Mikoflyukan

Mikoflyukan – anti-mycotic medicine.

Form of release and structure

Dosage forms of Mikoflyukan:

• Tablets: flat, round, with a facet, almost white or white color; on 50 mg (on one of the parties the letter "F" is squeezed out, on other party – figure "50") and on 150 mg (on one of the parties dividing risk, on other party the text of "F150") (on 1, 4 or 7 pieces in the blister, 1 blister in a cardboard pack is squeezed out);
• Solution for infusions: transparent colourless liquid (on 100 ml in bottles from polyethylene of low density, 1 bottle in a cardboard pack).

Structure of 1 tablet:

• Active ingredient: флуконазол – 50 or 150 mg;
• Auxiliary components: lactose, cellulose microcrystallic, croscarmellose sodium, silicon dioxide colloid, K30 povidone, magnesium the stearate, talc purified.

Structure of 1 ml of solution:

• Active ingredient: флуконазол – 2 mg;
• Auxiliary components: dinatrium эдетат, sodium chloride, water for injections.

Indications to use

• The general diseases caused by cryptococci: sepsis, meningitis, infections of skin and lungs, as at patients with a normal immune response, and at various forms of an immunosuppression (including patients with AIDS, recipients of transplanted organs); as a part of the supporting treatment for prevention of a cryptococcal infection at patients with AIDS;
• Generalized candidiasis: the disseminated candidiasis (with infection of eyes, an endocardium, respiratory organs, abdominal organs, urinogenital system), a kandidemiya; carrying out a course of therapy to patients with malignant new growths during immunodepressive or cytostatic therapy, and also in case of existence of other factors contributing to development of these states – for treatment and prevention is allowed;
• Candidiasis of mucous membranes (a throat, a gullet, an oral cavity), a kandiduriya, noninvasive bronchopulmonary candidiases, the skin and mucous and chronic oral atrophic candidiasis (caused by carrying dentures); orofaringealny candidiasis at patients with AIDS – for prevention of a recurrence;
• Genital candidiasis: vaginal (recurrent and acute) – for treatment and prevention of frequency of a recurrence (within a year existence of three and more episodes); a candidosis balanitis (for drug in the form of tablets);
• Fungal infections at malignant tumors against the background of beam or chemotherapy – for prevention;
• Orofaringealny candidiasis at patients with AIDS – for prevention of a recurrence;
• Expressed or it is long the remaining neutropenia, other conditions of high risk of a generalized infection – for prevention of candidiasis;
• Skin mycoses: bodies, stop, inguinal area, chromophytosis, onychomycosis, skin candidosis infections (tablets);
• Deep local mycoses at normal immunity: паракокцидиомикоз, кокцидиомикоз, histoplasmosis, sporotrichosis.

Contraindications

Absolute:

• Period of breastfeeding (lactation);
• Concomitant use with terfenadiny (against the background of regular reception of a flukonazol in a dose of 400 mg/days and more) or astemizoly;
• Hypersensitivity to drug components, a flukonazol, and also azolny antifungal substances / means.

Relative (drug is used with care):

• Liver failure;
• Emergence of rash in patients with superficial and invasive/system fungal infections against the background of therapy flukonazoly;
• Concomitant use of a flukonazol (to 400 mg/days) with terfenadiny;
• Potentially proaritmogenny states at patients with multiple factors of risk, such as disturbances of electrolytic balance, organic heart diseases, a concomitant use with the medicines causing arrhythmias;
• Pregnancy: флуконазол apply in case of heavy and potentially life-threatening fungal infections of the woman if the expected advantage for mother is much higher than possible risk for a fruit.

Route of administration and dosage

Tablets
Pill is taken inside, in the daily dose depending on character and weight of a fungal infection. Duration of therapy is caused by the clinical performance of a flukonazol confirmed with results of mycologic researches.

