Index of drugs

Treatment of the following infections in adult patients: cryptococcal meningitis; kokcydioidomykozy; invasive candidiasis; yeast infection of mucous membranes (including throat, esophageal, candidurial and chronic mucocutaneous infection); chronic oral candidiasis (inflammation of the mouth) in the event that dental hygiene is insufficient.Prevention of the following infections in adult patients: recurrences of meningitis in high-risk patients; recurrence of yeastitis of the mouth, throat and esophagus in HIV-infected patients who are at increased risk of relapse; fungal infections in patients with prolonged neutropenia (eg in patients with blood cancers, receiving chemotherapy or in patients after transplantation of hematopoietic stem cells.The following infections in newborns, infants, children and adolescents aged 0 to 17 years: treatment of yeast infections of the mucosa (mouth, throat and esophagus), invasive candidiasis and cryptococcal meningitis and 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. Do not use in the treatment of onychomycosis of the scalp. Official guidance on the proper use of antifungal drugs should be taken into account.

1 ml of solution contains 2 mg of fluconazole; The drug contains sodium: 9 mg (0.154 mmol) in 1 ml.

Antifungal medicine from the group of triazoles. It inhibits the synthesis of ergosterol, necessary for the synthesis of the fungal cell membrane. Works on:Candida spp. (exceptC. krusei), Cryptococcus neoformans, Cryptococcus gattii, Blastomyces dermatiditis, Coccidioides immitis, Histoplasma capsulatum, Paracoccidioides brasiliensis. The binding to proteins is small (11-12%). Fluconazole 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 concentrations of fluconazole in the skin, exceeding the plasma concentrations, concern the horny layer, epidermal-cutaneous connec- tion and sweat glands. It is metabolized only to a small extent (about 11%). The main route of excretion of the drug are kidneys, about 80% of the applied dose is present in the urine in unchanged form. T_0,5 is 30 hours.

Hypersensitivity to Fluconazole, to other azole derivatives or to any of the excipients. The use of QT prolonging drugs that are metabolised by CYP3A4, such as cisapride, astemizole, pimozide, quinidine, Erythromycin, is contraindicated. Terfenadine is contraindicated in patients receiving multiple doses of fluconazole, ≥400 mg / day.

Fluconazole has not been shown to be more effective than Griseofulvin in the treatment of tinea head skin in children, and the overall recovery rate was less than 20%, therefore fluconazole should not be used to treat mycosis of the scalp. Data on the efficacy of fluconazole in the treatment of cryptococcosis involving other areas (eg cryptococcosis of the lung or skin) are limited - no precise dosing recommendations. Data on the efficacy of fluconazole in the treatment of other forms of endemic mycosis such as paracoccidioidomycosis, lymphocutaneous sporotrichosis and histoplasmosis are limited - no precise dosing recommendations. Use with caution in patients with impaired renal or hepatic function. Patients receiving fluconazole should be monitored for symptoms of hepatic impairment. Patients who have had biochemical liver dysfunction during treatment with fluconazole should be monitored for the presence of more severe hepatic disease. Carefully use in patients with a predisposition to arrhythmia. for example.with myocardial diseases, electrolyte disturbances and concomitantly treated with products that may cause heart rhythm disturbances. Co-administration of fluconazole and halofantrine is not recommended due to the risk of QT interval prolongation. Patients receiving terfenadine and fluconazole at doses of <400 mg / day should be carefully monitored. Use caution when using fluconazole in combination with drugs with which it interacts, especially those with a narrow therapeutic range, metabolised by CYP2C9, CYP2C19, CYP3A4. Discontinue use in patients with superficial mycosis if a rash associated with fluconazole develops. The occurrence of rash in patients with invasive or systemic infections is an indication for accurate observation and discontinuation of the drug in the case of developing bullous lesions or erythema multiforme. The sodium content of the preparation (0.154 mmol / ml) should be considered in patients who control the sodium content of the diet.

Standard doses of fluconazole (<200 mg / day) and short-term treatment should not be used during pregnancy unless absolutely necessary. High doses of fluconazole should not be used during pregnancy, in particular when given in a prolonged manner, except in life-threatening situations. Breastfeeding may be continued after a single dose of fluconazole ≤200 mg. Breast-feeding should be discontinued during treatment with multiple and / or higher doses.

