MIKOSIST
Active material: Fluconazole
When ATH: J02AC01
CCF: Antifungal agent
ICD-10 codes (testimony): B35.0, B35.1, B35.2, B35.3, B35.4, B36.0, B37.0, B37.1, B37.2, B37.3, B37.4, B37.6, B37.7, B37.8, B38, B39, B41, B42, B45, H19.2, Z29.8
When CSF: 08.01.01
Manufacturer: GEDEON RICHTER Ltd. (Hungary)
Pharmaceutical form, composition and packaging
◊ Capsules hard gelatin, size №4 (Cones-Snap), with a light blue opaque cap (L 910) and white opaque body (L 500); contents of capsules – white or almost white powder or dense mass of powder.
| 1 caps. | |
| fluconazole | 50 mg |
Excipients: colloidal silicon dioxide, magnesium stearate, talc, povidone K30, corn starch, lactose bezvodnaya.
The composition of hard gelatin capsules: Titanium dioxide (C.I.77891/E171), indigokarmin (C.I.73015/Е132), gelatin.
7 PC. – blisters (1) – packs cardboard.
◊ Capsules hard gelatin, size №2 (Cones-Snap), with turquoise opaque lid (L 890) and white opaque body (L 500); contents of capsules – white or almost white powder or dense mass of powder.
| 1 caps. | |
| fluconazole | 100 mg |
Excipients: colloidal silicon dioxide, magnesium stearate, talc, povidone K30, corn starch, lactose bezvodnaya.
The composition of hard gelatin capsules: Titanium dioxide (C.I.77891/E171), indigokarmin (C.I.73015/Е132), gelatin.
7 PC. – blisters (4) – packs cardboard.
◊ Capsules hard gelatin, size №1 (Cones-Snap), with blue opaque cap (54.038) and white opaque body (L 500); contents of capsules – white or almost white powder or dense mass of powder.
| 1 caps. | |
| fluconazole | 150 mg |
Excipients: colloidal silicon dioxide, magnesium stearate, talc, povidone K30, corn starch, lactose bezvodnaya.
The composition of hard gelatin capsules: Titanium dioxide (C.I.77891/E171), indigokarmin (C.I.73015/Е132), gelatin.
1 PC. – blisters (1) – packs cardboard.
1 PC. – blisters (2) – packs cardboard.
Solution for infusion colorless or slightly colored, clear.
| 1 ml | 1 fl. | |
| fluconazole | 2 mg | 200 mg |
Excipients: sodium chloride, water d / and.
100 ml – glass bottles (1) – packs cardboard.
Pharmacological action
Antifungal agent. Fluconazole, representative of the class of triazole antifungal agents, It is a potent selective inhibitor of sterol synthesis in the fungal cells.
It is active against agents of opportunistic fungal infections, incl. caused by Candida spp., Cryptococcus neoformans, Microsporum spp., Trichophyton spp. Fluconazole is also shown activity in models of endemic mycoses, including infections, caused by Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum.
Pharmacokinetics
The pharmacokinetic parameters of fluconazole are similar with on / in the introduction and ingestion.
Absorption
After oral administration fluconazole is well absorbed. Bioavailability is 90%. After oral administration at a dose on an empty stomach 150 mg Cmax is 90% the content of the plasma with / in a dose of drug in the 2.5-3.5 mg / l. Simultaneous food intake has no effect on absorption when administered. Cmax achieved through 0.5-1.5 hours after administration of fluconazole. Plasma concentration is proportional to the dose.
Distribution
90% Css It is achieved by 4-5 day drug treatment (when receiving 1 time / day).
Bolus (1 day), in 2 times the average daily dose, achieves 90% Level Css for the 2nd day. In Кажущийсяd It is approaching the total water content in the body. Protein binding – 11-12%.
Fluconazole penetrates well into all body fluids. Fluconazole concentration in saliva and sputum are similar plasma concentrations. Patients with fungal meningitis fluconazole levels in the cerebrospinal fluid are about 80% the levels in plasma.
In the stratum corneum, epidermis, derma and sweat liquid reaches high concentrations, which exceed serum.
