Solution for infusions: transparent, colourless or slightly painted (on 100 ml in bottles, on 1 bottle in a cardboard pack);
Capsules: firm, gelatinous, with the opaque white case (L500), filled inside with powder of almost white or white color or powdery dense weight; on 50 mg – the size No. 4, with a light blue opaque lid (L910) (on 7 pieces in blisters, on 1 blister in a cardboard pack); on 100 mg – the size No. 2, with a turquoise opaque lid (L890) (on 7 pieces in blisters, on 1 or 4 blisters in a cardboard pack); on 150 mg – the size No. 1, with a blue opaque lid (L860) (on 1 piece in blisters, on 1, 2 or 4 blisters in a cardboard pack).

Is a part of 1 capsule:

Active agent: флуконазол – 50/100/150 mg;
Auxiliary components (capsules on 50/100/150 mg respectively): magnesium stearate – 1,2/2,4/3,6 mg, povidone – 3,6/7,2/10,8 mg, anhydrous lactose – 49,5/99/148,5 mg, corn starch – 12,1/24,2/36,3 mg, talc – 3,3/6,6/9,9 mg, colloid silicon dioxide – 0,3/0,6/0,9 mg;
Lid (capsules on 50/100/150 mg respectively): titanium dioxide (E171, C.I.77891) – 4/4/1,5%, indigo carmine (E132, C.I.73015) – 0,0086/0,0471/0,2513%, gelatin – to 100% (for all types of capsules);
The case (capsules on 50/100/150 mg respectively): titanium dioxide (E171, C.I.77891) – 2/2/2%, gelatin – to 100% (for all types of capsules).

For infusions is a part of 10 ml of solution:

Active agent: флуконазол – 20 mg;
Auxiliary components: sodium chloride – 90 mg, water for injections – to 10 ml.

Indications to use

Generalized candidiasis: a kandidemiya, the disseminated candidiasis and other forms of invasive candidosis infections (an infection of eyes, an endocardium, an abdominal cavity, urinary and respiratory tracts), including at the patients receiving a course of cytostatic or immunodepressive therapy and also in the presence of other factors contributing to development of candidiasis (with the medical and preventive purpose);
Cryptococcosis: cryptococcal infections of skin and lungs, cryptococcal sepsis and meningitis, a cryptococcosis at acquired immunodeficiency syndrome (for the purpose of prevention of a recurrence); at organ transplantation or other cases of an immunodeficiency;
Candidiases of mucous membranes, including candidiasis of a gullet, throat, oral cavity (including the atrophic candidiasis connected with carrying dentures), and also a kandiduriya, noninvasive bronchopulmonary infections;
Genital candidiasis: vaginal (chronic recurrent or acute form); candidosis balanitis (capsules);
Fungal infections at the patients with malignant new growths predisposed to development of such infections because of carrying out chemotherapy with cytostatics or radiation therapy; orofaringealny candidiasis at patients with AIDS (for the purpose of prevention);
Skin mycoses, including mycoses of inguinal area and a trunk;
Deep local mycoses, including a coccidioidosis, histoplasmosis and a paracoccidioidosis at patients with normal immunity;
Onychomycosis, mycoses of feet, chromophytosis (capsules).

Contraindications

Absolute:

Lactose intolerance, deficit of lactase, glyukozo-galaktozny malabsorption;
Simultaneous use with terfenadiny (at constant reception of Mikosist in a daily dose from 400 mg), tsizapridy (drugs promote increase in risk of emergence of heavy disturbances of a heart rhythm and lengthening of an interval of QT);
Simultaneous use with astemizoly;
Breastfeeding period;
Hypersensitivity to components of drug or to other relatives on structure to azolny connections.

Relative (Mikosist needs to apply with care at the following diseases / states):

Liver and/or renal failure;
Rash at administration of drug at patients with system and/or invasive fungal infections and superficial fungus diseases;
Potentially proaritmogenny states at patients with multiple factors of risk, including disturbances of electrolytic balance, organic heart troubles, simultaneous use with the drugs causing arrhythmias;
Intolerance of acetylsalicylic acid;
Simultaneous use with terfenadiny (at a daily dose of a flukonazol to 400 mg);
Simultaneous use with rifabutiny or other medicines which are metabolized with the participation of system of P450 cytochrome;
Pregnancy.

Route of administration and dosage

Mikosist in the form of solution for infusions enter intravenously kapelno with a speed no more than 20 mg (10 ml) 1 minute; capsules should be accepted inside.

It is not necessary to adjust daily doses upon transition from one dosage form to another.

