Expiration date: 11/2025

Structure and Composition: 

The capsules. 1 capsulse contains Fluconazole 50 or 150 mg

Excipients: lactose monohydrate, corn starch, silica colloidal anhydrous sodium lauryl sulfate, magnesium stearate

Composition capsules:

body capsule 50 mg: gelatin, titanium dioxide E171

the capsule casing 150 mg: Titanium dioxide E171 E131 patent blue dye gelatin

cap capsules of 50 mg and 150: E171 titanium dioxide colorant E131 patent blue gelatin

caps. 50 mg: 7 in pieces blister. in box 1 blister caps. 150 mg: 1 by volume in the blister. 1 blister in a box (1 pc.).

Description pharmaceutical form:

50 mg capsules: Hard gelatin capsules ?4. Lid - light blue, body - white.

100 mg capsules: Hard gelatin capsules ?2. Lid - blue, body - white.

150 mg capsules: Hard gelatin capsules ?1. Lid and housing - light blue.

200 mg capsules: Hard gelatin capsules. Lid - deep purple color, body - white.

The contents of capsules - powder white or nearly white.

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 / kg. Simultaneous food intake has no effect on the absorption of the drug taken orally. plasma concentration peaking 0.5-1.5 h after administration, T1 / 2 of fluconazole is approximately 30 hours.

Plasma concentrations are directly proportional to the dose. 90% of the level of the equilibrium concentration is achieved in 4-5-th day drug treatment (when taking 1 per day).

Application of the first day dose of 2 times the usual daily, 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, including cerebrospinal fluid. 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.

Less than 5% of fluconazole is metabolized during the first passage through the liver. The long T1 / 2 allows the use of a single dose of the drug for the treatment of vaginal candidiasis and provides the drug 1 time per day for other indications. 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 representative of the class of triazole antifungal agents, is a potent selective inhibitor of the fungal enzyme 14- & alpha-demethylase. The drug inhibits the transition lanosterol to ergosterol - the main component of fungal cell membranes.

The drug is effective for opportunistic fungal infections, including caused by Candida spp. (Candida albicans, Candida tropicalis), 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 (in t. h. in AIDS patients, organ transplant )
  
• prevention of 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 and the passing rate of cytotoxic 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), prophylactic use to reduce the frequency of relapses of vaginal candidiasis (3 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
  
• chromophytosis
  
• onychomycosis
  
• skin candidiasis
  
• deep endemic mycoses, including coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immunity.
  

Contraindications:

Hypersensitivity to fluconazole, other ingredients or other azole compounds concomitant use of terfenadine (on the background of continuous use of fluconazole 400 mg / day or more), cisapride or astemizole and other drugs prolonging the QT interval and increase the risk of severe arrhythmias lactation children under 3 years of age (for a given dosage form).

Precautions: hepatic and / or renal failure, rash during treatment with fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections, concomitant use of terfenadine and fluconazole at a dose of less than 400 mg / day, potentially proaritmogennoe condition in patients with multiple factors risk (organic heart disease, electrolyte imbalance, concomitant use of drugs that can cause cardiac arrhythmias), patients with intolerance to acetylsalicylic acid and pregnancy.

Application of pregnancy and breastfeeding:

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

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

Side effect:

From the digestive system: nausea, diarrhea, flatulence, vomiting, abdominal pain, change in taste, rarely - elevated liver enzymes and liver dysfunction (jaundice, hyperbilirubinemia, increased ALT, ACT and AP, hepatitis, hepatocellular necrosis, in t .ch. fatal).

From the nervous system: headache, dizziness, rarely - seizures.

From the side of hematopoiesis: rarely - agranulocytosis, neutropenia. Patients Hematologic changes may occur with severe fungal infections (leukopenia and thrombocytopenia).

Cardio-vascular system: increased QT interval duration in the electrocardiogram (ECG), flickering / ventricular flutter.

Allergic reactions: skin rash, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), asthma (often in case of intolerance of acetylsalicylic acid), anaphylactoid reactions (including angioedema, face edema, urticaria, pruritus).

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

Drug Interactions:

A single dose of fluconazole in the treatment of vaginal candidiasis is not accompanied by significant interactions. However, when using higher or more doses of the drug in conjunction with other drugs are possible drug interactions listed below.

fluconazole interaction with terfenadine, astemizole, and cisapride may lead to increased concentrations of these drugs in the plasma, which in turn can cause QT prolongation and lead to serious disturbances of heart rhythm. Fluconazole inhibits enzymes P450 system in the liver, thus reducing, metabolism terfenadine, astemizole and cisapride. Co-administration of fluconazole and these drugs is contraindicated.

The joint appointment of warfarin and fluconazole marked lengthening of PT. In connection with this need to control MF patients concomitantly receiving fluconazole and coumarin anticoagulants.

Fluconazole extend T1 / 2 oral hypoglycemic agents (sulfonylureas). Diabetic patients can simultaneously assign fluconazole and sulfonylureas, but must take into account the potential risk of hypoglycemia.

It is necessary to take into account that during the second simultaneous appointment of hydrochlorothiazide and fluconazole, fluconazole concentration in plasma increases.

Rifampicin accelerates metabolism of fluconazole. It is necessary to appropriately increase the dose of fluconazole when used simultaneously.

In patients undergoing kidney transplantation, fluconazole can increase the plasma concentration of cyclosporine. In this regard, it is recommended monitoring the concentration of cyclosporine in patients receiving both cyclosporine and fluconazole.

