Tsiskan

General characteristics. Structure:

Active ingredient: 50 mg, 100 mg, 150 mg or 200 mg of a flukonazol.

Excipients: lactose, magnesium stearate, talc, silicon dioxide colloid, starch sodium glycollate.

Pharmacological properties:

Flukonazol. Antifungal drug, derivative triazole, is powerful selection inhibitor of synthesis of sterol in a cell of mushrooms.

Drug is active concerning causative agents of opportunistic mycoses, including Candida spp., Cryptococcus spp., Micosporum spp., Trichophyton spp. Also activity of a flukonazol on models of endemic mycoses, including the infections caused by Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum is shown.

Pharmacokinetics. Absorption. After intake флуконазол it is well absorbed from a GIT, bioavailability makes 90%.

After administration of drug inside on an empty stomach in a dose of 150 mg of Cmax in a blood plasma makes 90% of content in plasma at in introduction in a dose of 2.5-3.5 mg/kg. The concomitant use of food does not influence absorption of the drug accepted inside. Cmax is reached in 0.5-1.5 h after reception. Concentration in plasma are in linear dependence on a dose.

Distribution. 90% the Css level are reached by 4-5 day of administration of drug (at reception of 1 times/days).

Reception of the shock dose (in the first day) twice exceeding a usual daily dose allows to reach the level corresponding to 90% of Css by second day of treatment.

Linkng with proteins of plasma makes 11-12%.

Vd of a flukonazol at intake and in introduction approaches the general content of water in an organism.

Flukonazol well gets into all biological liquids of an organism. Concentration of drug in saliva and a phlegm are similar to its concentration in plasma. At patients with fungal meningitis the maintenance of a flukonazol in cerebrospinal fluid reaches 80% of the level of its content in plasma.

In a corneous layer, epidermis, a derma and stalemate liquid high concentration which exceed serumal are reached.

Metabolism. Metabolites in peripheral blood are not revealed.

Removal. T1/2 of a flukonazol makes about 30 h.

Flukonazol is brought generally by kidneys, about 80% of the entered dose are removed with urine in not changed look. The clearance of a flukonazol is directly proportional to KK.

Indications to use:

— a cryptococcosis, including cryptococcal meningitis and other localizations of this infection (including lungs, skin), as at patients with a normal immune response, and at patients with various forms of immunosuppression (including patients AIDS, at organ transplantation);

— prevention of a cryptococcal infection at patients AIDS;

— 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 OIT, the patients taking a course of cytostatic or immunosuppressive therapy and also in the presence of other factors contributing to development of candidiasis;

— candidiasis of mucous membranes, including oral cavities and drinks (including the atrophic candidiasis of an oral cavity connected with carrying dentures), a gullet, noninvasive bronchopulmonary candidiases, a kandiduriya, skin candidiasis, prevention of a recurrence of oropharyngeal candidiasis at patients AIDS;

— vaginal candidiasis (acute or chronic recuring), preventive use for the purpose of reduction of frequency of a recurrence of vaginal candidiasis (3 and more episodes a year);

— candidosis balanitis;

— 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.

— skin mycoses (including mycoses of feet, bodies, inguinal area); chromophytosis, onychomycosis, skin candidiasis;

— deep local mycoses (including a coccidioidomycosis, a paracoccidioidomycosis, a sporotrichosis and histoplasmosis) at patients with normal immunity.

Route of administration and doses:

The adult at cryptococcal meningitis and a cryptococcal infection of other localization in the first day usually appoint 400 mg, and then continue treatment in a dose of 200-400 mg of 1 times/days. Duration of a course of treatment at cryptococcal infections depends on the clinical performance confirmed with data of a mycologic research, at cryptococcal meningitis the course of treatment makes, at least, 6-8 weeks.

For prevention of a recurrence of cryptococcal meningitis at patients AIDS after end of a full course of primary treatment, флуконазол appoint in a dose 200 mg/days during a long span.

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

At oropharyngeal candidiasis drug is usually appointed on 50-100 mg of 1 times/days; treatment duration - 7-14 days. If necessary, at patients with the expressed decrease in immunity treatment can be longer.

For prevention of a recurrence of oropharyngeal candidiasis at patients about AIDS after end of a full course of primary therapy drug can be appointed on 150 mg once a week.

At atrophic candidiasis of an oral cavity, connected with carrying dentures, флуконазол usually appoint on 50 mg of 1 times/days within 14 days in combination with local antiseptic agents for processing of a prosthesis.

At candidiasis of other localization (for an exception of genital candidiasis), for example at an esophagitis, noninvasive bronchopulmonary damage, a kandiduriya, candidiasis of skin and mucous membranes, etc., the effective dose usually makes 50-100 mg/days with treatment duration - 14-30 days.

