Mikosist - antifungal drug.
Release form and composition
Mikosist release in two dosage forms:
- Capsules: gelatinous, hard, with a white opaque body (L500), filled inside with almost white or white powder or a dense powdery mass; 50 mg each - size No. 4, with an opaque light blue cap (L910); 100 mg each - size No. 2, with an opaque turquoise lid (L890); 150 mg each - size No. 1, with an opaque blue lid (L860) (50 mg each: in blisters, 7 pcs., 1 blister in a cardboard box; 100 mg: blisters, 7 pcs., 1 or 4 blisters in a carton box; 150 mg each: in blisters 1 each, 1, 2 or 4 blisters in a carton box);
- Solution for infusion: clear, slightly colored or colorless (in bottles of 100 ml, 1 bottle in a carton box).
The composition of 1 capsule 50/100/150 mg includes, respectively:
- Active ingredient: fluconazole - 50/100/150 mg;
- Auxiliary components: anhydrous lactose - 49.5 / 99 / 148.5 mg; corn starch - 12.1 / 24.2 / 36.3 mg; Povidone - 3.6 / 7.2 / 10.8 mg; talc - 3.3 / 6.6 / 9.9 mg; magnesium stearate - 1.2 / 2.4 / 3.6 mg; colloidal silicon dioxide, 0.3 / 0.6 / 0.9 mg;
- Case: titanium dioxide (E17.1C.I.77891) - 2/2/2%; gelatin - up to 100% (for all forms of release);
- Lid: titanium dioxide (Е171, CI77891) - 4/4 / 1.5%; indigo carmine (Е132, CI73015) - 0.0086 / 0.0471 / 0.2513%; gelatin - up to 100% (for all forms of release).
The composition of 1 bottle with solution for infusion includes:
- Active ingredient: fluconazole - 200 mg;
- Auxiliary components: sodium chloride - 900 mg, water for injection - up to 100 ml.
Indications for use
- Cryptococcosis: cryptococcal sepsis and meningitis, cryptococcal infections of the skin and lungs, cryptococcosis in patients with acquired immunodeficiency syndrome (AIDS) (to prevent recurrence), organ transplantation or other cases of immunodeficiency;
- Generalized candidiasis: candidemia, disseminated candidiasis and other forms of invasive candidal infections (urinary and respiratory tract infections, eyes, endocardium, abdominal cavity), including in patients receiving immunosuppressive or cytostatic therapy, as well as in the presence of other factors predisposing to candidiasis (for treatment and prophylaxis);
- Genital candidiasis: vaginal (chronic, recurrent or acute); candidal balanitis (capsules);
- Candidiasis of the mucous membranes of the oral cavity, including atrophic candidiasis of the oral cavity, esophagus, pharynx, non-invasive bronchopulmonary infections, candiduria, associated with the wearing of dental prostheses.
- Mycoses of the skin, including mycoses of the groin and trunk;
- Fungal infections in patients with malignant neoplasms (for prophylaxis) predisposed to the development of such infections as a result of radiation therapy or cytostatic therapy; oropharyngeal candidiasis in patients with AIDS (for the prevention of recurrence);
- Deep endemic mycoses, including coccidioidosis, paracoccidioidosis, and histoplasmosis in patients with normal immunity;
- Mycoses of the feet, onychomycosis, pityriasis versicolor (capsules).
- Glucose-galactose malabsorption, lactase deficiency, lactose intolerance;
- Simultaneous therapy with terfenadine (with continuous use of Mikosist from 400 mg per day), cisapride, since both drugs increase the risk of developing severe cardiac arrhythmias and contribute to prolongation of the QT interval;
- Simultaneous therapy with astemizole;
- Lactation period;
- Hypersensitivity to the components of the drug or to azole compounds similar in structure.
Conditions / diseases in which Mikosist should be used with caution:
- Hepatic and / or renal failure;
- The appearance of a rash when taking fluconazole in patients with systemic / invasive fungal infections and superficial fungal infections;
- Simultaneous therapy with terfenadine and fluconazole in a daily dose of up to 400 mg;
- Simultaneous therapy with rifabutin or other drugs metabolized by cytochrome P450 isoenzymes;
- Intolerance to acetylsalicylic acid (ASA);
- Potentially proarrhythmic conditions in patients with multiple risk factors, including organic heart disease, electrolyte imbalance, co-administration with drugs causing arrhythmias;
Dosing and Administration
Capsules are inside; the solution is administered intravenously at a rate of not more than 20 mg in 1 minute (10 ml).
In the case of transferring a patient from an intravenous solution to the drug intake or vice versa, there is no need to change the daily dose.
