Mikoflucan

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Mikoflucan: instructions for use and reviews

1. Release form and composition
2. Pharmacodynamics and pharmacokinetics
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Special instructions
8. Drug interactions
9. Analogs
10. Terms and conditions of storage
11. Terms of dispensing from pharmacies
12. Reviews
13. Price in pharmacies

Latin name: Mycoflucan

ATX code: J02AC01

Active substance: fluconazole

Manufacturer: Dr. Reddy's Laboratories Ltd. (India)

Description and photo update: 2019-05-08

Mikoflucan is an antimycotic drug.

Release form and composition

Dosage forms:

Tablets: flat, round, chamfered, almost white or white; 50 mg each (on one side the letter "F" is embossed, on the other side - the number "50") and 150 mg each (on one side of the dividing line, on the other side the inscription "F150" is embossed) (1, 4 or 7 pcs. In a blister, 1 blister in a cardboard box);
Solution for infusion: clear, colorless liquid (100 ml in low-density polyethylene bottles, 1 bottle in a cardboard box).

Composition of 1 tablet:

Active ingredient: fluconazole - 50 or 150 mg;
Auxiliary components: lactose, microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, povidone K30, magnesium stearate, purified talc.

Composition of 1 ml solution:

Active ingredient: fluconazole - 2 mg;
Auxiliary components: disodium edetate, sodium chloride, water for injection.

Pharmacodynamics and pharmacokinetics

According to the instructions, Mikoflucan belongs to a new category of triazole antifungal drugs. Its highly specific action is to inhibit the activity of fungal enzymes associated with cytochrome P ₄₅₀. Also, the drug inhibits the transition of lanosterol, which is part of the fungal cells, into ergosterol, increases the permeability of cell membranes, disrupting their growth and replication, and does not have antiandrogenic activity.

Fluconazole is highly selective for cytochrome P _{450 of} fungi, but it practically does not change the synthesis of these enzymes in the human body (unlike ketoconazole, itraconazole, econazole and clotrimazole, fluconazole inhibits oxidation processes in human liver microsomes, which depend on cytochrome P ₄₅₀).

The drug is widely used in the treatment of opportunistic mycoses, including those caused by Trichophyton spp., Microsporum spp., Coccidioides immitis and Cryptococcus neoformans (including intracranial infections), Candida spp. (including generalized types of candidiasis developing against the background of immunosuppression), as well as Histoplasma capsulatum and Blastomyces dermatitidis (including immunosuppression).

When taken orally, fluconazole is well absorbed. Its total bioavailability and plasma concentration is more than 90% of the plasma level of this substance during infusion. Oral absorption of the substance is not related to food intake in any way.

The maximum concentration of fluconazole after oral administration on an empty stomach of 150 mg of the drug is achieved in 0.5-1.5 hours and is 90% of the substance content in the plasma, administered intravenously at a dose of 2.5-3.5 mg / l.

The concentration of the active substance of the drug in plasma is directly proportional to the dose. Approximately 90% of the equilibrium plasma concentration of fluconazole (Css) at a dosage of 1 tablet once a day is usually recorded on the 4-5th day. When a "loading" dose is administered on the first day of treatment, 2 times the standard daily dose, a concentration corresponding to 90% Css is reached by the second day.

Fluconazole easily penetrates into all body fluids. Its level in peritoneal fluid, breast milk, sputum, saliva, and joint fluid corresponds to that in plasma. The stable concentration of the substance in the vaginal secretion is determined 8 hours after oral administration and remains unchanged for at least 24 hours. Fluconazole is well absorbed into the cerebrospinal fluid, in which its content reaches 85% of the plasma concentration (with fungal meningitis).

Selective accumulation of fluconazole occurs in the stratum corneum, dermis and secretion of sweat glands, which leads to a significant excess of local concentrations in comparison with serum.

The apparent volume of distribution practically coincides with the total concentration of water in the body. The connection of fluconazole with plasma proteins is low and amounts to 11–12%.

