Fluconazole-Vertex capsules 150mg, 2pcs

Composition

1 capsule contains:  

Active ingredient:

fluconazole 150 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

Antifungal agent, has a highly specific effect, inhibiting the activity of fungal enzymes dependent on cytochrome P 450. Blocks the conversion of lanosterol in fungal cells into membrane lipid-ergosterol; 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.

It is active in opportunistic mycoses, including those caused by Candida spp. (including generalized forms of candidiasis against 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 those caused by immunosuppression).

Pharmacokinetics

After oral use, fluconazole is well absorbed, food intake does not affect the rate of absorption of fluconazole, its bioavailability is 90%.

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, cmax is 90% of the plasma concentration when administered intravenously at a dose of 2.5-3.5 mg/l. T_1/2 of fluconazole is 30 hours. Binding to plasma proteins is 11-12%. The plasma concentration is directly related to the dose. 90% of the equilibrium concentration is reached by the 4th-5th day of treatment with the drug (when taken once a 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.

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

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

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

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 Cryptocom the Cove infection 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). The treatment may be performed in patients with malignant-governmental tumors, patients in intensive care, patients, passing-ing the course of cytostatic or immunosuppressive therapy, and the presence of other predisposing factors to the development of Candida;
• 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 Oro-fringillinae candidiasis in patients with AIDS,
• genital candidiasis: vaginal candidiasis (acute and chronic relapse-ating rific), 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 CITO a static or radiotherapy;
• fungal skin infections, including athlete’s foot, body, groin; tinea versicolor, onychomycosis; candidiasis of the skin;
• deep endemic mycoses, including coccidioidomycosis and histoplasmosis in patients with normal immune systems.

Contraindications

• Hypersensitivity to fluconazole, other components of the drug or to other azole compounds;

• concomitant use of terfenadine (compared to the continuous use of fluconazole at a dose of 400 mg per day or more), cisapride or astemizole and other drugs, lengthening of the Q-T interval and increase the risk of severe rhythm disorders;

• lactose intolerance,

• lactase deficiency; glucose-galactose malabsorption; lactation; children’s age up to 3 years (for this dosage form).

With caution: hepatic and/or renal insufficiency, rash on the background of fluconazole use 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 per day, potentially proarrhythmogenic conditions in patients with multiple risk factors (organic heart disease, electrolyte disturbances, concomitant use of drugs that cause arrhythmias); patients with intolerance to acetylsalicylic acid, pregnancy.

Side effects

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

Nervous system disorders: headache, dizziness, rarely convulsions.

Hematopoietic disorders: rarely-agranulocytosis, neutropenia. Patients with severe fungal infections may have hematological changes (leukopenia and thrombocytopenia).

From the cardiovascular system: increased 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: 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 Q-T 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, pro-thrombin 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 dose of fluconazole accordingly when they are used 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 dose should be reduced accordingly.
• Clinical studies have shown that as a result of slowing the metabolism of zidovudine, its concentration in plasma 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.
• Increases the pharmacological effects 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). Fluconazole increases serum phenytoin concentrations. With simultaneous use, it is necessary to monitor the doses of phenytoin and adjust them accordingly.
• Increases the concentration of tacrolimus — the risk of nephrotoxicity.
• Doctors should keep in mind that interactions with other drugs have not been specifically studied, but they are possible.

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 mg once a day. Depending on the response, the dose can be increased to 400 mg once a day. The duration of treatment for cryptococcal infections depends on the clinical efficacy confirmed by microbiological research. The recommended duration of treatment for the initial treatment of cryptococcal meningitis is 10-12 weeks after the negative result of microbiological examination of the cerebrospinal fluid sample.

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 per day for a long period of time.

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 per day; with severe systemic candidiasis, it is possible to increase the dose to 800 mg per 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 symptoms of the disease disappear.

For oropharyngeal candidiasis, the drug is usually prescribed 50-100 mg once a 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, flu-conazole is usually prescribed 50 mg once a day for 14 days in combination with local antiseptics to treat 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 per day with a treatment duration of 14-30 days; for severe candidiasis of the mucous membranes — 100-200 mg per day.

To prevent relapses of oropharyngeal candidiasis in AIDS patients after completing a full course of primary therapy, the drug can be prescribed 150 mg once a week.

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 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 once a day. Fluconazole is prescribed a few days before the expected appearance of neutropenia; after an increase in the number of neutrophils more than 1000/mm, 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 for mycoses of the feet, longer therapy (up to 6 weeks) may be required.

For 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 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 grows). It normally takes 3-6 months and 6-12 months, respectively, for the nails to regrow on the fingers and feet.

With 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 can be 11-24 months for coccidiomycosis 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 a day.

For mucosal candidiasis, the recommended dose of fluconazole is 3 mg / kg per day. On the first day, a shock dose of 6 mg/kg may be prescribed in order to achieve 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.

To prevent fungal infections in immunocompromised children who are at risk of developing neutropenia due to cytotoxic chemotherapy or radiation therapy, the drug is prescribed at 3-12 mg / kg per day, depending on the severity and duration of the induced neutropenia.

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

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 initiated 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. With long-term treatment with fluconazole, 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 activity of “liver” enzymes and monitor the patient for possible toxic effects. When increasing the activity 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.

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.

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

The dye azorubin included in the preparation can cause an allergic reaction, including bronchial asthma. Allergic reactions are more common in patients who are intolerant to acetylsalicylic acid.

Influence on the ability to drive a car or other mechanical means: experience with the use of fluconazole indicates that a violation of the ability to drive a car and mechanisms associated with the use of the drug is unlikely.

Form of production

Solid gelatin capsules No. 3 with a white body, orange lid (for a dosage of 50 mg) and No. 0 white (for a dosage of 150 mg).

The contents of the capsules are a powder or compacted mass of white or white with a yellowish tinge of color, which disintegrates when pressed.

Storage conditions

 In a dark place, at a temperature not exceeding 25 °C.

Shelf life

2 years

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