Antifungal agent has the action of highly specific inhibiting activity of enzymes of fungal cytochrome P450-dependent. Blocks the conversion of lanosterol in fungi cell membrane lipid – ergosterol; increases the permeability of cell membranes, violates 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 to a lesser extent inhibits cytochrome P450 dependent oxidative processes in human liver microsome). Antiadrogennoy has no activity.
Active opportunistic mycosis, including caused by Candida spp. (Including generalized forms of candidiasis in the background immunosuppression), Cryptococcus neoformans iCoccidioides immitis (including intracranial infections), Microsporum spp. and Trichophyton spp .; at endemic mycosis, caused by Blastomyces dermatidis, Histoplasma capsulatum (including at immunosuppression).
After oral administration fluconazole is well absorbed, food intake does not affect the rate of absorption of fluconazole, its bioavailability – 90%.
The time to reach maximum concentration after oral administration of 150 mg of the drug on an empty stomach – 0.5-1.5 h, C max is 90% of the plasma concentration at / in a dose of 2.5-3, 5 mg / l.T 1/2 of fluconazole was 30 hours Connection to plasma proteins -. 11-12%. plasma concentration is in direct proportion to the dose. 90% of the equilibrium concentration level is achieved in 4-5 th day of drug treatment (at reception times 1 day).
Administering a loading dose (first day), a 2-times the normal daily, it allows to achieve a concentration level corresponding to 90% of the equilibrium concentration of the second day.
Fluconazole penetrates well into all body fluids. The concentration of active substance in breast milk, articular fluid, saliva, sputum, peritoneal fluid and its levels are similar to those in plasma. Constant values in the vaginal secretions are reached at 8 hours after oral administration and are maintained at this level for at least 24 hours.
Fluconazole well penetrates into cerebrospinal fluid (CSF) – in fungal meningitis concentration in CSF is about 85% of its level in plasma. The sweat liquid, epidermis and the stratum corneum (selective accumulation) achieved a concentration in excess serum. After oral administration of 150 mg on day 7, the concentration in the stratum corneum – 23.4 g / g, and 1 week after the second dose – 7.1 g / g; concentration in the nails after 4 months of application in a dose of 150 mg 1 time per week – 4.05 g / g in healthy and 1.8 mg / g in the infected nails. The volume of distribution is close to the total water content in the body.
It is an inhibitor of CYP2C9 isozyme in the liver. Excreted mainly by the kidneys (80% – unchanged, and 11% – as metabolites). Fluconazole clearance is proportional to creatinine clearance. Fluconazole metabolites were found in the peripheral blood.
The pharmacokinetics of fluconazole depends essentially on the renal function, the inverse relationship exists between the half-life and creatinine clearance. After dialysis for 3 hours fluconazole concentration in plasma decreased by 50%.
Children on doctor’s orders, children older than 3 years, adults
1 capsule contains:
The active ingredient is:
150 mg fluconazole.
colloidal silicon dioxide (Aerosil)
sodium lauryl sulfate,
Solid gelatine capsules:
Dosing 50 mg – gelatin, titanium dioxide, dye azorubin, sunset yellow dye and dosages of 150 mg – gelatin, titanium dioxide.
- cryptococcosis, including cryptococcal meningitis and other localizations of this infection (in Vol. H. Lungs, skin), in patients with a normal immune response, and in patients with various forms of immunosuppression (in Vol. H. In AIDS patients, in organ transplantation); the drug can be used for the prevention kriptokok kovoy-infection in patients with AIDS;
- 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 cancerous tumors-tion, patients in intensive care units, patients, passing-ing the course of cytostatic or immunosuppressive therapy, as well as the presence of other factors predisposing to the development of candidiasis;
- mucosal candidiasis in t h of the oral cavity and pharynx (including atrophic oral candidiasis associated with wearing dentures..), Esophagus, non-invasive bronchopulmonary candidiasis, candiduria, skin candidosis..; prevention of relapse of oro-pharyngeal candidiasis in patients with AIDS;
- genital candidiasis: vaginal candidiasis (acute and chronic relapse-al), prophylactic use to reduce the frequency of relapses crowbars-tional candidiasis (3 or more episodes a year); Candida balanitis;
- prevention of fungal infections in patients with malignant novoobrazova-niyami who are predisposed to such infections as a result of chemotherapy cyto-statics or radiotherapy;
- skin fungal infections including tinea pedis, body, groin; pityriasis versicolor, onychomycosis; Skin candidiasis;
- deep endemic mycoses, including coccidioidomycosis and histoplasmosis in patients with normal immunity.