The half-life of fluconazole is 30 hours. The compound belongs to inhibitors of the CYP2C9 isoenzyme in the liver and is excreted mainly through the kidneys (80% of fluconazole in unchanged form and 11% in the form of products of its metabolism).

There is a direct proportional relationship between fluconazole clearance and creatinine clearance. The pharmacokinetics of Mikoflucan significantly depends on the functional state of the kidneys, and creatinine clearance and half-life are inversely related.

Within 3 hours after hemodialysis, the content of fluconazole in plasma decreases by 50%. The pharmacokinetics of the substance are identical with infusion and oral administration, allowing you to easily switch from one form of the drug to another during treatment.

Indications for use

Systemic diseases caused by cryptococci: sepsis, meningitis, infections of the skin and lungs, both in patients with a normal immune response and in various forms of immunosuppression (including AIDS patients, organ transplant recipients); as part of maintenance treatment for the prevention of cryptococcal infection in AIDS patients;
Generalized candidiasis: disseminated candidiasis (with infection of the eyes, endocardium, respiratory system, abdominal organs, genitourinary system), candidemia; it is allowed to conduct a course of therapy for patients with malignant neoplasms during the period of immunosuppressive or cytostatic therapy, as well as in the presence of other factors predisposing to the development of these conditions - for treatment and prevention;
Candidiasis of the mucous membranes (pharynx, esophagus, oral cavity), candiduria, non-invasive bronchopulmonary candidiasis, mucocutaneous and chronic oral atrophic candidiasis (caused by wearing dentures); oropharyngeal candidiasis in AIDS patients - for the prevention of relapse;
Genital candidiasis: vaginal (recurrent and acute) - for the treatment and prevention of the frequency of relapses (during the year, there are three or more episodes); candidal balanitis (for the drug in the form of tablets);
Fungal infections in malignant tumors against the background of radiation or chemotherapy - for prevention;
Oropharyngeal candidiasis in patients with AIDS - to prevent relapse;
Severe or long-term neutropenia, other conditions of high risk of generalized infection - for the prevention of candidiasis;
Mycoses of the skin: body, feet, groin area, pityriasis versicolor, onychomycosis, skin candidal infections (tablets);
Deep endemic mycoses with normal immunity: paracoccidioidomycosis, coccidioidomycosis, histoplasmosis, sporotrichosis.

Contraindications

Absolute:

Breastfeeding (lactation) period;
Simultaneous administration with terfenadine (against the background of regular intake of fluconazole at a dose of 400 mg / day or more) or astemizole;
Hypersensitivity to drug components, fluconazole, and azole antifungal agents / agents.

Relative (the drug is used with caution):

Liver failure;
The appearance of a rash in patients with superficial and invasive / systemic fungal infections during therapy with fluconazole;
Concomitant use of fluconazole (up to 400 mg / day) with terfenadine;
Potentially proarrhythmogenic conditions in patients with multiple risk factors, such as electrolyte imbalance, organic heart disease, concomitant use with drugs that cause arrhythmias;
Pregnancy: fluconazole is used in case of severe and potentially life-threatening fungal infections of a woman, if the expected benefit to the mother is significantly higher than the possible risk to the fetus.

Instructions for the use of Mikoflucan: method and dosage

Tablets

Tablets are taken orally, in a daily dose, depending on the nature and severity of the fungal infection. The duration of therapy is due to the clinical efficacy of fluconazole, confirmed by the results of mycological studies.

Recommended doses for adult patients and children over 15 years old, weighing more than 50 kg:

Cryptococcal meningitis and cryptococcal infections of other localizations: first day - 400 mg, then 200-400 mg 1 time / day, course duration - at least 6-8 weeks;
Prevention of recurrence of cryptococcal meningitis in patients with AIDS (upon completion of the full course of primary therapy): 200 mg / day, long-term;
Candidemia, disseminated candidiasis, other invasive candidal infections: the first day - 400 mg, then 200 mg / day (in case of insufficient clinical action, the dose can be increased to 400 mg / day), the duration of the course depends on the therapeutic efficacy of the drug;
Oropharyngeal candidiasis: 150 mg 1 time / day, course duration - 7-14 days; if necessary, patients with a pronounced decrease in immunity may be allowed to prolong therapy;
Prevention of recurrence of oropharyngeal candidiasis in patients with AIDS (upon completion of the full course of primary therapy): 150 mg once a week, for a long time;
Atrophic candidiasis of the oral cavity associated with the use of dentures: 50 mg 1 time / day, course duration - 14 days; at the same time the prosthesis is treated with local antiseptic preparations;
Other types of candidiasis (with the exception of genital) - esophagitis, non-invasive bronchopulmonary lesions, candiduria, candidiasis of the skin and mucous membranes: 150 mg / day, course duration - 14-30 days;
Vaginal candidiasis: 150 mg once; in order to reduce the frequency of relapses, Mikoflucan can be used at a dose of 150 mg once a month, the duration of the course is determined individually and can be from 4 to 12 months, in some cases, more frequent use of the drug may be necessary;
Balanitis caused by Candida: 150 mg once;
Prevention of candidiasis: from 50 to 400 mg (depending on the level of risk of infection) 1 time / day. In the case of a high probability of generalized infection, for example, in patients with long-term or expected severe neutropenia, a dose of 400 mg 1 time / day is recommended; prescribe fluconazole a few days before the probable appearance of neutropenia, and after an increase in the number of neutrophils ≥1000 / mm ^3, therapy is continued for another 7 days;
Mycoses of the skin, including mycoses of smooth skin, groin and skin of the feet: 50 mg 1 time / day or 150 mg 1 time / week; the standard duration of the course of therapy is 2-4 weeks, but with mycosis of the feet, longer treatment may be necessary - up to 6 weeks;
Pityriasis versicolor: 300 mg once a week for 2 weeks; in some cases, a single dose of 300-400 mg is sufficient, in a number of other episodes a third dose of 300 mg per week is required; alternative: 50 mg once a day for 2-4 weeks;
Onychomycosis: 150 mg once a week; the course of therapy continues until the infected nail is replaced with a regrown uninfected one (for full regrowth of nails on the fingers it takes from 3 to 6 months, on the toes - from 6 to 12 months);
Deep endemic mycoses: 200-400 mg / day, course duration - up to 2 years; the duration of therapy is determined individually and can be 11-24 months for coccidioidomycosis, 2-17 months for paracoccidioidomycosis, 1-16 months for sporotrichosis, and 3-17 months for histoplasmosis.

In children, the duration of therapy, as in adult patients, depends on the clinical picture and the mycological effect of the drug. The maximum daily dose in childhood is no more than 400 mg, the frequency of use is 1 time / day.

Esophageal 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 old (21-29 kg) - 50-100 mg;
10-15 years (30-50 kg) - 100-150 mg.

The duration of the course of therapy is at least 3 weeks, after the regression of symptoms, Mikoflucan should be continued for another 2 weeks.

Mucosal candidiasis - daily dose of 3 mg / kg, depending on age (body weight):

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

The duration of the course of therapy is at least 3 weeks.

Generalized candidiasis and cryptococcal infection (including meningitis) - daily dose 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 old (30-40 kg) - 200-350 mg;
13-15 years old (41-50 kg) - 250-400 mg.

The duration of the course of therapy is 10-12 weeks, until the absence of pathogens in the cerebrospinal fluid, confirmed by the results of laboratory tests.

Prevention of fungal infections in children with reduced immunity, in whom the risk of developing an infection is associated with neutropenia resulting from chemotherapy 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 old (21-29 kg) - 50-300 mg;
10-12 years old (30-40 kg) - 100-350 mg;
13-15 years old (41-50 kg) - 100-400 mg.

The duration of the course of therapy is until the confirmed elimination of induced neutropenia.

Children with impaired renal function should reduce the daily dose of the drug according to the severity of renal failure (similar to the scheme for adults).

Patients with renal insufficiency with creatinine clearance (CC) less than 50 ml / min, in the case of a single dose of the drug, a dose change is not required.

