Index of drugs

Treatment of fungal infections.In adult patients to treat the following infections: cryptococcal meningitis; coccidioidomycosis; invasive candidiasis; yeast infections of mucous membranes, including throat, esophageal, urinary yeast infections and chronic yeast infections of the skin and mucous membranes; chronic atrophic candidiasis (associated with the use of dental prostheses), if oral hygiene or local treatment are insufficient; vaginal fever, acute or recurrent when local treatment is inadequate; yeast acorn inflammation when local treatment is inadequate; skin fungus, including foot, trunk, shank, dandruff dermatitis, dermal skin inflammation, when systemic treatment is recommended; onychomycosis when it is considered that other medicines are unsuitable.In adult patients in the prevention of the following infections: relapse of cryptococcal meningitis in patients with an increased risk of relapse; relapse of yeast inflammation of the mouth, throat and esophagus in HIV-infected patients who are at increased risk of relapse; recurrence of vaginal candidiasis (4 or more infections during the year); fungal infections in patients with prolonged neutropenia (eg in patients with blood tumors, receiving chemotherapy or in patients after transplantation of hematopoietic stem cells.For use in the following infections in newborns, infants, children and adolescents aged 0 to 17 years (syrup); tablets - in children from 3 years: treatment of yeast infections of the mucosa (mouth, throat and esophagus), invasive candidiasis and cryptococcal meningitis and in the prevention of yeast infections in immunocompromised patients. The drug can be used as a maintenance treatment to prevent the recurrence of cryptococcal meningitis in children at high risk of relapse. Treatment can be started prior to receiving the results of culture or other laboratory tests. However, after receiving them, the available treatment should be adjusted accordingly. Official guidance on the proper use of antifungal drugs should be taken into account.

1 tabl contains 50 mg, 100 mg or 200 mg Fluconazole (and 84 mg, 80 mg and 160 mg lactose, respectively). 1 ml of syrup contains 5 mg of fluconazole (and 4 g of sucrose and 3.5 g of sorbitol respectively).

Antifungal medicine from the group of triazoles. The action consists mainly in inhibiting the cytochrome-dependent P-450 demethylation of 14 alpha-lanosterol, which is an important link in the fungal ergosterol biosynthesis. The accumulation of 14 alpha-methyl sterols correlates with the subsequent loss of ergosterol in the fungal cell membrane and may affect the antifungal activity of fluconazole.In vitro fluconazole has antifungal activity on the most common clinical strainsCandida (includingC. albicans, C. parapsilosis, C. tropicalis). strainsC. glabrata exhibit a wide range of sensitivity, whileC. krusei they are resistant to fluconazole. Fluconazole also works antifungalin vitro onCryptococcus neoformans andCr. gattiias well as endemic moldBlastomyces dermatiditis, Coccidioides immitis, Histoplasma capsulatum andParacoccidioides brasiliensis. Following oral administration, fluconazole is well absorbed and plasma concentrations (and overall bioavailability) reach 90% of the concentrations found after intravenous administration. Simultaneous food intake does not interfere with the absorption of the drug. The maximum plasma concentration after fasting is between 0.5 h and 1.5 h after taking the dose. After repeated administration of a single daily dose, a concentration corresponding to 90% of the steady-state concentration is reached after 4-5 days. Administration of a loading dose (within one day), constituting a double daily dose, makes it possible to achieve 90% of the plasma concentration on the 2nd day. The binding to proteins is small (11-12%). The drug penetrates well into all body fluids. Fluconazole concentrations in saliva and sputum are similar to those in plasma.In patients with fungal meningitis, fluconazole concentrations in the cerebrospinal fluid reach 80% of the plasma concentration. High levels of fluconazole in the skin, exceeding the plasma concentrations, are achieved in the stratum corneum, epidermis and dermis and sweat glands. Fluconazole accumulates in the stratum corneum. Fluconazole is only slightly metabolised. It is an inhibitor of CYP2C9, CYP3A4 and CYP2C19. T_0,5 drug in the plasma is about 30 h. It is mainly excreted by the kidneys, about 80% of the applied dose is present in the urine in unchanged form.

Hypersensitivity to the active substance, related azole compounds or to any of the excipients. The administration of terfenadine to patients receiving fluconazole at multiple doses of 400 mg daily or more is contraindicated. The use of other drugs that prolong the QT interval and are metabolised by cytochrome P450 (CYP3A4), such as cisapride, astemizole, pimozide, quinidine and Erythromycin, is contraindicated in patients receiving fluconazole.