Deduction
T1/2 is about 30 no. Fluconazole is derived mainly kidneys; about 80% the administered dose found in the urine in unchanged form. The clearance of fluconazole is proportional QC. Fluconazole metabolites were detected in the blood.
Testimony
- Kryptokokkoz, including cryptococcal meningitis and other localizations of this infection (incl. lungs, skin), both in patients with normal immune response as well as in patients with various forms of immunosuppression (incl. AIDS patients, organ transplantation); drug can be used to prevent cryptococcal infection in AIDS patients and organ transplant;
- Generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive Candida infections (incl. infection of the peritoneum, endokarda, eye, respiratory and urinary tract). Treatment can be performed in patients with malignant tumors, Patients in intensive care units, patients, receiving cytotoxic or immunosuppressive agents, and the presence of other factors, predisposing to candidiasis;
- Mucosal candidiasis, incl. oral cavity and pharynx (including atrophic oral candidiasis, associated with wearing dentures), esophagus, non-invasive bronchopulmonary infections, kandidurija, skin candidosis; prevention of relapse of oropharyngeal candidiasis in patients with AIDS;
- Genital candidiasis: vaginal candidiasis (acute and chronic recurrent), prophylactic treatment to reduce the frequency of relapses vaginal candidiasis (3 or more episodes per year); kandidoznыj ʙalanit;
- Prevention of fungal infections in patients with malignant tumors, who are predisposed to such infections as a result of cytotoxic chemotherapy or radiotherapy;
- Fungal infections of the skin, including tinea pedis, body, groin, chromophytosis, onychomycosis and skin candidiasis;
- Deep endemic mycoses, coccidioidomycosis, Paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immunity.
Dosage regimen
Adults at cryptococcal meningitis and cryptococcal infections at other sites administered on the first day 400 mg, and then continue treatment at a dose 200-400 mg 1 time / day. The duration of treatment of cryptococcal infections depends on the clinical effectiveness, confirmed by mycological examination; cryptococcal meningitis treatment is generally continued, at least, 6-8 weeks.
To prevention of relapse of cryptococcal meningitis in patients with AIDS after completing a full course of primary treatment therapy fluconazole 200 mg / day can continue for a very long period of time.
At kandidemii, disseminated candidiasis and other invasive Candida infections dose averages 400 mg on the first day, and then – by 200 mg / day. When insufficient clinical efficacy dose may be increased to 400 mg / day. The duration of therapy depends on the clinical effectiveness.
At orofaringealьnom kandidoze the drug is prescribed an average of 50-100 mg 1 time / day; duration of therapy – 7-14 days. If necessary in patients with severe depression of immunity, treatment may be longer.
At atrophic oral candidiasis, associated with wearing dentures, the drug is prescribed in high doses 50 mg 1 times / day for 14 days in combination with local antiseptic agents for treatment of prosthesis.
At other Candida infections of the mucous membranes (for isklyucheniem genitalynogo candidiasis), eg, эzofagite, non-invasive bronchopulmonary lesions, kandidurii, candidiasis of the skin and mucous membranes, effective dose averages 50-100 mg / day when the duration of treatment 14-30 days.
To prevention of relapse of oropharyngeal candidiasis in patients with AIDS after completing a full course of primary therapy, fluconazole may be appointed by 150 mg 1 times / week.
At vaginal candidiasis fluconazole take a single oral dose 150 mg. To reduce the frequency of recurrent vaginal candidiasis preparation may be used in a dose of 150 mg 1 times / month. The duration of therapy is determined individually; it ranges from 4 to 12 Months. Some patients may require more frequent use of.
At ʙalanite, caused by Candida, Fluconazole prescribe a single dose 150 mg orally.
To preventions candidiasis The recommended dose of fluconazole 50-400 mg 1 times / day depending on the degree of risk of fungal infection. If you have a high risk of generalized infection, for example in patients with severe or long-anticipated persistent neutropenia, The recommended dose is 400 mg 1 time / day. Fluconazole administered a few days before the expected occurrence of neutropenia; after increasing the number of neutrophils more than 1000 / ml treatment was continued for 7 d.
