After oral administration fluconazole is well absorbed, bioavailability – 90%.The maximum concentration after oral administration, fasted 150 mg of 90% in plasma when administered intravenously at a dose of 2.5 – 3.5 mg / l.Simultaneous food intake has no effect on the absorption of the drug taken orally. Plasma concentration reaches its peak after 0.5-1.5 hours after administration, the elimination half-life of fluconazole is approximately 30 hours. Plasma deca durabolin before and after concentrations are directly proportional to the dose. 90% of the level of the equilibrium concentration is achieved in 4-5 day drug treatment (at reception 1 times / day). The introduction of a bolus (the first day), 2 times the usual daily dose, achieves a level corresponding to 90% of the equilibrium concentration, to the second day. The apparent volume of distribution close to the total water content in the body.Plasma protein binding -. 11-12% Fluconazole penetrates well into all body fluids. Drug concentrations in saliva and sputum are similar to its level in plasma. In patients with fungal meningitis, fluconazole content in cerebrospinal fluid is 80% of that in plasma. In the stratum corneum, epidermis, dermis and sweat liquid reaches high concentrations that exceed the whey. Fluconazole is derived mainly kidneys; approximately 80% of the administered dose is excreted in the urine in unchanged form. Fluconazole clearance is proportional to creatinine clearance. Fluconazole metabolites detected in the peripheral blood.
- cryptococcosis, including cryptococcal meningitis and other localization of the infection (including lung, skin), in patients with a normal immune response, and patients with various forms of immunosuppression (in t. h. in AIDS patients, organ transplant ); drug can be used to prevent cryptococcal infection in AIDS patients;
- generalized candidiasis including candidemia, disseminated candidiasis and other forms of invasive Candida infections (infections of the peritoneum, endocardium, eyes, respiratory and urinary tract). The treatment can be carried out in patients with cancer, patients in intensive care units, patients undergoing a course of cytostatic or immunosuppressive therapy, as well as the presence of other factors predisposing to the development of candidiasis;
- mucosal candidiasis, including oral cavity and pharynx (including atrophic oral candidiasis associated with wearing dentures), esophageal, non-invasive bronchopulmonary candidiasis, candiduria, candidiasis of the skin; Prevention of relapse of oropharyngeal candidiasis in patients with AIDS;
- genitalny candidiasis: vaginal candidiasis (acute and chronic recurrent), prophylactic use to reduce the frequency of relapses of vaginal candidiasis (3 or more episodes per year); Candida balanitis;
- prevention of fungal infections in patients with malignancies who are predisposed to such infections result in cytostatic chemotherapy or radiotherapy;
- fungal infections of the skin, including tinea pedis, body, groin; pityriasis versicolor, onychomycosis; Skin candidiasis;
- deep endemic mycoses, including coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immunity.Contraindications
- concomitant use of terfenadine, astemizole or other drugs prolonging the QT interval.
- hypersensitivity to the drug or similar in structure azole compounds.
- child (up to 3 years).Precautions
Hepatic and / or renal insufficiency, concomitant use of potentially hepatotoxic drugs, alcoholism.
Pregnancy and lactation
Use of the drug in pregnant women is inappropriate, except in severe or life-threatening forms of fungal infections if the intended effect is greater than the potential risk to the fetus.
Fluconazole is in the breast milk in the same concentration as in plasma, so his appointment during lactation are not recommended.
