Fluconazole capsules 50 mg 7 pcs
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Active ingredients
Fluconazole
Composition
Fluconazole 50 mg; Excipients: lactose monohydrate; pregelatinized starch; silica colloidal anhydrous; magnesium stearate; sodium lauryl sulfate.
Pharmacological effect
Antifungal agent, has a highly specific effect, inhibiting the activity of enzymes of fungi, dependent on cytochrome P450. Blocks the conversion of lanosterol of fungal cells into membrane lipid - ergosterol; increases the permeability of the cell membrane, disrupts its growth and replication. Fluconazole, being highly selective for cytochrome P450 fungi, almost does not inhibit these enzymes in the human body (compared with itraconazole, clotrimazole, econazole and ketoconazole, it is less suppressive for cell-dependent gamma cells) in human liver microsomes). Does not possess antiadrogenic activity.; It is active in opportunistic mycoses, incl. caused by candida spp. (including generalized forms of candidiasis on the background of immunosuppression), Cryptococcus neoformans and Coccidioides immitis (including intracranial infections), Microsporum spp. and Trichophyton spp .; in case of endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulatum (including immunosuppression).
Pharmacokinetics
After ingestion, fluconazole is well absorbed, food intake does not affect the rate of absorption of fluconazole, its bioavailability - 90%; Time to reach the maximum concentration after oral administration on an empty stomach 150 mg of the drug - 0.5-1.5 hours, Cmax is 90% of the concentration in plasma with intravenous injection in a dose of 2.5–3.5 mg / l T1 / 2 of fluconazole is 30 h. Communication with plasma proteins is 11–12%. Plasma concentration is directly dose dependent. The 90% level of the equilibrium concentration is reached by the 4–5th day of drug treatment (when taken 1 time per day). The administration of a loading dose (on the first day), which is 2 times higher than the usual daily dose, makes it possible to achieve a concentration level corresponding to 90% equilibrium concentration, by the second day.; Fluconazole penetrates well into all biological fluids of the body. The concentration of the active substance in breast milk, articular fluid, saliva, sputum and peritoneal fluid is similar to its plasma levels. Constant values in vaginal secretion are reached 8 hours after ingestion and are held at this level for at least 24 hours. Fluconazole penetrates well into the cerebrospinal fluid (CSF) - with fungal meningitis the concentration in CSF is about 85% of its plasma level.In the sweat fluid, epidermis and the stratum corneum (selective accumulation) concentrations exceeding the serum levels are achieved. After ingestion of 150 mg on the 7th day, the concentration in the stratum corneum of the skin is 23.4 mcg / g, and 1 week after the second dose is taken - 7.1 mcg / g; concentration in the nails after 4 months of application at a dose of 150 mg 1 time per week - 4.05 mcg / g in healthy and 1.8 mcg / g in the affected nails. The volume of distribution approaches the total water content in the body.; It is an inhibitor of CYP2C9 isoenzyme in the liver. Excreted mainly by the kidneys (80% - unchanged, 11% - in the form of metabolites). Fluconazole clearance is proportional to creatinine clearance. No peripheral blood fluconazole metabolites were found. Fluconazole pharmacokinetics significantly depends on the functional state of the kidneys, and there is an inverse relationship between the half-life and creatinine clearance. After hemodialysis for 3 hours, plasma concentration of fluconazole is reduced by 50%.
Indications
Systemic lesions caused by Cryptococcus, including meningitis, sepsis, infections of the lungs and skin, both in patients with a normal immune response, and in patients with various forms of immunosuppression (including in AIDS patients, in organ transplantation); prevention of cryptococcal infection in AIDS patients. Generalized candidiasis: candidemia, disseminated candidiasis (with lesions of the endocardium, abdominal organs, respiratory organs, eyes and urogenital organs), including in patients receiving a course of cytostatic or immunosuppressive therapy, as well as in the presence of other factors predisposing to their development - treatment and prevention. Candidiasis of the mucous membranes: oral cavity, pharynx, esophagus, non-invasive bronchopulmonary candidiasis, candiduria, mucocutaneous and chronic oral atrophic candidiasis (associated with the wearing of dental prostheses). Genital candidiasis: vaginal (acute and recurrent), balanitis. Prevention of fungal infections in patients with malignant tumors on the background of chemotherapy or radiation therapy; prevention of recurrence of oropharyngeal candidiasis in AIDS patients. Skin mycoses: feet, body, groin, onychomycosis, pityriasis versicolor, skin candidal infections. Deep endemic mycoses (coccidioidosis, sporotrichosis and histoplasmosis) in patients with normal immunity.