The recommended doses for adult patients and children are more senior than 15 years, with body weight it is more than 50 kg:

• Cryptococcal meningitis and cryptococcal infections of other localizations: the first days – 400 mg, further 200-400 mg of 1 times/days, course duration – at least 6-8 weeks;
• Prevention of a recurrence of cryptococcal meningitis at patients with AIDS (upon completion of a full course of primary therapy): 200 mg/days, long time;
• Kandidemiya, the disseminated candidiasis, other invasive candidosis infections: the first days – 400 mg, further on 200 mg/days (in case of insufficient clinical action it is possible to increase a dose to 400 mg/days), duration of a course depends on a therapeutic effectiveness of drug;
• Orofaringealny candidiasis: 150 mg of 1 times/days, course duration – 7-14 days; if it is necessary, to patients with the expressed decrease in immunity therapy is allowed to be prolonged;
• Prevention of a recurrence of oropharyngeal candidiasis at patients with AIDS (upon completion of a full course of primary therapy): 150 mg once a week, long time;
• The atrophic candidiasis of an oral cavity connected with use of dentures: 50 mg of 1 times/days, course duration – 14 days; at the same time local antiseptic drugs process a prosthesis;
• Other types of candidiasis (except for genital) – an esophagitis, noninvasive bronchopulmonary defeats, a kandiduriya, candidiasis of skin and mucous membranes: 150 mg/days, course duration – 14-30 days;
• Vaginal candidiasis: once 150 mg; for the purpose of decrease in frequency of a recurrence it is possible to use Mikoflyukan in a dose 150 mg once a month, duration of a course is defined individually and can make from 4 to 12 months, in certain cases, perhaps, more frequent use of drug will be necessary;
• The balanitis caused by Candida: once 150 mg;
• Prevention of candidiasis: from 50 to 400 mg (depending on risk level of development of an infection) 1 times/days. In case of high probability of a generalized infection, for example, the patient with it is long the remaining or expected expressed neutropenia, the dose of 400 mg of 1 times/days is recommended; appoint флуконазол some days before probable emergence of a neutropenia, and after increase in number of neutrophils ^1000/mm3 therapy is continued by 7 more days;
• Skin mycoses, including mycoses of smooth skin, inguinal area and skin of feet: 50 mg of 1 times/days or 150 mg 1 time/week; the standard duration of a course of therapy – 2-4 weeks, but at mycosis of feet can be necessary more prolonged treatment – up to 6 weeks;
• Chromophytosis: 300 mg once a week within 2 weeks; regarding cases of rather single dose of 300-400 mg, in some other episodes the third reception of 300 mg a week is required; alternative option: 50 mg of 1 times/days for 2-4 weeks;
• Onychomycosis: 150 mg once a week; the course of therapy proceeds before substitution of the infected nail grown not infected (full growth of nails on fingers of hands requires from 3 to 6 months, on toes – from 6 to 12 months);
• Deep local mycoses: 200-400 mg/days, course duration – up to 2 years; therapy duration individually is defined and can make for a koktsidiomikoz – 11-24 month, a parakoktsidiomikoza – 2-17 months, a sporotrichosis – 1-16 months, histoplasmosis – 3-17 months.

Children have therapy duration, as well as at adult patients, depends on a clinical picture and mycologic effect of drug. The maximum daily dose at children's age – no more than 400 mg, frequency rate of use – 1 times/days.

Gullet candidiasis – in a daily dose of 3 mg/kg, depending on age (body weight):

• 3-6 years (15-20 kg) – 50 mg;
• 7-9 years (21-29 kg) – 50-100 mg;
• 10-15 years (30-50 kg) – 100-150 mg.

Therapy course duration – is not less than 3 weeks, after regression of symptoms it is necessary to continue Mikoflyukan's reception 2 more weeks.

Candidiasis of mucous membranes – a daily dose of 3 mg/kg, depending on age (body weight):

• 3-6 years (15-20 kg): the first day of-100-150 mg, further – on 50 mg;
• 7-9 years (21-29 kg): the first day – 100-200 mg, further – on 100 mg;
• 10-12 years (30-40 kg): the first day – 100-150 mg, further – on 50-100 mg;
• 13-15 years (41-50 kg): the first day – 250-300 mg, further – on 100-150 mg.

Therapy course duration – is not less than 3 weeks.

Generalized candidiasis and cryptococcal infection (including meningitis) – a daily dose of 6-12 mg/kg, depending on age (body weight):

• 3-6 years (15-20 kg) – 100-250 mg;
• 7-9 years (21-29 kg) – 100-300 mg;
• 10-12 years (30-40 kg) – 200-350 mg;
• 13-15 years (41-50 kg) – 250-400 mg.

