Expiration date: 05/2025

Release form and composition:

hard gelatine capsules, size ?3, with a blue cap and white body

1 caps. contains fluconazole 150 mg

Excipients: lactose monohydrate, pregelatinized corn starch, colloidal silicon dioxide, sodium lauryl sulphate, magnesium stearate.

Pharmachologic effect:

Antifungal drug from the group of triazole. It has a highly specific action, inhibiting the activity of fungal enzymes dependent on cytochrome P450. Blocks the conversion of lanosterol fungal cell membrane lipid - ergosterol, increases the permeability of cell membranes, violates its growth and replication.

It is active against fungi: Candida spp, Micrsprum spp, Trichphytn spp, Cryptcccus nefrmans, Bastmyces dermatitidis, Cccidiides immitis, Histpasma capsuatum....

Fluconazole, being highly selective for fungal cytochrome P450, practically does not inhibit these enzymes in the body.

Pharmacokinetics:

Suction

After receiving Medoflucon inside fluconazole is well absorbed from the gastrointestinal tract. Simultaneous food intake has no effect on the absorption of the drug. The bioavailability is about 90%. Cmax plasma achieved through 0.5-1.5 h after administration of fasting, 150 mg.

Distribution

Binding to plasma proteins - 11-12%. Plasma concentration directly proportional to the dose. When receiving the drug orally 1 time / day Css achieved in 4-5 day of treatment. After a few introductions 1 dose per day 90% Css achieved in 4-5 day of treatment. Ingestion or in / in a loading dose (on the first day of treatment) to 2 times the usual daily dose, achieves 90% Css to the 2nd day of treatment.

Fluconazole penetrates well into all body fluids like after ingestion and after / in the introduction. Concentrations of drug in breast milk, joint fluid, saliva, sputum, peritoneal fluid, and similar to its level in plasma. A constant level is achieved in vaginal secretions after 8 hours after oral administration and is maintained at this level for at least 24 hours. It penetrates into the cerebrospinal fluid of patients with meningitis candidiasis fluconazole content in cerebrospinal fluid reaches 85% of its level in plasma.

In the stratum corneum and epidermis, dermis and sweat fluid to achieve high concentrations of the drug in excess of plasma.

After oral administration of 150 mg on day 7 the concentration in the stratum corneum of 23.4 g / g, and a week after the second dose - 7.1 g / g concentration in the nails after 4 months using 150 mg 1 time per week is 4.05 g / g in healthy and 1.8 ug / g - in the affected nails.

Vd is close to the total water content in the body.

Metabolism

Fluconazole metabolites detected in the peripheral blood.

breeding

T1 / 2 is 30 h.

Fluconazole is derived mainly kidneys (80% - unchanged, 11% - in the form of metabolites). Fluconazole clearance is proportional to creatinine clearance.

Pharmacokinetics in special clinical situations

The pharmacokinetics of fluconazole significantly depends on renal function, with an inverse relationship between the T1 / 2 and creatinine clearance. After dialysis for 3 hr in the plasma concentration of fluconazole is reduced by 50%.

Indications:

• System cryptococcosis, including cryptococcal meningitis, sepsis, infections at other sites (e.g., lung, skin), in patients with a normal immune response, and patients with various forms of immunodepression (including AIDS patients, recipients of transplanted organs )
  
• Prevention of relapse of cryptococcosis in AIDS patients
  
• Generalized candidiasis including candidemia, disseminated candidiasis with endocardial lesions, abdominal, respiratory, eye, urogenital organs (including in patients receiving a course of cytostatic and immunosuppressive therapy, as well as the presence of other factors predisposing to the development of candidiasis)
  
• Candidiasis mucous membranes, including oral cavity and pharynx, esophagus, non-invasive bronchopulmonary candidiasis, candiduria, mucocutaneous and chronic oral atrophic candidiasis (associated with wearing dentures)
  
• Genital candidiasis: vaginal candidiasis (acute or recurrent), balanitis
  
• Prevention of fungal infections in patients with malignant tumors to chemotherapy or radiation therapy
  
• Prevention of relapse of oropharyngeal candidiasis in patients with AIDS
  
• Fungal infections of the skin, including tinea pedis, body, groin, pityriasis versicolor, onychomycosis and skin candida infection
  
• Deep endemic mycoses (coccidioidomycosis, histoplasmosis and sporotrichosis) in patients with normal immunity.
  

Dosage and administration:

Set individually depending on the nature and severity of mycotic infections.

The drug is taken by mouth or injected into / in the drip basically 1 time / day. B / drip is administered at a rate not exceeding 20 mg / min. When translating from / in the introduction to the capsules and vice versa is not necessary to change the daily dose.

