Mycosyst, 150mg capsules, 1pc

Composition

1 capsule contains:

Active ingredient:

fluconazole 150 mg;

Auxiliary substances:

colloidal silicon dioxide;

magnesium stearate;

talc;

povidone;

corn starch;

anhydrous lactose.

Pharmacological action

Fluconazole is a representative of the class of triazole derivatives and is a selective inhibitor of sterol synthesis in fungal cells. Blocks the conversion of lanosterol from fungal cells to ergosterol; increases the permeability of the cell membrane. Fluconazole, being highly selective for fungal cytochrome P450, practically does not inhibit the cytochrome P450 system in the human body (in comparison with itraconazole, clotrimazole, econazole and ketoconazole, it suppresses oxidative processes dependent on cytochrome P450 in human liver microsomes to a lesser extent). It has no androgenic activity.

The drug is active in mycoses caused by Candida spp., Cryptococcus neoformans, Microsporum spp., Trichophyton spp., Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum.

Pharmacokinetics

After oral use, fluconazole is well absorbed, its bioavailability is 90%. Tmax after oral use on an empty stomach is 150 mg — 0.5-1.5 hours, and_cmax is 90% of the plasma concentration when administered intravenously at a dose of 2.5-3.5 mg / kg. Simultaneous food intake does not affect the absorption of the drug taken orally.

Plasma concentrations are directly proportional to the dose. 90% C_ss is achieved by the 4th-5th day of treatment with the drug (when taken once a day). The use of a dose on the first day,2 times higher than the usual daily dose, allows you to achieve a plasma concentration of fluconazole equal to 90% of the C_{ss value} by day 2. The apparent vd approaches the total water content of the body. Binding to plasma proteins is 11-12%.

Fluconazole penetrates well into all body fluids.

In the stratum corneum of the epidermis, dermis and sweat fluid, high concentrations are achieved that exceed serum levels. After oral use of 150 mg on the 7th day, the concentration in the stratum corneum of the skin is 23.4 mcg/g, and 1 week after taking the second dose-7.1 mcg/g; the concentration in the nails after 4 months of use at a dose of 150 mg once a week is 4.05 mcg / g in healthy and 1.8 mcg/g in affected nails.

Concentrations of the drug in saliva, sputum, breast milk, joint and peritoneal fluid are similar to its concentration in blood plasma. In patients with fungal meningitis, the content of fluconazole in the cerebrospinal fluid reaches 80% of its concentration in plasma.

Constant values in vaginal secretions are reached 8 hours after oral use and are kept at this level for at least 24 hours. It is an inhibitor of the CYP2C9 isoenzyme in the liver. The pharmacokinetics of fluconazole significantly depend on the functional state of the kidneys, and there is an inverse relationship between T_1/2 and creatinine clearance.

T_1/2 of fluconazole is about 30 h. Fluconazole is mainly excreted by the kidneys; approximately 80% of the administered dose is excreted unchanged by the kidneys,11% – in the form of metabolites. The clearance of fluconazole is proportional to creatinine clearance. No metabolites of fluconazole were detected in the peripheral blood.

After hemodialysis for 3 hours, the concentration of fluconazole in plasma decreases by 50%.

Indications

• skin, nail and internal organ fungi
• mucosal candidiasis
• antifungal cover up during antibiotic treatment.

Use during pregnancy and lactation

The use of fluconazole during pregnancy is possible only if the potential benefit to the mother outweighs the risk to the fetus.

Fluconazole is detected in breast milk at the same concentration as in plasma, so its use during lactation is contraindicated.

Contraindications

• concomitant use of terfenadine (compared to the continuous use of fluconazole at a dose of 400 mg/day and higher) and cisapride, because both drugs known to prolong the QT interval and increase the risk of developing severe arrhythmias;
• couse of astemizole;
• lactation (breastfeeding);
• lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
• hypersensitivity to the drug or similar in the structure of the azole compounds.

With caution: hepatic and/or renal insufficiency; rash associated with the use of fluconazole in patients with superficial fungal infection and invasive/systemic fungal infections; concomitant use of fluconazole with rifabutin or other drugs metabolized by cytochrome P450 isoenzymes; concomitant use of terfenadine and fluconazole at a dose of less than 400 mg/day; potentially proarrhythmogenic conditions in patients with multiple risk factors (organic heart disease, disorders of the electrolyte balance, simultaneous use of drugs that cause arrhythmias); intolerance to acetylsalicylic acid; pregnancy.

Side effects

From the digestive system:  nausea, vomiting, diarrhea, flatulence, abdominal pain, taste changes, impaired liver function (hyperbilirubinemia, increased activity of hepatic transaminases, alkaline phosphatase, jaundice, hepatitis, hepatocellular necrosis, including fatal ones).

Nervous system disorders:  headache, dizziness, convulsions.

From the side of hematopoietic organs:  leukopenia, thrombocytopenia, neutropenia, agranulocytosis.