Therapy course duration – 10-12 weeks, to the absence confirmed with results of laboratory researches in liquor of activators.

Prevention of fungal infections at children with the lowered immunity at which the risk of development of an infection is connected with the neutropenia which appeared owing to himio-or radiation therapy, a daily dose of 3-12 mg/kg depending on age (body weight):

• 3-6 years (15-20 kg) – 50-250 mg;
• 7-9 years (21-29 kg) – 50-300 mg;
• 10-12 years (30-40 kg) – 100-350 mg;
• 13-15 years (41-50 kg) – 100-400 mg.

Therapy course duration – before the confirmed elimination of the induced neutropenia.

Children with renal failures should reduce a daily dose of drug according to degree of manifestation of a renal failure (similar to the scheme for adults).

To patients with a renal failure at the clearance of creatinine (CC) less than 50 ml/min., in case of a single dose of Mikoflyukan change of a dose it is not required.

The mode of dosing is required to be corrected depending on KK at repeated use of a flukonazol as follows – the shock dose from 50 mg to 400 mg, further – a daily dose is originally entered (depending on indications):

• KK> 40 ml/min.: usual dose of 1 times/days;
• KK of 21-40 ml/min.: usual dose of 1 times at 48 o'clock (2 days) or half of a daily dose of 1 times/days;
• KK of 10-20 ml/min.: usual dose of 1 times at 72 o'clock (3 days) or third part of a daily dose of 1 times/days.

The patients who are regularly on dialysis after each session of a hemodialysis have to receive one dose of drug.

In case of lack of renal failures, dose adjustment of a flukonazol is not required from elderly patients.

Solution for infusions
Solution is entered intravenously (in/in) kapelno with a speed up to 200 mg/h. The daily dose of drug depends on character and weight of a fungal infection.

There is no need to change a daily dose in case of transition with in/in introductions to tablets and vice versa. In this regard at infusional therapy flukonazoly for adult patients and children the schemes of a drug dosing provided for tablets Mikoflyukan are used.

Infusions are carried out by means of ordinary sets for a transfusion, as solvent one of the listed solutions is used: 20% of glucose, Ringer, Hartman, chloride potassium in glucose, 4,2% of Natrii hydrocarbonas, 0,9% of sodium of chloride.

Use of drug for newborns (taking into account the slowed-down removal of a flukonazol): the first 2 weeks of life – 1 dose (in mg/kg), same, as well as for children of more advanced age, but with an interval of 3 days (72 hours); from 2 to 4 weeks of life – the same dose, but with an interval of 2 days (48 hours).

Adult patients and children at KK do not need ≤50 ml/min. in case of a single dose of Mikoflyukan of change of a dose. The mode of dosing is required to be corrected depending on KK at repeated use of a flukonazol as follows: the shock dose from 50 mg to 400 mg, further – a daily dose is originally entered (depending on indications into % of recommended):

• MM> 50 – 100%;
• KK <50 (without dialysis) – 50%;
• Constant hemodialysis – 100% after each session.

Content in solution of 0,9% of sodium of chloride provides 15 mmol of ions of sodium and chlorine in 100 ml, patients with need of limited consumption of sodium or liquid need to consider liquid rate of administering.

Side effects

• Allergic reactions: infrequently – an enanthesis; seldom – a Lyell's disease (a toxic epidermal necrolysis), anaphylactoid reactions (including a face edema, a Quincke's disease, a small tortoiseshell, a skin itch), a mnogoformny exudative erythema (including Stephens-Johnson's syndrome);
• Central nervous system: infrequently – dizziness, a headache; seldom – spasms;
• Alimentary system: infrequently – nausea, vomiting, diarrhea, an abdominal pain, a meteorism, taste change; seldom – abnormal liver functions (a hyperbilirubinemia, increase in activity of ACT, ALT and ShchF, jaundice, hepatitis and a hepatocellular necrosis) up to a lethal outcome;
• Hemopoietic bodies: seldom – thrombocytopenia, a neutropenia, a leukopenia, an agranulocytosis;
• Cardiovascular system: seldom – blinking/trembling of ventricles, lengthening of duration of an interval of QT;
• Another: seldom – an alopecia, a renal failure, a hypercholesterolemia, a hypopotassemia, a gipertriglitseridemiya.

