Fluconazole-OBL, 150mg capsules 1pc

Composition

Active ingredient:  

fluconazole 50 mg and 150 mg.

Auxiliary substances:

corn starch,

povidone (low molecular weight polyvinylpyrrolidone),

calcium stearate.

Hard gelatin capsules:

titanium dioxide,

proprietary blue dye,

gelatin,

preservatives-methylhydroxybenzoate,

propylhydroxybenzoate.

Pharmacological action

Pharmacotherapeutic group:

antifungal agent Pharmacodynamics :

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

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

Pharmacokinetics:

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

The use of a dose on the first day,2 times higher than the usual daily dose, allows you to reach the level of the drug in plasma, 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. Binding to plasma proteins is small-11-12%.

Fluconazole penetrates well into all body fluids, including CSF. 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 fluid, high concentrations are achieved that exceed serum levels.

Less than 5% of fluconazole is metabolized on its first pass through the liver. The half-life (T 1/2) of fluconazole is about 30 hours. Fluconazole is mainly excreted by the kidneys; approximately 80% of the administered dose is excreted unchanged by the kidneys. The clearance of fluconazole is proportional to creatinine clearance. No metabolites of fluconazole were detected in the peripheral blood.

Indications

· Cryptococcosis, including cryptococcal meningitis and other localization of the infection (including the lungs, skin), as in patients with normal immune response and in patients with various forms of immunosuppression (including patients with AIDS, organ transplant); the drug can be used for the prevention of cryptococcal infections in AIDS patients;

· generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive Candida infections (infection of the peritoneum, endocardium, eyes, respiratory and urinary tract). Treatment can be performed in patients with malignant neoplasms, patients in intensive care units, patients undergoing 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 oral candidiasis associated with wearing dentures), esophagus, non-invasive bronchopulmonary candidiasis, candiduria, candidiasis of the skin; 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 recurrences 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 with cytostatics or radiation therapy;

· fungal skin infections, including athlete’s foot, body, groin; tinea versicolor, onychomycosis; candidiasis of the skin;

· deep endemic mycoses, including coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immune systems.

Contraindications

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

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 terfenadine and fluconazole at a dose of less than 400 mg / day, potentially proarrhythmogenic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance, concomitant use of drugs that cause arrhythmias); patients with acetylsalicylic acid intolerance, pregnancy.

Side effects

From the digestive system: nausea, diarrhea, flatulence, vomiting, abdominal pain, change in taste, rarely – increased activity of “liver” enzymes and liver dysfunction (jaundice, hyperbilirubinemia, increased activity of alanine aminotransferase (ALT), asparaginases (AST) and alkaline phosphatase (ALP), hepatitis, hepatocellular necrosis), including fatalities.

Nervous system disorders: headache, dizziness; rarely-convulsions.

From the side of hematopoietic organs:  rarely-agranulocytosis, neutropenia. Patients with severe fungal infections may have hematological changes (leukopenia and thrombocytopenia).

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

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

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

Interaction

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

· Interaction of fluconazole with terfenadine, cisapride and astemizole can lead to an increase in the concentration of these drugs in plasma, which in turn can cause prolongation of the QT interval and lead to serious cardiac arrhythmias. Fluconazole inhibits enzymes of the P-450 system in the liver, thus reducing the metabolism of terfenadine, cisapride and astemizole. Concomitant use of fluconazole and these drugs is contraindicated.

* When warfarin and fluconazole are co-administered, prothrombin time is prolonged. Therefore, it is necessary to monitor prothrombin time in patients receiving concomitant treatment with fluconazole and coumarin anticoagulants.

* Fluconazole prolongs the T 1/2 of oral hypoglycemic drugs (sulfonylureas). In patients with diabetes mellitus, you can simultaneously prescribe fluconazole and sulfonylureas, but it is necessary to take into account the possible risk of hypoglycemia.

· It should be taken into account that with repeated simultaneous use of hydrochlorothiazide and fluconazole, the concentration of fluconazole in plasma increases.

Rifampicin accelerates the metabolism of fluconazole. It is necessary to increase the dosage of fluconazole accordingly when using them simultaneously.