Increased sensitivity to fluconazole, other ingredients or other azole compounds;
simultaneous reception of terfenadine (with the constant reception fluconazole 400 mg per day and more) cisapride or astemizole and other drugs, prolonging Q-T interval and increases the risk of severe solutions of Nara-rate;
Lactase deficiency; glucose-galactose malabsorption; lactation; Children under 3 years of age (for a given dosage form).
With caution: hepatic and / or renal failure, occurrence of rash on the pho-no use of fluconazole in patients with superficial fungal infection and invariant-invasive / systemic fungal infections, simultaneous terfenadine and fluconazole less than 400 mg per day, potentially proaritmogennoe condition in a pas cients with multiple risk factors (organic heart disease, disorders of electrolyte balance-tion, simultaneous reception of drugs that cause arrhythmias); patients with intolerance to acetylsalicylic acid and pregnancy.
From the digestive system: decrease in appetite, change in taste, nausea, vomiting, diarrhea, flatulence, abdominal pain, rarely – increased activity “pechenoch-tion” of enzymes and liver dysfunction (jaundice, hyperbilirubinemia, for higher activity of alanine aminotransferase (ALT), asparaginaminotransferazy (AST) and alkaline phosphatase (ALP), hepatitis, hepatocellular necrosis), including: fatal is-swing.
From the nervous system: headache, dizziness, rarely – seizures.
From the side of hematopoiesis: rare – agranulocytosis, neutropenia. Patients hematological changes may occur with severe fungal infections (leukopenia and thrombocytopenia).
From the cardiovascular system: prolongation of Q-T interval in the electrocardiogram (ECG), the flicker / ventricular flutter.
Allergic reactions: skin rash, erythema multiforme exudative (including Stevens-Johnson syndrome..), Toxic epidermal necrolysis (Lyell’s syndrome), bronchial asthma (often in case of intolerance of acetylsalicylic acid), anafilak-toidnye reaction (in t. h. angioneurotic edema, swelling of the face, urticaria, itching).
Other: rarely – renal dysfunction, alopecia, hypercholesterolemia, gipertrig-litseridemiya, hypokalemia.
How to accept, acceptance rate and dosage
Inside. The daily dose depends on the nature and severity of the fungal infection.
Adults with cryptococcal meningitis and cryptococcal infection at other sites on the first day is usually administered 400 mg and the treatment is then continued at a dose of 200 mg 1 time per day. Depending on the answer, the dose can be increased to 400 mg 1 time per day. Duration of treatment for cryptococcal infections depends on the clinical efficacy, confirmed by microbiological examination. Recommended duration of treatment in the initial therapy kriptokokovogo meningitis is 10-12 weeks after a negative result of microbiological examination of samples of cerebrospinal fluid.
For the prevention of relapse of cryptococcal meningitis in AIDS patients, followed for the full course-consummate primary treatment, fluconazole is administered in a dose of 200 mg per day for a long period of time.
If 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 per day; in severe systemic candidiasis – possibly increasing the dose to 800 mg per day. Flow rate of length of therapy depends on clinical efficacy; should continue for at least 2 weeks after receiving negative blood culture, or after the disappearance of symptoms.
If oropharyngeal candidiasis preparation is usually administered 50-100 mg 1 time per day; Duration of treatment – 7-14 days. If necessary, in patients with severe depression of immunity treatment may be longer (3 weeks).