At mycosis of the skin, including tinea pedis, smooth skin, groin and skin candidosis, The recommended dose is 150 mg 1 times / week or 50 mg 1 time / day. Duration of therapy in conventional cases is 2-4 of the week, however athlete's foot may require longer therapy (to 6 Sun.).
At pityriasis versicolor The recommended dose is 300 mg 1 times / week. during 2 weeks; some patients required a third dose 300 mg / Sun., while in some cases it is sufficient a single dose of the drug in 300-400 mg. Alternative treatment is the use of the drug 50 mg 1 times / day for 2-4 Sun.
At onixomikoze The recommended dose is 150 mg 1 times / week. Treatment should be continued until infected nail replacement (sprouting uninfected nail). For the re-growth of the fingernails and feet normally required 3-6 months and 6-12 months, respectively.
At Deep endemic mycoses may be required drug dose 200-400 mg / day for up to 2 years. The duration of therapy is determined individually; it is 11-24 months with coccidioidomycosis, 2-17 Months – when paracoccidioidomycosis, 1-16 Months – and when sporotrichosis 3-17 Months – if histoplasmosis.
In children, as in the similar infections adult, the duration of treatment depends on the clinical and mycological effect. In children drug should not be administered in a daily dose of, greater than that of adults. The drug is used on a daily basis 1 time / day.
For the treatment of generalizovannogo candidiasis infections and kriptokokkovoy The recommended dose is 6-12 mg / kg / day, depending on the severity of the disease.
To prevention of fungal infections children immunocompromised, in which the risk of infection associated with neutropenia, developing as a result of cytotoxic chemotherapy or radiotherapy, the drug is prescribed for 3-12 mg / kg / day, depending on the severity and duration of neutropenia induced by conservation.
At mucosal candidiasis The recommended dose of fluconazole 3 mg / kg / day. The first day can be assigned to the loading dose 6 mg / kg in order to more quickly achieve permanent equilibrium concentrations.
In appointing the solution d / Infusion newborn should be considered, that fluconazole appears slowly, so first 2 weeks of life drug administered in the same dose (calculated in mg / kg body weight), and that older children, but the intervals 72 no. For children 3 and 4 of the week life of the same dose is administered at intervals of 48 no.
In children with impaired renal function the daily dose should be reduced (in the same proportion, in adults) in accordance with the severity of renal insufficiency.
In elderly patients in the absence of renal failure should follow the usual dose regimen of the drug.
Patients with renal insufficiency (CC<50 ml / min) requires correction mode.
Fluconazole is derived mainly from the urine in unchanged form. For a single admission of his change of dose is not required. With the reappointment of patients with impaired renal function should be introduced on a loading dose 50 mg 400 mg.
At CC>50 ml / min It applies average recommended dose; at KK from 11 to 50 ml / min applied dose, component 50% Recommended by. Patients, regular hemodialysis, One dose administered after each dialysis.
Terms of administration of the solution for infusion
Fluconazole is a solution for infusion is administered in / in the drip at a rate of no more than 20 mg (10 ml) min. When translating from / in the introduction to the capsules and vice versa there is no need to change the daily dose.
The solution for infusion is compatible with the following solutions: 20% Dextrose (Glucose), Ringer, Hartmann's solution, potassium chloride dextrose, solution of sodium bicarbonate 4.2%, 0.9% sodium chloride solution.
Infusion of fluconazole can be carried out using conventional kits for transfusion, Using one of the above liquids.
Side effect
From the digestive system: nausea, vomiting, flatulence, stomach ache, diarrhea; rarely – abnormal liver function (giperʙiliruʙinemija, increase in liver enzymes / ALT, IS, ALP /).
CNS: headache; rarely – convulsions.
From the hematopoietic system: rarely – leukopenia, thrombocytopenia, neutropenia, agranulocytosis.
Allergic reactions: skin rash; rarely – malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), anaphylactoid reactions.
Other: rarely – impairment of renal function, alopecia, hypercholesterolemia, hypertriglyceridemia, kaliopenia.