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

* Fluconazole increases the concentration of theophylline in plasma. Therefore, monitoring of theophylline concentrations in patients receiving concomitant treatment with theophylline and fluconazole is recommended.

* Fluconazole may increase the plasma concentrations of indinavir and midazolam. When these drugs are co-administered with fluconazole, their dosage should be reduced accordingly.

* Clinical studies have shown that as a result of slowing the metabolism of zidovudine, its plasma concentration may increase when administered concomitantly with fluconazole. Patients receiving both medications at the same time should be monitored, as this may increase the frequency of side effects of zidovudine.

* Fluconazole increases serum phenytoin concentrations. With simultaneous use, it is necessary to monitor the dose of phenytoin and adjust them accordingly.

* Increases the effectiveness of rifabutin (when used simultaneously, cases of uveitis have been described) and phenytoin to a clinically significant extent (when used in combination, it is necessary to control the concentration of phenytoin in plasma).

* Increases tacrolimus concentration – risk of nephrotoxicity.

How to take, course of use and dosage

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; for cryptococcal meningitis, it is usually continued for at least 6-8 weeks.

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

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

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

For atrophic oral candidiasis associated with wearing dentures, fluconazole is usually prescribed 50 mg 1 time / day for 14 days in combination with local antiseptics for the treatment of the prosthesis.

For other localizations of candidiasis (with the exception of genital candidiasis), for example, esophagitis, non-invasive bronchopulmonary lesions, 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; for severe mucosal candidiasis – 100-200 mg/day. To prevent relapses of oropharyngeal candidiasis in patients with AIDS after completing a 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 orally at a dose of 150 mg. To reduce the frequency of relapses 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.

When balanitis caused by Candida, fluconazole is prescribed once in 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 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 1 time / 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 mycoses of the feet, skin of the groin area, and candidiasis of the skin, 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, but with mycoses 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 once a day for 2-4 weeks.

For onychomycosis, the recommended dose is 150 mg once a week. Treatment should be continued until the infected nail is replaced (uninfected nail regrowth). It normally takes 3-6 months and 6-12 months, respectively, for the nails to regrow on the fingers and feet.

Deep endemic mycoses may require the 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 for coccidioidomycosis; 2-17 months for paracoccidioidomycosis; 1-16 months for sporotrichosis and 3-17 months for 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 of adults. The drug is used daily 1 time/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 constant equilibrium concentrations more quickly.

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 which the risk of infection is associated with neutropenia, developing 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.

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

Dosage for patients with renal insufficiency

, Fluconazole is mainly excreted unchanged by the kidneys. With a single dose, no dose change is required.

Adult patients with impaired renal function with repeated use of the drug should first be prescribed a “shock” dose from 50 mg to 400 mg. If the creatinine clearance (CC)is more than 50 ml / min, the usual dose of the drug is used (100% of the recommended dose). With creatinine clearance from 11 to 50 ml/min, a dose equal to 50% of the recommended dose is used, or the usual dose 1 time in 2 days. 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 of the drug should be reduced (in the same proportion as in adults), in accordance with the severity of renal failure.

In elderly patients with no impaired renal function, the usual dosage regimen should be followed.

Overdose

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

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

Special instructions

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

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

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 for possible toxic effects. When increasing the level of “liver” enzymes, the doctor should 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.

People with AIDS are more likely to develop severe skin reactions when using many medications. In cases where patients with a superficial fungal infection develop a rash and it is considered 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 discontinue fluconazole if bullous changes or erythema multiforme occur.

Prothrombin time should be monitored in patients receiving concomitant treatment with fluconazole and coumarin anticoagulants.

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

The proprietary blue dye included in the preparation may 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.

Form of production

of capsule No. 1 with a blue body and lid (for a dosage of 150 mg). The contents of the capsules are white or almost white powder.

Storage conditions

Store in a dry place, protected from light, at a temperature of 15-25 °C.

Shelf

life is 2 years.

Active ingredient

Fluconazole

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

Children over 3 years of age, Children as prescribed by a doctor, For adults

Indications

Thrush, Fungus