Recommended dosing regimen for adults:
- Cryptococcal infections: the daily dose on the first day of therapy is 400 mg, then 200-400 mg once a day. The duration of treatment is determined by clinical efficacy confirmed by mycological studies and, in most cases, varies from 42 to 56 days. In the case of cryptococcal meningitis, the recommended duration of treatment is 70-84 days after a negative result of a microbiological examination of a cerebrospinal fluid sample. To complete the course of primary treatment in order to prevent the recurrence of cryptococcal meningitis, patients with AIDS should take 200 mg of Mycosyst per day for a long time;
- Candidemia, disseminated candidiasis and other invasive candidal infections: daily dose - 400 mg on the first day, then 200 mg, with a possible doubling of the dose if necessary. The duration of Mycosyst therapy depends on clinical efficacy. In the case of severe systemic candidiasis, the dose of the drug may be increased to 800 mg per day. Therapy should be continued for at least 14 days after the disappearance of signs of the disease or upon receipt of a negative blood culture;
- Oropharyngeal candidiasis, including in patients with impaired immunity: daily dose - 50-100 mg for 1-2 weeks. To prevent recurrence of oropharyngeal candidiasis, patients with AIDS after the end of the full course of primary treatment should take 150 mg of the drug 1 time in 7 days. If necessary (especially in the case of severe impairment of immunity), the duration of therapy may be increased;
- Atrophic candidiasis of the oral cavity, which is associated with the wearing of dentures: daily dose - 50 mg for 14 days in combination with antiseptic preparations for the treatment of the prosthesis;
- Other candidal infections (esophagitis, non-invasive bronchopulmonary infections, candiduria, candidiasis of the skin and mucous membranes, and others): daily dose - 50-100 mg for 14-30 days;
- Severe candidiasis of the mucous membranes: daily dose - 100-200 mg;
- Fungal infections in patients with malignant tumors (prophylaxis): the daily dose is 50 mg, the drug should be taken as long as the patient is in an increased risk group due to radiation or cytostatic therapy;
- Vaginal candidiasis: 150 mg once. To reduce the recurrence rate, 150 mg of the drug should be taken 1 time per month for 4–12 months; in some cases more frequent use may be required;
- Balanitis caused by Candida spp.: Capsules - 150 mg once;
- Prevention of candidiasis: the daily dose ranges from 50-400 mg (determined by the risk of developing a fungal infection). The recommended dose of Mikosist in the presence of a high risk of generalized infection, for example, in patients with long-lasting or expected severe neutropenia, is 400 mg per day. Mikosist should start taking a few days before the expected appearance of neutropenia; after increasing the number of neutrophils> 1000 / mm³, therapy should be continued for another 7 days;
- Skin mycoses (including candidiasis), including mycoses of the groin area, skin, and feet: capsules - 150 mg 1 time in 7 days or 50 mg per day. Typically, the duration of the treatment course varies from 7 to 14 days, but in cases of mycoses of the feet, it can be increased to 42 days;
- Pityriasis versicolor: Capsules - 300 mg 1 time per 7 days for 2 weeks, however, a third dose of 300 mg per 7 days may be required, while in some cases a single dose of 300 mg may be sufficient. An alternative treatment regimen is 50 mg per day for 14-28 days;
- Onychomycosis: capsules - 150 mg 1 time in 7 days. The drug should be continued until the healthy nail completely replaces the infected nail. In most cases, for the re-growth of the nails on the fingers and toes it is required to continue taking Mycosyst for 3-6, 6-12 months respectively;
- Deep endemic mycoses: 200-400 mg per day. The duration of therapy is determined individually: with coccidioses, it can vary within 11-24 months, with paracoccidioidosis - 2-17 months, with histoplasmosis - 3-17 months. In some cases, you may need to use the drug for 2 years.
The duration of Mikosistom therapy in children is determined depending on the clinical and mycological effect. The daily dose for this age group of patients should not exceed that in adults. The drug should be used daily 1 time per day.
Recommended dosing regimen:
- Candidiasis of the mucous membranes: 3 mg per 1 kg of body weight per day. It is allowed to administer a loading dose of Mycosyst (6 mg per 1 kg of body weight) on the first day of therapy;
- Generalized candidiasis and cryptococcal infection: 6-12 mg per 1 kg of body weight per day (depending on the severity of the disease);
- Prevention of fungal infections in children with reduced immunity, in whom the risk of developing an infection is associated with neutropenia resulting from radiation therapy or cytotoxic therapy: 3-12 mg per 1 kg of body weight per day (depending on the duration of preservation and severity of induced neutropenia).