Contraindications
- Concomitant use of terfenadine, astemizole or other drugs, and, prolonging the QT interval;
- Children up to age 6 months (orally);
- Hypersensitivity to the drug or similar in structure azole compounds.
Pregnancy and lactation
Use of the drug during pregnancy Mikosist inappropriate, except for serious or life-threatening forms of fungal infections, if the expected benefit to the mother outweighs the potential risk to the fetus.
Fluconazole is found in the breast milk at the same concentration, as in plasma, therefore his appointment during lactation is not recommended.
Cautions
In rare cases, fluconazole was accompanied by toxic changes in the liver, incl. fatal, mainly in patients with severe concomitant diseases. There was no explicit dependence of the frequency of hepatotoxic effects of fluconazole of the total daily dose, duration of therapy, sex and age of the patient. Fluconazole hepatotoxicity is usually reversible; its signs disappeared after cessation of therapy. When clinical signs of liver damage, that may be associated with fluconazole, the drug should be discontinued.
AIDS patients are more prone to the development of severe skin reactions in the application of many drugs. When the patient, receiving treatment for superficial fungal infections, rash, which can be associated with fluconazole, the drug should be discontinued. If a rash in patients with invasive / systemic fungal infections should be carefully monitored and cancel fluconazole when a bullous lesions or erythema multiforme.
Care must be taken while the application of fluconazole with cisapride, astemizolom, rifaʙutinom, tacrolimus or other drugs, metabolized by cytochrome P450 isoenzymes.
Overdose
Symptoms: hallucinations, paranoidalynoe behavior.
Treatment: recommended gastric lavage and symptomatic therapy. As fluconazole is excreted in the urine, forced diuresis enhances its excretion. Hemodialysis for 3 h decreases the concentration of fluconazole in the plasma 50%.
Drug Interactions
When using fluconazole and warfarin there was an increase in prothrombin time 12%. In this connection, it is recommended to monitor the prothrombin time in patients, receiving Mikosist in conjunction with anti kumarinovyh.
With simultaneous use of fluconazole increases T1/2 oral hypoglycemic drugs – sulfonylureas (hlorpropamyda, glibenclamide, tolbutamide and glipizide) in healthy volunteers. Co-administration of fluconazole and oral hypoglycemic agents may be, but should take into account the possibility of hypoglycemia.
Concomitant use of fluconazole and phenytoin may cause a higher concentration of phenytoin to a clinically significant degree. If you want the combined use of two drugs, monitoring of phenytoin levels is necessary and the selection of the dose for therapeutic concentration in serum.
Simultaneous administration of fluconazole and rifampicin reduces the AUC by 25% and shortening T1/2 of fluconazole 20%. Patients, receiving both rifampicin, you must take into account the feasibility of increasing the dose of fluconazole.
It is recommended to control the concentration of cyclosporine in the blood of patients, receiving fluconazole, tk. when using Fluconazole and cyclosporine in patients with renal transplant acceptance fluconazole 200 mg / day Slowly increase the concentration of cyclosporine.
Sick, receiving high doses of theophylline, or who have a chance of developing theophylline intoxication, must be supervised for early detection of the symptoms of an overdose of theophylline, tk. simultaneous administration of fluconazole reduces the average rate of clearance from the plasma theophylline.
With simultaneous use of fluconazole and cisapride described cases of adverse reactions from the heart, including paroxysms of ventricular tachycardia (the type of arrhythmia “pirouette”).
There are reports about the interaction of fluconazole and rifabutin, accompanied by an increase in serum levels of the last. With simultaneous use of fluconazole and rifabutin described cases of uveitis. It is necessary to carefully monitor patients, while receiving rifabutin and fluconazole.
With simultaneous use of zidovudine and fluconazole marked increase in the concentration of zidovudine in plasma, which is caused by a decrease in the conversion of the latter into the main metabolite, so you should expect an increase in adverse reactions.
Conditions of supply of pharmacies
The drug is in the form of capsules is resolved to application as an agent Valium holidays.
A preparation in the form of a solution for infusion by prescription.
Conditions and terms
The drug should be stored at a temperature of from 15 ° to 30 ° C.. Shelf life of capsules – 5 years, solution for infusion – 2 year.