Adults are recommended to apply the following mode of dosing:

The disseminated candidiasis, kandidemiya and other invasive infections caused by fungi Candida: in the first day – in a daily dose of 400 mg, further – on 200 mg a day. In case of need the dose is increased twice, at heavy system candidiasis – to 800 mg a day. Duration of a course depends on clinical performance of drug, at the same time Mikosist's use needs to be continued within not less than 14 days after disappearance of symptoms of a disease or at confirmation of a negative hemoculture;
Cryptococcal infections: in the first day – in a daily dose of 400 mg, further - once a day on 200-400 mg. Duration of a course is defined by the clinical performance confirmed with results of mycologic researches. Most often therapy is carried out from 6 weeks to 2 months. At treatment of cryptococcal meningitis more prolonged use of Mikosist – from 10 weeks to 2 months after a negative take of a microbiological research of test of cerebrospinal fluid is shown. Upon termination of a full course of primary therapy for the purpose of prevention of a recurrence of cryptococcal meningitis by the patient with AIDS prolonged use of Mikosist on 200 mg a day is recommended;
The atrophic candidiasis of an oral cavity connected with dentures: 14 days in a daily dose of 50 mg. Therapy should be combined using antiseptic agents for processing of a prosthesis;
Orofaringealny candidiasis, including patients with immunity disturbances: 7-14 days in a daily dose of 50-100 mg. For prevention to patients with AIDS after end of a full course of primary therapy of Mikosist appoint on 150 mg of 1 times in 7 days. If necessary (in particular at heavy disturbances of immunity) duration of treatment is increased;
Other candidosis infections (kandiduriya, esophagitis, noninvasive bronchopulmonary infections, candidiasis of skin and mucous membranes): 14-30 days in a daily dose of 50-100 mg;
Vaginal candidiasis: once 150 mg. To reduce the frequency of a recurrence of Mikosist in the same dose it is necessary to accept for 4-12 months, in some cases perhaps more frequent use once a month;
Heavy candidiasis of mucous membranes: on 100-200 mg a day;
The balanitis caused by Candida spp.: once 150 mg of Mikosist in the form of capsules;
Prevention of candidiasis: the daily dose is defined by a risk degree of development of a fungal infection and can vary ranging from 50 to 400 mg. With high risk of a generalized infection (for example, patients with it is long the remaining or expected expressed neutropenia) Mikosist appoint 400 mg a day. Drug needs to begin to be accepted some days before the expected development of a neutropenia, after increase in quantity of neutrophils more than 1000/mm ³ therapy should be continued within 7 days;
Fungal infections at patients with malignant new growths (prevention): drug in a daily dose of 50 mg needs to be accepted until the patient is in group of the increased risk owing to performing cytostatic or radiation therapy;
Chromophytosis: 2 receptions on 300 mg of Mikosist in the form of capsules with a break of 7 days. In some cases reception of the third dose – 300 mg with observance of the same break can be required, but quite often happens enough and a single dose of 300 mg. As the alternative scheme of treatment daily reception of 50 mg of Mikosist a day on an extent from 2 weeks to 1 month is possible;
Skin mycoses (including candidiases), including mycoses of inguinal area, feet: on 50 mg a day or 1 time in 7 days on 150 mg of drug in the form of capsules. As a rule, duration of therapy varies within 7-14 days, however at treatment of mycoses of feet its increase up to 42 days is possible;
Deep local mycoses: on 200-400 mg a day for 2 years. Duration of a therapeutic course is defined individually: a paracoccidioidosis – 2-17 months, a coccidioidosis – 11-24 months, histoplasmosis – 3-17 months;
Onychomycosis: 150 mg of Mikosist in the form of capsules of 1 times in 7 days. Administration of drug needs to be continued until the healthy nail does not replace infected completely. Most often for the repeated growth of nails on fingers of hands and legs it is required to continue administration of drug within from 3 to 6 and from 6 to 12 months respectively.

At children duration of therapy is defined by clinical and mycologic effect. The daily dose for this age category of patients should not exceed that at adults. The Mikosist it is necessary to apply daily once a day.

Children are recommended to observe the following mode of dosing:

Cryptococcal infection and generalized candidiasis: on 6-12 mg/kg a day (is defined by weight of disease);
Candidiasis of mucous membranes: on 3 mg/kg a day. Appointment of a shock dose of Mikosist (twice more than usual) in the first day of treatment is allowed;
Fungal infections at children with the lowered immunity at which the risk of development of an infection is connected with the neutropenia arising because of carrying out cytotoxic chemotherapy or radiation therapy (prevention): on 3-12 mg/kg a day (depends on duration of preservation and expressiveness of the induced neutropenia).

