Fluconazole-OBL capsules 150 mg

Active substance: 

fluconazole 50mg and 150mg.

Excipients:

corn starch,

povidone (low molecular weight polyvinylpyrrolidone),

calcium stearate.

Hard gelatin capsules:

titanium dioxide

patented blue dye,

gelatin,

preservatives - methylhydroxybenzoate,

propylhydroxybenzoate. 

Pharmacotherapeutic group:

antifungal agent 

Pharmacodynamics:

Fluconazole, a member of the triazole antifungal class, is a potent selective inhibitor of the fungal enzyme 14-α-demethylase. The drug prevents the transition of lanosterol to ergosterol - the main component of the cell membranes of fungi.

The drug is effective for opportunistic mycoses, including caused by Candida spp. (Candida albicans, Candida tropicalis), Cryptococcus neoformans, Microsporum spp., Trichophyton spp. Fluconazole activity has also been shown in models of endemic mycoses, including infections caused by Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum.

Pharmacokinetics:

After oral administration, fluconazole is well absorbed, its bioavailability is 90%. The maximum concentration (Cmax) after oral administration, 150 mg on an empty stomach is 90% of the plasma content 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 concentration reaches a peak after 0.5-1.5 hours (TCmax) after administration. Plasma concentrations are in direct proportion to dose. 90% level of equilibrium concentration is achieved by 4-5 days of treatment with the drug (when taken 1 time / day).

The use on the first day of a dose 2 times the usual daily dose allows you to achieve a plasma level of the drug equal to 90% of the equilibrium concentration by the second day. The apparent volume of distribution approaches the total volume of water in the body. Plasma protein binding is small - 11-12%.

Fluconazole penetrates well into all body fluids, including cerebrospinal fluid. Concentrations of the drug in saliva and sputum are similar to its plasma levels. In patients with fungal meningitis, the content of fluconazole in the cerebrospinal fluid reaches 80% of its plasma level.

In the stratum corneum, epidermis, dermis and sweat, high concentrations are reached that exceed serum.

Less than 5% of fluconazole is metabolized the first time it passes through the liver. The half-life (T1 / 2) of fluconazole is about 30 hours. Fluconazole is excreted mainly by the kidneys; approximately 80% of the administered dose is excreted by the kidneys unchanged. Fluconazole clearance is proportional to creatinine clearance. No metabolites of fluconazole were found in peripheral blood.

· Cryptococcosis, including cryptococcal meningitis and other localizations of this infection (including lungs, skin), both in patients with a normal immune response and in patients with various forms of immunosuppression (including in patients with AIDS, during transplantation organs); the drug can be used to prevent cryptococcal infection in AIDS patients;

· Generalized candidiasis, including candidaemia, disseminated candidiasis and other forms of invasive candidiasis infections (infections of the peritoneum, endocardium, eyes, respiratory and urinary tracts). Treatment can be carried out in patients with malignant neoplasms, patients in intensive care units, patients undergoing a course of cytostatic or immunosuppressive therapy, as well as in the presence of other factors predisposing to the development of candidiasis;

· Candidiasis of the mucous membranes, including the oral cavity and pharynx (including atrophic candidiasis of the oral cavity associated with wearing dentures), the esophagus, non-invasive bronchopulmonary candidiasis, candiduria, skin candidiasis; prevention of recurrence of oropharyngeal candidiasis in AIDS patients;

· Genital candidiasis: vaginal candidiasis (acute and chronic recurrent), prophylactic use to reduce the recurrence rate of vaginal candidiasis (3 or more episodes per year); candida balanitis;

· Prevention of fungal infections in patients with malignant neoplasms who are predisposed to such infections as a result of chemotherapy with cytostatics or radiation therapy;

Mycoses of the skin, including mycoses of the feet, body, inguinal region; pityriasis versicolor, onychomycosis; candidiasis of the skin;

Deep endemic mycoses, including coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immunity.

Hypersensitivity to fluconazole, other components of the drug or other azole compounds; concomitant use of terfenadine (against the background of continuous administration of fluconazole at a dose of 400 mg / day or more), cisapride or astemizole and other drugs that extend the QT interval and increase the risk of severe rhythm disturbances; lactation period; children's age up to 3 years (for this dosage form).

With caution: hepatic and / or renal failure, the appearance of a rash during the use of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections, the simultaneous administration of terfenadine and fluconazole in a dose of less than 400 mg / day, potentially proarrhythmogenic conditions in patients with multiple factors risk (organic heart disease, electrolyte imbalance, simultaneous use of drugs that cause arrhythmias); patients with intolerance to acetylsalicylic acid, pregnancy.

From the digestive system:  nausea, diarrhea, flatulence, vomiting, abdominal pain, taste change, rarely - increased activity of "liver" enzymes and impaired liver function (jaundice, hyperbilirubinemia, increased activity of alanine aminotransferase (ALT), asparaginaminotransferase (AST) and alkaline phosphatases (ALP), hepatitis, hepatocellular necrosis), including fatal.

