Flukonazol

General characteristics. Structure:

Active ingredient: 50 mg of a flukonazol.

Excipients: lactose, calcium phosphate double-base, microcrystallic cellulose, talc.

Medicine of broad antifungal action.

Pharmacological properties:

Pharmacodynamics. Flukonazol is the representative of a new class of triazolny antifungal means, is strong and specific inhibitor of synthesis of sterol in a cell of mushrooms.

In vitro Flukonazol possesses a wide range of activity, but also Amphotericinum is less powerful, than кетоконазол. However, in vivo флуконазол is much more active, than кетоконазол and, in certain cases, has the same activity as Amphotericinum against the superficial and systemic infections caused by Candida, Cryptococcus, Aspergillus and various dermatophytes.

Flukonazol has highly specific effect on the fungal enzymes dependent on R-450 cytochrome.

Pharmacokinetics. At intake флуконазол it is well soaked up, its general bioavailability exceeds 90%. The concomitant use of food does not influence drug absorption. Concentration in plasma reaches peak in 0,5-1,5 hours after reception, and the elimination half-life makes about 30 hours. 90% the level of equilibrium concentration are reached by 4-5 day of treatment by drug at reception of 1 times a day. Concentration in plasma are proportional to the accepted dose. The obvious volume of distribution approaches the general content of water in an organism. Linkng with proteins of plasma - low (12%).

Flukonazol well gets into all biological liquids of an organism. Concentration of drug in saliva and a phlegm are similar to its levels in plasma. At patients with fungal meningitis the maintenance of a flukonazol in cerebrospinal fluid reaches 80% of level it in plasma. In a corneous layer, epidermis, a derma and stalemate liquid high concentration which exceed serumal are reached. Flukonazol collects in a corneous layer.

Generally флуконазол it is removed by kidneys: about 80% of drug are removed with urine in an invariable look. The clearance of a flukonazol is proportional to clearance of creatinine. Metabolites of a flukonazol in peripheral blood are not revealed. The long elimination half-life of plasma (30 hours) at people allows to accept drug once a day at treatment of oropharyngeal candidiasis and to use single appointment at treatment of vaginal candidiasis.

Indications to use:

Flukonazol apply at the following diseases:
- genital candidiasis; vulvovaginal candidiasis (acute and chronic recuring), preventive use for the purpose of reduction of frequency of a recurrence of vulvovaginal candidiasis (3 and more episodes a year); candidosis balanitis;

- candidiasis of mucous membranes, including oral cavities and drinks, a gullet, noninvasive bronchopulmonary candidiases, a kandiduriya, candidiases of skin and mucous membranes, and also the atrophic candidiasis of an oral cavity connected with carrying dentures (treatment can be carried out at patients with the normal or lowered immunity function); prevention of a recurrence of oropharyngeal candidiasis at patients with AIDS;

- skin mycoses, including mycoses of feet, bodies, inguinal area; chromophytosis; onychomycosis; skin candidiasis; deep local mycoses, including кокцидиомикоз, паракокцидиомикоз, a sporotrichosis and гистопламоз at patients with normal immunity;

- generalized candidiasis, including a kandidemiya, the disseminated candidiasis and other forms of invasive candidosis infections (an infection of a peritoneum, an endocardium, eyes, respiratory and uric ways). Treatment can be carried out at patients with malignant new growths, sick intensive care units, the patients taking a course of cytostatic or immunosuppressive therapy and also in the presence of other factors contributing to development of candidiasis;

- cryptogoats, including cryptococcal meningitis and other localizations of this infection (lungs, skin, etc.), as at patients with a normal immune response, and at patients with various forms of immunosuppression (including at patients with AIDS, at organ transplantation); drug can be used as means of a maintenance therapy for prevention of a cryptococcal infection at patients with AIDS;

- prevention of fungal infections at patients with malignant new growths which are predisposed to such infections as a result of chemotherapy with cytostatics or radiation therapy;

Route of administration and doses:

The daily dose of a flukonazol depends by nature and weights of a fungal infection. The single peroral dose happens enough in most cases for treatment of acute vulvovaginal candidiasis. Treatment of other forms of a disease demands repeated use of drug up to clinically and laboratory confirmation of an active stage of a fungal infection. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually need a maintenance therapy for the purpose of the prevention of a recurrence.

The adult at cryptococcal meningitis and cryptococcal infections of other localizations in the first day usually appoint 400 mg, and then continue treatment in a dose of 200-400 mg of 1 times a day. Treatment duration at cryptococcal infections depends on the clinical performance confirmed with a mycologic research; at cryptococcal meningitis it is usually continued by 6-8 weeks. For prevention of a recurrence of cryptococcal meningitis at patients with AIDS, after end of a full course of primary treatment, флуконазол appoint in a dose 200 mg a day during a long span.

At a kandidemiya, the disseminated candidiasis and other invasive candidosis infections the dose usually makes 400 mg in the first days, and then on 200 mg. At insufficient clinical performance the dose of drug can be increased to 400 mg a day. Duration of therapy depends on clinical performance.

At oropharyngeal candidiasis drug usually appoint in a dose 50 mg once a day; duration of treatment is 7-14 days. If necessary, at patients with the expressed decrease in immunity, treatment can be longer.

