Description
Release form
Capsules
Packing
2 pcs
Pharmacological action
Pharmacodynamics
Antifungal agent, has a highly specific effect, inhibiting the activity of fungal enzymes dependent on cytochrome P450. Histoplasma capsulatum (including immunosuppression).
Pharmacokinetics
After oral administration, fluconazole is well absorbed, food intake does not affect the rate of absorption of fluconazole, its bioavailability is 90%.
The time to reach the maximum concentration after ingestion of 150 mg of the drug on an empty stomach is 0.5-1.5 hours, Cmax is 90% of the concentration in plasma with iv administration at a dose of 2.5-3.5 mg / L. 2 fluconazole is 30 hours. Communication with plasma proteins – 11-12%. Plasma concentration is directly dependent on the dose. 90% level of equilibrium concentration is reached by the 4th 5th day of treatment with the drug (when taken once a day).
The introduction of a loading dose (on the first day), 2 times the normal daily, allows you to reach a concentration level corresponding to 90% of the equilibrium concentration by the second day.
Fluconazole penetrates well into all body fluids. 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 the vaginal secretion are reached 8 hours after ingestion and are kept at this level for at least 24 hours.
Fluconazole penetrates well into the cerebrospinal fluid (CSF) – with fungal meningitis, the concentration in the CSF is about 85% of its plasma level. In sweat fluid, epidermis and stratum corneum (selective accumulation), concentrations exceeding serum are achieved. After oral administration of 150 mg on the 7th day, the concentration in the stratum corneum of the skin is 23.4 μg / g, and 1 week after taking the second dose – 7.1 μg / g the concentration in the nails after 4 months of use at a dose of 150 mg 1 once a week – 4, 05 mcg / g in healthy and 1.8 mcg / g in affected nails. The volume of distribution approaches the total water content in the body.
Is an inhibitor of the CYP2C9 isoenzyme in the liver. It is excreted mainly by the kidneys (80% – unchanged, 11% – in the form of metabolites). Fluconazole clearance is proportional to creatinine clearance. No metabolites of fluconazole were found in peripheral blood.
The pharmacokinetics of fluconazole significantly depends on the functional state of the kidneys, while there is an inverse relationship between the elimination half-life and creatinine clearance. After hemodialysis for 3 hours, the concentration of fluconazole in the plasma is reduced by 50%.
Indications of
cryptococcosis, including cryptococcal meningitis and other localizations of this infection (including lungs, skin), both in patients with a normal immune response and in patients with various forms of immunosuppression (including in patients with AIDS , for organ transplantation) the drug can be used to prevent cryptococcal infection in patients with AIDS
generalized candidiasis, including candidaemia, disseminated candidiasis and other forms of invasive candida infections (infections of the peritoneum, endocardium, eyes, respiratory x and urinary tract). Treatment can be carried out in patients with malignant neoplasms, patients in the intensive care unit, patients, undergoing a course of 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), the esophagus, non-invasive bronchopulmonary candidiasis, candiduria, skin candidiasis prevention of recurrence of oropharyngeal candidiasis in AIDS patients
genital candidiasis: vaginal candidiasis (acute and chronic relapsing) in order to reduce the recurrence rate of vaginal candidiasis (3 or more episodes per year) candidal balanitis
prevention of fungal infections in patients with malignant new entities which are prone to such infections as a result of chemotherapy with cytostatics or radiation therapy
mycosis of the skin, including mycosis of the feet, body, inguinal pityriasis (multicolored) lichen, onychomycosis, candidiasis of the skin
deep endemic mycoses, including coccidioidomycosis, paracoccidiomycosis and sporotomyosis, immunity.
Contraindications
hypersensitivity to the drug (including history of other azole antifungal drugs)
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 extend the QT
interval, children under 4 years of age.
Precautions: liver and / or renal failure, rash on the background of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections, concomitant use of terfenadine and fluconazole in a dose of less than 400 mg / day, concomitant use of potentially hepatotoxic drugs, alcoholism potentially proarrhythmogenic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance, concomitant use of drugs that cause 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 benefits of fluconazole for the mother significantly exceed 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.
Composition
1 capsule contains:
Active ingredient:
fluconazole 150 mg.
