Expiration date: 01/2025

Structure and Composition:

The capsules. 1 caps. contains Fluconazole 50, 100 or 150 mg

Additional ingredients: colloidal silicon dioxide, magnesium stearate, talc, povidone (PVP K30) corn starch lactose (anhydrous)

composition of hard gelatin capsules:

lower part - titanium dioxide (C.I. 77891 / E171), gelatin

upper part - indigo carmine (C.I. 73015 / E132), titanium dioxide (C.I. 77891 / E171), gelatin

in a blister made of PVC and aluminum foil 7 pcs. In the paper cartons 1 blister (50 mg) in a blister pack 7 pcs. bundle in a cardboard blister 4 (100 mg) in a blister 1 pc. In the paper cartons 1 or 2 blisters (150 mg).

Solution for infusion 100 ml (1 fl.)

fluconazole 200 mg

Excipients: sodium chloride, water for injection

in bottles of 100 ml per box 1 bottle.

Description pharmaceutical form:

Capsules 50 mg: content - white or nearly white powder or powdered dense mass. Hard gelatin capsule size ?4 (Coni-Snap). The upper part - light blue, opaque (L910), bottom - white, opaque (L500).

Capsules 100 mg: content - white or nearly white powder or powdered dense mass. Hard gelatin capsule size ?2 (Coni-Snap). The upper part - turquoise, opaque (L890), bottom - white, opaque (L500).

Capsules 150 mg: content - white or nearly white powder or powdered dense mass. Hard gelatin capsule size ?1 (Coni-Snap). The upper part - blue, opaque (L860), bottom - white, opaque (L500).

Solution for infusion: colorless or slightly colored clear solution.

Pharmacokinetics:

After oral administration fluconazole is well absorbed, bioavailability - 90%. Cmax after oral administration on an empty stomach, at a dose of 150 mg is 90% of the content in plasma with a / in a dose of 2.5-3.5 mg / l. Simultaneous food intake has no effect on the absorption of the drug taken orally. The concentration in plasma reaches a peak after 0.5-1.5 hours after administration, T1 / 2 -. About 30 hours, plasma concentrations are directly proportional to the dose. 90% of the level of the equilibrium concentration is achieved in 4-5 day drug treatment (when taking 1 per day or after a few injections of 1 dose per day).

Administering a loading dose (first day), 2 times the normal daily dose, achieves a level corresponding to 90% of the equilibrium concentration of the second day. The apparent volume of distribution close to the total water content in the body. Binding to plasma proteins - 11-12%.

Fluconazole penetrates well into all body fluids. Drug concentrations in saliva and sputum are similar to its level in plasma. In patients with fungal meningitis, fluconazole content in cerebrospinal fluid is 80% of its level in plasma.

In the stratum corneum, epidermis, dermis and liquid sweat to achieve high concentrations which exceed the serum.

Fluconazole is derived mainly kidneys approximately 80% of the administered dose is excreted in the urine in unchanged form. Fluconazole clearance is proportional to creatinine clearance. Fluconazole metabolites detected in the peripheral blood.

Description of the pharmacological actions:

Fluconazole - a new class of triazole antifungal agents is a selective inhibitor of sterol synthesis in the fungal cell. Effective for opportunistic fungal infections, including 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.

Indications:

• cryptococcosis, including cryptococcal meningitis and other localization of the infection (including lung, skin), in patients with a normal immune response, and patients with various forms of immunosuppression (including AIDS patients, organ transplant ) for preventing cryptococcal infection in AIDS patients
  
• generalized candidiasis including candidemia, disseminated candidiasis and other forms of invasive Candida infections (infections of the peritoneum, endocardium, eyes, respiratory and urinary tract). The treatment can be carried out in patients with cancer, patients in intensive care units, patients undergoing a course of cytostatic or immunosuppressive therapy, as well as the presence of other factors predisposing to the development of candidiasis
  
• mucosal candidiasis, including oral cavity and pharynx (including atrophic oral candidiasis associated with wearing dentures), esophageal, non-invasive bronchopulmonary candidiasis, candiduria, skin candidiasis prevention of relapse of oropharyngeal candidiasis in patients with AIDS
  
• Genital candidiasis: vaginal candidiasis (acute and chronic recurrent, including prophylactic use to reduce the frequency of relapses of vaginal candidiasis with three or more episodes per year), candidal balanitis
  
• prevention of fungal infections in patients with malignancies who are predisposed to such infections as a result of chemotherapy or radiation therapy with cytostatics
  
• fungal infections of the skin, including tinea pedis, body, groin pityriasis versicolor, onychomycosis candidiasis skin
  
• deep endemic mycoses, including coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immunity.
  