From the nervous system:  headache, dizziness; rarely - cramps.

From the hemopoietic organs:  rarely - agranulocytosis, neutropenia. In patients with severe fungal infections, hematological changes (leukopenia and thrombocytopenia) may occur.

From the cardiovascular system:  an increase in the duration of the Q - T interval on the electrocardiogram (ECG), ventricular fibrillation / flutter.

Allergic reactions:  skin rash, erythema multiforme exudative (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), bronchial asthma (more often with intolerance to acetylsalicylic acid), anaphylactoid reactions (including angioedema, swelling of the face, urticaria, skin itching).

Other:  rarely - impaired renal function, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

A single dose of fluconazole in the treatment of vaginal candidiasis is not accompanied by significant interactions. However, when applying several or higher doses of the drug simultaneously with other drugs, the following drug interactions are possible:

· The interaction of fluconazole with terfenadine, cisapride and astemizole can lead to an increase in the concentration of these drugs in the plasma, which in turn can cause a prolongation of the QT interval and lead to serious heart rhythm disturbances. Fluconazole inhibits the enzymes of the P450 system in the liver, thus reducing the metabolism of terfenadine, cisapride and astemizole. The simultaneous administration of fluconazole and these drugs is contraindicated.

With the combined use of warfarin and fluconazole, an extension of the prothrombin time is noted. In this regard, it is necessary to control prothrombin time in patients simultaneously receiving fluconazole and coumarin anticoagulants.

· Fluconazole prolongs T1 / 2 of oral hypoglycemic drugs (sulfonylureas). In patients with diabetes mellitus, fluconazole and sulfonylurea derivatives can be prescribed at the same time, however, the possible risk of hypoglycemia should be taken into account.

· It must be taken into account that with repeated simultaneous administration of hydrochlorothiazide and fluconazole, the concentration of fluconazole in the plasma rises.

Rifampicin accelerates the metabolism of fluconazole. It is necessary to accordingly increase the dosage of fluconazole with their simultaneous use.

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

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

· Fluconazole may increase the plasma concentration of indinavir and midazolam. With the simultaneous administration of these drugs with fluconazole, their dosage should be accordingly reduced.

· Clinical studies have shown that as a result of a slowdown in the metabolism of zidovudine, its concentration in plasma may increase with simultaneous administration with fluconazole. It is necessary to monitor patients simultaneously receiving both of these drugs, since in this case the frequency of side effects of zidovudine may increase.

· Fluconazole increases serum phenytoin concentrations. With the simultaneous appointment, it is necessary to control the doses of phenytoin and accordingly adjust them.

· Increases the effectiveness of rifabutin (with simultaneous use, cases of uveitis have been described) and phenytoin to a clinically significant degree (with combined use, monitoring the concentration of phenytoin in the plasma is necessary).

· Increases tacrolimus concentration - risk of nephrotoxicity.

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

Adults  with cryptococcal meningitis and cryptococcal infections of other localizations are usually prescribed 400 mg on the first day, and then continue treatment at a dose of 200-400 mg 1 time / day. The duration of treatment for cryptococcal infections depends on the clinical efficacy confirmed by mycological examination; with cryptococcal meningitis, it usually lasts at least 6-8 weeks.

To prevent the relapse of cryptococcal meningitis in AIDS patients, after completing the full course of primary treatment, fluconazole is prescribed at a dose of 200 mg / day for a long period of time. The duration of the drug is determined by the doctor.

For candidaemia, disseminated candidiasis, and other invasive candidiasis infections, the dose is usually 400 mg on the first day, and then 200 mg each. With insufficient clinical effectiveness, the dose of the drug can be increased to 400 mg / day; in severe systemic candidiasis, a dose increase of up to 800 mg per day is possible. The duration of therapy depends on clinical efficacy; should be continued for at least 2 weeks after receiving negative blood culture or after the disappearance of the symptoms of the disease.

With oropharyngeal candidiasis, the drug is usually prescribed 50-100 mg 1 time / day; the duration of treatment is 7-14 days. If necessary, in patients with a pronounced decrease in immunity, treatment may be longer (3 weeks).

With atrophic candidiasis of the oral cavity associated with wearing dentures, fluconazole is usually prescribed 50 mg 1 time / day for 14 days in combination with local antiseptic agents for treating the prosthesis.

With other localizations of candidiasis (with the exception of genital candidiasis), for example, with esophagitis, non-invasive bronchopulmonary damage, candiduria, candidiasis of the skin and mucous membranes, etc., the effective dose is usually 50-100 mg / day with a treatment duration of 14-30 days; with severe mucous candidiasis - 100-200 mg / day. For the prevention of recurrence of oropharyngeal candidiasis in patients with AIDS, after completion of the full course of primary therapy, the drug can be prescribed 150 mg once a week. The duration of treatment is determined by the doctor.

