Флукомабол®

General characteristics. Structure:

Active ingredient: 200 mg of a flukonazol.

Vpomogatelny substances: sodium chloride, water for injections.

Pharmacological properties:

Pharmacodynamics. Antifungal means, possesses highly specific action, inhibiting activity of enzymes of the mushrooms dependent on P450 cytochrome. Blocks transformation of a lanosterol of cells of mushrooms into ergosterol; increases permeability of a cellular membrane, breaks its growth and replication.

Flukonazol, being high-selective for P450 cytochrome of mushrooms, practically does not oppress these enzymes in a human body (in comparison with itrakonazoly, Clotrimazolum, ekonazoly and ketokonazoly to a lesser extent suppresses oxidizing processes, dependent on P450 cytochrome, in microsomes of a liver of the person). Has no antiadrogenny activity.

It is active at opportunistic mycoses, including the caused Candida spp. (including generalized forms of candidiasis against the background of an immunosuppression), Cryptococcus neoformans and Coccidioides immitis (including intracranial infections), Microsporum spp. and Trichophyton spp; at the local mycoses caused by Blastomyces dermatidis, Histoplasma capsulatum (including at an immunosuppression).

Pharmacokinetics. Absorption - high (food does not influence absorption speed), bioavailability - 90%. TCmax after intake on an empty stomach of 150 mg is 0.5-1.5 h and Cmax at peroral introduction makes 90% of concentration in plasma at in introduction in a dose of 2.5-3.5 mg/kg. Communication with proteins of plasma - 11-12%. Concentration in plasma is in direct dependence on a dose. Css is reached by 4-5 day of reception (at reception of 1 times a day). Introduction of the "shock" dose (in the first day) twice exceeding a usual daily dose allows to reach the concentration corresponding to 90% of Css by 2nd day.

Well gets into all liquids of an organism. Concentration of active agent in breast milk, joint liquid, saliva, a phlegm and peritoneal liquid is similar that in plasma. Constant values in a vaginal secret are reached in 8 h after intake and keep on this value not less than 24 h. Well gets into SMZh, at fungal meningitis concentration in SMZh makes about 85% of that in plasma. In stalemate liquid, epidermis and a corneous layer (the selection accumulation) the concentration exceeding serumal are reached.

After intake of 150 mg for the 7th day concentration in a corneous layer of skin - 23.4 mkg/g, and in 1 week after reception of the second dose - 7.1 mkg/g; concentration in nails after 4 months of use in a dose of 150 mg once a week - 4.05 mkg/g in healthy and 1.8 mkg/g in the affected nails. The volume of distribution approaches the general content of water in an organism.

Elimination half-life - 30 h. Is CYP2C9 isoenzyme inhibitor in a liver. It is removed preferential by kidneys (80% - in not changed look, 11% - in the form of metabolites). The clearance of a flukonazol is proportional to KK.

The pharmacokinetics of a flukonazol significantly depends on a functional condition of kidneys, at the same time there is inverse relation between T1/2 and KK. After a hemodialysis during 3 h concentration of a flukonazol in plasma decreases by 50%.

Indications to use:

The systemic lesions caused by Cryptococcus mushrooms including meningitis, sepsis, infections of lungs and skin, as at patients with a normal immune response, and at patients with various forms of an immunosuppression (including at patients with AIDS, at organ transplantation); prevention of a cryptococcal infection at patients with AIDS.

Generalized candidiasis: a kandidemiya, the disseminated candidiasis (with defeat of an endocardium, abdominal organs, a respiratory organs, eyes and urinogenital bodies), including at the patients receiving a course of cytostatic or immunodepressive therapy and also in the presence of other factors contributing to their development - treatment and prevention.

Candidiasis of mucous membranes: oral cavities, drinks, a gullet, noninvasive bronchopulmonary candidiases, a kandiduriya, the skin and mucous and chronic peroral atrophic candidiasis (connected with carrying dentures).

Genital candidiasis: vaginal (acute and recurrent), balanitis.

Prevention of fungal infections at patients with malignant tumors against the background of himio-or radiation therapy; prevention of a recurrence of oropharyngeal candidiasis at patients with AIDS.
Skin mycoses: stop, bodies, inguinal area, onychomycosis, chromophytosis, skin candidosis infections.