At the atrophic candidiasis of an oral cavity connected with carrying dentures, drug usually appoint in a dose 50 mg within 14 days in combination with local antiseptic agents for processing of a prosthesis once a day.

At acute vulvovaginal candidiasis Flukonazol 3 times at an interval of the 72nd hour apply inside in a dose 150 mg. For decrease in frequency of a recurrence of chronic vulvovaginal candidiasis drug can be used in a dose of 100-150 mg – once a week 6 months, then 150 mg within 6 months once a month. At the balanitis caused by Candida флуконазол appoint once in a dose 150 mg inside. For prevention of candidiasis the recommended dose of a flukonazol makes 50-400 mg of 1 times a day depending on risk of development of a fungal infection.

At skin mycoses, including mycoses of feet, skin of inguinal area and skin candidiases, the recommended dose makes 150 mg once a week or 50 mg of 1 times a day. Therapy duration in everyday occurences makes 2-4 weeks, however, at mycoses of feet longer therapy can be required (up to 6 weeks). At treatment of a chromophytosis the recommended dose makes 50 mg of 1 times a day within 2-4 weeks.

At an onychomycosis the recommended dose makes 150 mg once a week. Treatment should be continued before substitution of the infected nail (growth неинфицирофанноо a nail). Repeated growth of nails on fingers of hands and feet normal requires 3-6 months and 6-12 months respectively. After successful treatment it is long the remaining persistent infections sometimes change of a shape of nails is observed.

Patients of advanced age in the absence of renal failures should adhere to the usual mode of a drug dosing. Patients with a renal failure (the clearance of creatinine is less than 40 ml/min.) should correct the mode of dosing.

Change of a dose of drug is not required to patients with a renal failure at a single dose. At repeated use the usual dose is appointed to the 1 and 2 days of treatment, and then it is necessary to correct intervals between receptions according to clearance of creatinine:

Clearance of creatinine (ml/min.)	Interval between receptions (hours)
> 41	24 (standard practice of drug)
21-40	48
10-20	72
The patients who are regularly on dialysis	One dose after each session of dialysis.

Features of use:

Use of drug during pregnancy Drug was a little used during pregnancy at the person. Undesirable changes of a fruit at animals were caused only at the high doses which are toxic for mother. These changes cannot be considered adequate to the changes happening at reception of a flukonazol in therapeutic doses. However it is necessary to avoid use of drug during pregnancy.

Use of drug in the period of a lactation. As there are no data concerning acceptable levels of a flukonazol in breast milk, its use by nursing mothers is not recommended.

It is not recommended to appoint use for children флуконазол to children up to 16 years.

Drug use by drivers and operators a mashinprimeneniye of a flukonazol does not influence ability of driving or control of cars.

Side effects:

Flukonazol, as a rule, is well had. Most often nausea, a headache and an abdominal pain meet.

At some patients, especially with such diseases as AIDS or malignant new growths, during treatment flukonazoly and similar drugs, changes of indicators of blood, an abnormal liver function and kidneys were observed, however clinical value and interrelation of these undesirable reactions with reception of a flukonazol are not established yet.

Exfoliative skin diseases, spasms, leukopenia, thrombocytopenia met, however in these cases relationship of cause and effect is not established.

Interaction with other medicines:

At use with warfarin the prothrombin time, despite insignificant expressiveness of these changes increases (on average by 12%). In this regard it is recommended to watch carefully indicators of a prothrombin time at the patients receiving drug in combination with coumarinic anticoagulants.

Flukonazol increases plasma elimination half-life of peroral gipoglikemiziruyushchy means - sulphonylurea derivatives (a chlorpropanide, Glibenclamidum, глипизид, Tolbutamidum) at healthy people. Combined use of a flukonazol and gipoglikemiziruyushchy means at patients with a diabetes mellitus is allowed, however the doctor has to mean a possibility of development of a gipolikemiya.

Simultaneous use of a flukonazol and Phenytoinum can lead to increase of concentration of Phenytoinum in plasma to clinically significant degree. Therefore in need of combined use of these drugs it is necessary to monitorirovat concentration of Phenytoinum with correction of its dose for the purpose of maintenance of level of drug within a therapeutic interval.

The combination with rifampicin leads to decrease in AUCNA 25% and to shortening of an elimination half-life of a flukonazol from plasma for 20%. Therefore the patient receiving at the same time rifampicin, it is reasonable to increase a dose of a flukonazol.

Studying of interaction with peroral contraceptive drugs and antipyrine showed that use of a flukonazol in the recommended doses can hardly exert impact on efficiency of these drugs.

Contraindications:

Flukonazol is not recommended to apply the patient with hypersensitivity to drug or relatives on structure to triazolny connections.

Overdose:

In case of overdose the symptomatic treatment is necessary (including the supporting measures and a gastric lavage).

Flukonazol is brought generally with urine therefore the artificial diuresis can, accelerate drug removal. After the three-hour session of a hemodialysis concentration of a flukonazol in plasma approximately decreases by 50%.

Storage conditions:

List B. To store in the place protected from moisture and light at a temperature not above +25 °C. To store in the place, unavailable to children. Period of validity 3 years.

Issue conditions:

According to the recipe

Packaging:

On 7 capsules in banks polymeric. 1 bank with a leaf insert in a cardboard pack.