Fluconazole increases the concentration of theophylline in the plasma. In this regard, it is recommended theophylline concentration monitoring in patients receiving theophylline simultaneously and fluconazole.

Fluconazole may increase the plasma concentration of indinavir and midazolam. When concomitant administration of these drugs with fluconazole their dosage should be reduced accordingly.

Clinical studies have shown that as a result of slowing metabolism of zidovudine may increase its concentration in the plasma, while the appointment with fluconazole. It is necessary to monitor the patients concomitantly receiving both drugs, as in this case, may increase the frequency of side effects of zidovudine.

Fluconazole increases plasma concentrations of phenytoin. When concomitant administration is necessary to control the dose of phenytoin and accordingly to correct them.

It improves the effectiveness of rifabutin (while the application described cases of uveitis) and phenytoin to a clinically significant extent (the combined use requires monitoring of phenytoin plasma concentrations).

Increasing the concentration of tacrolimus - the risk of nephrotoxicity.

Dosage and administration:

Inside. The daily dose depends on the nature and severity of the fungal infection.

In cryptococcal meningitis and cryptococcal infections at other sites for adults on the first day is usually prescribed 400 mg, and then continue treatment at a dose of 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 completing the full course of treatment of primary fluconazole administered in a dose of 200 mg / day for a long period of time.

When candidemia, disseminated candidiasis and other invasive Candida infections, the dose is usually within the first day of 400 mg, then - 200 mg. With the lack of clinical efficacy of the dose can be increased to 400 mg / day for severe systemic candidiasis may increase the dose to 800 mg / day. The duration of therapy depends on the clinical efficacy should be continued for at least 2 weeks after receiving a negative blood culture or after the disappearance of symptoms.

In oropharyngeal candidiasis drug is usually administered 50-100 mg 1 time per day duration of treatment - 7-14 days. If necessary, in patients with a severely reduced immune treatment may be longer.

In atrophic oral candidiasis associated with wearing dentures usually administered fluconazole at 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), such as oesophagitis, noninvasive bronchopulmonary lesions, candiduria, candidiasis of the skin and mucous membranes, etc. the effective dose is usually 50-100 mg / day when the duration of 14-30 days of treatment for severe mucosal candidiasis - 100-200 mg / day.

For the prevention of relapse of oropharyngeal candidiasis in patients with AIDS, after the completion of a full course of primary therapy, the drug can be assigned to 150 mg 1 time per week.

Vaginal candidiasis fluconazole taking a single oral dose of 150 mg. To reduce the frequency of relapses vaginal candidiasis drug may be used in a dose of 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 of Candida, fluconazole administered a single dose of 150 mg orally.

For the prevention of candidiasis recommended dose of fluconazole is 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 is 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 is 150 mg 1 time per week or 50 mg 1 time per day. Duration of therapy in ordinary cases is 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 - 300 mg per week, while in some cases, a single receiving 300-400 mg alternative regimen is the use of 50 mg 1 time daily for 2-4 weeks.

In onychomycosis the recommended dose is 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 requires 3-6 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 can be 11-24 months - with coccidioidomycosis, 2-17 months - with paracoccidioidomycosis 1-16 months - with sporotrichosis and 3-17 months - with histoplasmosis.

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 of fluconazole is 3 mg / kg / day. The first day can be assigned to the loading dose (6 mg / kg) in order to more quickly achieve constant equilibrium concentrations.

For the treatment of generalized candidiasis and cryptococcal infections 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, when the risk of infection associated with neutropenia, developing as a result of cytotoxic chemotherapy or radiation therapy, the drug is prescribed for 3-12 mg / kg / day, depending on the severity and duration of preservation-induced neutropenia.

The maximum daily dose for children - 12 mg / kg.

Dosing in patients with renal insufficiency

Fluconazole is derived mainly kidneys unchanged. When receiving a single dose of its change is not required.

Adult patients with impaired renal function when re-appointment of the drug should first appoint 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 11 to 50 ml / min the dose applied, equal to 50% of the recommended or usual dose of 1 every 2 days. Patients regularly on dialysis one dose is applied after each hemodialysis session.

In children with renal impairment 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.

Overdose:

Symptoms include nausea, vomiting, diarrhea, and in severe cases may experience seizures, hallucinations, paranoid behavior.

Treatment: symptomatic, gastric lavage as the fluconazole excreted by the kidneys, forced diuresis is recommended. Haemodialysis for 3 hours reduces the plasma concentration of 2-fold.

Special instructions:

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

Since fluconazole excreted mainly by the kidneys, caution should be exercised in patients with renal insufficiency. In the treatment of multiple doses of fluconazole, dosing should be based on Cl creatinine.

Caution must be exercised in the appointment of fluconazole in patients with impaired liver function. During treatment should regularly monitor the level of liver enzymes and conduct observation of the patient in order to identify possible toxic effects. At higher levels of liver enzymes physician must weigh the benefit of the therapy and the risk of severe liver injury. Hepatotoxic action of Fluconazole is usually reversible symptoms disappear after cessation of therapy.

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 it 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.

It is necessary to monitor the PV in patients concomitantly receiving fluconazole and coumarin anticoagulants.

Treatment should continue until clinical remission.

Premature discontinuation of treatment leads to relapse.

Incoming 200 mg capsules in the Diflazon azorubin E122 colorant can cause allergic reactions, including asthma. Allergic reactions are more common in patients with intolerance to acetylsalicylic acid.

Effects on ability to drive a car or other mechanical means: not know about the negative impact on the ability of driving and operating other machines.