Fluconazole-Vertex, 150 mg capsules 4 pcs

Antifungal agent, has a highly specific action by inhibiting the activity of cytochrome P450-dependent fungal enzymes.

Blocks conversion of fungal cells lanosterol to ergosterol; increases cell membrane permeability, disrupts cell growth and replication. Fluconazole, being highly selective for cytochrome P450 of fungi, practically does not inhibit these enzymes in humans (in comparison with itraconazole, clotrimazole, econazole and ketoconazole it inhibits cytochrome P450 dependent oxidative processes in human liver microsomes to a lesser extent). It does not have antiandrogenic activity.

Active in opportunistic mycoses, including those caused by Candida spp. (including generalized candidiasis against immunosuppression), Cryptococcus neoformans and Coccidioides immitis (including meningitis and encephalitis), Microsporum spp. and Trichophyton spp; in endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulatum (including immunosuppression).

Indications

cryptococcosis, including cryptococcal meningitis and other localizations of this infection (including lungs, skin), both in patients with normal immune response and in patients with various forms of immunosuppression (including Generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidiasis infections (infections of peritoneum, endocardium, eyes, respiratory and urinary tract).

It may be administered in patients with malignant tumors, patients of intensive therapy departments, patients undergoing cytostatic or immunosuppressive therapy and in case of other factors predisposing to candidiasis development; – candidiasis of mucous membranes, including oral cavity and pharynx (including oral cavity atrophic candidiasis, associated with wearing dentures), esophagus, non-invasive bronchopulmonary candidiasis, candiduria, skin candidiasis; prevention of relapse 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 malignancies who are predisposed to such infections due to cytostatic chemotherapy or radiotherapy; – skin mycoses, including foot, body and inguinal mycoses; – shingles; – onychomycosis; – skin candidiasis; – deep endemic mycoses, including coccidiomycosis and histoplasmosis, in patients with normal immunity.

Active ingredient

Fluconazole

Composition

Dosage 150 mg
active ingredient: fluconazole – 150.0 mg;
excipients: lactose monohydrate – 138.8 mg; corn starch – 49.0 mg; povidone K-17 (polyvinylpyrrolidone low molecular weight) – 7.0 mg; calcium stearate – 3.0 mg; colloidal silicon dioxide – 1.5 mg; sodium lauryl sulfate – 0.7 mg;
hard gelatin capsules #0: [titanium dioxide – 2.0%, gelatin – up to 100%].

Interaction

Prothrombin time is increased (on average by 12%) when using fluconazole with warfarin. It is recommended to control prothrombin time when combining fluconazole with coumarin anticoagulants Fluconazole increases T1/2 of plasma oral hypoglycemic agents – sulfonylurea derivatives (chlorpropamide, glibenclamide, glipizide, tolbutamide) in healthy subjects. Concomitant use of fluconazole and oral hypoglycemic agents in patients with diabetes is allowed, but the physician should consider the possibility of hypoglycemia.

Concomitant use of fluconazole and phenytoin may lead to an increase in plasma concentrations of phenytoin to a clinically significant degree. Therefore, if co-administration of these drugs is necessary, phenytoin concentrations should be monitored with dose adjustments to maintain drug concentrations within the therapeutic interval. Combination with rifampicin decreases AUC by 25% and decreases T1/2 of fluconazole from plasma by 20%.

Therefore it is reasonable to increase fluconazole dose in patients receiving rifampicin concomitantly. It is recommended to monitor cyclosporine blood concentration in patients receiving fluconazole as fluconazole and cyclosporine administration in patients with kidney transplantations. Administration of fluconazole in dose 200 mg/day leads to slow increase of cyclosporine concentration in plasma.

Patients who receive high doses of theophylline or who are likely to develop theophylline intoxication should be monitored for symptoms of theophylline overdose because concomitant administration of fluconazole leads to decreased plasma clearance of theophylline.

There have been reports of interaction of fluconazole and rifabutin accompanied by increased serum concentrations of the latter. There have been cases of uveitis during concomitant use of fluconazole and rifabutin. Patients receiving rifabutin and fluconazole at the same time should be closely monitored.

In patients receiving combination of fluconazole and zidovudine there is increased concentration of zidovudine that is caused by decrease of conversion of zidovudine to its main metabolite, therefore it is necessary to expect increase of side effects of zidovudine. In concomitant use of fluconazole, terfenadine and cisapride there have been described cases of adverse cardiac reactions, including arrhythmias of the “pirouette” type. Concomitant use of fluconazole and hydrochlorothiazide may increase fluconazole concentration by 40%.

Increases the concentration of midazolam, due to which the risk of psychomotor effects increases (more pronounced when using fluconazole orally than intravenously). Increases the concentration of tacrolimus, due to which the risk of nephrotoxic effects increases.

Directions for use

Oral. Adults and children over 15 years of age (body weight over 50 kg) in cryptococcal meningitis and cryptococcal infections of other localizations are usually prescribed 400 mg (8 50 mg capsules) on the first day, and then treatment continues at a dose of 200 mg (4 50 mg capsules) – 400 mg (8 50 mg capsules) once daily.