In atrophic oral candidiasis , associated with wearing dentures, Flu-konazol usually administered at 50 mg 1 time per day for 14 days in combination with the seats antiseptic-tion for the treatment of the prosthesis.
In other localizations candidiasis (except genital candidiasis), such as esophagitis, noninvasive bronchopulmonary lesion, candiduria candidiasis of skin and mucous membranes and t. D., The effective dose is typically 50-100 mg daily when duration of treatment 14-30 days; in severe mucosal candidiasis – 100-200 mg per day.
For the prevention of recurrence of oropharyngeal candidiasis in AIDS patients after completing the full course of drug therapy primary may be designated by 150 mg 1 time per week.
Vaginal candidiasis fluconazole receiving a single oral dose of 150 mg. To reduce the frequency of relapses vaginal candidiasis preparation may be used in a dose of 150 mg 1 time per month. Duration of treatment is determined individually; it varies from 4 to 12 months. Some patients may require more frequent application.
If balanitis , caused by Candida, Fluconazole is administered once at a dose of 150 mg orally.
For the prevention of candidiasis The recommended dose of fluconazole is 50-400 mg 1 time per day, depending on the degree of risk of fungal infection.
If you have you HIGH-risk of generalized infection , for example, in patients with an expected severe or long-lasting neutropenia, the recommended dose is 400 mg 1 time per day. Fluconazole is administered a few days before the expected occurrence of neutropenia; after increasing the number of neutrophils over 1000 / mm treatment continued for 7 days.
In skin mycosis, including tinea pedis, groin skin and skin candidosis D komenduemaya dose is 150 mg 1 time per week or 50 mg 1 time per day. Duration of therapy in normal cases is 2-4 weeks, but may stop in mycosis con-Bova longer therapy (6 weeks).
With pityriasis versicolor – 300 mg 1 time per week for 2 weeks, some patients required a third dose to 300 mg per week, while in some cases, is sufficiently precise single dose of 300-400 mg; alternative treatment regimen is under-Menenius 50 mg 1 time per day for 2-4 weeks.
In onychomycosis recommended dose is 150 mg 1 time per week. Treatment should be continued until the replacement of the infected nail (nail sprouting uninfected). and 6-12 months, respectively, for re-growth of the fingernails and feet normally requires 3-6 months.
With deep endemic mycosis may be required to use the drug in a dose of 200-400 mg per day for up to 2 years. Duration of treatment is determined individually; it can be 11-24 months with coccidioidomycosis and histoplasmosis at 3-17 months.
In children , as well as with similar infections in adults, duration of treatment depends on the clinical and mycological effect. In children, the drug should not be used in a daily dose, which would be higher than that in adults. The drug is used daily 1 times a day.
When mucosal candidiasis fluconazole recommended dose is 3 mg / kg per day. On the first day it can be administered a loading dose of 6 mg / kg in order to more rapidly reach equilibrium concentrations.
For the treatment of generalized candidiasis and cryptococcal infection recommended dose is 6-12 mg / kg per day depending on the disease severity.
For the prevention of fungal infections in children immunocompromised, in whom the risk of infection associated with neutropenia that develops as a result of cytotoxic-cal chemotherapy or radiation therapy, the drug is prescribed for 3-12 mg / kg per day, depending on the severity and duration of preservation-induced neutropenia.
The maximum daily dose for children is – 12 mg / kg.
In the dark place at a temperature not higher than 25 ° C.
A single dose of fluconazole in the treatment of vaginal candidiasis is not accompanied by Xia significant interactions. However, when using higher or more doses of the drug simultaneously with other drugs, the following drugs interact:
- fluconazole interaction with terfenadine, astemizole, and cisapride may lead to increased concentrations of these drugs in the plasma, which in turn can cause a lengthening of the interval Q-T and lead to serious disturbances of heart rhythm. Fluconazole inhibits enzymes P450 system in the liver, thus reducing, metabolism terfenadine, astemizole and cisapride. Simultaneously, the value of fluconazole and these drugs is contraindicated.