Contraindications
Hypersensitivity to the drug (including to other azole antifungal drugs in history); simultaneous administration of terfenadine (against the background of continuous administration of fluconazole at a dose of 400 mg / day or more) or astemizole, as well as other drugs that prolong the QT interval; children up to 4 years old; With caution: hepatic and / or renal failure, the appearance of a rash against the background of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections, simultaneous administration of terfenadine and fluconazole at a dose of less than 400 mg / day, simultaneous receiving potentially hepatotoxic drugs, alcoholism, potentially pro-arrhythmogenic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance, simultaneous administration of drugs, causing arrhythmias), pregnancy.
Use during pregnancy and lactation
The use of the drug in pregnant women is impractical, with the exception of severe or life-threatening forms of fungal infections, when the potential benefit of using fluconazole for the mother greatly exceeds the risk to the fetus. Since the concentration of fluconazole in breast milk and plasma is the same, use of the drug during lactation is contraindicated.
Dosage and administration
Inside.; Adults and children over 15 years old (weighing more than 50 kg) with cryptococcal meningitis and cryptococcal infections of other sites on the first day are usually prescribed 400 mg (8 capsules 50 mg each), and then continue treatment at a dose of 200 mg (4 capsules on 50 mg) - 400 mg (8 capsules on 50 mg) once a day. The duration of treatment for cryptococcal infections depends on the clinical efficacy confirmed by mycological examination; for cryptococcal meningitis, the treatment should be at least 6–8 weeks. To prevent relapse of cryptococcal meningitis in AIDS patients, after completing the full course of primary therapy, fluconazole is prescribed at a dose of 200 mg (4 capsules of 50 mg) per day for a long period time.; For candidemia, disseminated candidiasis and other invasive candidal infections, the dose in the first day is 400 mg (8 capsules 50 mg), and then 200 mg (4 capsules 50 mg) per day. With insufficient clinical efficacy, the dose of the drug can be increased to 400 mg (8 capsules of 50 mg) per day. The duration of therapy depends on the clinical efficacy. In case of oropharyngeal candidiasis, the drug is usually prescribed 150 mg once a day, the duration of treatment is 7-14 days.If necessary, in patients with markedly reduced immunity, treatment may be longer.; To prevent recurrence of oropharyngeal candidiasis in AIDS patients after completing the full course of primary therapy, 150 mg once a week. In case of atrophic oral candidiasis associated with the wearing of dental prostheses - 50 mg 1 time per day for 14 days in combination with local antiseptic drugs for the treatment of the prosthesis.; At other localizations of candidiasis (except for genital), for example, with esophagitis, non-invasive bronchopulmonary nom lesion, candiduria, candidiasis of the skin and mucous membranes, etc., the effective dose is usually 150 mg / day with a duration of treatment of 14-30 days.; For vaginal candidiasis, fluconazole is taken once orally at a dose of 150 mg. To reduce the frequency of recurrences of vaginal candidiasis, the drug can be used at a dose of 150 mg once a month. The duration of therapy is determined individually, it varies from 4 to 12 months. Some patients may need more frequent use.; For Candida-induced balanitis, fluconazole is administered orally once at a dose of 150 mg / day; For the prevention of candidiasis, the recommended dose is 50–400 mg once a day, depending on the risk of developing a fungal infection. For the prevention of candidiasis in patients with malignant tumors, the recommended dose of fluconazole is 150-400 mg 1 time per day, depending on the degree of risk of developing a fungal infection. If there is a high risk of generalized infection, for example, in patients with expected severe or prolonged neutropenia, the recommended dose is 400 mg / day. Fluconazole is prescribed a few days before the expected appearance of neutropenia; after increasing the number of neutrophils more than 1 thousand / μl, the treatment is continued for another 7 days. With mycoses of the skin, including mycoses of the feet, skin of the inguinal region, and candidiasis of the skin, the recommended dose is 150 mg once a week or 50 mg once a day , dosing regimen depends on the clinical and mycological effect. The duration of therapy in normal cases is 2–4 weeks, however, with mycoses of the feet, longer therapy may be required (up to 6 weeks) .; For pitya verpus, 300 mg (2 capsules of 150 mg) once a week for 2 weeks,some patients require a third dose of 300 mg per week, while in some cases a single dose of 300–400 mg is sufficient; An alternative treatment regimen is the use of 50 mg 1 time per day for 2-4 weeks. With onychomycosis, the recommended dose is 150 mg 1 time per week. Treatment should be continued until the infected nail is replaced (the uninfected nail grows). It usually takes 3–6 months and 6–12 months for re-growth of nails on the fingers and feet, respectively.; For deep endemic mycoses, you may need to use the drug at a dose of 200 mg (4 capsules 50 mg each) - 400 mg (8 capsules per 50 mg) per day for up to 2 years. The duration of therapy is determined individually; it can be 11–24 months with coccidioidomycosis, 2–17 months with paracoccidioidomycosis, 1–16 months with sporotrichosis, and 3–17 months with histoplasmosis. In children, as with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. In children, the drug should not be used in a daily dose that would exceed that in adults, i.e. no more than 400 mg / day. The drug is used daily 1 time per day.