Symptoms of overdose are hallucinations and paranoid behavior. Symptomatic therapy, an artificial diuresis, a gastric lavage is recommended. Carrying out a hemodialysis for 3 hours approximately reduces concentration of a flukonazol in a blood plasma by 50%.

Special instructions

Therapy should be continued to an absolute recovery (kliniko-hematologic remission) as premature interruption of treatment leads to resuming of a disease.

It is admissible to begin treatment in the absence of results of laboratory analyses, including crops, but after their receiving it is necessary to carry out the corresponding correction of antifungal therapy.

In the course of treatment control of indicators of blood, function of a liver and kidneys is necessary; at simultaneous use of anticoagulants of a coumarinic row it is necessary to control a prothrombin ratio (in case of abnormal liver functions and kidneys administration of drug is required to be stopped).

Exceptional cases of maintenance of reception of a flukonazol are celebrated by toxic changes of function of a liver. At the hepatotoxic effects connected with flukonazoly explicit dependence on the accepted daily dose, duration of a course of treatment, age and a sex of the patient is noted. The hepatotoxic action of drug is usually reversible, upon completion of therapy its signs pass. In case of clinical symptoms of damage of a liver which can be connected with use of a flukonazol drug is required to be cancelled.

At patients with AIDS tendency to development of heavy skin answers at use of many medicines is increased, including Mikoflyukan.

When at a superficial fungal infection rash develops, and its education can be connected using a flukonazol, drug needs to be cancelled. In case of rash at their invasive/system fungal infections it is required to control carefully, and at emergence of a mnogoformny erythema or violent changes – to cancel reception of a flukonazol.

Medicinal interaction

• Coumarinic anticoagulants (warfarin): флуконазол increases their prothrombin time by 12% (on average) therefore careful control of this indicator is required;
• Hydrochlorothiazide: promotes increase in concentration in plasma of a flukonazol for 40% (change of the mode of dosing of Mikoflyukan it is not required if patients at the same time receive diuretics);
• Zidovudine: its concentration increases that is caused by decrease in transformation of a zidovudine in its main metabolite thereof growth of its side effects is possible;
• The combined contraceptives: repeated use of a flukonazol in doses from 50 to 200 mg does not exert impact on their efficiency;
• Midazolam: its concentration and risk of development of psychomotor reactions increases (it is more expressed at reception of a flukonazol inside, than at infusional introduction);
• Sulphonylurea drugs (Glibenclamidum, глипизид, Chlorproramidum and Tolbutamidum): their _T1/2 is extended owing to what the hypoglycemia can develop (periodic control of concentration of glucose in blood is required, dose adjustment of antidiabetic medicines is in case of need made);
• Rifabutin: increase in its serumal concentration is possible, uveitis cases owing to the combined use of a rifabutin and a flukonazol therefore at use careful monitoring is required are described;
• Rifampicin: lowers AUC (by 25%) and duration _{of T1/2} of a flukonazol (for 20%) in this connection increase in its dose is required;
• Takrolimus: its concentration increases owing to what the risk of nephrotoxic influence increases;
• Theophylline: duration of its _T1/2 is extended and the risk of development of intoxication increases (it is required to adjust doses);
• Terfenadin: the concomitant use with flukonazoly in doses of 400 mg a day and more is contraindicated; in doses to 400 mg of a flukonazol a day терфенадин it is necessary to accept under careful observation of the doctor;
• Phenytoinum: its concentration to clinically significant level increases (control of level and selection of a dose for the purpose of providing in serum of therapeutic concentration of Phenytoinum is required);
• Tsizaprid: undesirable effects from cardiovascular system are possible, including Bouveret's ventricular disease (arrhythmia like "pirouette");
• Cyclosporine: it is necessary to trace the size of its concentration in blood.

Terms and storage conditions

To store in the place, unavailable to children, dry and protected from light, at a temperature up to 25 °C.

Period of validity:

• Solution for infusions – 2 years;
• Tablets – 3 years.