Allergic reactions:  skin rash, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), anaphylactoid reactions (including angioedema, facial edema, urticaria, pruritus of the skin), bronchial asthma (more often with acetylsalicylic acid intolerance).

From the CCC side:  prolongation of the QT interval on the ECG, ventricular fibrillation/flutter.

Other services:  impaired renal function, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Interaction

Anticoagulants. Patients taking fluconazole and coumarin-type indirect anticoagulants should be carefully monitored PV, since it can increase.

Preparations of sulfonylureas. Concomitant use of fluconazole may prolong the T_1/2of sulfonylurea derivatives, so the possibility of hypoglycemia should be taken into account when using them together.

Phenytoin. Concomitant use of fluconazole and phenytoin may be accompanied by an increase in the concentration of phenytoin to a clinically significant extent, which requires a reduction in its dose.

Rifampicin. With simultaneous use of rifampicin and fluconazole, the_cmax and T_1/2of the latter decreases, so if combined use is necessary, the dose of fluconazole should be increased.

Rifabutin. The combined use of fluconazole and rifabutin is accompanied by an increase in the serum concentration of the latter, and uveitis may develop.

Cyclosporine. When using fluconazole and cyclosporine together, it is recommended to monitor the concentration of the latter in the blood, since it may increase.

Terfenadine. Given the occurrence of serious, life-threatening arrhythmias in patients taking antifungal agents-azole derivatives in combination with terfenadine, their combined use is contraindicated.

Cisapride. Adverse cardiac reactions, including ventricular tachycardia, have been reported with concomitant use of fluconazole and cisapride. Simultaneous use is contraindicated.

Zidovudine. When combined with fluconazole, an increase in the concentration of zidovudine in blood plasma is possible. Patients taking this combination should be monitored for side effects of zidovudine.

Theophylline. Taking fluconazole leads to a decrease in the average rate of clearance of theophylline from blood plasma, therefore, the risk of developing toxic effects of theophylline and its overdose increases.

Midazolam. Concomitant use of fluconazole and midazolam leads to a significant increase in the concentration of the latter in blood plasma and the risk of psychomotor reactions.

Hydrochlorothiazide. Concomitant use of fluconazole and hydrochlorothiazide increases the concentration of fluconazole in blood plasma by 40%.

Tacrolimus. Concomitant use of fluconazole and tacrolimus increases the concentration of the latter in the blood serum, which leads to an increased risk of nephrotoxicity.

Caution should be exercised when using fluconazole in patients receiving concomitant treatment with other drugs that are metabolized by the cytochrome P450 system.

How to take it, course of use and dosage

Use in adults

For cryptococcal infections, the usual dose of fluconazole is 400 mg once a day on the first day of treatment, then 200-400 mg once a day. The duration of treatment for cryptococcal infections depends on the clinical efficacy confirmed by mycological examination, and usually ranges from 6 to 8 weeks.

The recommended duration of treatment in the treatment of cryptococcal meningitis is 10-12 weeks after a negative result of microbiological examination of the cerebrospinal fluid sample.

To prevent recurrence of cryptococcal meningitis in AIDS patients after completing a full course of primary therapy, fluconazole is prescribed to the patient at a dose of at least 200 mg per day for a long period.

For candidaemia, disseminated candidiasis and other invasive candida infections, the daily dose of fluconazole is 400 mg on the first day and 200 mg on subsequent days. If necessary, the dose of the drug can be increased to 400 mg / day. The duration of treatment depends on the clinical efficacy.

In severe systemic candidiasis, the dose may be increased to 800 mg / day. The duration of therapy depends on the clinical efficacy. It should be continued for at least 2 weeks after receiving a negative hemoculture or after the symptoms of the disease disappear.

In oropharyngeal candidiasis, including patients with immune disorders, the usual dose of fluconazole is 50-100 mg / day for 7-14 days. To prevent relapses of oropharyngeal candidiasis in AIDS patients after completing a full course of primary therapy — 150 mg once a week. If necessary, treatment can be extended, especially for severe immune disorders.

For atrophic oral candidiasis associated with wearing dentures, fluconazole is usually prescribed 50 mg / day for 14 days in combination with antiseptic agents to treat the prosthesis.

For other candida infections, such as esophagitis, noninvasive bronchopulmonary infections, candidiasis, candidiasis of the skin and mucous membranes, the daily dose is 50-100 mg for 14-30 days.

For severe candidiasis of the mucous membranes-100-200 mg / day.

To prevent fungal infections in patients with malignant neoplasms, the dose of fluconazole should be 50 mg / day as long as the patient is at increased risk due to cytostatic or radiation therapy.

For vaginal candidiasis — 150 mg once. To reduce the frequency of relapses, use 150 mg once a month for 4-12 months, sometimes more frequent use may be required.

For balanitis caused by Candida spp., fluconazole is prescribed once in a dose of 150 mg orally (capsules).