The product should not be used to treat mycosis of the scalp. Data on the efficacy of fluconazole in the treatment of cryptococcosis and other locations (eg cryptococcosis of the lungs or skin), as well as other forms of endemic mycosis (such as paracoccidioidomycosis, lymphocutaneous sporotrichosis and histoplasmosis) are limited, and therefore no precise dosing recommendations. Caution should be exercised when administering fluconazole in patients with impaired renal function and in patients with impaired hepatic function. If liver dysfunction occurs during treatment with Fluconazole, the patient should be carefully monitored for any serious damage to the organ. In the event of symptoms suggestive of a strong effect on the liver (significant asthenia, anorexia, prolonged nausea, vomiting and jaundice), the use of fluconazole should be immediately discontinued and the patient should consult a physician. Due to the risk of QT prolongation and cardiac arrhythmiastorsade de pointes caution should be exercised in patients with cardiac arrhythmia risk factors such as: myocardial disease, electrolyte disturbances and concomitant use of drugs that may cause arrhythmias. Co-administration of fluconazole and halofantrine is not recommended (it prolongs the QT interval and is a CYP3A4 substrate). If a patient with surface mycosis, treated with fluconazole, develops a rash, fluconazole should be discontinued. If the rash develops in a patient treated with fluconazole due to an invasive, systemic fungal infection, the patient should be closely monitored; if bladder changes or erythema multiforme occur, fluconazole should be discontinued. Patients receiving concomitant fluconazole and drugs with a narrow therapeutic index should be monitored for CYP2C9, CYP2C19 and CYP3A4. Patients receiving terfenadine and fluconazole at doses lower than 400 mg per day should be carefully monitored. The tablets contain lactose - they should not be used in patients with rare hereditary problems of galactose intolerance, lactase deficiency (Lapp type) or malabsorption of glucose-galactose. The syrup contains sucrose and sorbitol - it should not be used in patients with rare inherited disorders associated with fluctuating intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency. 10 ml of syrup contains about 3.5 g sorbitol, which at a dose of 10 g and more may have a slight laxative effect; 10 ml of syrup contains 4 g of sucrose - this should be taken into account in patients with diabetes.

Fluconazole at standard doses and for a short period should not be used during pregnancy unless absolutely necessary. Fluconazole in high doses, especially long-term, should not be used during pregnancy, except for life-threatening infections. Data from a few hundred pregnant women taking standard doses (<200 mg / day) of fluconazole, administered as a single or multiple dose in the first trimester of pregnancy, did not show any adverse effects in the fetus.There have been reports of numerous congenital malformations (including short head, dysplasia of the ears, large anterior fontanel, hip fracture, and bone-bone radius of the radius) and children whose mothers were treated for high-dose fluconazole with coccidioidomycosis (400-800 mg / day) ) for 3 months or longer. The relationship between the administration of fluconazole and the occurrence of these defects is not known. Fluconazole is excreted in human milk reaching levels lower than in serum. Breastfeeding can be continued with a standard single dose of 200 mg or less. Breast feeding is not recommended after taking multiple doses of fluconazole or after a high dose.

Common: headache, abdominal pain, vomiting, diarrhea, nausea, increased ALT, AST, blood alcohol phosphatase, rash. Uncommon: anemia, decreased appetite, insomnia, dizziness, paresthesia, dizziness, change of taste, peripheral vertigo, constipation, indigestion, bloating, dry mouth, cholestasis, jaundice, increased bilirubin, drug eruption, urticaria , pruritus, increased sweating, muscle pain, fatigue, feeling unwell, asthenia, fever. Rare: agranulocytosis, leukopenia, thrombocytopenia, nautropenia, anaphylaxis, hypercholesterolemia, hypertriglyceridemia, hypokalaemia, tremor, cardiac arrhythmiatorsade de pointes, QT prolongation, hepatic failure, hepatic cell necrosis, hepatitis, liver cell damage, toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized pustular exanthema, exfoliative dermatitis, angioedema, facial edema, alopecia. The use of the preparation was rarely associated with severe toxic liver damage, including fatal outcome, mainly in patients with severe underlying disease. In cases of hepatotoxic effects of fluconazole, no clear relationship was observed with the total daily dose of the drug, the length of therapy and with gender or age of patients. Hepatotoxic effects of fluconazole usually resolved after discontinuation of therapy.

