis of sterols in fungal cells. It has high activity against Candida spp., Microsporum spp., Trichophyton spp., Cryptococcus neoformans, Blastomyces dermatitidis, Coccidioides immitis, Histoplasma capsulatum.
The maximum concentration of the drug in the blood serum is achieved immediately after i.v. administration. The half-life of the drug is about 30 hours. The concentration in the blood plasma is directly proportional to the administered dose. 90% of the equilibrium concentration level is achieved by the 4th-5th day of treatment with the drug when administered once a day. Binding to blood plasma proteins is 11-12%. Fluconazole penetrates well into all biological fluids, organs and tissues of the body. The drug concentrations in saliva and sputum are similar to its levels in blood plasma. In patients with fungal meningitis, the content of fluconazole in the cerebrospinal fluid reaches 80% of its level in blood plasma. High concentrations are achieved in the stratum corneum of the skin, epidermis, dermis, exceeding those in blood serum. Fluconazole accumulates and is stored in the stratum corneum of the skin for a long time. It is excreted mainly in the urine; approximately 80% - in the urine in unchanged form. Fluconazole clearance is proportional to creatinine clearance.
Indication
Fungal infections - cryptococcosis, including cryptococcal meningitis; systemic candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidal infection (peritoneum, endocardium, eyes, respiratory and urinary tract); candidiasis of the mucous membranes (oral cavity, pharynx, esophagus, non-invasive bronchopulmonary candidiasis, candiduria, atrophic candidiasis of the oral cavity caused by wearing dentures); genital candidiasis (acute and chronic recurrent vaginal candidiasis, balanitis); skin mycoses, including mycoses of the skin of the feet, body, inguinal region; tinea versicolor; onychomycosis; deep endemic mycoses; prevention of fungal infections in patients with malignant neoplasms during treatment with cytostatics or radiation therapy, or in other conditions caused by immunosuppression.
Application
Intravenously drip, at a rate of no more than 10 ml/min, once a day.
For vaginal candidiasis, candidal balanitis, 100-200 mg/day is prescribed; often after a single administration of the drug, recovery occurs. For other forms of candidiasis of the mucous membranes, 50-100 mg is recommended once a day for 14-30 days. For systemic candidiasis and cryptococcal infections, including meningitis, 400 mg is administered on the first day, then 200-400 mg once a day depending on the severity of the infection; the duration of therapy depends on clinical effectiveness; usually the course of treatment for cryptococcal meningitis lasts 6-8 weeks. For skin mycoses, the recommended dose is 150-200 mg once a week or 50 mg once a day, the duration of therapy is usually 2-4 weeks. However, for mycoses of the feet, treatment may be required for up to 6 weeks.
In onychomycosis, the recommended dose is 150-200 mg once a week; treatment should be carried out until the affected nail is completely replaced by a healthy one. Prevention of fungal infections in patients with malignant neoplasms - 100 mg every other day, while the patient is in an increased risk group, due to radiation or chemotherapy. Elderly patients in the absence of impaired renal function should adhere to the usual dosage regimen of the drug.
In case of impaired renal function, the dose of fluconazole for a single dose does not change. When re-prescribing the drug to patients with impaired renal function, a loading dose of 50 to 400 mg should be administered first. If creatinine clearance (CC) is more than 50 ml/min, the drug is prescribed in the usual dose (100% of the recommended dose). With CC from 11 to 50 ml/min, a dose equal to 50% of the recommended dose is used. For patients on chronic hemodialysis, one dose of the drug is administered after each hemodialysis session.
Children over 1 year of age with normal renal function are administered fluconazole once daily at a rate of 1-3 mg per 1 kg of body weight for candidiasis of the mucous membranes and 3-12 mg/kg per day for systemic candidiasis or cryptococcosis, depending on the severity of the disease. For children with impaired renal function, the daily dose of the drug should be reduced (in the same proportion as for adults) according to the degree of renal failure.
Fluconazole is administered slowly to newborns. In the first 2 weeks of life, the drug is prescribed in the same dose as for older children, but with an interval of 72 hours. Children aged 2-4 weeks are given the same dose with an interval of 48 hours.
Contraindication
Hypersensitivity to fluconazole or structurally similar triazole compounds, pregnancy, breastfeeding, children under 16 years of age (except for severe or life-threatening forms of infections, when the expected therapeutic effect outweighs the possible risk to the fetus or the patient).
Side effects
Nausea, diarrhea, abdominal pain, skin rash, headache.
Special instructions
If the activity of liver enzymes in the blood increases, the feasibility of further use of the drug should be determined depending on the ratio of the expected therapeutic effect and the risk of continuing treatment. If a skin rash appears, the use of the drug should be discontinued.
Fluconazole enhances the effect of anticoagulants, hypoglycemic agents, hydrochlorothiazide, diphenin. When combined with rifampicin, the half-life of fluconazole is reduced, which requires a slight increase in its dose.
Overdose
Symptomatic treatment is carried out. After a 3-hour hemodialysis session, the concentration of fluconazole in the blood plasma decreases by approximately 50%.
Storage conditions
In a dry place, protected from light, at a temperature not exceeding 30 °C.
