Pharmacological properties
Pharmacodynamics. Fluconazole is a new, synthetically obtained active substance of the triazole group. It is used to treat superficial and systemic mycoses. It has a fungistatic effect and is active against many pathogenic fungi, such as Candida albicans, C. tropicalis, Cryptococcus neoformans, Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis, Sporothrix schenkii, Paracoccidioides brasiliensis, as well as against most dermatophytes. It is less active against Aspergillus spp. and Penicillium marneffei. S. krusei, C. glabrato, Fusarium spp. and Zygomycetes are resistant to the drug.
Fluconazole is a potent, selective inhibitor of the fungal enzyme 14α-demethylase. It inhibits the synthesis of ergosterol, a major component of fungal cell membranes.
Pharmacokinetics. The binding of fluconazole to blood plasma proteins is low (11-12%).
Fluconazole penetrates well into body fluids. The concentration of the drug in saliva and sputum corresponds to the concentration in blood serum. T ½ is about 30 hours. Less than 5% of fluconazole is metabolized during the first pass through the liver. About 80% is not metabolized and is excreted in the urine unchanged, the rest is excreted in the form of metabolites.
Indication
Treatment of infections caused by microorganisms sensitive to fluconazole:
systemic candidiasis in patients with / without neutropenia, including disseminated candidiasis (including chronic), as well as other progressive forms of candidal infection, such as peritoneal, endocardial, respiratory, urinary tract infections. Fluconazole can be used in the treatment of patients with malignant neoplasms, as well as receiving cytostatic and immunosuppressive agents, and in patients in intensive care units; candidiasis of the mucous membranes: oropharyngeal, esophagopharyngeal candidiasis, non-invasive lung infections, candiduria, superficial and chronic atrophic candidiasis of the oral cavity (including HIV-infected and immunodeficient patients); for the prevention of candidiasis in patients before myelotransplantation, as well as in patients with malignant neoplasms prone to the development of such infections as a result of cytostatic or radiotherapy; Cryptococcosis: cryptococcal meningitis and lesions of other locations (lungs, skin).
Application
If the patient cannot take the drug orally, treatment with fluconazole solution for infusion is recommended. The infusion rate should not exceed 200 mg/h. As soon as possible, the patient should be transferred to the oral form of the drug. The daily dose should not be changed.
On the first day of therapy, a dose 2 times higher than that prescribed for this patient according to individual indications is prescribed.
adults
Systemic candidiasis, including in patients without neutropenia or with persistent neutropenia: 400 mg/day on the first day of treatment, on the following days - doses of 200-400 mg/day. The duration of treatment is determined individually. Treatment should be continued for at least 2 more weeks after obtaining a negative blood culture or the disappearance of symptoms of the disease. In severe infection, the daily dose may be increased to 800 mg.
Mucosal candidiasis, including in HIV-infected patients and other patients with impaired immune status, is prescribed in a daily dose of 50-100 mg. In primary infection, the duration of treatment is usually 7-14 days or 3 weeks in immunocompromised patients. In severe mucosal infections, a 30-day course of treatment at a dose of 100-200 mg/day may be required.
Cryptococcal meningitis in patients: 400 mg/day on the 1st day of treatment, then 200-400 mg/day for 6-8 weeks. Maintenance therapy in patients with cryptococcal meningitis, patients with AIDS, is carried out by oral administration of the drug at a dose of 200 mg/day.
For the prevention of candidiasis in patients before myelotransplantation, as well as in patients with malignant neoplasms prone to the development of such infections as a result of cytostatic or radiotherapy, it is prescribed in a dose of 50 to 400 mg/day.
For the prevention of candidiasis, fluconazole should be administered a few days before the expected development of neutropenia and treatment should be continued for at least another 7 days after the neutrophil count exceeds 1000/mm3.
children
The duration of treatment for children, as for similar infections in adults, depends on the clinical and mycological effects. Children should not exceed the maximum daily dose for adults. Fluconazole is prescribed once a day.
Children with normal renal function for the treatment of severe forms of candidiasis are prescribed at a dose of 6-12 mg/kg/day. For the prevention of fungal infection and for the treatment of superficial mycoses, a dose of 3-6 mg/kg/day is prescribed. Taking into account the individual patient's response, the daily dose may be increased to 12 mg/kg for life-threatening infections.
For children aged 5 to 13 years, the maximum dose is 400 mg of fluconazole per day.
newborns
During the first 2 weeks of life, newborns are prescribed the same doses as older children, but the interval between their administrations should be 72 hours. Children aged 2 to 4 weeks are prescribed the same dose every 48 hours.
For patients with renal insufficiency, the following dosage regimen should be used:
| Creatinine clearance, ml/min | dosage regimen |
| over 40 | Every 24 hours (normal mode) |
| 21-40 | Every 48 hours or 1/2 the usual dose per day |
| Every 72 hours or 1/3 of the usual daily dose |
|
For children with renal insufficiency, the dose is reduced accordingly.