Infusion Medoflucon can be carried out using conventional kits for transfusion, using one of the following infusion solutions, which is suitable for formulation: 20% dextrose solution, Ringer's solution, Hartmann solution in dextrose, potassium chloride, sodium bicarbonate 4.2% aminofuzin, isotonic sodium chloride.

Adults with cryptococcal infection, candidemia, disseminated candidiasis and other invasive Candida infections drug appointed interior or / drip in the first day of 400 mg, followed by 200-400 mg 1 time / day. The duration of treatment depends on the presence of clinical and mycological effect (in cryptococcal meningitis it is usually continued for at least 6-8 weeks).

For the prevention of relapse of cryptococcal meningitis in patients with AIDS or drug appointed interior / drip in a dose of 200 mg / day for a long time.

In oropharyngeal candidiasis (including patients with impaired immunity) drug is prescribed inside or / in 50-100 mg 1 time / day for 7-10 days, in immunocompromised patients - for 14 days or more. For the prevention of relapse of oropharyngeal candidiasis in patients with AIDS, after the completion of a full course of primary therapy, fluconazole may be assigned inside on 150 mg 1 times / week.

In atrophic oral candidiasis associated with wearing dentures, the drug is administered orally at a dose of 50 mg 1 time / day for 14 days in combination with a local antiseptic for the treatment of the prosthesis.

Vaginal candidiasis drug is administered a single oral dose of 150 mg. To reduce the frequency of relapses vaginal candidiasis drug may be used in a dose of 1 150 mg once / month for 4-12 months. Some patients may require more frequent application.

When balanitis caused of Candida, a drug administered a single oral dose of 150 mg / day.

For the prevention of candidiasis recommended dose by ingestion is 50-400 mg 1 time / day, depending on the degree of risk of fungal infection. If you have a high risk of generalized infection, eg in patients with severe or long-anticipated persistent neutropenia, the recommended dose is 400 mg 1 time / day. Fluconazole is administered a few days before the expected occurrence of neutropenia after the increase in the number of neutrophils more than 1000 cells / ml treatment was continued for 7 days.

When candidemia, disseminated candidiasis and other invasive Candida infections, the drug is introduced into / in the drip in the first day at a dose of 400 mg in the following days - 200 mg / day. Depending on the clinical efficacy of the dose can be increased to 400 mg / day. The duration of treatment depends on the clinical effectiveness.

In other Candida infections (including with esophagitis, non-invasive bronchopulmonary infections, candiduria, candidiasis of the skin and mucous membranes) dose for ingestion (except genital candidiasis), or administration / drip is usually 50-100 mg / day for 14-30 days.

When skin infections including tinea pedis, smooth skin, groin and candida infections, the recommended dose is 150 mg 1 time / week. or 50 mg 1 time / day. Duration of therapy in ordinary cases is 2-4 weeks. However if athlete's foot may require a more prolonged treatment (up to 6 weeks.).

In pityriasis versicolor the recommended dose is 300 mg 1 time / week. for 2 weeks, some patients required a third dose of 300 mg / wk., while in some cases it is sufficient single dose of the drug in doses of 300-400 mg. An alternative regimen is the use of the drug at 50 mg 1 times / day for 2-4 weeks.

In onychomycosis the recommended dose is 150 mg 1 time / week. Treatment should be continued until the replacement of the infected nail (uninfected nail sprouting). For the re-growth of nails on the fingers and feet normally required 3-6 months and 6-12 months, respectively.

In deep endemic mycoses may require use of the drug at a dose of 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 with paracoccidioidomycosis, 1-16 months with sporotrichosis and 3-17 months in histoplasmosis.

For the prevention of fungal infections in patients with malignancies dose of fluconazole at / in the drip is 50 mg 1 time / day for as long as the patient is at high risk due to cytostatic or radiation therapy.

In elderly patients with no signs of renal failure, the drug is used in high doses.

In children, the drug should not be applied in a daily dose greater than that of adults. Features of the formulation makes it impossible to use of the drug inside the very small children. Fluconazole is used every day 1 time / day.

When mucosal candidiasis fluconazole recommended dose is 3 mg / kg / day for at least 3 weeks, with esophageal candidiasis dose of 3 mg / kg body weight for at least 3 weeks, within 2 weeks after symptoms regression.

For the treatment of generalized candidiasis and cryptococcal infections (including meningitis), the recommended dose for ingestion or / drip is 6-12 mg / kg / day, depending on the severity of the disease for 10-12 weeks (before laboratory confirmation the absence of pathogens in the CSF).

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

Neonates fluconazole children displayed more slowly, so the first 2 weeks of life, the drug is prescribed in / drip in the same dose (in mg / kg body weight) as older children, but with an interval of 72 hours. Children aged 3 and 4 weeks the same dose administered every 48 hours.

