Fluconazole-Vertex capsules 150mg, 1pc

Composition

1 capsule contains:

Active ingredient:

fluconazole 50 mg or 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

Pharmacotherapeutic group: antifungal agent. KodATH:  J02 AC 01

Pharmacological properties

Pharmacodynamics

Fluconazole is a representative of the class of triazole antifungal agents, is a powerful selective inhibitor of the fungal enzyme 14-α-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 dermatidis, Coccidioides immitis and Histoplasma capsulatum. However, blastomycetes, histoplasmas, paracoccidioid, and sporotrix are less sensitive to fluko-nasol than to other azoles.

Pharmacokinetics

After oral use, fluconazole is well absorbed, its bioavailability is 90%. The maximum concentration (Cmax) after oral use, on an empty stomach of 150 mg is 90% of the plasma content when administered intravenously at a dose of 2.5-3.5 mg/kg.

Simultaneous food intake does not affect the absorption of the drug taken orally. The plasma concentration reaches a peak in 0.5-1.5 hours (TMAX) after use. Plasma concentrations are directly proportional to the dose. 90% of the equilibrium concentration is reached by 4-5 days of treatment with the drug (when taken once a day).

The use of a dose on the first day,2 times higher than the usual daily dose, allows you to reach the level of the drug in plasma, equal to 90% of the equilibrium concentration, by the second day. The apparent volume of distribution approaches the total volume of water in the body. Binding to plasma proteins is small – 11-12%.

Fluconazole penetrates well into all body fluids, including cerebrospinal fluid. The concentrations of the drug in saliva and sputum are similar to those in plasma. In patients with fungal meningitis, the content of fluconazole in the cerebrospinal fluid reaches 80% of its plasma level.

In the stratum corneum, epidermis, dermis and sweat fluid, high concentrations are achieved that exceed serum levels.

Less than 5% of fluconazole is metabolized on its first pass through the liver. The half-life (T 1/2) of fluconazole is about 30 hours. Long-term T 1/2 allows you to change a single dose of the drug for the treatment of vaginal candidiasis and provides the drug once a day for other indications. Fluconazole is mainly excreted by the kidneys; approximately 80% of the administered dose is excreted unchanged by the kidneys. The clearance of fluconazole is proportional to creatinine clearance. No metabolites of fluconazole were detected in the peripheral blood.

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;
• 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 the ICU, patients undergoing cytotoxic 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 oropharyngeal candidiasis in patients with AIDS,
• genital 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;
• prevention of fungal infections in patients with malignancies who are predisposed to such infections as a result of chemotherapy with cytostatics or radiation therapy;
• fungal skin infections, including athlete’s foot, body, groin; tinea (colored) versicolor, onychomycosis; candidiasis of the skin;
• deep endemic mycoses, including coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immune systems.

Use during pregnancy and lactation

The use of the drug in pregnant women is impractical, except for severe or life-threatening forms of fungal infections, if the intended effect exceeds the possible risk to the fetus.

Fluconazole is found in breast milk at the same concentration as in plasma, so its use during lactation is not recommended.

Contraindications

Hypersensitivity to fluconazole, other components of the drug or other azole compounds; concomitant use of terfenadine (against the background of constant use of fluconazole at a dose of 400 mg per day or more), cisapride or astemizole and other drugs that prolong the Q-T interval and increase the risk of severe rhythm disorders; lactose intolerance; lactase deficiency; glucose-galactose malabsorption; lactation period; children under 3 years of age (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, abdominal pain, vomiting, nausea, diarrhea, flatulence, rarely-impaired liver function (jaundice, hepatitis, hepatonecrosis, hyperbilirubinemia, increased activity of alanine aminotransferase, aspartate aminotransferase, increased activity of alkaline phosphatase, hepatocellular necrosis), including severe.

Nervous system disorders:  headache, dizziness, excessive fatigue, rarely-convulsions.

From the side of hematopoietic organs:  rarely-leukopenia, thrombocytopenia (bleeding, petechiae), neutropenia, agranulocytosis.

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).

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

Other services:  rarely-impaired renal function, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

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 administered 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 disappearance of symptoms of the disease.

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.

With 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 the use of 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.

For the prevention of fungal infections in children with reduced immunity, in which the risk of infection is associated with neutropenia, developing as a result of cytotoxic chemotherapy or radiation therapy, the drug is prescribed at 3-12 mg / kg per day, depending on the severity and duration of preservation of induced neutropenia.

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

Dosage for patients with renal insufficiency

, Fluconazole is mainly excreted unchanged by the kidneys. With a single dose, no dose change is required.

Adult patients with impaired renal function with repeated use of the drug should first be prescribed a “shock” dose from 50 mg to 400 mg. If the creatinine clearance (CC) is greater than 50 ml / min, the usual dose of the drug is used (100% of the recommended dose).

With creatinine clearance from 11 to 50 ml/min, a dose equal to 50% of the recommended dose is used, or the usual dose is 1 time in 2 days. Patients who are regularly on dialysis, one dose of the drug is used after each hemodialysis session.

In children with impaired renal function, the daily dose of the drug should be reduced (in the same proportion as in adults), in accordance with the severity of renal failure.

In elderly patients with no impaired renal function, the usual dosage regimen should be followed.

Overdose

Symptoms: nausea, vomiting, diarrhea, convulsions, 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 plasma concentration by 2 times.

Interaction with other medicinal products 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. Therefore, monitoring of cyclosporine concentrations in patients receiving concomitant treatment with cyclosporine and fluconazole is recommended.
• 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 drugs 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.

Special instructions

Treatment should be continued until clinical and hematological remission occurs. Premature discontinuation of treatment leads to relapses.

During treatment, it is necessary to monitor blood parameters, kidney and liver function. If you experience impaired renal and hepatic function, you should stop taking the drug.

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.

Patients People with AIDS 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 cisapride, rifabutin, or other drugs that are metabolized by the cytochrome P450 system.

Form of production

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

Store in a dry place, protected from light, at a temperature of 15-25 °C.

Shelf life

2 years

Active ingredient

Fluconazole

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

For adults and children as prescribed by a doctor

Indications

Nail Fungus, Skin Fungus, Fungus, Thrush