Fluconazole-OBL, 150mg capsules 2pcs

Composition

1 capsule contains:

Active ingredient:

fluconazole 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

Fluconazole, a representative of the class of triazole antifungal agents, is a powerful selective inhibitor of the fungal enzyme 14-a-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.

Indications

Cryptococcosis, including cryptococcal meningitis and infections of other localization (for example, lungs, skin), including in patients with a normal immune response and in patients with AIDS, recipients of transplanted organs and patients with other forms of immunodeficiency; maintenance therapy to prevent recurrence of cryptococcosis in AIDS patients.

Generalized candidiasis, including candidaemia, disseminated candidiasis, and other forms of invasive candida infection, such as peritoneal, endocardial, eye, respiratory, and urinary tract infections, including in patients with malignant tumors who are in the ICU and are receiving cytotoxic or immunosuppressive agents, as well as in patients with other factors predisposing to the development of candidiasis.

Candidiasis of the mucous membranes, including the mucous membranes of the oral cavity and pharynx, esophagus, non-invasive bronchopulmonary infections, candiduria, cutaneous-mucous and chronic atrophic candidiasis of the oral cavity (associated with wearing dentures), including in patients with normal and suppressed immune function; prevention of relapse of oropharyngeal candidiasis in AIDS patients.

Genital candidiasis; acute or recurrent vaginal candidiasis; prevention to reduce the frequency of recurrent vaginal candidiasis (3 or more episodes per year); candidal balanitis.

Mycoses of the skin, including mycoses of the feet, body, groin, pityriasis versicolor, onychomycosis and skin candida infections.

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

Prevention of fungal infections in patients with malignant tumors predisposed to the development of such infections as a result of cytotoxic chemotherapy or radiation therapy.

Contraindications

Concomitant use of terfenadine during repeated use of fluconazole at a dose of 400 mg / day or more;

concomitant use of cisapride; hypersensitivity to fluconazole;

hypersensitivity to azole derivatives with a similar structure to fluconazole;

lactation period; children under 3 years of age (for this dosage form).

Side effects

Nervous system disorders:  headache, dizziness, convulsions, changes in taste.

From the digestive system:  abdominal pain, diarrhea, flatulence, nausea, dyspepsia, vomiting, hepatotoxicity (including rare cases with fatal outcome), elevated ALP, bilirubin, serum aminotransferases (ALT and AST), liver dysfunction, hepatitis, hepatocellular necrosis, jaundice.

From the cardiovascular system:  increased QT interval on the ECG, ventricular fibrillation/flutter.

Dermatological reactions:  rash, alopecia, exfoliative skin diseases, including Stevens-Johnson syndrome and toxic epidermal necrolysis.

From the hematopoietic system:  leukopenia, including neutropenia and agranulocytosis, thrombocytopenia.

From the side of metabolism:  elevated plasma cholesterol and triglycerides, hypokalemia.

Allergic reactions:  anaphylactic reactions (including angioedema, facial edema, urticaria, pruritus).

Interaction

When used concomitantly with warfarin, fluconazole increases the prothrombin time (by 12%), which may lead to the development of bleeding (hematomas, bleeding from the nose and gastrointestinal tract, hematuria, melena). In patients receiving coumarin anticoagulants, prothrombin time should be constantly monitored.

After oral use of midazolam, fluconazole significantly increases the concentration of midazolam and psychomotor effects, and this effect is more pronounced after oral use of fluconazole than when it is used intravenously. If concomitant benzodiazepine therapy is necessary, patients taking fluconazole should be monitored for appropriate benzodiazepine dose reduction.

Concomitant use of fluconazole and cisapride may result in adverse cardiac reactions, including ventricular fibrillation / flutter (pirouette-type arrhythmia). The use of fluconazole at a dose of 200 mg 1 time/day and cisapride at a dose of 20 mg 4 times/day leads to a pronounced increase in plasma concentrations of cisapride and an increase in the QT interval on the ECG. Concomitant use of cisapride and fluconazole is contraindicated.

In patients after kidney transplantation, the use of fluconazole at a dose of 200 mg / day leads to a slow increase in the concentration of cyclosporine. However, with repeated use of fluconazole at a dose of 100 mg / day, no changes in the concentration of cyclosporine in bone marrow recipients were observed. With the simultaneous use of fluconazole and cyclosporine, it is recommended to monitor the concentration of cyclosporine in the blood.

Repeated use of hydrochlorothiazide simultaneously with fluconazole leads to an increase in the concentration of fluconazole in plasma by 40%. The effect of this degree of severity does not require a change in the dosage regimen of fluconazole in patients receiving diuretics at the same time, but this should be taken into account.

Concomitant use of a combined oral contraceptive with fluconazole at a dose of 50 mg did not significantly affect the level of hormones, whereas with daily use of 200 mg of fluconazole, the AUC of ethinyl estradiol and levonorgestrel increased by 40% and 24%, respectively, and with 300 mg of fluconazole once a week, the AUC of ethinyl estradiol and norethindrone increased by 24% and 13%, respectively. Thus, repeated use of fluconazole at these doses is unlikely to affect the effectiveness of the combined oral contraceptive.