At newborns флуконазол it is removed more slowly therefore in the first 14 days of life of Mikosist it is necessary to apply in the same dose (in mg on 1 kg of body weight), as at children of more advanced age, having increased at the same time an interval between drug use till 72 o'clock. To children 3-4 weeks of life appoint drug with a break of 48 hours.

Correction of the mode of dosing of Mikosist is not required to patients of advanced age in the absence of functional disturbances of kidneys.

Dose adjustment is not required to patients with a renal failure at single use of drug. At course appointment originally it is necessary to apply a shock dose (from 50 to 400 mg), further the daily dose is adjusted as follows (frequency rate of use – once a day):

The clearance of creatinine is more than 50 ml in a minute: 100% recommended (according to indications) doses;
The clearance of creatinine is less than 50 ml in a minute (without dialysis): 50% recommended (according to indications) doses.

The patient who is on continuous dialysis after each session appoint 100% of the recommended dose.

Solution for infusions is compatible to solution of sodium chloride, hydrosodium carbonate (0,9%), potassium chloride in glucose, Hartman's solutions, Ringera and 20% glucose solution. It is possible to carry out infusions of a flukonazol with use of one of the listed above solutions by means of usual sets for a transfusion.

Side effects

At Mikosist's use disturbances from some systems of an organism can develop:

Nervous system: dizziness, spasms, headache;
Alimentary system: an abdominal pain, diarrhea, a meteorism, an abnormal liver function (a hepatocellular necrosis, including with a lethal outcome, jaundice, hepatitis, a hyperbilirubinemia, increase in activity of an alkaline phosphatase, hepatic transaminases), taste change, nausea, vomiting;
Cardiovascular system: trembling and/or ventricular fibrillation, increase on the electrocardiogram of duration of an interval of QT;
Metabolism: gipertriglitseridemiya, hypopotassemia, hypercholesterolemia;
Bodies of a hemopoiesis: agranulocytosis, thrombocytopenia, neutropenia, leukopenia;
Allergic reactions: a mnogoformny exudative erythema (including Stephens-Johnson's syndrome), bronchial asthma (in most cases at intolerance of acetylsalicylic acid), anaphylactoid reactions (including a face edema, a skin itch, a small tortoiseshell, a Quincke's disease), a Lyell's disease, skin rash;
Others: alopecia, functional disturbances of kidneys.

Special instructions

Treatment needs to be carried out before emergence of kliniko-hematologic remission as premature phase-out of Mikosist can lead to development of a recurrence.

In rare instances use of a flukonazol was followed by manifestations of toxic action on a liver (including a lethal outcome), most often – at patients with the serious accompanying diseases. In this regard during Mikosist's use it is necessary to control function of a liver, and at emergence of signs of its defeat which can be connected with administration of drug, therapy should be cancelled.

During treatment development of exfoliative skin reactions (Stephens-Johnson's syndrome, a toxic epidermal necrolysis) was in rare instances noted. Patients with malignant new growths and AIDS are more inclined to development of heavy skin reactions.

If during treatment at patients with a superficial fungal infection it is observed developing of rash which can be connected with Mikosist's reception, therapy it is necessary to cancel. Especially careful control when developing rash is required to patients with system invasive fungal infections.

At development of a mnogoformny erythema or violent defeats drug is cancelled.

At simultaneous therapy with indirect anticoagulants of a coumarinic row it is recommended to control a prothrombin time.

As Mikosist can cause dizziness, during treatment by the patient it is necessary to be careful when performing potentially dangerous types of the works demanding bystry psychomotor reactions and special attention including control of motor transport.

Medicinal interaction

At simultaneous use of Mikosist with some medicines there can be following effects (_T1/2 – a substance elimination half-life; _Cmax – the maximum concentration of drug in blood):

Zidovudine: increase in its concentration in a blood plasma and probability of development of side effects;
Sulphonylurea drugs: lengthening of their _T1/2 in this connection at use of this combination of medicines it is necessary to consider possibility of a hypoglycemia;
Takrolimus: increase in its concentration in blood serum and risk of development of nephrotoxicity;
Theophylline: decrease in average speed of its clearance from a blood plasma, increase in risk of development of its toxic action and overdose;
Phenytoinum: clinically significant increase in its concentration (dose adjustment can be required);
Rifampicin: reduction of its _Cmax and _T1/2 (dose adjustment of a flukonazol can be required);
Midazolam: substantial increase of its concentration in a blood plasma and risk of development of psychomotor reactions;
Rifabutin: increase in its serumal concentration, probability of development of a uveitis;
Cyclosporine: increase in its concentration in blood;
Hydrochlorothiazide: increase in concentration of a flukonazol in a blood plasma.