Orally.Adults. cryptococcosis. Treatment of cryptococcal meningitis: loading dose - 400 mg of the first day; Next dose - 200-400 mg per day; treatment time - usually 6-8 weeks; in life-threatening infections, the daily dose can be increased to 800 mg. Maintenance treatment to prevent the recurrence of cryptococcal meningitis in patients with an increased risk of recurrence: 200 mg / day; unlimited time of use.coccidioidomycosis: 200-400 mg; duration of treatment - 11-24 months or more, depending on the patient; In some infections, especially meningitis, a dose of 800 mg per day may be considered.Invasive invasive candidates: loading dose - 800 mg of the first day; next dose - 400 mg per day. The usual duration of treatment for yeast infections is 2 weeks after the first negative blood culture and the disappearance of the signs and symptoms characteristic of candidiasis.Treatment of candidiasis mucous membranes. Oral candidiasis: loading dose - 200-400 mg of the first day; next dose - 100-200 mg per day; duration of treatment - 7-21 days (until oral candidosis disappears); can be used longer in patients with severe weakened immune system function. Esophageal candidiasis: loading dose - 200-400 mg of the first day; next dose - 100-200 mg per day; duration of treatment - 14-30 days (until esophageal candidiasis disappears); can be used longer in patients with severe weakened immune system function. The occurrence of yeasts in the urine: 200-400 mg per day; treatment time - 7-21 days; can be used longer in patients with severe weakened immune system function. Chronic atrophic candidiasis: 50 mg daily; treatment time - 14 days. Chronic candidiasis of skin and mucous membranes: 50-100 mg per day; treatment time - up to 28 days; can be used longer in patients with severe weakened immune system function.Prevention of recurrent yeastitis in HIV-infected patients who are at increased risk of relapse. Oral candidiasis and esophageal candidiasis: 100-200 per day or 200 mg 3 times per week; unlimited duration of use in patients with chronic weakening of the immune system.Genital candidosis. Acute vaginal candidiasis and parenchymal acinar: a single dose of 150 mg. Treatment and prevention of recurrence of vaginal candidiasis (4 or more infections in a year): 150 mg every third day, a total of 3 doses (days 1, 4 and 7), followed by a maintenance dose of 150 mg once a week; duration of treatment - maintenance dose of 6 monthsMycosis of the skin. Foot mycosis, athlete's torso, thrush of the lower leg, skin candidosis: 150 mg once per week or 50 mg once a day; treatment time - 2-4 weeks; in foot tinea, it may be necessary to use up to 6 weeks. Dandruff versicolor: 300-400 mg once a week for 1-3 weeks or 50 mg once a day for 2-4 weeks. Onychomycosis: 150 mg once a day week .; treatment should be continued until the infected nail is replaced by a new, uninfected; the time required for the regrowth of a new hand or foot nail is 3-6 or 6-12 months, respectively; the rate of regrowth may, however, vary between patients, also depending on their age.Prevention of yeast infections in patients with prolonged neutropenia: 200-400 mg; treatment should begin several days before the expected onset of neutropenia and continue for 7 days after it has resolved, when the neutrophil count rises above 1,000 cells per mm³. Youth (12-17 years). Depending on body weight and maturity, it should be assessed which dosage (for adults or for children) is the most appropriate. The clearance of fluconazole in children is greater than in adults. Doses of 100, 200 and 400 mg in adults correspond to doses of 3, 6 and 12 mg / kg. in children, enabling a comparable level of exposure. The safety and efficacy profile of fluconazole in the treatment of genital candidiasis in children and adolescents has not been established; if it is necessary to treat genital candidiasis in adolescents (12-17 years), the same dosage should be used as in adults. Children and adolescents should not exceed the maximum daily dose of 400 mg. Infants and children from 28 days to 11 years old (tablets - children 3-11 years, syrup - children 0-11 years). Candidiasis of mucous membranes: initial dose - 6 mg / kg; next dose - 3 mg / kg per day; the starting dose can be used on the first day of treatment to achieve a faster balance. Invasive candidiasis and cryptococcal meningitis: dose - 6-12 mg / kg daily depending on the severity of the disease. Maintenance treatment to prevent the recurrence of cryptococcal meningitis in children at high risk of relapse: dose - 6 mg / kg, daily, depending on the severity of the disease. Prevention of yeast infections in immunocompromised patients: dose - 3-12 mg / kg daily, depending on the severity and duration of neutropenia (see dosage in adults).Newborns between the ages of 0 and 27 days (only syrup). Newborns 0-14 days: the same dose in mg / kg as in infants and children should be administered every 72 hours; the maximum dose of 12 mg / kg should not be exceeded. administered to 72 h. Newborns 15-27 days: the same dose in mg / kg. as in infants and children should be administered every 48 hours; the maximum dose of 12 mg / kg should not be exceeded. up to 48 hours. In patients (including children and adolescents) with renal impairment, receiving multiple doses of fluconazole, a 50-400 mg dose should be given initially, based on the recommended daily dose for the given indication. After this loading dose, the daily dose (as indicated) is determined as follows: creatinine clearance> 50 ml / min - 100% of the recommended dose; creatinine clearance ≤ 50 ml / min (without dialysis) - 50% of the recommended dose; regular dialysis - 100% of the dose recommended after each dialysis; On days on which dialysis is not performed, the dose should be reduced according to creatinine clearance.
Fluconazole can be administered orally or intravenously; the route of administration depends on the clinical condition of the patient. If the route of administration is changed from intravenous to oral and vice versa, no dosage adjustment is necessary. Table. should be swallowed whole, regardless of the meals taken.