Fluconazole-Vertex capsules 150 mg, 4 pcs.

Composition

of fluconazole 150 mgvspomogatelny substances:lactose monohydrate; pregelatinized starch; colloidal anhydrous silicon dioxide; magnesium stearate; sodium lauryl sulfate capsule shell composition for 50 mg: titanium dioxide E-171; dye “Sunset” yellow E-110; gelatin composition of the capsule shell for 150 mg: titanium dioxide E-171; dye “Sunset” yellow T-110;dye “Ponceau-4R” E-124;gelatin

Pharmacological action

Antifungal agent, has a highly specific effect, inhibiting the activity of fungal enzymes dependent on cytochrome P 450. Blocks the conversion of lanosterol from fungal cells to ergosterol; increases the permeability of the cell membrane, disrupts its growth and replication. Fluconazole, being highly selective for fungal cytochrome P450, practically does not inhibit these enzymes in the human body (in comparison with itraconazole, clotrimazole, econazole and ketoconazole, it suppresses oxidative processes dependent on cytochrome P450 in human liver microsomes to a lesser extent). It has no antiandrogenic activity. Active in opportunistic mycoses, including those caused by Candida spp. (including generalized forms of candidiasis on the background of immunosuppression), Cryptococcus neoformans and Coccidioides immitis (including meningitis and encephalitis), Microsporum spp. and Trichophyton spp. ; in endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulatum (including those caused by immunosuppression).

Indications

— cryptococcosis, including cryptococcal meningitis and other localization of the infection (including the lungs, skin), as in patients with normal immune response and in patients with various forms of immunosuppression (including patients with AIDS, organ transplant); the drug can be used for the prevention of cryptococcal infections in AIDS patients; generalized candidiasis, including candidemia, disseminated candidiasis and other forms invasiveness infections (infection of the peritoneum, endocardium, eyes, respiratory and urinary tract). Treatment can be performed in patients with malignant neoplasms, patients in intensive care units, patients undergoing cytostatic or immunosuppressive therapy, as well as in the presence of other factors predisposing to the development of candidiasis;- candidiasis of the mucous membranes, including the oral cavity and pharynx (including atrophic candidiasis of the oral cavity associated with wearing dentures), esophagus, non-invasive bronchopulmonary candidiasis, candiduria, candidiasis of the skin; prevention of relapses of oropharyngeal candidiasis in AIDS patients;- genital candidiasis: vaginal candidiasis (acute and chronic recurrent), prophylactic use to reduce the frequency of relapses of vaginal candidiasis (3 or more episodes per year);- candidal balanitis;- prevention of fungal infections in patients with malignant neoplasms who are predisposed to such infections as a result of cytostatic chemotherapy or radiation therapy;- mycoses of the skin, including mycoses of the feet, body, groin area;- pityriasis versicolor;— onychomycosis;- candidiasis of the skin;- deep endemic mycoses, including coccidiomycosis and histoplasmosis, in patients with normal immunity.

Use during pregnancy and lactation

The use of the drug in pregnant women is impractical, except for severe or life-threatening forms of fungal infections, when the potential benefit of using fluconazole for the mother significantly exceeds the risk to the fetus. Since the concentration of fluconazole in breast milk and plasma is the same, it is contraindicated to use the drug during lactation.

Recommendations for use

Inside. Adults and children over 15 years of age (body weight more than 50 kg) with cryptococcal meningitis and cryptococcal infections of other localizations are usually prescribed 400 mg (8 capsules of 50 mg) on the first day, and then continue treatment at a dose of 200 mg (4 capsules of 50 mg) – 400 mg (8 capsules of 50 mg) 1 time/day. The duration of treatment for cryptococcal infections depends on the clinical efficacy confirmed by mycological examination; for cryptococcal meningitis, the course of treatment should be at least 6-8 weeks. To prevent recurrence of cryptococcal meningitis in AIDS patients, after completing a full course of primary therapy, fluconazole is prescribed at a dose of 200 mg (4 capsules of 50 mg)/day for a long period of time. For candidaemia, disseminated candidiasis, and other invasive candida infections, the dose is 400 mg (8 capsules of 50 mg) on the first day, and then 200 mg (4 capsules of 50 mg)/day. In case of insufficient clinical efficacy, the dose of the drug can be increased to 400 mg (8 capsules of 50 mg)/day. The duration of therapy depends on the clinical efficacy of the drug (100% of the recommended dose). With creatinine clearance from 11 to 50 ml / min,50% of the recommended dose or the usual dose is used 1 time in 2 days. In patients with impaired renal function, fluconazole is administered according to the following scheme. Creatinine clearance Interval / daily dose greater than 40 ml / min 24 h (normal dosage regimen) 21-40 ml / min 48 h (1 time in two days) or half of the usual daily dose (1 time in 24 hours)10-20 ml/min 72 h (1 time in three days) or 1/2 of the usual daily dose (1/3 in 24 hours)For patients undergoing hemodialysis, one dose of the drug is used after each hemodialysis session.