Contraindications:

• hypersensitivity to the drug or similar in structure azole compounds
  
• concomitant use of terfenadine, astemizole, cisapride and other drugs that prolong the QT interval
  
• pregnancy
  
• breastfeeding
  
• Children up to age 6 months (caps.).
  

Application of pregnancy and breastfeeding:

Use of the drug in pregnant women is inappropriate, except in severe or life-threatening forms of fungal infections if the intended effect is greater than the potential risk to the fetus.

Fluconazole is in the breast milk at the same concentration as in plasma, so its function during breast feeding is not recommended.

Side effect:

From the digestive system: nausea, diarrhea, flatulence, abdominal pain, rarely - liver dysfunction (hyperbilirubinemia, increased alanine aminotransferase activity, aspartate aminotransferase, increased alkaline phosphatase activity).

From the nervous system: headache, rarely - seizures.

From the side of hematopoiesis: 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 - renal dysfunction, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Drug Interactions:

When using fluconazole and warfarin increased the prothrombin time (an average of 12%). In this connection, it is recommended to closely monitor the performance of the prothrombin time in patients receiving the drug in combination with coumarin anticoagulants.

Fluconazole increases the plasma half-life of oral hypoglycemic agents - sulfonylureas (chlorpropamide, glibenclamide, glipizide, tolbutamide) in healthy people. The combined use of fluconazole and oral hypoglycemic agents in patients with diabetes may be, however, the physician should bear in mind the possibility of hypoglycemia.

Simultaneous administration of fluconazole and phenytoin can lead to an increase in the plasma concentration of phenytoin to a clinically significant degree. Therefore, if necessary, the joint use of these drugs need to monitor the concentration of phenytoin with the dose adjusted to maintain drug levels within the therapeutic range.

Combination with rifampicin reduces AUC by 25% and shorten the half-life of fluconazole from plasma by 20%. Therefore, patients receiving concomitant rifampicin, the dose of Fluconazole is expedient to increase.

It is recommended to monitor the blood concentration of cyclosporine in patients receiving fluconazole since in patients receiving a transplanted kidney Fluconazole, 200 mg / day results in a slow increase in the plasma concentration of cyclosporine.

Patients who are receiving high doses of theophylline or who have a chance of developing theophylline toxicity should be kept under observation for early detection of the symptoms of theophylline overdose because receiving fluconazole reduces the average clearance rate of theophylline plasma.

With simultaneous use of fluconazole and cisapride described cases of adverse reactions on the part of the heart, including paroxysms of ventricular tachycardia (torsades de points).

There are reports about the interaction of fluconazole and rifabutin, the latter accompanied by an increase in serum levels. With simultaneous use of fluconazole and rifabutin uveitis cases are described. We must carefully monitor patients while receiving rifabutin and fluconazole.

In patients receiving the combination of zidovudine and fluconazole observed increased concentrations of zidovudine, which is caused by a decrease in the conversion of the latter into its main metabolite, so you should expect an increase in the side effects of zidovudine.

Dosage and administration:

Orally (capsule) in / (a ??solution for infusion). Adults with cryptococcal meningitis and cryptococcal infections at other sites on the first day - usually 400 mg, then - 200-400 mg 1 time per day. The duration of treatment for cryptococcal infections depends on the clinical efficacy, confirmed by mycological examination in cryptococcal meningitis it is usually continued for at least 6-8 weeks.

For the prevention of recurrence of cryptococcal meningitis in AIDS patients, after completion of the primary full course of treatment - 200 mg / day for a long period of time.

When candidemia, disseminated candidiasis and other invasive Candida infections, the usual dose - 400 mg on the first day, then - 200 mg. When insufficient clinical efficacy of the dose can be increased to 400 mg / day. The duration of therapy depends on clinical efficacy.

In oropharyngeal candidiasis - 50-100 mg 1 time per day duration of treatment - 7-14 days. If necessary, in patients with severe depression of immunity treatment may be longer.

In atrophic oral candidiasis associated with wearing dentures - 50 mg 1 time per day for 14 days in combination with local antiseptic agents for treatment of prosthesis.