Deep local mycoses (coccidioidosis, sporotrichosis and histoplasmosis) at patients with normal immunity.

Route of administration and doses:

Inside, in/in kapelno (with a speed no more than 20 mg/min.).

The adult, at cryptococcal infections, kandidemiya, the disseminated candidiasis, other invasive candidosis infections in 1 day appoint 400 mg, then - on 200-400 mg of 1 times a day. Duration of treatment depends on clinical and mycologic reaction (at cryptococcal meningitis makes at least 6-8 weeks).

For prevention of cryptococcal meningitis at patients with AIDS therapy in a dose of 200 mg/days it is possible to continue a long time.

At oropharyngeal candidiasis - 50-100 mg of 1 times a day within 7-10 days, at patients with an immunosuppression are 14 days and more.

For prevention of a recurrence of oropharyngeal candidiasis at patients with AIDS after end of a full course of primary therapy - on 150 mg once a week.
At the atrophic peroral candidiasis connected with carrying dentures - 50 mg of 1 times a day within 14 days in combination with local antiseptic HP for processing of a prosthesis.

At other candidiases of mucous membranes (except for genital candidiasis) - 50-100 mg/days, treatment duration - 14-30 days.

At vaginal candidiasis - 150 mg once, inside. For decrease in frequency of a recurrence use on 150 mg within 4-12 months once a month, more frequent use can sometimes be required.

At the balanitis caused by Candida - 150 mg/days once.

For prevention of candidiasis the recommended dose - 50-400 mg/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 - 400 mg/days Flukonazol are appointed some days before the expected emergence of a neutropenia; after increase in number of neutrophils more than 1 thousand / мкл treatment is continued during 7 days.

At damages of skin, including mycoses of feet, skin of inguinal area, and candidiases - 150 mg once a week or 50 mg of 1 times a day, treatment duration - 2-4 weeks (to 6 weeks at mycoses of feet).

At a chromophytosis - 300 mg once a week during 2 weeks, some patients need the third dose of 300 mg a week while regarding cases the single dose of 300-400 mg is accorded sufficient; the alternative scheme of treatment is use on 50 mg during 2-4 weeks once a day.

At an onychomycosis - 150 mg once a week; treatment continues before change of the infected nail. Repeated growth of nails on fingers of hands and feet normal requires 3-6 months and 6-12 months according to.

At deep local mycoses - 200-400 mg/days during up to 2 years. 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 1 time a day (use special dosage forms for children).

To children at candidiasis of a gullet appoint 3 mg/kg/days once during not less than 3 weeks and during 2 weeks after regression of symptoms; at candidiasis of mucous membranes - 3 mg/kg/days once during not less than 3 weeks; at treatment of generalized candidiasis and cryptococcal infection (including meningitis) - 6-12 mg/kg/days during 10-12 weeks (before laboratory confirmation of lack of activators in liquor).

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 - 3-12 mg/kg/days depending on expressiveness and duration of preservation of the induced neutropenia.

For newborn children an interval between administrations of drug - 72 h, to children at the age of 2-4 weeks enter the same dose with an interval of 48 h.

At children with renal failures 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. Patients with a renal failure (KK less than 50 ml/min.) should correct the mode of dosing, as shown below.

At HPN the "shock" dose of 50-400 mg is originally entered; at KK more than 50 ml/min. appoint a usual daily dose, at KK of 11-50 ml/min. - 50% of the recommended dose or a usual dose of 1 times in 2 days; the patient who is on a hemodialysis - 1 dose after each dialysis.

Features of use:

Treatment needs to be continued before emergence of kliniko-hematologic remission. The premature termination of treatment leads to a recurrence.

Treatment can be begun in the absence of results of crops or other laboratory analyses, but at their existence the corresponding correction of fungicidal therapy is recommended.

During treatment it is necessary to control blood indicators, function of kidneys and a liver. At emergence of renal failures and a liver it is necessary to stop administration of drug.

The hepatotoxic action of a flukonazol is usually reversible, symptoms disappear after the therapy termination.

