Description of the drug FLUCONAZOLE

pharmachologic effect

The abstract contains information that the drug acts as an antifungal agent, specifically inhibiting the synthesis of fungal sterols. Belongs to the class of triazole compounds.

There is a specific effect on fungal enzymes that depend on cytochrome P450. The active substance demonstrates activity against a variety of strains of Candida spp. (including effective against visceral candidiasis), Cryptococcus neoformans (including effective against intracranial infections), Trichophytum spp, Microsporum spp. The drug is also active against microorganisms that are causative agents of endemic mycoses: Coccidioides immitis, Hystoplasma capsulatum, Blastomyces dermatitidis.

The drug stops the conversion of fungal cells into lanosterol into ergosterol. Under its influence, the permeability of the cell membrane increases, the process of its growth and replication is inhibited. It is highly selective for cytochrome P450 of fungi, but in the human body it almost does not inhibit these enzymes. Does not demonstrate antiandrogenic activity.

Pharmacodynamics

An antifungal agent that has a highly specific effect, inhibiting the activity of fungal enzymes dependent on cytochrome P450. Blocks the conversion of lanosterol from fungal cells into the 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 cytochrome P450-dependent oxidative processes in human liver microsomes to a lesser extent). Does not have antiadrogenic activity.

Active against opportunistic mycoses, incl. caused by Candida spp. (including generalized forms of candidiasis due to immunosuppression), Cryptococcus neoformans and Coccidioides immitis (including intracranial infections), Microsporum spp. and Trichophyton spp.; for endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulatum (including immunosuppression).

Pharmacokinetics and pharmacodynamics

Wikipedia indicates that after oral administration, the drug is actively absorbed into the human gastrointestinal tract. In plasma, the concentration of the active substance is more than 90% of the level that is observed if intravenous administration is practiced. The absorption of the substance is not affected by food intake, so it does not matter how you take it, before or after meals. After taking the medicine orally, the highest concentration in the blood occurs after 0.5–1.5 hours. The half-life from the blood is 30 hours. That is, you can take the product once a day. For vaginal candidiasis, a single dose of the drug is sufficient, for which one tablet or another form of the drug is used.

11–12% of the active substance binds to blood plasma proteins. When the drug begins to work depends on the treatment regimen. If you take the medicine once daily, then a stable concentration of the active component in the human blood is observed on the fourth or fifth day (in 90% of people). If on the first day of treatment the patient is given a double daily dose, then this effect is observed already on the second day of treatment.

Penetrates into all fluids in the body. It is excreted from the body through the kidneys, approximately 80% is excreted unchanged.

Pharmacokinetics

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

The time to reach maximum concentration after oral administration 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. T1/2 of fluconazole is 30 hours. Communication with plasma proteins is 11–12%. Plasma concentration is directly dependent on dose. A 90% level of equilibrium concentration is achieved by the 4th–5th day of treatment with the drug (when taken once a day).

Administration of a loading dose (on the first day), 2 times higher than the usual daily dose, allows one to achieve a concentration level corresponding to 90% of the equilibrium concentration by the second day.

Fluconazole penetrates well into all biological fluids of the body. 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 secretions are achieved 8 hours after oral administration and are maintained at this level for at least 24 hours. Fluconazole penetrates well into the cerebrospinal fluid (CSF) - with fungal meningitis, the concentration in the CSF is about 85% of its level in plasma. In sweat fluid, epidermis and stratum corneum (selective accumulation) concentrations exceeding serum levels are achieved. After oral administration 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; concentration in 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 of the body.