Side effects
From the digestive system: loss of appetite, changes in taste, abdominal pain, vomiting, nausea, diarrhea, flatulence, rarely - liver dysfunction (jaundice, hepatitis, gepatonekroz, hyperbilirubinemia, increased alanine aminotransferase activity, aspartate aminotransferase, increased alkaline phosphatase activity, hepatocellular necrosis ), including severe.; From the nervous system: headache, dizziness, excessive fatigue, rarely - convulsions.; From the side of blood-forming organs: rarely - leukopenia, thrombocytopenia (hemorrhage, petechiae), neutropenia, agranulocytosis. erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), anaphylactoid reactions (including angioedema, swelling of the face, urticaria, itchy skin) .; From the side of the cardiovascular system : increase the duration of the QT interval, ventricular fibrillation / flutter.; Other: rarely - impaired renal function, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.
Overdose
Symptoms: hallucinations, paranoid behavior.; Treatment: symptomatic - gastric lavage, forced diuresis. Hemodialysis for 3 hours reduces plasma concentration by approximately 50%.
Interaction with other drugs
With the use of fluconazole with warfarin, PV increases (on average by 12%). In this regard, it is recommended to carefully monitor the performance of PV in patients receiving the drug in combination with coumarin anticoagulants. Fluconazole increases the half-life from 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 is allowed, but the physician should be aware of the possibility of hypoglycemia. The simultaneous use of fluconazole and phenytoin can lead to an increase in plasma phenytoin concentration to a clinically significant degree. Therefore, if necessary, the joint use of these drugs should monitor the concentration of phenytoin with the correction of its dose in order to maintain the level of the drug within the therapeutic interval. Combination with rifampicin leads to a decrease in AUC by 25% and shortening the plasma half-life of fluconazole by 20%. 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, since the use of fluconazole and cyclosporine in patients with a transplanted kidney (Fluconazole intake at a dose of 200 mg / day) leads to a slow increase in plasma cyclosporine concentration. Patients who receive high doses of theophylline or who are likely to develop theophylline intoxication should be monitored with the purpose of early detection of symptoms of an overdose of theophylline, since receiving fluconazole leads to a decrease in the average rate of plasma clearance of theophylline from plasma. With simultaneous use of fluconazole with terfenadine and cisapride, cases of unwanted heart reactions are described, including paroxysmal ventricular tachycardia (torsades de points); Simultaneous use of fluconazole and hydrochlorothiazide may lead to an increase fluconazole in plasma by 40%; there are reports of the interaction of fluconazole and rifabutin, accompanied by an increase in serum levels of the latter.With simultaneous use of fluconazole and rifabutin, cases of uveitis are described. Patients receiving rifabutin and fluconazole at the same time should be carefully observed. In patients receiving the combination of fluconazole and zidovudine, there is an increase in the concentration of zidovudine, which is caused by a decrease in the conversion of the latter to its main metabolite, therefore, an increase in side effects of zidovudine is connection with which increases the risk of psychomotor effects (most pronounced when using fluconazole orally than i / v); increases the concentration of tacrolimus, due to what increases the risk of nephrotoxicity.
special instructions
Treatment should continue until clinical and hematologic remission. Premature discontinuation of treatment leads to relapses. During the treatment, it is necessary to monitor blood parameters, kidney and liver function. If a violation of the functions of the kidneys and liver occurs, the drug should be discontinued. In rare cases, the use of fluconazole was accompanied by toxic changes in the liver, including fatal, mainly in patients with serious concomitant diseases. In the case of hepatotoxic effects associated with fluconazole, they are not markedly dependent on the total daily dose, duration of therapy, sex and age of the patient. The hepatotoxic effect of fluconazole has usually been reversible; his symptoms disappeared after cessation of therapy. When clinical signs of liver damage appear that may be associated with fluconazole, the drug should be discontinued. Patients with AIDS are more likely to develop severe skin reactions with the use of many drugs. In cases where a rash develops in patients with a surface fungal infection and is regarded as definitely associated with fluconazole, the drug should be discontinued. When a rash appears in patients with invasive / systemic fungal infections, they should be carefully monitored and fluconazole should be canceled when a bullous change or erythema multiforme occurs. Care should be taken when taking fluconazole with cisapride, rifabutin or other drugs metabolized by the cytochrome P 450 system.