Common: headache, abdominal pain, diarrhea, nausea, vomiting, increased alkaline phosphatase, AST and ALT, rash. Uncommon: anemia, decreased appetite, insomnia, drowsiness, convulsions, disturbances of taste, constipation, dyspepsia, bloating, dry mouth, jaundice, cholestasis, increased bilirubin, drug eruption, urticaria, pruritus , severe sweating, muscle pain, fatigue, feeling unwell, weakness, fever. Rare: agranulocytosis, leukopenia, neutropenia, thrombocytopenia, anaphylactic reactions, hypercholesterolemia, hypertriglyceridaemia, hypokalaemia, tremor, QT interval prolongation, torsade de pointes, hepatic failure, hepatic cell necrosis, hepatitis, liver cell damage (the use of fluconazole was rarely associated with severe toxic liver damage, including fatalities, mainly in patients with severe underlying diseases), toxic epidermal necrolysis, Stevens syndrome - Johnson, acute generalized pustular exanthema, exfoliative dermatitis, angioneurotic edema, swelling of the face, alopecia.

Intravenously, infused at a rate not exceeding 10 ml / min.Adults. cryptococcosis - Treatment of cryptococcal meningitis: 400 mg on day 1, then 200-400 mg / day, usually for 6-8 weeks; in life-threatening infections, the dose may be increased to 800 mg / day. Maintenance treatment to prevent the recurrence of cryptococcal meningitis in high-risk patients: 200 mg / day.coccidioidomycosis: 200-400 mg / day, usually for 11-24 months or more; for some infections a dose of 800 mg / day should be considered, especially in meningitis.Invasive candidiasis: 800 mg on day 1, then 400 mg / day; the usually recommended length of treatment for yeast blood infection is 2 weeks after the first negative blood culture result and the disappearance of the signs and symptoms characteristic of candidiasis.Treatment of candidiasis mucous membranes - Oral candidiasis: 200-400 mg on day 1, then 100-200 mg / day, usually for 7-21 days or longer for patients with weakened immune function. Esophageal candidiasis: 200-400 mg on day 1, then 100-200 mg / day, usually for 14-30 days or longer for patients with weakened immune function. Candidature: 200-400 mg / day, usually for 7-21 days or longer for patients with weakened immune function. Chronic atrophic candidiasis: 50 mg / day for 14 days. Chronic mucocutaneous candidiasis: 50-100 mg / day for 28 days or more for patients with weakened immune function and depending on the degree of infection.Prevention of recurrence of yeast mucositis in HIV-infected patients who are at high risk of relapse - Oral candidiasis, esophageal candidiasis: 100-200 mg / day or 200 mg three times a week, no duration of treatment for patients with chronic weakening of the immune system.Prevention of fungal infections in patients with prolonged neutropenia: 200-400 mg / day, the treatment should start several days before the expected occurrence of neutropenia and continue for 7 days after an increase in the neutrophil count to> 1,000 / mm³. Children and youth. In the pediatric population, a dose of 400 mg / day should not be exceeded. Depending on the severity and degree of maturity, it should be estimated which dosage (for adults or children) is the most suitable for adolescents aged 12-17. Clinical data indicate that children have a greater clearance of fluconazole than adult patients. The doses of 100, 200 and 400 mg in adults correspond to 3, 6 and 12 mg / kg. doses in children.Newborns from the 28th day of life, infants and children up to 11 years old - Mucosal candidosis: 6 mg / kg / day on day 1, then 3 mg / kg / day. Invasive candidiasis, cryptococcal meningitis: 6-12 mg / kg / day. Maintenance treatment to prevent the recurrence of cryptococcal meningitis in children at risk of relapse: 6 mg / kg / day. Prevention of yeast infections in immunocompromised children: 3-12 mg / kg / day depending on the severity and duration of neutropenia.Newborns up to the 27th day of lifeDuring the first and second weeks of a child's life, the same dose should be given in mg / kg, as in older children, but administered every 72 h (do not exceed the maximum dose of 12 mg / kg given every 72 h); At 3 and 4 weeks of age, the same dose should be given every 48 hours (do not exceed the maximum dose of 12 mg / kg administered every 48 hours). There is little pharmacokinetic data to support such a dosage regimen in newborns.Special groups of patients. Patients with impaired renal function. In the case of a single administration, no dose adjustment is necessary. In patients (including the pediatric population) with impaired renal function, a loading dose of 50 mg to 400 mg should be given at the beginning of multidose fluconazole therapy based on the recommended daily dose for the indication. After the loading dose, the daily dosage (as indicated) should be determined based on the creatinine clearance (CCr):> 50 ml / min - administered 100% of the recommended dose; ≤50 ml / min (patients not on dialysis) - 50% of the recommended dose; patients regularly dialyzed - 100% of the recommended dose after each dialysis (on days on which dialysis is not performed, patients should receive a reduced dose consistent with CCr). The pharmacokinetics of fluconazole in children with renal failure have not been studied. There is no need to change the dosage in elderly patients with normal renal function.