Fluconazole

Pharmacological properties

fluconazole is a new one, obtained by synthesis of the triazole group as the active substance. It is used to treat superficial and systemic mycoses. possesses a fungistatic effect and is active against many pathogenic fungi, such as candida albicans, p. tropicalis, cryptococcus neoformans, coccidioides immitis, histoplasma capsulatum, blastomyces dermatitidis, sporothrix schenkii, paracoccidioides brasiliensis, as well as for most dermatophytes. less active against aspergillus spp. and penicillium marneffei. resistant to the drug c. krusei, p. glabrato, fusarium spp. and zygomycetes.

Fluconazole is a potent selective inhibitor of the fungal enzyme 14α-demethylase. It slows down the synthesis of ergosterol, the main component of the membranes of fungal cells.

Pharmacokinetics The binding of fluconazole to plasma proteins is low (11–12%).

Fluconazole penetrates well into body fluids. The concentration of fluconazole in saliva and sputum corresponds to the concentration in the blood serum. T_½ is about 30 hours. Less than 5% of fluconazole is metabolized during the initial passage through the liver. About 80% are not metabolized and excreted in the urine unchanged, the remainder is excreted in the form of matabolites.

Indications

Treatment of infections caused by fluconazole-sensitive microorganisms:

• 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 those receiving cytostatic and immunosuppressive drugs, and in patients who are in intensive care units;
• mucosal candidiasis: oropharyngeal, esophagopharyngeal candidiasis, non-invasive infections of the lungs, candiduria, superficial and chronic atrophic candidiasis of the oral cavity (including HIV-infected and immunocompromised 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 due to cytostatic or radiotherapy;
• cryptococcosis: cryptococcal meningitis and lesions of a different location (lungs, skin).

Application

If the patient cannot take the drug orally, it is recommended that fluconazole solution be administered for infusion. the infusion rate should not exceed 200 mg / h. as soon as possible, the patient must be transferred to the oral form of the drug. the daily dose is not necessary.

On the first day of therapy, a dose is prescribed 2 times higher than that prescribed for this patient according to individual indications.

Adults

Systemic candidiasis, including in patients without neutropenia or with persistent neutropenia: 400 mg / day on the first day of treatment, on subsequent days - doses of 200-400 mg / day. The duration of treatment is determined individually. Treatment should be continued for at least another 2 weeks after receiving negative blood culture or the disappearance of symptoms of the disease. In severe infections, the daily dose may be increased to 800 mg.

Candidiasis of the mucous membranes, including in HIV-infected patients and other patients with impaired immune status, is prescribed in a daily dose of 50-100 mg. In primary infections, the duration of treatment is usually 7–14 days or 3 weeks in immunocompromised patients. In severe infections of the mucous membranes, 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, in the future - 200-400 mg / day for 6-8 weeks. Maintenance therapy in patients with cryptococcal meningitis, AIDS patients, 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 due to cytostatic or radiotherapy, a dose of 50 to 400 mg / day is prescribed.

For the prevention of candidiasis, fluconazole should be prescribed a few days before the expected development of neutropenia and continue treatment for at least another 7 days after the number of neutrophils exceeds 1000 / mm³.

Children

The duration of treatment for children, as well 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 in a daily dose.

Children with normal kidney 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. Given the individual response of the patient, the daily dose can 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 in the same doses as older children, but the interval between their administrations should be 72 hours. Children aged 2 to 4 weeks are prescribed in the same dose every 48 hours.

For patients with renal failure, the following dosage regimen should be used:

For children with renal failure, the dose is reduced accordingly