Fluconazole-Vertex capsules 50mg, 7pcs

Composition

1 capsule contains

Active ingredient:

fluconazole 50 mg

Auxiliary substances:

corn starch,

povidone (polyvinylpyrrolidone),

colloidal silicon dioxide (aerosil),

sodium lauryl sulfate,

calcium stearate,

lactose.

Hard gelatin capsules:

for a dosage of 50 mg-gelatin,

titanium dioxide,

dye azorubin,

dye sunset yellow and for a dosage of 150 mg-gelatin, titanium dioxide.

Pharmacological action

Fluconazole is an antifungal agent, has a highly specific effect, inhibiting the activity of fungal enzymes dependent on cytochrome P 450. It blocks the conversion of lanosterol from fungal cells to membrane lipid-ergosterol; it increases the permeability of the cell membrane, disrupts its growth and replication.

Fluconazole, being highly selective for fungal cytochrome P450, practically does not inhibit these enzymes in the human body (in comparison with itraconazole, clotrimazole, econazole and ketoconazole, it suppresses oxidative processes dependent on cytochrome P450 in human liver microsomes to a lesser extent). It has no antiadrogenic activity.

Active in opportunistic mycoses, including those caused by Candida spp. (including generalized forms of candidiasis on the background of immunosuppression), Cryptococcus neoformans and Coccidioides immitis (including intracranial infections), Microsporum spp. and Trichophyton spp. ; in endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulatum (including immunosuppression).

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;
• 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; prevention of relapse of oropharyngeal Candidasa AIDS;
• genitally 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;
• generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive Candida infections (infection of the peritoneum, endocardium, eyes, respiratory and urinary tract). The treatment may be performed in patients with malignant tumors, patients in intensive care, patients undergoing cytotoxic or immunosuppressive therapy, and the presence of other predisposing factors to the development of candidiasis;
• fungal skin infections, including athlete’s foot, body, groin; tinea (colored) versicolor, onychomycosis and cutaneous Candida infections;
• deep endemic mycoses, including coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immunity;
• prevention of fungal infections in patients with malignancies who are predisposed to such infections as a result of chemotherapy with cytostatics or radiation therapy.

Contraindications

• hypersensitivity to fluconazole, other components of the drug or azole compounds with similar structure to fluconazole;
• concomitant use of terfenadine (compared to the continuous use of fluconazole at a dose of 400 mg/day or more);
• simultaneous reception of cisapride, astemizole, as well as other drugs that lengthen the QT interval;
• lactation;
• children up to age 4 years.

With caution:

hepatic and/or renal failure, rash on the background of 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 at least 400 mg/day, concomitant use of potentially hepatotoxic drugs, alcoholism, potentially pruritogens status in patients with multiple risk factors (organic heart disease, electrolyte imbalance, concomitant use of drugs that cause arrhythmia), pregnancy.

Side effects

From the digestive system: decreased appetite, changes in taste, nausea, vomiting, abdominal pain, flatulence, diarrhea, rarely-impaired liver function (hyperbilirubinemia, increased activity of alanine aminotransferase, aspartate aminotransferase, increased activity of alkaline phosphatase, jaundice, hepatitis, hepatocellular necrosis).

From the nervous system: headache, dizziness, excessive fatigue, rarely-convulsions.

Hematopoietic disorders: rarely-leukopenia, thrombocytopenia (bleeding, petechiae), neutropenia, agranulocytosis.

From the cardiovascular system: increased duration of the Q-T interval, ventricular fibrillation/flutter.

Allergic reactions:

skin rash, rarely-erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome), anaphylactoid reactions (including angioedema, facial edema, urticaria, pruritus of the skin).

Other services:

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

Interaction

When using fluconazole with warfarin, the prothrombin time increases (on average by 12%). In this regard, it is recommended to carefully monitor the prothrombin time indicators in patients receiving the drug in combination with coumarin anticoagulants. It is possible to increase the half-life of oral hypoglycemic agents – sulfonylurea derivatives (chlorpropamide, glibenclamide, glipizide, tolbutamide) when taken simultaneously with fluconazole.