In other locales candidiasis (except genital candidiasis), such as oesophagitis, noninvasive bronchopulmonary lesions, candiduria, candidiasis of the skin and mucous membranes, etc., the effective dose - 50-100 mg / day, with a duration of treatment 14-30 days. For the prevention of relapse of oropharyngeal candidiasis in patients with AIDS, after the completion of a full course of primary therapy - 150 mg 1 time per week.

Vaginal candidiasis - a single oral dose of 150 mg. To reduce the frequency of relapses of vaginal candidiasis - 150 mg 1 time per month. The duration of therapy is determined individually, it varies from 4 to 12 months. Some patients may require more frequent application.

When balanitis caused by Candida, - a single dose of 150 mg orally.

For the prevention of candidiasis recommended dose - 50-400 mg 1 time per 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 - 400 mg 1 time per day. Fluconazole is administered a few days before the expected occurrence of neutropenia after the increase in the number of neutrophils over 1000 / mm3 treatment should be continued for a further 7 days.

When mycosis of the skin, including tinea pedis, skin groin and skin candidiasis the recommended dose - 150 mg 1 time per week or 50 mg 1 time per day. Duration of therapy in normal cases - 2-4 weeks, but with athlete's foot may require a more prolonged treatment (up to 6 weeks).

When pityriasis versicolor - 300 mg 1 time per week for 2 weeks, and some patients required a third dose of 300 mg per week, while in some cases it is sufficient single dose of 300-400 mg alternative regimen is the use of 50 mg 1 time daily for 2-4 weeks.

In onychomycosis the recommended dose - 150 mg 1 time per 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 - at a dose of 200-400 mg / day for up to 2 years. The duration of therapy is determined individually with coccidioidomycosis - 11-24 months paracoccidioidomycosis - 2-17 months sporotrichosis - 1-16 months histoplasmosis - 3-17 months.

In children, as well as with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. In children, the drug should not be applied in a daily dose that would be higher than that of adults. The drug is used every day 1 time per day.

When mucosal candidiasis recommended dose - 3 mg / kg / day. The first day can be assigned to a loading dose of 6 mg / kg in order to more quickly achieve constant equilibrium concentrations.

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

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 radiotherapy - at 3-12 mg / kg / day, depending on the severity and duration of preservation-induced neutropenia.

Neonates fluconazole displayed slowly, so the first two weeks of life drug administered in the same dose (in mg / kg) as that of the older children, but with a 72 hour interval. Children aged 3 and 4 weeks of life the same dose administered every 48 hours.

In children with impaired renal function daily dose should be reduced (in the same proportion as in adults), in accordance with the severity of renal insufficiency.

In elderly patients without renal dysfunction should follow the usual dose regimen of the drug. Patients with renal insufficiency (Cl creatinine <50 ml / min), the dosing regimen should be adjusted as described below.

Fluconazole is derived mainly from the urine in unchanged form. When receiving a single dose of its change is not required. With the reappointment of the drug to patients with impaired renal function should first enter a loading dose of 50 to 400 mg. When Cl creatinine more than 50 ml / min, applied the usual dose (100% of the recommended dose). When Cl creatinine of 11 to 50 ml / min is applied dose equal to 50% of the recommended. Patients regularly on dialysis one dose is applied after each hemodialysis session.

A solution for infusion is compatible with the following solvents: 20% glucose solution, Ringer's solution, Hartmann's solution, sodium chloride, potassium glucose, sodium bicarbonate, 4.2% aminofuzinom, isotonic sodium chloride solution.

Overdose:

Symptoms: hallucinations, paranoid behavior.

Treatment: symptomatic, gastric lavage, forced diuresis. Haemodialysis for 3 hours reduces the plasma concentration of approximately 50%.

Special instructions:

In rare cases, the use of fluconazole was accompanied by toxic liver changes, including fatalities, primarily in patients with serious underlying medical conditions. In the case of hepatotoxic effects associated with fluconazole, no obvious dependence of the total daily dose, duration of therapy, the patient's age and sex. Hepatotoxic effects of fluconazole was usually reversible signs of it disappeared after discontinuation of therapy. When clinical signs of liver damage, which 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. In cases where patients with superficial fungal infection develops a rash, and she is regarded as definitely related to fluconazole, the drug should be discontinued. When a rash in patients with invasive / systemic fungal infections, they should be monitored closely and fluconazole cancel the appearance of bullous erythema multiforme or changes.

Care must be taken while taking fluconazole with cisapride, rifabutin or other drugs metabolized by the cytochrome P450 system.