Dosing and Administration
Inside. Adults in cryptococcal meningitis and cryptococcal infections at other sites on the first day is usually prescribed 400 mg, and then continue treatment at a dose of 200-400 mg 1 time / day. The duration of treatment for cryptococcal infections depends on the clinical efficacy, confirmed by mycological examination; cryptococcal meningitis it is usually continued for at least 6-8 weeks. For the prevention of relapse of cryptococcal meningitis in patients with AIDS, after the completion of a full course of primary therapy, fluconazole administered at a dose of 200 mg / day for a long period of time.When candidemia, disseminated candidiasis and other invasive Candida infections dose is usually 400 mg in the first day, and then – 200 mg. When insufficient clinical efficacy of the dose can be increased to 400 mg / day. The duration of therapy depends on clinical efficacy. In oropharyngeal candidiasis drug is usually administered 50-100 mg 1 time / day; Duration of treatment – 7-14 days. If necessary, in patients with a severely reduced immune treatment may be longer. In atrophic oral candidiasis associated with wearing dentures, fluconazole is usually prescribed 50 mg 1 times / day for 14 days in combination with a local antiseptic for the treatment of prosthetic . In other locales candidiasis (except genital candidiasis), such as oesophagitis, noninvasive bronchopulmonary lesions, candiduria, candidiasis of the skin and mucous membranes, etc., the effective dose is usually 50-100 mg / day when the duration of treatment 14-30 days . For the prevention of relapse of oropharyngeal candidiasis in patients with AIDS, after the completion of a full course of primary therapy, the drug can be assigned to 150 mg 1 time per week. Vaginal candidiasis fluconazole taking a single oral dose of 150 mg. To reduce the frequency of relapses vaginal candidiasis drug may deca durabolin before and after be used in a dose of 150 mg 1 time per month. The duration of therapy is determined individually; it varies between 4 and 12 months. Some patients may require more frequent application. When balanitis caused of Candida, fluconazole administered a single dose of 150 mg orally. For the prevention of candidiasis recommended dose of fluconazole is 50-400 mg 1 time / day, depending on the degree of risk of fungal infection. If you have a high risk of generalized infection, eg in patients with severe or long-anticipated persistent neutropenia, the recommended dose is 400 mg 1 time / day. Fluconazole is administered a few days before the expected occurrence of neutropenia; after increasing the number of neutrophils over 1000 / mm3, treatment was continued for 7 days. When skin mycoses, mycoses including feet, groin skin, and skin candidosis recommended dose is one 150 mg weekly or 50 mg 1 time / day. Duration of therapy in normal cases sostavlyaet2-4 weeks, however athlete’s foot may require a more prolonged treatment (up to 6 weeks). When pityriasis versicolor – 300 mg 1 time per week for 2 weeks, some patients required a third dose of 300 mg per week, while in some cases it is sufficient single dose of 300-400 mg; Alternative treatment scheme is the use of 50 mg 1 time a day for 2-4 weeks. In onychomycosis the recommended dose is 150 mg 1 time per week. Treatment should be continued until the replacement of the infected nail (uninfected nail sprouting). For the re-growth of nails on the fingers and feet normally required 3-6 months and 6-12 months, respectively. In deep endemic mycoses may require use of the drug at a dose of 200-400 mg / day for up to 2 years. The duration of therapy is determined individually; it can be 11-24 months with coccidioidomycosis; 2-17 months in paracoccidioidomycosis; Sporotrichosis 1-16 months at 3-17 months and at histoplasmosis. In children , as well as with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. In children, the drug should not be applied in a daily dose that would be higher than that of adults. The drug is used every day 1 time / day. When mucosal candidiasis recommended dose of fluconazole is 3 mg / kg / day. The first day can be assigned to a loading dose of 6 mg / kg in order to more quickly achieve constant equilibrium concentrations.For the treatment of generalized candidiasis and cryptococcal infections the recommended dose is 6-12 mg / kg / day, depending on the severity of the disease. For the prevention of fungal infections in children immunocompromised, in whom the risk of infection associated with neutropenia, developing as a result of cytotoxic chemotherapy or radiation therapy, the drug is prescribed for 3-12 mg / kg / day, depending on the severity and duration of preservation-induced neutropenia. in children with impaired renal function the daily dose should be reduced (in the same proportion as in adults), in accordance with the severity of renal failure. in elderly patients without renal dysfunction should follow the usual dose regimen of the drug. Patients with renal insufficiency (creatinine clearance less than 50 mL / min), the dosing regimen should be adjusted as indicated below. Use of the drug in patients with impaired renal function. Fluconazole is derived mainly from the urine in unchanged form. When receiving a single dose of its change is not required. With the reappointment of the drug to patients with impaired renal function sleduetsnachala enter a loading dose of 50 mg to 400 mg. If creatinine clearance (CC) is greater than 50 ml / min, applied the usual dose (100% of the recommended dose). When CC from 11 to 50 ml / min is applied dose equal to 50% of the recommended. Patients regularly on dialysis; a single dose of the drug is used after each hemodialysis session.