At vaginal candidiasis флуконазол accept once inside in a dose 150 mg. For decrease in frequency of a recurrence of vaginal candidiasis drug can be used in a dose of 150 mg of 1 time/month. Duration of therapy is determined individually; it varies from 4 to 12 months. More frequent use can be required by some patients.

At a candidosis balanitis 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/days depending on a risk degree of development of a fungal infection. With high risk of a generalized infection, for example at patients from the expected expressed or it is long the remaining neutropenia, the recommended dose makes 400 mg of 1 time/days Flukonazol appoint some days before the expected emergence of a neutropenia; after increase in number of neutrophils more 1000/mkl treatment is continued within 7 days.

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

At a chromophytosis the dose makes 300 mg of 1 time/week within 2 weeks. Some patients need purpose of drug within 3 weeks, at the same time in some cases is accorded rather single welcome of 300-400 mg of drug; the alternative scheme of treatment is use of drug in a dose of 50 mg of 1 times/days during 2-4 weeks.

At an onychomycosis the recommended dose makes 150 mg of 1 time/week. Treatment should be continued before substitution of the infected nail (growth of not infected nail). Repeated growth of nails on fingers of hands and feet normal requires 3-6 months and 6-12 months respectively.

At deep local mycoses use of drug in a dose of 200-400 mg/days during up to 2 years can be required. Duration of therapy is determined individually; it can make 11-24 months at a coccidioidomycosis, 2-17 months at a paracoccidioidomycosis, 1-16 months at a sporotrichosis and 3-17 months at histoplasmosis.

At children, as well as at similar infections at adults, duration of treatment depends on clinical and mycologic effect. At children drug should not be used in a daily dose which would exceed that at adults. Drug is used daily by 1 times/days.

At candidiasis of mucous membranes the recommended dose of a flukonazol makes 3 mg/kg/days. In the first day the shock dose of 6 mg/kg/days for the purpose of more bystry achievement of constant equilibrium concentration can be appointed.

For treatment of generalized candidiasis or a cryptococcal infection the recommended dose makes 6-12 mg/kg/days depending on disease severity.

For prevention of fungal infections at children with reduced immunity at which the risk of development of an infection is connected with the neutropenia developing as a result of cytotoxic chemotherapy or radiation therapy drug appoint in a dose 3-12 mg/kg/days depending on expressiveness and duration of preservation of the induced neutropenia.

At children with a renal failure the daily dose of drug should be reduced (in the same proportional dependence, as at adults), according to degree of manifestation of a renal failure.

At patients of advanced age in the absence of renal failures it is necessary to adhere to the usual mode of a drug dosing.

Flukonazol is brought preferential with urine in not changed look. With renal failures at a single dose of drug of dose adjustment it is not required to patients. At repeated purpose of drug at KK> 50 ml/min. use drug in the usual recommended dose. At KK from 50 to 11 ml/min. the dose makes 50% of recommended.

At patients at whom the hemodialysis is regularly carried out drug is appointed once after each session of a hemodialysis.

Features of use:

Use at pregnancy and feeding by a breast. Use of drug at pregnancy is inexpedient, except for severe or life-threatening forms of fungal infections if the estimated effect exceeds possible risk for a fruit.

Flukonazol is defined in breast milk in the same concentration, as well as in plasma therefore drug is contraindicated to use in the period of a lactation.

Use at abnormal liver functions. In rare instances use of a flukonazol was followed by toxic changes of a liver (including with a lethal outcome), mainly, at patients with serious associated diseases. In case of the hepatotoxic effects connected with action of a flukonazol explicit dependence them from a daily dose, duration of therapy, gender and age of the patient is noted. The hepatotoxic action of a flukonazol usually was reversible; its signs disappeared after the therapy termination. At emergence of clinical signs of damage of a liver which can be connected with flukonazoly drug should be cancelled.

Use at renal failures. Flukonazol is brought preferential with urine in not changed look. With renal failures at a single dose of drug of dose adjustment it is not required to patients. At repeated purpose of drug at KK> 50 ml/min. use drug in the usual recommended dose. At KK from 50 to 11 ml/min. the dose makes 50% of recommended.

At patients at whom the hemodialysis is regularly carried out drug is appointed once after each session of a hemodialysis

Use for children. Drug is contraindicated to children up to 6 months.

At children, as well as at similar infections at adults, duration of treatment depends on clinical and mycologic effect. At children drug should not be used in a daily dose which would exceed that at adults. Drug is used daily by 1 times/days.

Use for elderly patients. At patients of advanced age in the absence of renal failures it is necessary to adhere to the usual mode of a drug dosing.