Concomitant use of fluconazole and phenytoin may lead to an increase in the concentration of phenytoin in plasma to a clinically significant degree. Therefore, if the combined use of these drugs is necessary, it is necessary to monitor the concentration of phenytoin with dose adjustment in order to maintain the level of the drug within the therapeutic interval.

Combination with rifampicin resulted in a 25% decrease in AUC and a 20% shortening of the plasma half-life of fluconazole. Therefore, it is advisable to increase the dose of fluconazole in patients receiving rifampicin at the same time.

It is possible to increase the concentration of cyclosporine when used simultaneously with fluconazole at a dose of 200 mg / day.

In the case of simultaneous use with theophylline, a decrease in the average rate of clearance of theophylline from plasma is possible. Concomitant use of fluconazole and cisapride can significantly increase the plasma concentration of cisapride; cases of adverse reactions from the heart, including ventricular fibrillation/flutter (torsades de points), an increase in the QT interval on the ECG, have been described.

Concomitant use of azole antifungal agents and terfenadine may lead to a significant increase in plasma levels of terfenadine: serious arrhythmias may occur as a result of an increase in the QT interval.

Concomitant use of fluconazole and hydrochlorothiazide may increase the plasma concentration of fluconazole by 40%. There are reports of interaction between fluconazole and rifabutin, accompanied by an increase in serum levels of the latter. Cases of uveitis have been reported with concomitant use of fluconazole and rifabutin. Patients receiving rifabutanand fluconazole concomitantly should be carefully monitored.

In patients receiving a combination of fluconazole and zidovudine, an increase in the concentration of zidovudine is observed, which is caused by a decrease in the conversion of the latter to its main metabolite, so an increase in the side effects of zidovudine should be expected.

Increases the concentration of midazolam, which increases the risk of psychomotor effects (more pronounced when using fluconazole inside than intravenously).

Increases the concentration of tacrolimus, which increases the risk of nephrotoxic effects.

How to take it, course of use and dosage

Inside, swallowing whole.

Adults and children over 15 years of age (with a body weight of more than 50 kg) with cryptococcal meningitis and cryptococcal infections of other localizations are usually prescribed 400 mg (8 capsules of 50 mg) on the first day, and then continue treatment at a dose of 200 mg (4 capsules of 50 mg) – 400 mg (8 capsules of 50 mg) once a day. The duration of treatment for cryptococcal infections depends on the clinical efficacy confirmed by mycological examination; for cryptococcal meningitis, the course of treatment should be at least 6-8 weeks.

To prevent recurrence of cryptococcal meningitis in AIDS patients, after completing a full course of primary therapy, fluconazole is prescribed at a dose of 200 mg (4 capsules of 50 mg) per day for a long period of time.

For candidaemia, disseminated candidiasis and other invasive candida infections, the dose is 400 mg (8 capsules of 50 mg) on the first day, and then 200 mg (4 capsules of 50 mg) per day. In case of insufficient clinical efficacy, the dose of the drug can be increased to 400 mg (8 capsules of 50 mg) per day. The duration of therapy depends on the clinical efficacy.

For oropharyngeal candidiasis, the drug is usually prescribed 150 mg once a day; the duration of treatment is 7-14 days. If necessary, in patients with a pronounced decrease in immunity, treatment can be longer.

To prevent relapses of oropharyngeal candidiasis in AIDS patients after completing a full course of primary therapy – 150 mg once a week.

In case of atrophic candidiasis of the oral cavity associated with wearing dentures,50 mg once a day for 14 days in combination with local antiseptic drugs 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 150 mg per day with a treatment duration of 14-30 days. 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 orally once at a dose of 150 mg per day.

For the prevention of candidiasis, the recommended dose is 50-400 mg once a day, depending on the degree of risk of developing a fungal infection. For the prevention of candidiasis in patients with malignant neoplasms, the recommended dose of fluconazole is 150-400 mg once a 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 / day. Fluconazole is prescribed a few days before the expected appearance of neutropenia; after an increase in the number of neutrophils more than 1 thousand/µl, treatment is continued for another 7 days.