With vaginal candidiasis, fluconazole is taken once by mouth at a dose of 150 mg. To reduce the recurrence rate of vaginal candidiasis, the drug can be used at a dose of 150 mg once a month. The duration of therapy is determined individually; it varies from 4 to 12 months. Some patients may require more frequent use.

With balanitis caused by Candida, fluconazole is prescribed once at a dose of 150 mg orally.

For the prevention of candidiasis, the recommended dose of fluconazole is 50-400 mg 1 time / day, depending on the degree of risk of developing a fungal infection. In the presence of a high risk of generalized infection, for example, in patients with expected severe or persistent neutropenia, the recommended dose is 400 mg 1 time / day. Fluconazole is prescribed a few days before the expected occurrence of neutropenia; after an increase in the number of neutrophils by more than 1000 / mm3, treatment is continued for another 7 days.

With skin mycoses, including foot mycoses, inguinal skin, and skin candidiasis, the recommended dose is 150 mg once a week or 50 mg once a day. The duration of therapy in normal cases is 2-4 weeks, however, with mycosis of the feet, longer therapy may be required (up to 6 weeks).

With pityriasis versicolor - 300 mg once a week for 2 weeks, some patients require a third dose of 300 mg per week, while in some cases a single dose of 300-400 mg is sufficient; an alternative treatment regimen is the use of 50 mg 1 time per day for 2-4 weeks.

With onychomycosis, the recommended dose is 150 mg once a week. Treatment should be continued until the replacement of the infected nail (growth of an uninfected nail). For repeated growth of nails on the fingers and toes, normally 3-6 months and 6-12 months respectively are required.

With deep endemic mycoses, it may be necessary to use the drug in 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 with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. In children, the drug should not be used in a daily dose that would exceed that in adults. The drug is used daily 1 time / day.

For candidiasis of the mucous membranes, the recommended dose of fluconazole is 3 mg / kg / day. On the first day, a loading dose of 6 mg / kg may be prescribed in order to more quickly achieve constant equilibrium concentrations.

For the treatment of generalized candidiasis or 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 that develops as a result of cytotoxic chemotherapy or radiation therapy, the drug is prescribed 3-12 mg / kg / day, depending on the severity and duration of persistence of induced neutropenia.

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

Dosage for patients with renal failure

Fluconazole is excreted mainly by the kidneys unchanged. With a single dose, a dose change is not required.

Adult patients with impaired renal function when re-prescribing the drug should first be assigned a “shock” dose of 50 mg to 400 mg. If creatinine clearance (CC) is more than 50 ml / min, the usual dose of the drug is used (100% of the recommended dose). With CC from 11 to 50 ml / min., A dose equal to 50% of the recommended, or a usual dose of 1 time in 2 days, is used. For patients who are regularly on dialysis, one dose of the drug is used after each hemodialysis session.

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

In elderly patients  in the absence of impaired renal function, the usual dosage regimen of the drug should be followed.

Symptoms: nausea, vomiting, diarrhea, in severe cases, convulsions, hallucinations, paranoid behavior can be noted.

Treatment: symptomatic, gastric lavage; because fluconazole is excreted by the kidneys; forced diuresis is recommended. Hemodialysis within 3 hours reduces the concentration in plasma by 2 times.

Treatment can be started in the absence of results of culture or other laboratory tests, but if they are available, appropriate correction of fungicidal therapy is recommended.

Since fluconazole is excreted primarily by the kidneys, caution should be exercised in patients with renal failure. When treating with multiple doses of fluconazole, dosing should be carried out taking into account QC.

Caution should be exercised when prescribing fluconazole to patients with impaired liver function. During treatment, it is necessary to regularly monitor the level of "liver" enzymes and monitor the patient in order to identify possible toxic effects. With an increase in the level of “liver” enzymes, the doctor must weigh the benefits of the therapy and the risk of developing severe liver damage. The hepatotoxic effect of fluconazole is usually reversible; symptoms disappear after discontinuation of therapy.

AIDS patients are more likely to develop severe skin reactions when using many drugs. In cases where a rash develops in patients with superficial fungal infection and is regarded as definitely associated with fluconazole, the drug should be discontinued. If a rash appears in patients with invasive / systemic fungal infections, they should be carefully monitored and fluconazole should be discontinued when bullous changes or erythema multiforme occur.

It is necessary to control prothrombin time in patients simultaneously receiving fluconazole and coumarin anticoagulants.

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

The patented blue dye, which is part of the drug, can cause an allergic reaction.

Influence on the ability to drive a car or other mechanical means: It is not known about the negative impact on the ability to drive a car and work with other mechanisms.

capsules 1 or 2 (for a dosage of 150 mg). The contents of the capsules are white or almost white powder.