Duration of treatment in cryptococcal infections depends on clinical efficacy confirmed by mycological examination; in cryptococcal meningitis the course of treatment should be at least 6-8 weeks. For prevention of relapse of cryptococcal meningitis in patients with AIDS, after completion of a full course of primary therapy, fluconazole is prescribed at a dose of 200 mg (4 capsules of 50 mg)/day for a long period of time. In candidemia, disseminated candidiasis and other invasive candidiasis infections, the dose is 400 mg (8 50 mg capsules) on the first day and then 200 mg (4 50 mg capsules)/day.

If clinical effect is insufficient the dose can be increased up to 400 mg (8 50 mg capsules)/day. The duration of therapy depends on the clinical efficacy of the drug (100% of the recommended dose). At IQ from 11 to 50 ml/min 50% of the recommended dose or the usual dose once every 2 days is used.

In patients with impaired renal function fluconazole is administered according to the following regimen. Creatinine clearanceInterval/daily dose more than 40 ml/min 24 hours (usual dosing regimen)21-40 ml/min48 hours (once every 2 days) or half of usual daily dose (once every 24 hours)10-20 ml/min72 hours (once every 3 days) or 1/2 of usual daily dose (1/3 every 24 hours) For patients on hemodialysis one dose of the drug is given after each hemodialysis session.

Special Instructions

Treatment should be continued until clinical and hematological remission occurs. Premature discontinuation of treatment leads to relapses. In rare cases fluconazole use was accompanied by toxic liver changes, including fatal, mainly in patients with serious comorbidities.

In the case of hepatotoxic effects associated with fluconazole, no clear dependence on the total daily dose, duration of therapy, gender and age of the patient was noted. Hepatotoxic effects of fluconazole were usually reversible; their signs disappeared after discontinuation of therapy. If clinical signs of liver damage appear, which may be associated with fluconazole, the drug should be discontinued. AIDS patients are more prone to develop severe skin reactions when using many drugs.

In cases where patients with superficial fungal infections develop a rash and it is considered definitely related to fluconazole, the drug should be discontinued. If rash appears in patients with invasive systemic fungal infections, they should be closely monitored and fluconazole should be discontinued if bullous changes or erythema multiforme appear. Caution should be exercised when concomitant administration of fluconazole with cisapride, rifabutin or other drugs metabolized by cytochrome P450 system.

Contraindications

– hypersensitivity to fluconazole, other drug components or azole substances with a similar structure to fluconazole;

– concomitant use of terfenadine during multiple uses of fluconazole at a dose of 400 mg/day or more (see “Interaction with other drugs.

– concomitant use with drugs that can prolong the QT interval and are metabolized by CYP3A4, such as cisapride, astemizole, erythromycin, pimozide, quinidine (see “Interaction with other medicinal products”).

– lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

– children under 3 years of age (for this dosage form).

With caution

– hepatic failure;

– renal failure;

– appearing rash on fluconazole in patients with superficial fungal infection and invasive/systemic fungal infections;

– concomitant use of terfenadine and fluconazole at a dose less than 400 mg/day;

– potentially proarrhythmic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalances and concomitant therapy contributing to such disorders).

Side effects

The undesirable phenomena presented below are listed according to the anatomico-physiological classification and frequency of occurrence.
Frequency of occurrence is defined as follows: often – more than 1%; infrequently – 0.1-1%; rarely – 0.01-0.1%; very rarely – less than 0.01%.

Digestive system: decreased appetite, change in taste, nausea, diarrhea, flatulence, abdominal pain, vomiting, abdominal pain; rarely – disorders of liver function (jaundice, hepatocellular necrosis, hyperbilirubinemia, increased alanine aminotransferase (ALT), aspartataminotransferase (ACT) and alkaline phosphatase (ALP) activity, hepatitis, hepatonecrosis), incl.including severe.

Nervous system disorders: headache, dizziness, excessive fatigability; rarely – seizures.

Blood organs: rare – leukopenia, thrombocytopenia (bleeding, petechiae), neutropenia, agranulocytosis.

Allergic reactions: skin rash, rare – erythema multiforme exudative (including Stevens-Johnson syndrome).Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome), anaphylactoid reactions (including angioedema, facial edema, urticaria, skin itching).

Cardiovascular system: QT interval prolongation, ventricular fibrillation/rattling.

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

Overdose

There have been reports of fluconazole overdose, and in one case a 42-year-old human immunodeficiency virus-infected patient developed hallucinations and paranoid behavior after taking 8200 mg of fluconazole. The patient was hospitalized and his condition normalized within 48 hours.
In cases of overdose, symptomatic treatment (including supportive measures and gastric lavage) may provide an adequate effect.
Fluconazole is mainly excreted through the kidneys, so formed diuresis can probably accelerate excretion of the drug. Hemodialysis session of 3 hours reduces fluconazole concentration in blood plasma by about 50%.

Pregnancy use

It is not advisable to use the drug in pregnant women, except for severe or life-threatening forms of fungal infections, when the potential benefits of fluconazole for the mother significantly exceed the risk to the fetus.

Since the concentration of fluconazole in breast milk and plasma is the same, it is contraindicated during lactation.

Similarities

Diflucan, Flucostat, Mycosist, Mycomax, Fluconazole-Teva, Fluconazole, Fluconazole Stada, Fluconazole Sandoz