Fluconazole-Vertex, 150 mg capsules 2 pcs

Antifungal agent, has a highly specific action by inhibiting the activity of cytochrome P450-dependent enzymes of fungi. It blocks transformation of lanosterol of fungi cells into membrane lipid – ergosterol; it increases cell membrane permeability, disrupts its growth and replication.

Fluconazole, being highly selective for cytochrome P450 of fungi, practically does not inhibit these enzymes in human body (in comparison with itraconazole, clotrimazole, econazole and ketoconazole it inhibits cytochrome P450 dependent oxidation processes in human liver microsomes to a lesser extent). It does not have antiadrogenic activity.

It is active in opportunistic mycoses, including those caused by Candida spp. (including generalized candidiasis against immunosuppression), Cryptococcus neoformans and Cossidioides immitis (including intracranial infections), Microsporum spp. and Trichophyton spp.; in endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulatum (including immunosuppression).

Pharmacokinetics

Fluconazole is well absorbed after oral administration, the absorption rate of fluconazole is not affected by food, its bioavailability is 90%.

The time of maximum concentration after oral administration on an empty stomach of 150 mg of the preparation is 0.5-1.5 h, C_max is 90% of concentrations in plasma in a dose of 2.5-3.5 mg/l.T_1/2 fluconazole is 30 h. Binding to plasma proteins is 11-12%. Plasma concentration is in direct dose dependence. 90% level of equilibrium concentration is reached by 4-5 days of treatment with the drug (when taken once daily).

The administration of a shock dose (on the first day), 2 times the usual daily dose, allows reaching the level of concentration corresponding to 90% of the equilibrium concentration by the second day.

Fluconazole penetrates well into all body fluids. Concentrations of the active substance in breast milk, joint fluid, saliva, sputum and peritoneal fluid are similar to its levels in plasma. Constant values in vaginal secretion are reached 8 hours after oral administration and are maintained at these levels for at least 24 hours.

Fluconazole penetrates cerebrospinal fluid (CSF) well – in fungal meningitis the concentration in CSF is about 85% of its level in plasma. In sweat fluid, epidermis and stratum corneum (selective accumulation), concentrations exceeding serum concentrations are achieved. After oral administration of 150 mg on day 7, the concentration in the stratum corneum of the skin is 23.4 µg/g, and 1 week after the second dose – 7.1 µg/g; the concentration in the nails after 4 months of use at a dose of 150 mg once a week is 4.05 µg/g in healthy and 1.8 µg/g in the affected nails. The volume of distribution approximates the total water content of the body.

It is an inhibitor of CYP2C9 isoenzyme in the liver. It is excreted mainly by the kidneys (80% – unchanged, 11% – as metabolites). Fluconazole clearance is proportional to creatinine clearance. No fluconazole metabolites were detected in peripheral blood.

The pharmacokinetics of fluconazole significantly depends on the functional state of the kidneys, and there is an inverse relationship between the elimination half-life and creatinine clearance. After hemodialysis within 3 hours plasma concentration of fluconazole decreases by 50%.

Indications

Active ingredient

Composition

1 capsule contains:

Active substance:

fluconazole 150 mg.

Associates:

Corn starch,

povidone (polyvinylpyrrolidone),

colloidal silicon dioxide (aerosil),

sodium lauryl sulfate,

calcium stearate,

lactose.

Solid gelatin capsules:

for 50 mg dosage – gelatin, titanium dioxide, azorubin dye, sunset yellow dye and for 150 mg dosage – gelatin, titanium dioxide.

How to take, the dosage

Ingestion. 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 mg once daily. Depending on response, the dose may be increased to 400 mg once daily. The duration of treatment for cryptococcal infections depends on clinical efficacy confirmed by microbiological testing. Recommended duration of treatment during initial therapy of cryptococcal meningitis is 10-12 weeks after negative results of microbiological examination of cerebrospinal fluid sample.

In order to prevent relapse of cryptococcal meningitis in AIDS patients, fluconazole is prescribed at a dose of 200 mg per day for an extended period after completion of the complete course of initial treatment.

In candidemia, disseminated candidiasis, and other invasive candidiasis infections, the dose is usually 400 mg the first day and 200 mg thereafter. If clinical efficacy is insufficient, the dose may be increased to 400 mg per day; in severe systemic candidiasis, the dose may be increased to 800 mg per day. Duration of therapy depends on clinical efficacy; it should be continued for at least 2 weeks after negative hemocultures or after disappearance of disease symptoms.

In oropharyngeal candidiasis the drug is usually prescribed 50-100 mg once a day; therapy duration is 7-14 days. If necessary, in patients with severe immune impairment the treatment may be longer (3 weeks).

In atrophic oral candidiasis associated with the wearing of dentures, fluconazole is usually prescribed 50 mg once daily for 14 days in combination with local antiseptic agents for denture treatment.

For other localizations of candidiasis (except genital candidiasis), such as esophagitis, noninvasive bronchopulmonary lesions, candiduria, candidiasis of the skin and mucous membranes, etc., Effective dose is usually 50-100 mg per day with treatment duration of 14-30 days; in severe candidiasis of mucous membranes – 100-200 mg per day.

For prevention of relapses of oropharyngeal candidiasis in AIDS patients after completion of the full course of primary therapy, the drug may be prescribed 150 mg once a week.

For vaginal candidiasis, fluconazole is taken once orally in a dose of 150 mg. To reduce the frequency of recurrence of vaginal candidiasis, the drug may be used in 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.