For the prevention of candidiasis, the recommended dose of fluconazole is 50-400 mg / day, depending on the degree of risk of fungal infection. If there is a high risk of generalized infection, for example in patients with expected severe or long-term persistent neutropenia, the recommended dose is 400 mg / day. Fluconazole is prescribed a few days before the expected occurrence of neutropenia; after an increase in the number of neutrophils more than 1000/mm3, treatment is continued for another 7 days.

For mycoses of the skin (including candidiasis), including mycoses of the feet, skin, groin, the recommended dose is 150 mg once a week or 50 mg/day. The duration of therapy in normal cases is 2-4 weeks, but with mycoses of the feet, longer therapy may be required — up to 6 weeks (capsules).

With pityriasis versicolor — 300 mg once a week for 2 weeks, some patients require a third dose of 300 mg / week, while in some cases a single dose of 300 mg is sufficient; an alternative treatment regimen is the use of 50 mg / day for 2-4 weeks (capsules).

For onychomycosis, the recommended dose is 150 mg once a week. Treatment should be continued until the infected nail is replaced with a healthy one. For the re-growth of nails on the fingers and feet, it normally takes 3-6 and 6-12 months, respectively (capsules).

With deep endemic mycoses, the drug may need to be used at a dose of 200-400 mg / day for 2 years. The duration of therapy is determined individually; it can be 11-24 months for coccidioidosis; 2-17 months for paracoccidioidosis and 3-17 months for histoplasmosis.

Use in children

The duration of treatment depends on the clinical and mycological effect. In children, the drug should not be used in a daily dose exceeding that of adults. Fluconazole is used daily once a day.

For mucosal candidiasis, the recommended dose of fluconazole is 3 mg / kg / day. On the first day, a shock dose of 6 mg/kg may be prescribed in order to achieve C_{ss more quickly}.

For the treatment of generalized candidiasis and cryptococcal infection, the recommended dose is 6-12 mg / kg / day, depending on the severity of the disease.

For the prevention of fungal infections in children with reduced immunity, in whom the risk of infection is associated with neutropenia, which develops as a result of cytotoxic chemotherapy or radiation therapy, the drug is prescribed at 3-12 mg / kg / day, depending on the severity and duration of preservation of induced neutropenia.

In newborns, fluconazole is excreted more slowly, so in the first 2 weeks of life, the drug is prescribed at the same dose (in mg/kg) as in older children, but with an interval of 72 hours. Children aged 3-4 weeks of life are given the same dose at intervals of 48 hours.

Use in elderly patients

In the absence of impaired renal function, the usual dosage recommendations should be followed. For patients with impaired renal function (creatinine clearance

Use in patients with renal insufficiency

, Fluconazole is mainly excreted unchanged by the kidneys. With a single dose of fluconazole, no dose change is required. If a course of treatment is necessary in patients (including children) with impaired renal function, an initial shock dose of 50 to 400 mg should be prescribed. In the future, the daily dose (depending on the indication) is determined according to the following method: with creatinine clearance >50 ml / min-100% of the recommended dose once a day; with creatinine clearance>

Overdose

Symptoms: nausea, vomiting, diarrhea; in severe cases, seizures, hallucinations, paranoid behavior may occur.

Treatment: symptomatic (gastric lavage, forced diuresis, hemodialysis). After a 3-hour hemodialysis session, the concentration of fluconazole in the blood plasma decreases by approximately 50%.

Special instructions

Treatment with fluconazole should be continued until clinical and hematological remission occurs. Premature discontinuation of treatment leads to relapses.

Since fluconazole is primarily excreted by the kidneys, caution should be exercised in patients with renal insufficiency. In long-term treatment with fluconazole, dosage should be adjusted for creatinine clearance. In rare cases, the use of fluconazole was accompanied by a toxic effect on the liver, including with a fatal outcome, mainly in patients with serious concomitant diseases. Liver function should be monitored. If there are signs of liver damage that may be associated with taking fluconazole, the drug should be discontinued.

While taking the drug, rare cases of exfoliative skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, were observed in patients. Patients with AIDS and malignant neoplasms are more likely to develop severe skin reactions when using many medications. If a patient develops a rash during treatment of a superficial fungal infection that may be associated with the use of fluconazole, the drug should be discontinued.

If a rash appears in patients with invasive / systemic fungal infections, they should be carefully monitored and discontinue fluconazole if bullous lesions or erythema multiforme occur. Caution should be exercised when taking fluconazole concomitantly with rifabutin or other drugs that are metabolized by the cytochrome P450 system.

It is necessary to control PV in patients receiving concomitant treatment with fluconazole and coumarin-type indirect anticoagulants.

Influence on the ability to drive a car and work with other mechanical means. Patients should be careful when driving vehicles or working with machinery, as dizziness may occur during treatment with fluconazole.

Form of production

Capsules

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

5 years

Active ingredient

Fluconazole

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

Pregnant women as prescribed by a doctor, For adults, Children as prescribed by a doctor

Indications

Thrush, Fungus, Nail Fungus, Skin Fungus