- The joint appointment of warfarin and fluconazole marked lengthening of the pro-thrombin time. In this connection it is necessary to monitor the prothrombin time in patients concomitantly receiving fluconazole and anticoagulants Kumari-new series.
- Fluconazole lengthens T1 / 2 oral hypoglycemic drugs (sulfonylurea derivatives). Diabetic patients can simultaneously assign fluconazole and sulfonylureas, but must take into account the potential risk of hypoglycemia.
- It is necessary to take into account that during the second simultaneous appointment of hydrochlorothiazide and fluconazole, fluconazole increased plasma concentrations.
- Rifampicin accelerates the metabolism of fluconazole. Must be appropriately Obra Zoom to increase the dose of fluconazole when used simultaneously.
- In patients undergoing kidney transplantation, fluconazole can increase the concentration of cyclosporine in the plasma. In this connection, it is recommended the monitoring of cyclosporine concentrations in patients concomitantly receiving fluconazole and tacrolimus.
- Fluconazole increases the concentration of theophylline in plasma. In this connection, it is recommended etsya monitoring the concentration of theophylline in patients concomitantly receiving fluconazole and theophylline.
- Fluconazole may increase the plasma concentration of indinavir and midazolam. When concomitant administration of these drugs with fluconazole, their dosage should be reduced by co-responsible.
- Clinical studies have shown that as a result of slowing down the metabolism of zidovudine may increase its concentration in the plasma, while the appointment with fluconazole. It should be monitored for patients receiving simultaneously mi both drugs, since in this case may be increased incidence of side effects of zidovudine.
- Enhances the pharmacological effects of rifabutin (with simultaneous application of uveitis cases are described) and phenytoin to a clinically significant degree (the combined use requires monitoring of phenytoin concentration in plasma). Fluconazole is Witzlaus serum concentrations of phenytoin. While the appointment of the non-necessity to control the dose of phenytoin and to adjust them.
- Increasing the concentration of tacrolimus – the risk of nephrotoxicity
- Physicians should take into account that the interaction with other drugs has not been studied specifically, but it is possible.
Treatment can begin when there is no culture results and other laboratory tests, but their presence is recommended corresponding correction fungicidal treatment.
Since fluconazole excreted mainly by the kidneys must be followed the PICs-vanced in renal failure patients. Prolonged treatment flukona-zolom dosing should take into account KK.
Caution should be exercised in the appointment of fluconazole patients with hepatic impairment function. During treatment should be monitored regularly activity of “liver” enzymes and conduct observation of the patient in order to identify possible toxic effects. With an increase in activity of “liver” enzymes, the physician must weigh the benefit brought by ongoing therapy, and the risk of severe liver injury th. Fluconazole hepatotoxicity usually is reversible: the symptoms disappear after cessation of therapy.
AIDS patients are more prone to develop severe skin reactions at 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. If a rash in patients with invasive / systemic fungal infections, they should be monitored closely and fluconazole cancel the appearance changes or bullous erythema multiforme.
It is necessary to monitor the prothrombin time in patients concomitantly receiving fluconazole and coumarin anticoagulants. Treatment should be continued until clinical and microbiological remission. Premature discontinuation of treatment leads to relapse.
Part of the dye azorubin drug may cause an allergic reaction in t. H. Bronchial asthma. Allergic reactions are more common in patients with non-portability of acetylsalicylic acid.
Effects on ability to drive a car or other mechanical means: experience with fluconazole indicates that a violation of the ACT-lities to drive and the mechanisms associated with the use of the drug, it is unlikely.
Symptoms : nausea, vomiting, diarrhea, and in severe cases may experience convulsions, hallucinations, paranoid behavior.
Treatment: symptomatic, gastric lavage; t. To. Fluconazole is excreted by the kidneys recommended forced diuresis. Hemodialysis for 3 hours reduces the plasma concentration of 2-fold.