Excipients:
corn starch,
povidone (polyvinylpyrrolidone),
silicon dioxide colloidal (aerosil),
sodium lauryl sulfate,
calcium stearate,
lactose.
Hard gelatin capsules:
for dosage of 50 mg – gelatin, titanium dioxide, dye azorubine, dye sunny sunset yellow and for dosage of 150 mg – gelatin, titanium dioxide.
Side effects of the
From the digestive system: decreased appetite, taste changes, abdominal pain, vomiting, nausea, diarrhea, flatulence, rarely – impaired liver function (jaundice, hepatitis, hepatonecrosis, hyperbilirubinemia, increased activity of alanine aminotransotransferase, alkaline phosphatase, hepatocellular necrosis), including heavy.
From the nervous system: headache, dizziness, excessive fatigue, rarely – cramps.
From the hemopoietic organs: rarely – leukopenia, thrombocytopenia (bleeding, petechiae), neutropenia, agranulocytosis.
Allergic reactions: skin rash, rarely – erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome), anaphylactoid reactions (including angioedema, swelling of the face, urticaria, itching of the skin).
From the cardiovascular system: an increase in the duration of the QT interval, ventricular fibrillation / flutter.
Other: rarely – impaired renal function, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.
Drug Interaction
When fluconazole is used with warfarin, PV is increased (by 12% on average). In this regard, it is recommended to carefully monitor the parameters of PV in patients receiving the drug in combination with coumarin anticoagulants.
Fluconazole increases the plasma half-life of oral hypoglycemic agents – sulfonylurea (chlorpropamide, glibenclamide, glipizide, tolbutamide) derivatives in healthy people. Co-administration of fluconazole and oral hypoglycemic agents in patients with diabetes is permitted, but the physician should keep in mind the possibility of developing hypoglycemia.
Concomitant administration of Fluconazole and phenytoin may increase the plasma phenytoin concentration to a clinically relevant level. Therefore, if necessary, the co-administration of these drugs should monitor the concentration of phenytoin with dose adjustment in order to maintain the drug level within the therapeutic interval.
Combination with rifampicin results in a 25% decrease in AUC and a 20% reduction in the plasma half-life of fluconazole. Therefore, it is advisable to increase the dose of Fluconazole in patients receiving concomitant rifampicin.
It is recommended that blood levels of cyclosporine be monitored in patients receiving fluconazole, as they should be controlled. the use of fluconazole and cyclosporine in patients with a transplanted kidney (administration of Fluconazole at a dose of 200 mg / day) leads to a slow increase in the concentration of cyclosporine in plasma.
Patients receiving high doses of theophylline or who are likely to develop theophylline intoxication should be monitored for early detection of symptoms of theophylline overdose. fluconazole administration results in a decrease in the average clearance rate of theophylline from plasma.
With concomitant use of fluconazole with terfenadine and cisapride, cardiac adverse events have been reported, including paroxysms of ventricular tachycardia (torsades de points).
Concomitant administration of fluconazole and hydrochlorothiazide may increase plasma concentrations of fluconazole by 40%.
Fluconazole and rifabutin have been reported to be associated with increased serum levels of the latter. When fluconazole and rifabutin are co-administered, cases of uveitis have been reported. Patients receiving rifabutin and fluconazole should be closely monitored.
In patients receiving a combination of fluconazole and zidovudine, an increase in zidovudine is observed, which is caused by a decrease in the latter’s metabolism into its major metabolite, therefore, an increase in the side effects of zidovudine should be expected.
Increases concentration of midazolam, in this connection increases the risk of developing psychomotor effects (most pronounced when using fluconazole orally rather than /). Increases the concentration of tacrolimus, and therefore increases the risk of nephrotoxic action.
Overdose
Symptoms: hallucinations, paranoid behavior.
Treatment: symptomatic – gastric lavage, forced diuresis. Hemodialysis reduces plasma concentrations by about 50% for 3 hours.
Storage conditions
In a dry, dark place at a temperature of 15 25 ° C.
Expiration
2 years
Deystvuyuschee substances
Fluconazole
Formulation
Dosage form
capsules
Vertex, Russia