Against the background of administration of drug at patients exceptional cases of development of exfoliative skin reactions, such as Stephens-Johnson's syndrome and a toxic epidermal necrolysis were celebrated. Patients with AIDS and malignant new growths are more inclined to development of heavy skin reactions at use of many drugs. At emergence in the patient during treatment of a superficial fungal infection of rash which can be connected using a flukonazol drug should be cancelled. At emergence of rash in patients with their invasive/system fungal infections it is necessary to observe and cancel carefully флуконазол at emergence of violent defeats or a mnogoformny erythema.

Control of a prothrombin ratio at simultaneous use with anticoagulants of a coumarinic row is necessary.

It is recommended to exercise control of concentration of cyclosporine in blood at the patients receiving флуконазол since at patients with the replaced kidney reception of a flukonazol in a dose of 200 mg/days leads to slow increase in concentration of cyclosporine in plasma

At pregnancy use of this cure opradano only for heavy and generalized potentially dangerous fungal infections life-threatening. During a lactation the termination of breastfeeding in usage time of a flukomabol is recommended.

Side effects:

From the alimentary system: nausea, diarrhea, a meteorism, an abdominal pain, taste change, vomiting, it is rare - an abnormal liver function (jaundice, a hyperbilirubinemia, increase in activity of ALT, nuclear heating plant and ShchF, hepatitis, a hepatocellular necrosis), including with a lethal outcome.

From a nervous system: a headache, dizziness, it is rare - spasms.
From bodies of a hemopoiesis: seldom - a leukopenia, thrombocytopenia, a neutropenia, an agranulocytosis.

Allergic reactions: skin rash, it is rare - a multiformny exudative erythema (including Stephens-Johnson's syndrome), a toxic epidermal necrolysis (Lyell's disease), anaphylactoid reactions (including a Quincke's disease, a face edema, a small tortoiseshell, a skin itch).

From CCC: increase in duration of an interval of Q-T, blinking/trembling of ventricles.

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

Interaction with other medicines:

Increases efficiency of coumarinic anticoagulants (increase in a prothrombin time; warfarin - on average for 12%), concentration of a zidovudine (increase in side effects of a zidovudine), cyclosporine (at use of a flukonazol in a dose of 200 mg/days), a rifabutina (at simultaneous use uveitis cases are described) and Phenytoinum in clinically significant degree (at the combined use control of concentration of Phenytoinum in plasma is necessary).

Extends T1/2 of theophylline and increases risk of development of intoxication (correction of its dose is necessary).

Increases concentration of midazolam - increase in risk of psychomotor effects (it is more expressed at use of a flukonazol inside, than in/in); a takrolimusa - risk of nephrotoxicity.

At a concomitant use with sulphonylurea derivatives (Chlorproramidum, Glibenclamidum, глипизид and Tolbutamidum) it is necessary to control periodically concentration of glucose in blood and if it is necessary, to make dose adjustment of hypoglycemic HP (since флуконазол extends T1/2).

The hydrochlorothiazide increases concentration of a flukonazol in plasma by 40%, rifampicin reduces T1/2 by 20% and AUC - for 25%.

Terfenadin and цизаприд increase risk of developing of arrhythmias, including paroxysms of ventricular tachycardia (torsades de pointes).

Contraindications:

Hypersensitivity (including to other azolny antifungal HP in the anamnesis), a concomitant use of a terfenadin (against the background of constant reception of a flukonazol in a dose of 400 mg/days and more) and an astemizola, the lactation period.

With care. A liver failure, emergence of rash against the background of use of a flukonazol for patients with a superficial fungal infection and invasive/system fungal infections, a concomitant use of a terfenadin and a flukonazol in a dose less than 400 mg/days, potentially proaritmogenny states at patients with multiple factors of risk (organic heart diseases, disturbances of electrolytic balance, a concomitant use of the HP causing arrhythmias), pregnancy.

Overdose:

Symptoms: hallucinations, paranoid behavior.

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

Storage conditions:

To store in the dry, protected from light and children place at a temperature not above 25 degrees Celsius. Not to freeze!

Issue conditions:

According to the recipe

Packaging:

On 100 ml of solution in bottles or bottles from glass. On 1 bottle or a bottle in cardboard packaging together with the instruction.