Special instructions. In rare instances use of a flukonazol was followed by toxic changes of a liver (including with a lethal outcome), mainly, at patients with serious associated diseases. In case of the hepatotoxic effects connected with action of a flukonazol explicit dependence them from a daily dose, duration of therapy, gender and age of the patient is noted. The hepatotoxic action of a flukonazol usually was reversible; its signs disappeared after the therapy termination. At emergence of clinical signs of damage of a liver which can be connected with flukonazoly drug should be cancelled.

Patients AIDS are more inclined to development of heavy skin reactions at use of many drugs. When at patients with a superficial fungal infection rash develops, and it is regarded as definitely connected with flukonazoly, drug should be cancelled. At emergence of rash in patients with invasive/system fungal infections, they should be observed and cancelled carefully флуконазол at emergence of violent changes or a mnogoformny erythema.

It is necessary to be careful at a concomitant use of a flukonazol with tsizapridy and other drugs, the metabolized isoenzymes of system of P450 cytochrome.

Side effects:

From the alimentary system: nausea, diarrhea, meteorism, abdominal pains; seldom - an abnormal liver function (a hyperbilirubinemia, increase in activity of ALT, nuclear heating plant, ShchF).

From TsNS: headache; seldom - spasms.

From system of a hemopoiesis: seldom - a leukopenia, thrombocytopenia, a neutropenia, an agranulocytosis.

Allergic reactions: skin rash; seldom - a malignant exudative erythema (Stephens-Johnson's syndrome), a toxic epidermal necrolysis (Lyell's disease), anaphylactoid reactions.

Others: seldom - a renal failure, an alopecia, a hypercholesterolemia, a gipertriglitseridemiya, a hypopotassemia.

Interaction with other medicines:

At simultaneous use of a flukonazol with warfarin the prothrombin time increases (on average by 12%). In this regard it is recommended to watch carefully indicators of a prothrombin time at the patients receiving drug together with coumarinic anticoagulants.

Flukonazol increases T1/2 from plasma of peroral hypoglycemic means of derivatives of sulphonylurea (Chlorproramidum, Glibenclamidum, глипизид, Tolbutamidum) at healthy people. Combined use of a flukonazol and peroral hypoglycemic means at patients with diabetes is allowed, however the doctor has to mean a possibility of development of a hypoglycemia.

At simultaneous use of a flukonazol and Phenytoinum increase in concentration of Phenytoinum in a blood plasma to clinically significant degree is possible. 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 therapeutic concentration in a blood plasma.

The combination with rifampicin leads to reduction of AUC by 25% and T1/2 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.

It is recommended to control concentration of cyclosporine in a blood plasma at the patients receiving флуконазол as use of a flukonazol and cyclosporine for patients with the replaced kidney leads to slow increase in concentration of cyclosporine in plasma.

Patients who receive theophylline in high doses or who have a probability of development of teofillinovy intoxication have to be under observation for the purpose of early identification of symptoms of overdose of theophylline as reception of a flukonazol leads to decrease in average speed of clearance of theophylline from plasma.

At simultaneous use of a flukonazol and tsizaprid cases of undesirable reactions from a myocardium are described, including paroxysms of ventricular arrhythmia like "pirouette".

There are messages on the interaction of a flukonazol and a rifabutin leading to increase in serumal levels of the last. At simultaneous use of a flukonazol and rifabutin uveitis cases are described. It is necessary to observe carefully the patients who are at the same time receiving рифабутин and флуконазол.

At the patients receiving a combination of a flukonazol and a zidovudine increase in concentration of a zidovudine which is caused by decrease in transformation of the last into its main metabolite therefore it is necessary to expect increase in side effects of a zidovudine is observed.

Contraindications:

— concomitant use of an astemizol and terfenadin;

— pregnancy;

— period of a lactation (breastfeeding);

— children's age up to 6 months;

— hypersensitivity to a flukonazol or relatives on structure to azolny connections.

Overdose:

Symptoms: hallucinations, paranoid behavior.

Treatment: gastric lavage, artificial diuresis, performing symptomatic therapy. The hemodialysis during 3 h reduces concentration of a flukonazol in plasma approximately by 50%.

Storage conditions:

List B. To store in the place, unavailable to children, at a temperature not above 30 °C. A period of validity - 3 years. Capsules of 150 mg on 1 piece in packaging are allowed for use as means of non-prescription dispensing.

Issue conditions:

According to the recipe

Packaging:

8 pieces - planimetric strip packagings (3) - packs cardboard.
7 pieces - planimetric strip packagings (1) - packs cardboard.
1 pieces - planimetric strip packagings (1) - packs cardboard.
4 pieces - planimetric strip packagings (2) - packs cardboard.