Funzol

General characteristics. Structure:

Active ingredient: флуконазол 100 mg.

Excipients: starch sodium glycollate, silicon dioxide anhydrous, DS lactose, magnesium stearate, sodium lauryl sulfate.

Structure of a cover of the capsule: the case - titanium dioxide, dye blue; a capsule lid - dye red, dye blue, titanium dioxide.

Pharmacological properties:

Antifungal means derivative of triazole. Is the selection inhibitor of synthesis of sterol in a cell of mushrooms. Flukonazol has high specificity concerning the fungal enzymes dependent on P450 cytochrome.

At intake and at in introduction флуконазол showed activity on various models of fungal infections at animals.

Flukonazol is active at opportunistic mycoses, including the caused Candida spp., including generalized candidiasis at animals with reduced immunity; Cryptococcus neoformans, including intracranial infections; Microsporum spp. and Trychoptyton spp. It is active on models of local mycoses at animals, including the infections caused by Blastomyces dermatitidis, Coccidioides immitis including intracranial infections, and Histoplasma capsulatum at animals with normal and with reduced immunity.

Pharmacokinetics. The pharmacokinetics of a flukonazol is similar at in introduction and at intake.

After intake флуконазол it is well absorbed, its levels in a blood plasma (and the general bioavailability) exceed 90% of levels of a flukonazol in a blood plasma at in introduction. The concomitant use of food does not influence absorption at intake. Cmax is reached in 0.5-1.5 h after reception of a flukonazol on an empty stomach. Concentration in a blood plasma is proportional to a dose.

90% of Css are reached by 4-5th day after the beginning of therapy (at multiple dose of 1 times/).

Introduction of the shock dose (in the 1st day) twice exceeding an average daily dose allows to reach Css of 90% by 2nd day. The seeming Vd approaches the general content of water in an organism. Linkng with proteins of a blood plasma low (11-12%).

Flukonazol well gets into all liquids of an organism. Levels of a flukonazol in saliva and a phlegm are similar to its concentration in a blood plasma. At patients with fungal meningitis levels of a flukonazol in cerebrospinal fluid make about 80% of its levels in a blood plasma.

In a corneous layer, epidermis derma and stalemate liquid high concentration which exceed serumal are reached. Flukonazol collects in a corneous layer. At reception in a dose of 50 mg 1 time / concentration of a flukonazol in 12 days made 73 mkg/g, and in 7 days after the treatment termination - only 5.8 mkg/g. At use in a dose of 150 mg of 1 time/week concentration of a flukonazol in a corneous layer for the 7th day made 23.4 mkg/g, and in 7 days after reception of the second dose – 7.1 mkg/g.

Concentration of a flukonazol in nails after 4-month use in a dose of 150 mg of 1 time/week made 4.05 mkg/g in healthy and 1.8 mkg/g in the affected nails; in 6 months after completion of therapy флуконазол was still defined in nails.

Flukonazol is brought, generally by kidneys; about 80% of the entered dose find in urine in not changed look. The clearance of a flukonazol is proportional to KK. The circulating metabolites are not found.

Long T1/2 from a blood plasma allows to accept флуконазол once at vaginal candidiasis and 1 time / or 1 time/week at other indications.

Indications to use:

The cryptococcosis, including cryptococcal meningitis and infections of other localization (for example, lungs, skin), including at patients with a normal immune response and at patients is AIDS, recipients of transplanted organs and patients with other forms of an immunodeficiency; a maintenance therapy for the purpose of prevention of a recurrence of a cryptococcosis at patients AIDS;

Generalized candidiasis, including a kandidemiya, the disseminated candidiasis and other forms of an invasive candidosis infection, such as infections of a peritoneum, endocardium, eyes, respiratory and uric ways, including at the patients with malignant tumors who are in OIT and receiving cytotoxic or immunosuppressive means and also at patients with other factors contributing to development of candidiasis.

Candidiasis of mucous membranes, including mucous membranes of an oral cavity and a throat, a gullet, noninvasive bronchopulmonary infections, a kandiduriya, the skin and mucous and chronic atrophic candidiasis of an oral cavity (connected with carrying dentures), including at patients with the normal and suppressed immune function; prevention of a recurrence of oropharyngeal candidiasis at patients AIDS.

Genital candidiasis; acute or recurrent vaginal candidiasis; prevention for the purpose of reduction of frequency of a recurrence of vaginal candidiasis (3 and more episodes a year); candidosis balanitis.

Skin mycoses, including mycoses of feet, bodies, inguinal area, a chromophytosis, onychomycoses and skin candidosis infections.

Deep local mycoses at patients with normal immunity, a coccidioidomycosis, a paracoccidioidomycosis, a sporotrichosis and histoplasmosis.

Prevention of fungal infections at the patients with malignant tumors predisposed to development of such infections as a result of cytotoxic chemotherapy or radiation therapy.