The dosage regimen needs to be adjusted depending on the QC with repeated use of fluconazole as follows - initially a loading dose of 50 mg to 400 mg is administered, then the daily dose (depending on the indications):

CC> 40 ml / min: usual dose 1 time / day;
QC 21-40 ml / min: the usual dose is 1 time in 48 hours (2 days) or half of the daily dose 1 time / day;
CC 10-20 ml / min: the usual dose is 1 time in 72 hours (3 days) or the third part of the daily dose 1 time / day.

Patients regularly on dialysis should receive one dose of the drug after each hemodialysis session.

In elderly patients, in the absence of impaired renal function, dose adjustment of fluconazole is not required.

Solution for infusion

The solution is administered intravenously (intravenously) dropwise at a rate of up to 200 mg / h. The daily dose of the drug depends on the nature and severity of the fungal infection.

There is no need to change the daily dose in case of switching from intravenous administration to tablets and vice versa. In this regard, when infusion therapy with fluconazole for adult patients and children, the dosage regimens given for Mikoflucan tablets are used.

Infusions are carried out using ordinary transfusion sets, one of the following solutions is used as a solvent: 20% glucose, Ringer's, Hartman's, potassium chloride in glucose, 4.2% sodium bicarbonate, 0.9% sodium chloride.

Use of the drug in newborns (taking into account the delayed elimination of fluconazole): the first 2 weeks of life - 1 dose (in mg / kg), the same as for older children, 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).

Adults and children with CC ≤50 ml / min in the case of a single dose of Mikoflucan do not need to change the dose. The dosage regimen needs to be adjusted depending on the QC with repeated use of fluconazole as follows: initially, a loading dose of 50 mg to 400 mg is administered, then the daily dose (depending on the indications in% of the recommended one):

CC> 50 - 100%;
CC <50 (without dialysis) - 50%;
Continuous hemodialysis - 100% after each session.

The content of 0.9% sodium chloride in the solution provides 15 mmol of sodium and chlorine ions in 100 ml, patients with the need for limited sodium or fluid intake need to take into account the rate of fluid administration.

Side effects

Allergic reactions: infrequently - skin rashes; rarely - Lyell's syndrome (toxic epidermal necrolysis), anaphylactoid reactions (including facial edema, angioedema, urticaria, itching of the skin), exudative erythema multiforme (including Stevens-Johnson syndrome);
Central nervous system: infrequently - dizziness, headache; rarely - convulsions;
Digestive system: infrequently - nausea, vomiting, diarrhea, abdominal pain, flatulence, change in taste; rarely - liver dysfunction (hyperbilirubinemia, increased activity of ACT, ALT and alkaline phosphatase, jaundice, hepatitis and hepatocellular necrosis) up to death;
Hematopoietic organs: rarely - thrombocytopenia, neutropenia, leukopenia, agranulocytosis;
Cardiovascular system: rarely - ventricular fibrillation / flutter, prolongation of the QT interval;
Other: rarely - alopecia, impaired renal function, hypercholesterolemia, hypokalemia, hypertriglyceridemia.

Overdose symptoms are hallucinations and paranoid behavior. Recommended symptomatic therapy, forced diuresis, gastric lavage. Conducting hemodialysis for 3 hours reduces the plasma concentration of fluconazole by approximately 50%.

special instructions

Therapy should be continued until complete recovery (clinical and hematological remission), since premature interruption of treatment leads to a resumption of the disease.

It is permissible to start treatment in the absence of laboratory test results, including culture, but after receiving them, an appropriate correction of antifungal therapy should be carried out.

In the course of treatment, it is necessary to monitor blood parameters, liver and kidney function; with the simultaneous use of coumarin anticoagulants, the prothrombin index should be monitored (in case of impaired liver and kidney function, the drug must be discontinued).

There have been rare cases of accompanying fluconazole intake with toxic changes in liver function. In the case of hepatotoxic effects associated with fluconazole, there was no obvious dependence on the daily dose taken, the duration of the course of treatment, the age and sex of the patient. The hepatotoxic effect of the drug is usually reversible; upon completion of therapy, its symptoms disappear. If clinical symptoms of liver damage appear, which can be associated with the use of fluconazole, the drug must be canceled.