Contraindications

-hypersensitivity to the drug (including other azole antifungal drugs in the anamnesis); – simultaneous use of terfenadine (against the background of constant use of fluconazole at a dose of 400 mg / day or more) or astemizole, as well as other drugs that prolong the QT interval — – children under 4 years of age. Caution Hepatic and/or renal failure, rash associated with the use of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections, concomitant use of potentially hepatotoxic drugs, potentially proarrhythmogenic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance, concomitant use of drugs that cause arrhythmias), pregnancy.

Side effects

The adverse events presented below are listed according to the anatomical and physiological classification and frequency of occurrence. The frequency of occurrence is determined as follows: often-more than 1%; infrequently-0.1-1%; rarely-0.01-0.1%; very rarely-less than 0.01%. From the digestive system: decreased appetite, changes in taste, nausea, diarrhea, flatulence, abdominal pain, vomiting, abdominal pain; rarely-impaired liver function (jaundice, hepatocellular necrosis, hyperbilirubinemia, increased activity of alanine aminotransferase (ALT), aspartate aminotransferase (ACT) and alkaline phosphatase (ALP), hepatitis, hepatonecrosis), including severe. From the nervous system: headache, dizziness, excessive fatigue; rarely-convulsions. Hematopoietic disorders: rarely-leukopenia, thrombocytopenia (bleeding, petechiae), neutropenia, agranulocytosis. Allergic reactions: skin rash; rarely-erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), anaphylactoid reactions (including angioedema, facial edema, urticaria, pruritus of the skin). From the cardiovascular system: increased duration of the QT interval, ventricular fibrillation/flutter. Other: rarely-impaired renal function, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Interaction

When using fluconazole with warfarin, the prothrombin time increases (on average by 12%). It is recommended to monitor prothrombin time when combining fluconazole with coumarin anticoagulants Fluconazole increases T1 / 2 from the plasma of oral hypoglycemic agents – sulfonylurea derivatives (chlorpropamide, glibenclamide, glipizide, tolbutamide) in healthy people. The combined use of Fluconazole and oral hypoglycemic agents in patients with diabetes mellitus is allowed, but the doctor should keep in mind the possibility of hypoglycemia. Concomitant use of fluconazole and phenytoin may lead to an increase in the concentration of phenytoin in plasma to a clinically significant degree. Therefore, if the combined use of these drugs is necessary, it is necessary to monitor the concentration of phenytoin with dose adjustment in order to maintain the concentration of the drug within the therapeutic interval. Combination with rifampicin resulted in a 25% decrease in AUC and a 20% reduction in plasma T1/2 of fluconazole. Therefore, it is advisable to increase the dose of fluconazole in patients receiving rifampicin at the same time. It is recommended to monitor the concentration of cyclosporine in the blood of patients receiving fluconazole, because when using fluconazole and cyclosporine in patients with a transplanted kidney, taking fluconazole at a dose of 200 mg / day leads to a slow increase in the concentration of cyclosporine in plasma. Patients who receive high doses of theophylline or who are likely to develop theophylline intoxication should be monitored for symptoms of overdose of theophylline, because simultaneous administration of fluconazole leads to a decrease in the clearance of theophylline from the blood plasma. There are reports of interaction between fluconazole and rifabutin, accompanied by an increase in the serum concentration of the latter. Cases of uveitis have been reported with concomitant use of fluconazole and rifabutin. Patients receiving rifabutin and fluconazole concomitantly should be carefully monitored. In patients receiving a combination of fluconazole and zidovudine, an increase in the concentration of zidovudine is observed, which is caused by a decrease in the conversion of the latter to its main metabolite, so an increase in the side effects of zidovudine should be expected.Concomitant use of fluconazole, terfenadine, and cisapride has been associated with adverse cardiac events, including pirouette-like arrhythmia. Concomitant administration of fluconazole and hydrochlorothiazide may increase the concentration of fluconazole by 40%. Increases the concentration of midazolam, and therefore increases the risk of psychomotor effects (more pronounced when using fluconazole inside than intravenously). Increases the concentration of tacrolimus, which increases the risk of nephrotoxic effects.

Overdose

Symptoms:hallucinations, paranoid behavior. Treatment:symptomatic (gastric lavage, forced diuresis). Hemodialysis reduces the concentration by 50% in the next 3 hours.

Special instructions

Treatment should be continued until clinical and hematological remission occurs. Premature discontinuation of treatment leads to relapses. In rare cases, the use of fluconazole was accompanied by toxic changes in the liver, including with a fatal outcome, mainly in patients with serious concomitant diseases. In the case of hepatotoxic effects associated with fluconazole, there was no obvious dependence on the total daily dose, duration of therapy, gender and age of the patient. The hepatotoxic effect of fluconazole was usually reversible; signs of it disappeared after discontinuation of therapy. If there are clinical signs of liver damage that may be associated with fluconazole, the drug should be discontinued. People with AIDS are more likely to develop severe skin reactions when using many medications. In cases where patients with a superficial fungal infection develop a rash and it is considered definitely associated with fluconazole, the drug should be discontinued. If a rash appears in patients with invasive systemic fungal infections, they should be carefully monitored and discontinue fluconazole if bullous changes or erythema multiforme occur. Caution should be exercised when taking fluconazole concomitantly with cisapride, rifabutin, or other drugs that are metabolized by the cytochrome P450 system.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Fluconazole

Conditions of release from pharmacies

By prescription

Dosage form

of capsule

Weight

Weight: 16 gr.