For mycoses of the skin, including mycoses of the feet, smooth skin, groin area, and candidiasis of the skin, the recommended dose is 150 mg once a week or 50 mg once a day, the dosage regimen depends on the clinical and mycological effect. 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 (2 capsules of 150 mg) 1 time 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 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 in a dose of 200 mg (4 capsules of 50 mg) – 400 mg (8 capsules of 50 mg) per day for up to 2 years. The duration of therapy is determined individually; it can be 11-24 months. with coccidioidomycosis; 2-17 months. for 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 of adults, i. e. no more than 400 mg per day. The drug is used daily 1 time a day.

Patients who are regularly on dialysis, one dose of the drug is used after each hemodialysis session.

Overdose

Symptoms:

hallucinations, paranoid behavior.

Treatment is symptomatic:

gastric lavage, forced diuresis.

Hemodialysis for 3 hours reduces the plasma concentration by approximately 50%.

Functional features

After oral use, fluconazole is well absorbed, its bioavailability is 90%.

The maximum concentration after oral use on an empty stomach of 150 mg of the drug is 90% of the plasma concentration when administered intravenously at a dose of 2.5-3.5 mg/l. Simultaneous food intake does not affect the absorption of oral fluconazole. The time to reach the maximum concentration after ingestion of 150 mg of the drug on an empty stomach is 0.5-1.5 hours.

The plasma concentration is directly related to the dose. The level of 90% of the equilibrium concentration is reached by 4-5 days of treatment with the drug (when taken 1 time/day). The introduction of a “shock” dose (on the first day),2 times higher than the usual daily dose, allows you to reach a concentration level corresponding to 90% of the equilibrium concentration by the second day. The volume of distribution approaches the total water content in the body. Binding to plasma proteins is 11-12%.

Fluconazole penetrates well into all body fluids. The concentration of the Active ingredient in breast milk, joint fluid, saliva, sputum and peritoneal fluid is similar to that in plasma. Constant values in vaginal secretions are reached 8 hours after oral use and are kept at this level for at least 24 hours

. Fluconazole penetrates well into the cerebrospinal fluid( CSF), with fungal meningitis, the CSF concentration is about 80% of its plasma level. In the sweat fluid, epidermis and stratum corneum of the skin (selective accumulation), concentrations exceeding serum are achieved.

On the 7th day after oral use of 150 mg of fluconazole, its concentration in the stratum corneum of the skin is 23.4 mcg/g,1 week after taking the second dose – 7.1 mcg/g. The concentration of fluconazole in healthy nails after 4 months of use at a dose of 150 mg once a week is 4.05 mcg/g and 1.8 mcg/g in the affected nails.

It is an inhibitor of the CYP2C9 isoenzyme in the liver. No metabolites of fluconazole were detected in the peripheral blood. It is mainly excreted by the kidneys (80% – unchanged,11% – in the form of metabolites). The half-life of fluconazole is about 30 hours. The clearance of fluconazole is proportional to the creatinine clearance.

After hemodialysis for 3 hours, the concentration of fluconazole in plasma decreases by 50%.

Special instructions

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

In the case of hepatotoxic effects associated with fluconazole, there was no obvious dependence on the total daily dose, duration of therapy, gender, and age of the patient. The hepatotoxic effect of fluconazole was usually reversible; signs of it disappeared after discontinuation of therapy. If there are clinical signs of liver damage that may be associated with fluconazole, the drug should be discontinued.

AIDS patients 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. Caution should be exercised when taking fluconazole concomitantly with rifabutin or other drugs that are metabolized by the cytochrome P450 system.

When using fluconazole together with oral hypoglycemic agents (chlorpropamide, glibenclamide, glipizide, tolbutamide) in patients with diabetes mellitus, blood glucose levels should be monitored (the possibility of hypoglycemia). It is recommended to monitor the concentration of cyclosporine in the blood when used simultaneously with fluconazole.

Patients who are receiving high doses of theophylline concomitantly with fluconazole, or who are likely to develop theophylline intoxication, should be monitored for early detection of symptoms of theophylline overdose.

Influence on the ability to drive a car and mechanisms

A violation of the ability to drive a car and mechanisms associated with the use of the drug is unlikely.

Composition

Capsule Form of production

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25°C. Keep out of reach of children.

Shelf life

2 years

Active ingredient

Fluconazole

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

For adults, Children over 3 years old

Indications

Thrush, Fungus