Side effect From the digestive system: changes in taste, vomiting, nausea, diarrhea, flatulence, abdominal pain, rarely – liver dysfunction (jaundice, hepatitis, gepatonekroz, hyperbilirubinemia, increased alanine aminotransferase activity, aspartate aminotransferase, increased alkaline phosphatase activity). From the nervous system: headache, dizziness, rarely – seizures. From the side of hematopoiesis:rarely – leukopenia, thrombocytopenia, neutropenia, agranulocytosis. Allergic reactions: skin rash, rarely – malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome ), anaphylactoid reactions. Other: rarely – renal dysfunction, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.
Overdose symptoms: hallucinations, paranoid behavior. Treatment: symptomatic, gastric lavage, forced diuresis. Haemodialysis for 3 hours reduces the plasma concentration of approximately 50%.
When using fluconazole and warfarin increased the prothrombin time (an average of 12%). In this connection, it is recommended to closely monitor the performance of the prothrombin time in patients receiving the drug in combination with coumarin anticoagulants.
Fluconazole increases the plasma half-life of oral hypoglycemic agents – sulfonylurea derivatives (hlorpropanid, glibenclamide, glipizide, tolbutamide) in healthy people. The combined use of fluconazole with oral hypoglycemic agents in patients with diabetes may be, however, the physician should bear in mind the possibility of hypoglycemia.
The simultaneous administration of fluconazole and phenytoin may result in an increase of phenytoin plasma concentrations to a clinically relevant extent. Therefore, if necessary, the joint use of these drugs need to monitor the concentration of phenytoin skorrektsiey the dose to maintain drug levels within the therapeutic range.
The combination with rifampicin causes decrease AUC and a 25% shortening the half-life of fluconazole from plasma by 20%. Therefore, patients receiving concomitant rifampicin, the dose of Fluconazole is expedient to increase.
It is recommended to monitor blood concentration of cyclosporine in patients receiving fluconazole since fluconazole and cyclosporine in patients with kidney transplant administration of fluconazole 200 mg / day leads to a slow increase in the concentration cyclosporine in plasma.
Patients who receive high doses of theophylline or who have a chance of developing theophylline toxicity should be kept under observation for early detection of the symptoms of theophylline overdose since receiving fluconazole reduces the average clearance of theophylline plasma velocity.
with simultaneous use of fluconazole and terfenadine, cisapride described cases of adverse reactions on the part of the heart, including paroxysms of ventricular tachycardia (torsades de points).
Concomitant use of fluconazole and hydrochlorothiazide may lead to an increase in the fluconazole plasma concentration by 40%.
There are reports about the interaction of fluconazole and rifabutin, accompanied by an increase in serum the last levels. With simultaneous administration of fluconazole and rifabutin uveitis cases are described. We must carefully monitor patients while receiving rifabutin and fluconazole.
Patients receiving the combination of zidovudine and fluconazole observed increased concentrations of zidovudine, which is caused by a decrease in the conversion of the latter into its main metabolite, so you should expect an increase in the side effects of zidovudine.
In rare cases, the use deca durabolin before and after of fluconazole was accompanied by toxic liver changes, including fatalities, primarily in patients with serious underlying medical conditions. In the case of hepatotoxic effects associated with fluconazole, no obvious dependence of the total daily dose, duration of treatment, gender, and age of the patient. Hepatotoxic effects of fluconazole was usually reversible; its signs disappeared after discontinuation of therapy. When clinical signs of liver damage, which may be associated with fluconazole, the drug should be discontinued.
AIDS patients are more prone to the development of severe skin reactions in the application of many drugs. In cases where patients with superficial fungal infection develops a rash, and she is regarded as definitely related to fluconazole, the drug should be discontinued. When a rash in patients with invasive / systemic fungal infections, they should be monitored closely and fluconazole cancel the appearance of bullous erythema multiforme or changes.