Concomitant use of fluconazole and phenytoin may be accompanied by a clinically significant increase in the concentration of phenytoin. With this combination, the concentration of phenytoin should be monitored and the dose adjusted accordingly to ensure therapeutic serum concentrations.

Concomitant use of fluconazole and rifabutin may lead to an increase in serum concentrations of the latter. Cases of uveitis have been reported with concomitant use of fluconazole and rifabutin. Patients receiving rifabutin and fluconazole concomitantly should be carefully monitored.

Concomitant use of fluconazole and rifampicin resulted in a 25% decrease in AUC and a 20% decrease in the duration of T1/2 of fluconazole. Patients taking rifampicin concomitantly should consider increasing the dose of fluconazole.

Concomitant use of fluconazole leads to an increase in T1/2 of oral sulfonylureas (chlorpropamide, glibenclamide, glipizide, and tolbutamide). Patients with diabetes mellitus can be prescribed together with fluconazole and oral sulfonylureas, but the possibility of hypoglycemia should be taken into account.

Concomitant use of fluconazole and tacrolimus leads to an increase in plasma concentrations of the latter. Cases of nephrotoxicity are described. With this combination, the condition of patients should be carefully monitored.

When azole antifungal agents and terfenadine are used simultaneously, serious arrhythmias may occur as a result of an increase in the QT interval. When taking fluconazole at a dose of 200 mg / day, an increase in the QT interval was not found, but the use of fluconazole at doses of 400 mg / day and above causes a significant increase in the concentration of terfenadine in plasma. Concomitant use of fluconazole at doses of 400 mg / day or more with terfenadine is contraindicated. Treatment with fluconazole at doses of less than 400 mg / day in combination with terfenadine should be carefully monitored.

When used concomitantly with fluconazole at a dose of 200 mg for 14 days, the average rate of plasma clearance of theophylline decreases by 18%. When prescribing fluconazole to patients taking theophylline in high doses, or patients with an increased risk of developing toxic effects of theophylline, the appearance of symptoms of overdose of theophylline should be monitored and, if necessary, therapy should be adjusted accordingly.

When used concomitantly with fluconazole, there is an increase in zidovudine concentrations, which is probably due to a decrease in the metabolism of the latter to its main metabolite. Before and after therapy with fluconazole at a dose of 200 mg / day for 15 days, patients with AIDS and ARC (AIDS-related complex) showed a significant increase in the AUC of zidovudine (20%).

When zidovudine was used in HIV-infected patients at a dose of 200 mg every 8 hours for 7 days in combination with or without fluconazole at a dose of 400 mg/day with an interval of 21 days between the two regimens, a significant increase in the AUC of zidovudine (74%) was found when used simultaneously with fluconazole.Patients receiving this combination should be monitored for side effects of zidovudine.

Concomitant use of fluconazole with astemizole or other drugs that are metabolized by cytochrome P450 isoenzymes may be accompanied by an increase in serum concentrations of these drugs. With such combinations, the patient’s condition should be carefully monitored.

How to take, course of use and dosage

Individual approach. It is intended for oral use.

For adults, depending on the indications, treatment regimen and clinical situation, the daily dose is 50-400 mg, the frequency of use is 1 time/day.

For children, the dose is 3-12 mg / kg / day, the frequency of use is 1 time/day.

In patients with impaired renal function, the dose of fluconazole is reduced depending on creatinine clearance.

The duration of treatment depends on the clinical and mycological effect.

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

It is used with caution in patients with liver function disorders associated with the use of fluconazole, when a rash appears during the use of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections, when terfenadine and fluconazole are used simultaneously at a dose of less than 400 mg / day, with potentially proarrhythmic conditions in patients with multiple risk factors (organic heart diseases, electrolyte balance disorders and concomitant therapy that contributes to the development of such disorders).

The hepatotoxic effect of fluconazole was usually reversible; signs of it disappeared after discontinuation of therapy. It is necessary to monitor the condition of patients who have impaired liver function indicators during treatment with fluconazole, in order to detect signs of more serious liver damage. If there are clinical signs or symptoms of liver damage that may be associated with fluconazole, it should be discontinued.

People with AIDS are more likely to develop severe skin reactions when using many medications. If a patient receiving treatment for a superficial fungal infection develops a rash that may be associated with the use of fluconazole, it should be discontinued. If a rash appears in patients with invasive / systemic fungal infections, they should be carefully monitored and discontinue fluconazole if bullous lesions or erythema multiforme occur.

Concomitant use of fluconazole at doses less than 400 mg / day and terfenadine should be carefully monitored.

When using fluconazole, increased QT interval and ventricular fibrillation/flutter were observed very rarely in patients with multiple risk factors, such as organic heart disease, electrolyte imbalance, and concomitant therapy that contributes to the development of such disorders.

Therapy can be started before receiving the results of seeding and other laboratory tests. However, anti-infective therapy should be adjusted accordingly when the results of these studies become known.

There have been reports of cases of superinfection caused by Candida strains other than Candida albicans, which often do not show sensitivity to fluconazole (for example, Candida krusei). In such cases, alternative antifungal therapy may be required.

Form of production

Capsules

Active ingredient

Fluconazole

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

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

Indications

Fungus, Thrush