Due to the fact that in newborns fluconazole is eliminated more slowly, in the first two weeks of life the drug should be used in the same dose (mg per 1 kg of body weight) as in older children, but the interval between doses should be 72 hours . Children 3-4 weeks of life the same dose should be administered at intervals of 48 hours.
Elderly patients do not require correction of the dosing regimen in the absence of renal dysfunction.
Fluconazole unchanged is excreted by the kidneys (predominantly). Dose adjustment with a single application of Mycosyst is not required. In the case of the appointment of a course of therapy to patients (including children) with functional disorders of the kidneys, initially, a loading dose will be applied, varying from 50-400 mg. Further, the daily dose depending on the evidence is determined as follows:
- Creatinine clearance is more than 50 ml per minute: 1 time per day 100% of the recommended dose;
- Creatinine clearance less than 50 ml per minute (without dialysis): 50% of the recommended dose once a day.
Patients on constant dialysis are prescribed 100% of the recommended dose after each session.
The solution for infusions of Mikosist is compatible with a solution of sodium chloride, sodium bicarbonate (0.9%), potassium chloride in glucose, a solution of Hartman, Ringer and 20% glucose solution.
Fluconazole infusion can be performed using conventional transfusion kits using one of the above solutions.
During the period of Mycosist therapy, side effects may occur on the part of some body systems:
- Digestive system: abnormal liver function (hepatocellular necrosis, including fatal, hepatitis, jaundice, increased alkaline phosphatase activity, hepatic transaminases, hyperbilirubinemia), change in taste, flatulence, abdominal pain, nausea, diarrhea, vomiting;
- Nervous system: convulsions, dizziness, headache;
- Organs of blood formation: agranulocytosis, neutropenia, thrombocytopenia, leukopenia;
- Allergic reactions: bronchial asthma (often with intolerance to ASK), anaphylactoid reactions (including skin itching, angioedema, urticaria, swelling of the face), Lyell's syndrome, erythema multiforme exudative (including Stevens-Johnson syndrome), skin rash;
- Cardiovascular system: fluttering / ventricular fibrillation, an increase in the electrocardiogram QT interval;
- Metabolism: hypokalemia, hypertriglyceridemia, hypercholesterolemia;
- Other: alopecia, impaired renal function.
Mikosistom therapy should be carried out before the emergence of clinical and hematological remission, as with the premature discontinuation of the drug may relapse.
The use of fluconazole in rare cases was accompanied by a toxic effect on the liver (including death), mainly in patients with serious concomitant diseases. In this regard, during the period of therapy with this drug, it is recommended to monitor liver function. Mikosist should be canceled if there are signs of liver damage that may be associated with its reception.
When taking Mikosist in rare cases, there was a development of exfoliative skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis). Patients with malignant neoplasms and AIDS are more likely to develop severe skin reactions with the use of many drugs. If during the treatment of a superficial fungal infection in a patient, a rash appears that can be associated with fluconazole, Mikosist should be canceled. In the event of a rash for patients suffering from systemic invasive fungal infections, careful monitoring is required and therapy should be discontinued if erythema multiforme or bullous lesions occur.
It is recommended to control the prothrombin time in patients receiving simultaneous therapy with fluconazole and indirect coumarin anticoagulants.
During therapy, patients should be careful when performing potentially hazardous types of work that require increased attention and quick psychomotor reactions, since Mikosist can cause dizziness.
The effect of fluconazole on drugs / substances with simultaneous use (Cmax - the maximum concentration of the drug in the blood; T1 / 2 - the half-life of the substance):
- Sulfonylurea preparations: can prolong their T1 / 2, therefore when using such a combination, the possibility of hypoglycemia should be considered;
- Phenytoin: may increase its concentration to a clinically significant extent, which requires a decrease in its dose;
- Rifampicin: reduces its Cmax and T1 / 2, and therefore the dose of fluconazole should be increased;
- Rifabutin: increases its serum concentrations; uveitis may develop;
- Cyclosporine: may increase its concentration in the blood;
- Zidovudine: may increase its plasma concentration. Patients receiving this combination should be monitored to detect side effects of zidovudine;
- Theophylline: reduces its average clearance rate from blood plasma and, as a result, increases the risk of its toxic action and overdose;
- Midazolam: significantly increases its concentration in plasma (increases the risk of developing psychomotor reactions);
- Tacrolimus: increases its concentration in serum, leading to an increased risk of nephrotoxicity.
Hydrochlorothiazide with simultaneous use with fluconazole increases its plasma concentration by 40%.
Terms and conditions of storage
Keep out of reach of children at temperature up to 30 ° С.
- Capsules - 5 years;
- Solution for infusions - 2 years.