For balanitis caused by Candida, fluconazole is given as a single oral dose of 150 mg.

For prevention of candidiasis, the recommended dose of fluconazole is 50-400 mg once daily, depending on the risk of fungal infection.

If there is a high risk of generalized infectionfor example, in patients with anticipated severe or prolonged neutropenia, the recommended dose is 400 mg once daily. Fluconazole is prescribed several days before the expected appearance of neutropenia; after neutrophil counts increase above 1000/mm3, treatment is continued for another 7 days.

In cases of skin mycoses, including foot mycoses, skin of the groin and skin candidiasis, the recommended dose is 150 mg once weekly or 50 mg once daily. Duration of therapy is usually 2-4 weeks, but in cases of athlete’s foot, longer therapy (up to 6 weeks) may be necessary.

In pityriasis, 300 mg 1 time per week for 2 weeks; some patients require a third 300 mg dose per week, while in some cases a single 300-400 mg dose is sufficient; alternatively, 50 mg 1 time per day for 2-4 weeks.

In onychomycosis, the recommended dose is 150 mg once weekly. Treatment should be continued until the infected nail is replaced (uninfected nail grows back). It normally takes 3-6 months and 6-12 months, respectively, for the nails on the fingers and toes to grow back.

In deep endemic mycoses the drug may need to be used at a dose of 200-400 mg per day for up to 2 years. The duration of therapy is determined individually; it may be 11-24 months for coccidiomycosis and 3-17 months for histoplasmosis.

In children, as in 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 once a day.

In mucosal candidiasis, the recommended dose of fluconazole is 3 mg/kg per day. A shock dose of 6 mg/kg may be administered on the first day in order to reach equilibrium concentrations more quickly.

For the treatment of generalized candidiasis or cryptococcal infection, the recommended dose is 6-12 mg/kg per day, depending on the severity of the disease.

For the prevention of fungal infections in immunocompromised children whose risk of infection is associated with neutropenia resulting from cytotoxic chemotherapy or radiation therapy, the drug is indicated at 3-12 mg/kg per day, depending on the severity and duration of induced neutropenia.

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

Interaction

Single administration of fluconazole in the treatment of vaginal candidiasis is not associated with significant interactions. However, the following drug interactions are possible when multiple or higher doses of the drug are used concomitantly with other medicinal products:

Special Instructions

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

As fluconazole is mainly excreted by the kidneys, caution should be exercised in patients with renal insufficiency. During long-term treatment with fluconazole, dosing should be adjusted for CK.

Caution should be exercised when prescribing fluconazole to patients with impaired liver function. Hepatic enzymes should be monitored regularly during treatment and the patient should be followed up to detect possible toxic effects. If the activity of liver enzymes increases, the physician should weigh the benefit of the therapy against the risk of severe liver damage. The hepatotoxic effects of fluconazole are usually reversible: symptoms disappear after therapy is stopped.

AIDS patients are more prone to develop severe skin reactions when using many drugs. If patients with superficial fungal infection develop a rash and it is considered to be 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.

Protrombin time should be monitored in patients receiving fluconazole and coumarin anticoagulants simultaneously. Treatment should be continued until clinical and microbiological remission occurs. Premature discontinuation of treatment leads to relapses.

The dye azorubin contained in the drug may cause allergic reactions, including bronchial asthma. Allergic reactions are more common in patients with intolerance to acetylsalicylic acid.

Influence on the ability to drive a car or other mechanical means: Experience with fluconazole suggests that impairment of driving and operating machinery associated with the use of the drug is unlikely.

Contraindications

Hypersensitivity to fluconazole, other drug components or other azole compounds;

concomitant use of terfenadine (while taking fluconazole continuously at a dose of 400 mg or more per day), cisapride or astemizole or other drugs that prolong the Q-T interval and increase the risk of severe rhythm disturbances;

Lactose intolerance;

Lactase deficiency; glucose-galactose malabsorption; lactation; children under 3 years of age (for this dosage form).

With caution: hepatic and/or renal impairment, rash on fluconazole in patients with superficial fungal infections and invasive/systemic fungal infections, simultaneous use of terfenadine and fluconazole at a dose of less than 400 mg daily, potentially proarrhythmogenic states in patients with multiple risk factors (organic heart disease, electrolyte imbalances, simultaneous use of drugs that cause arrhythmias); Patients with intolerance to acetylsalicylic acid, pregnancy.

Side effects

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

Nervous system disorders:headache, dizziness, rarely – seizures.

Hematopoietic organs: rarely – agranulocytosis, neutropenia. In patients with severe fungal infections hematological changes (leukopenia and thrombocytopenia) may be noted.

Cardiovascular system: prolongation of the Q-T interval in the electrocardiogram (ECG), ventricular fibrillation/tripping.

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), anaphylac-toid reactions (including angioedema, facial edema, urticaria, skin itching).

Others: rarely – renal dysfunction, alopecia, hypercholesterolemia, hypertrig-lyceridemia, hypokalemia.

Overdose

Symptoms: Nausea, vomiting, diarrhea, in severe cases seizures, hallucinations, paranoid behavior may be noted.

Treatment: symptomatic, gastric lavage; since. Since fluconazole is excreted by the kidneys, forced diuresis is recommended. Hemodialysis for 3 h reduces plasma concentrations by a factor of 2.

Similarities