Patients with AIDS have an increased tendency to develop severe cutaneous responses with the use of many drugs, including Mycoflucan.

When a rash develops with a superficial fungal infection, and its formation can be associated with the use of fluconazole, the drug must be canceled. If a rash appears in invasive / systemic fungal infections, they must be carefully monitored, and if erythema multiforme or bullous changes appear, fluconazole should be discontinued.

Drug interactions

Coumarin anticoagulants (warfarin): fluconazole increases their prothrombin time by 12% (on average), therefore, careful monitoring of this indicator is required;
Hydrochlorothiazide: increases the plasma concentration of fluconazole by 40% (a change in the dosage regimen of Mikoflucan is not required if patients are simultaneously receiving diuretics);
Zidovudine: its concentration increases, which is caused by a decrease in the transformation of zidovudine into its main metabolite, as a result of which its side effects may increase;
Combined contraceptives: their effectiveness is not affected by repeated use of fluconazole in doses from 50 to 200 mg;
Midazolam: increases its concentration and the risk of developing psychomotor reactions (more pronounced when taking fluconazole orally than when administered by infusion);
Sulfonylurea preparations (glibenclamide, glipizide, chlorpropamide and tolbutamide): their T _{1/2 is} lengthened, as a result of which hypoglycemia may develop (periodic monitoring of blood glucose concentration is required, if necessary, the dose of antidiabetic drugs is adjusted);
Rifabutin: an increase in its serum concentrations is possible, cases of uveitis have been described due to the combined use of rifabutin and fluconazole, therefore, when using it, careful monitoring is required;
Rifampicin: reduces the AUC (by 25%) and the duration of T _{1/2 of} fluconazole (by 20%), and therefore requires an increase in its dose;
Tacrolimus: its concentration increases, as a result of which the risk of nephrotoxic effects increases;
Theophylline: the duration of its T _{1/2 is} lengthened and the risk of intoxication increases (dose adjustment is required);
Terfenadine: simultaneous administration with fluconazole at doses of 400 mg per day or more is contraindicated; in doses up to 400 mg of fluconazole per day, terfenadine should be taken under close medical supervision;
Phenytoin: its concentration is increased to a clinically significant level (level control and dose selection are required in order to ensure a therapeutic concentration of phenytoin in serum);
Cisapride: possible undesirable effects on the part of the cardiovascular system, including paroxysmal ventricular tachycardia (arrhythmia of the "pirouette" type);
Cyclosporine: should monitor the value of its concentration in the blood.

Analogs

The analogues of Mikoflucan are: Fluconazole, Fluconazole Teva, Flucostat, Fucis, Flucorus, Flucomabol, Mikomax, Mikosist, Medoflucon, Diflucan, Diflazon.

Terms and conditions of storage

Store out of reach of children, dry and protected from light, at temperatures up to 25 ° C.

Shelf life:

Solution for infusion - 2 years;
Tablets - 3 years.

Terms of dispensing from pharmacies

The tablets are available without a prescription, the infusion solution is available with a prescription.

Reviews about Mikoflucan

Reviews of Mikoflucan as a drug for the treatment of various fungal infections with a moderate price are mostly favorable. The drug has proven to be highly effective in treating mycosis of the feet, but the duration of therapy in this case should be quite long. A positive result is observed with regular use of the drug and observance of hygiene rules (disinfection of the patient's shoes 1-2 times a month).

Also, patients note the rapid disappearance of symptoms of vaginal candidiasis during therapy with Mikoflucan, as well as an improvement in the condition in chronic pharyngomycosis and fungal chronic tonsillitis with exacerbations more than 10 times a year. The patients showed predominantly complete cure, confirmed by mycological and clinical studies. However, the drug should only be used as directed by a physician.

The price of Mikoflucan in pharmacies

The average price for a package of Mikoflucan containing 150 mg of fluconazole is in the range of 180-195 rubles. The solution for infusion is currently not available in pharmacies.

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!