Patients with renal insufficiency (KKt50 ml / min) require a correction mode. In patients (including children) with impaired renal function should initially assign inside or / drip in a loading dose of 50 mg to 400 mg. Subsequently, with CC 50 ml / min, the average daily dose is administered at from 50 QC to 11 ml / min - 50% of the recommended daily dose or high dose of 1 every 2 days. Patients who are on hemodialysis, appoint 1 dose of the drug after each session.

Side effects:

From the digestive system: loss of appetite, nausea, constipation or diarrhea, flatulence, abdominal pain, toothache, rarely - liver dysfunction (ikterichnost sclera, jaundice, hyperbilirubinemia, increased activity of ALT, AST and ALP).

CNS: headache, dizziness, fatigue, rarely - seizures.

Hematopoietic system: rarely - leukopenia, thrombocytopenia (bleeding, petechiae), neutropenia, agranulocytosis.

Allergic reactions: skin rash, rarely - erythema multiforme, a malignant exudative erythema (Stevens-Johnson syndrome) and toxic epidermal necrolysis (Lyell's syndrome), anaphylactoid reactions.

Other: rarely - renal dysfunction, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Contraindications:

• Hypersensitivity to the drug or similar in structure triazole compounds.
  

Pregnancy and lactation:

Use of the drug Medoflucon during pregnancy is possible only when the intended benefits to the mother outweighs the potential risk to the fetus.

If necessary, use during lactation should decide the issue of termination of breastfeeding, because Fluconazole is excreted in breast milk in the same concentration as in plasma.

Special instructions:

With extreme caution should be used drug in the liver and / or kidney failure while receiving potentially hepatotoxic drugs, alcoholism.

Treatment should be continued until clinical and laboratory remission. Premature discontinuation of treatment leads to relapse.

Treatment can be started in the absence of culture results or other laboratory tests, but if any corresponding correction is recommended fungicide treatment.

In the course of treatment is necessary to monitor blood counts, liver and renal function. If the intake of the drug lead to abnormalities in the kidneys and liver, taking Medoflucon should be discontinued. Hepatotoxic action of Fluconazole is usually reversible, symptoms disappear after cessation of therapy. In rare cases, the use of fluconazole was accompanied by toxic effects on the liver, including fatalities, primarily in patients with serious underlying medical conditions of patients.

When a skin rash in patients with immunosuppression should be carefully monitored, and if the progression of skin rash treatment should be discontinued (risk of the syndrome of Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).

When applied against treatment Medoflucon cyclosporine in patients after renal transplantation should be carefully monitored in the plasma levels of cyclosporin, as Medoflucon receiving 200 mg / day results in a slow increase in the plasma concentration of cyclosporine.

Use in Pediatrics

With careful use medication in children. Safety and effectiveness of Medoflucon in children under the age of 6 months have not been established.

Overdose:

Symptoms: hallucinations, paranoid behavior.

Treatment: gastric lavage, diuresis, when necessary, a symptomatic therapy, hemodialysis for 3 hours reduces the plasma concentration of about 50%.

Drug Interactions:

In an application Medoflucon with terfenadine, astemizole, and cisapride increases their concentration in plasma and increased risk of serious, life-threatening arrhythmias, including ventricular tachycardia paroxysms (pirouette type of arrhythmia).

In an application Medoflucon and indirect anticoagulants increases their effect and increases (using warfarin an average of 12%), prothrombin time (prothrombin time monitoring is recommended).

Medoflucon a joint application and oral hypoglycemic drugs (sulfonylurea derivatives) increased T1 / 2 of the latter, which can lead to hypoglycemia (dose required correction hypoglycemic agents).

In an application Medoflucon with hydrochlorothiazide, and other diuretics may increase the plasma concentrations of fluconazole by 40%.

In an application with rifampicin Medoflucon T1 / 2 of rifampicin is reduced by 20%, AUC - 25% (combined, if necessary, should increase the dose of fluconazole).

In an application Medoflucon and theophylline increases T1 / 2 of the latter and increases the risk of toxic effects (requires dose adjustment of theophylline).

With simultaneous application Medoflucon phenytoin and may increase the plasma concentration of the latter (recommended control phenytoin concentrations in plasma and, if necessary, its correction dose).

On an application Medoflucon zidovudine and an increase in the concentration of the latter in plasma and increased risk of side effects of zidovudine.

At simultaneous application with cyclosporine Medoflucon rifabutin and an increase in their concentration in plasma are described cases of uveitis in the background of the simultaneous application.

Be wary of Medoflucon concurrently with other drugs metabolized isoenzymes of cytochrome P450.

Pharmaceutical incompatibility.

Fluconazole incompatibilities with other medicinal products are not described, but it is not recommended to mix the solution Medoflucon with solutions of other drugs prior to infusion.

Conditions and terms:

The drug should be stored in a dry, dark place at a temperature no higher than 25 ° C. Shelf life caps - 4, the solution for infusion - 3 years.

Avoid freezing solution for infusion.