Route of administration and doses:

Individual. It is intended for intake and in/in introductions.

For adults, depending on indications, the scheme of treatment and a clinical situation, the daily dose makes 50-400 mg, frequency rate of use - 1 time /

For children the dose makes 3-12 mg/kg/, frequency rate of use - 1 time /

At patients with a renal failure the dose of a flukonazol is reduced depending on KK.

Duration of treatment depends on clinical and mycologic effect.

Features of use:

With care apply at disturbances of indicators of function of a liver against the background of use of a flukonazol, at emergence of rash against the background of use of a flukonazol for patients with a superficial fungal infection and invasive/system fungal infections, at simultaneous use of a terfenadin and flukonazol in a dose less than 400 mg/, at potentially pro-arhythmic states at patients with multiple factors of risk (organic heart diseases, disturbances of electrolytic balance and the accompanying therapy promoting development of similar disturbances).

The hepatotoxic action of a flukonazol usually was reversible; its signs disappeared after the therapy termination. It is necessary to control a condition of patients at whom during treatment flukonazoly indicators of function of a liver, for the purpose of identification of signs of more serious damage of a liver are broken. At emergence of clinical signs or symptoms of damage of a liver which can be connected with flukonazoly it should be cancelled.

Patients AIDS are more inclined to development of heavy skin reactions at use of many drugs. At emergence in the patient receiving treatment concerning a superficial fungal infection, rash which can be connected using a flukonazol it it is necessary to cancel. 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.

Simultaneous use of a flukonazol in doses less than 400 mg of a terfenadin should be carried out under careful control.

At use of a flukonazol increase in an interval of QT and blinking/trembling of ventricles noted very seldom at patients with multiple factors of risk, such as organic heart diseases, disturbances of electrolytic balance and the accompanying therapy promoting development of similar disturbances.

Therapy can be begun before obtaining results of crops and other laboratory researches. However anti-infectious therapy needs to be skorrigirovat as appropriate when results of these researches become known.

There were messages on cases of the superinfection caused by others, than Candida albicans, strains of Candida which often do not show sensitivity to a flukonazol (for example, Candida krusei). In similar cases alternative antifungal therapy can be required.

Side effects:

From a nervous system: headache, dizziness, spasms, taste change.

From the alimentary system: an abdominal pain, diarrhea, a meteorism, nausea, dyspepsia, vomiting, a hepatotoxic (including exceptional cases with a lethal outcome), increase in the ShchF level, bilirubin, serumal level of aminotransferases (ALT and nuclear heating plant), an abnormal liver function, hepatitis, a hepatocellular necrosis, jaundice.

From cardiovascular system: increase in an interval of QT at an ECG, blinking/trembling of ventricles.

Dermatological reactions: rash, an alopecia, exfoliative skin diseases, including Stephens-Johnson's syndrome and a toxic epidermal necrolysis.

From system of a hemopoiesis: a leukopenia, including a neutropenia and an agranulocytosis, thrombocytopenia.

From a metabolism: increase in level of cholesterol and triglycerides in plasma, a hypopotassemia.

Allergic reactions: anaphylactic reactions (including a Quincke's disease, a face edema, urticaria, an itch).

Interaction with other medicines:

At simultaneous use with warfarin флуконазол raises a prothrombin time (for 12%) in this connection development of bleedings is possible (hematomas, bleedings from a nose and a GIT, a hamaturia, a melena). At the patients receiving coumarinic anticoagulants it is necessary to control a prothrombin time constantly.

After midazolam intake флуконазол significantly increases concentration of midazolam and psychomotor effects, and this influence is more expressed after reception of a flukonazol inside, than at its use in / century. In need of the accompanying therapy by benzodiazepines of the patients accepting флуконазол it is necessary to observe for the purpose of the corresponding dose decline of benzodiazepine.

At simultaneous use of a flukonazol and tsizaprid undesirable reactions from heart are possible, including blinking/trembling of ventricles (arrhythmia like "pirouette"). Use of a flukonazol in a dose of 200 mg of 1 time(s) of a tsizaprid in a dose of 20 mg 4 leads to the expressed increase in plasma concentration of a tsizaprid and increase in an interval of QT at an ECG. The concomitant use of a tsizaprid and a flukonazol is contraindicated.

Patients have after transplantation of a kidney a use of a flukonazol in a dose of 200 mg / leads to slow increase in concentration of cyclosporine. However at multiple dose of a flukonazol in a dose of 100 mg / change of concentration of cyclosporine at recipients of marrow was not observed. At simultaneous use of a flukonazol and cyclosporine it is recommended to monitorirovat concentration of cyclosporine in blood.

Repeated use of a hydrochlorothiazide along with flukonazoly leads to increase in concentration of a flukonazol in plasma for 40%. The effect of such degree of manifestation does not demand change of the mode of dosing of a flukonazol from the patients receiving at the same time diuretics, however it is necessary to consider it.

At simultaneous use of the combined oral contraceptive with flukonazoly in a dose of 50 mg of significant effect on the level of hormones it is not established whereas at daily reception of 200 mg of a flukonazol of AUC ethinylestradiol and levonorgestrel increase by 40% and 24% respectively, and at priyeme300 mg of a flukonazol - AUC ethinylestradiol and norethindrone increase once a week for 24% and 13% respectively. Thus, repeated use of a flukonazol in the specified doses can hardly exert impact on efficiency of the combined oral contraceptive.

Simultaneous use of a flukonazol and Phenytoinum can be followed by clinically significant increase in concentration of Phenytoinum. At this combination it is necessary to control concentration of Phenytoinum and as appropriate to correct its dose for the purpose of ensuring therapeutic concentration in blood serum.

Simultaneous use of a flukonazol and rifabutin can lead to increase in serumal concentration of the last. At simultaneous use of a flukonazol and rifabutin uveitis cases are described. The patients who are at the same time receiving рифабутин and флуконазол need to be observed carefully.

Simultaneous use of a flukonazol and rifampicin leads to decrease in AUC by 25% and duration of T1/2 of a flukonazol for 20%. At the patients who are at the same time accepting rifampicin it is necessary to consider expediency of increase in a dose of a flukonazol.

Flukonazol at a concomitant use leads to increase in T1/2 of peroral drugs of sulphonylurea (Chlorproramidum, Glibenclamidum, a glipizid and Tolbutamidum). A sick diabetes mellitus it is possible to appoint jointly флуконазол and peroral drugs of sulphonylurea, but at the same time it is necessary to consider a possibility of development of a hypoglycemia.

Simultaneous use of a flukonazol and takrolimus leads to increase in plasma concentration of the last. Nephrotoxicity cases are described. At this combination it is necessary to control a condition of patients carefully.

At simultaneous use of azolny antifungal means and a terfenadina developing of serious arrhythmias as a result of increase in an interval of QT is possible. At reception of a flukonazol in a dose of 200 mg / increases in an interval of QT it is not established, however use of a flukonazol in doses of 400 mg causes significant increase in concentration of a terfenadin in plasma above. The concomitant use of a flukonazol in doses of 400 mg more with terfenadiny is contraindicated. Treatment flukonazoly in doses less than 400 mg / in combination with terfenadiny should be carried out under careful control.

At simultaneous use with flukonazoly in a dose of 200 mg within 14 days the average speed of plasma clearance of theophylline decreases by 18%. At purpose of a flukonazol the patients accepting theophylline in high doses or the patient with the increased risk of development of toxic effect of theophylline should watch emergence of symptoms of overdose of theophylline and, if necessary, to correct therapy as appropriate.

At simultaneous use with flukonazoly increase in concentration of a zidovudine which is probably caused by decrease in metabolism of the last to its main metabolite is noted. Before therapy using a flukonazol in a dose of 200 mg / within 15 days AIDS and ARC (the complex connected about AIDS) significant increase in AUC of a zidovudine (20%) is established to patients.

At use for HIV-positive patients of a zidovudine in a dose of 200 mg each 8 h within 7 days in combination with flukonazoly in a dose of 400 mg / or without it at an interval of 21 days between two schemes, significant increase in AUC of a zidovudine (74%) at simultaneous use with flukonazoly is established. The patients receiving such combination should be observed for the purpose of identification of side effects of a zidovudine.

Simultaneous use of a flukonazol with astemizoly or other drugs which metabolism is carried out by isoenzymes of system of P450 cytochrome can be followed by increase in serumal concentration of these means. At such combinations it is necessary to control a condition of patients carefully.

Contraindications:

Simultaneous use of a terfenadin during repeated use of a flukonazol in a dose of 400 mg more; simultaneous use of a tsizaprid; hypersensitivity to a flukonazol; hypersensitivity to derivatives of an azol with similar with flukonazoly structure.

Use at pregnancy and feeding by a breast
Adequate and controlled researches of safety of use of a flukonazol for pregnant women were not conducted. It is necessary to avoid use of a flukonazol at pregnancy, except for hard cases and potentially life-threatening fungal infections when the expected advantage of treatment exceeds possible risk for a fruit.

Women of childbearing age during treatment should use well-tried remedies of contraception.

Flukonazol is defined in breast milk in the concentration close to plasma therefore use in the period of a lactation (breastfeeding) is not recommended.

Use at abnormal liver functions
Flukonazol it is necessary to apply with care at patients with the expressed abnormal liver functions.

Use at renal failures
Flukonazol it is necessary to apply with care at patients with the expressed renal failures. At a renal failure the dose of a flukonazol should be reduced.

Use for children
It is contraindicated at children's age till 1 year.

Issue conditions:

According to the recipe

Packaging:

Capsules on 100 mg, 150 mg, 50 mg 7 - blisters (1) - packs cardboard.