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

The pharmacokinetics of fluconazole depends significantly 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 for use

The following indications for use of the drug are determined:

• infectious diseases caused by candida ( disseminated candidiasis , generalized candidiasis , other forms of invasive candidiasis ;
• candidiasis of the mucous membranes (including the pharynx, oral cavity, esophagus);
• candiduria;
• chronic atrophic and mucocutaneous candidiasis of the oral cavity (develops in people with dentures);
• non-invasive bronchopulmonary infections;
• genital candidiasis ( vaginal candidiasis in acute form and with relapses);
• prevention of recurrent manifestations of vaginal candidiasis (if the disease develops three times a year), candidal balanitis ;
• cryptococcal infection, cryptococcal meningitis;
• onychomycosis;
• dermatomycosis (including mycoses of the body, feet, groin area);
• pityriasis versicolor;
• endemic mycoses deep;
• prevention of the development of fungal infections in people who have undergone cytostatic or radiation therapy.

Indications for the drug Fluconazole

cryptococcosis, including cryptococcal meningitis and other localizations of this infection (including lungs, skin), both in patients with a normal immune response and in patients with various forms of immunosuppression (including in patients with AIDS, organ transplantation ); the drug can be used to prevent cryptococcal infection in patients with AIDS;

generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidal infections (infections of the peritoneum, endocardium, eyes, respiratory and urinary tract). Treatment can be carried out in patients with malignant neoplasms, patients in the intensive care unit, patients undergoing cytostatic or immunosuppressive therapy, as well as in the presence of other factors predisposing to the development of candidiasis;

candidiasis of the mucous membranes, incl. oral cavity and pharynx (including atrophic candidiasis of the oral cavity associated with wearing dentures), esophagus, non-invasive bronchopulmonary candidiasis, candiduria, cutaneous candidiasis; 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 relapses of vaginal candidiasis (3 or more episodes per year); candidal balanitis;

prevention of fungal infections in patients with malignant neoplasms who are predisposed to such infections as a result of chemotherapy with cytostatics or radiation therapy;

mycoses of the skin, including mycoses of the feet, body, and groin area; pityriasis versicolor (varicolored) lichen, onychomycosis; skin candidiasis;

deep endemic mycoses, including coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immunity.

Contraindications

There are the following contraindications for the use of this medicine:

• manifestation of high sensitivity to fluconazole or to azole compounds, which are similar in chemical structure to fluconazole;
• concurrent use of terfenadine if the patient receives a dose of Fluconazole 400 mg per day or more;
• concomitant use of astemizole or any other drugs that increase the QT interval;
• age up to 4 years.

It should be taken with caution in case of liver failure, also kidney failure, when a rash appears in people suffering from a superficial fungal infection, in potentially pro-arrhythmogenic conditions in people with risk factors (organic heart disease, taking medications that provoke the development of arrhythmia , electrolyte imbalance). How to take Fluconazole in this case, you should definitely ask a specialist.

Side effects

When treated with the drug, the patient may develop the following side effects:

• abdominal pain, diarrhea ;
• headache;
• nausea , flatulence ;
• skin rash;
• hepatotoxic effects;
• anaphylactic reactions.

How to take the medicine when such effects occur, and whether it is worth continuing treatment, should be individually consulted with a doctor.

Instructions for use of Fluconazole (Method and dosage)

The drug is prescribed for oral administration (Fluconazole Stada capsules, Fluconazole Teva, tablets) or for intravenous administration. There are also other forms of medication, the active ingredient of which is fluconazole - suppositories, ointment.

The solution is infused at a rate not exceeding 10 ml per minute.

Fluconazole tablets, instructions for use

The dosage of the drug depends on the disease and its severity.

Patients with disseminated candidiasis and candidemia are prescribed 400 mg on the first day, then the dose should be reduced to 200 mg. For the treatment of generalized candidiasis, are advised to take 6–12 mg per 1 kg of weight per day.

For patients with oropharyngeal candidiasis , 50 mg to 100 mg of Fluconazole is indicated once a day, the treatment period is 1-2 weeks.

People suffering from atrophic candidiasis of the oral mucosa are advised to take 50 mg once a day. Treatment is combined with the use of local products for the treatment of prostheses. When treating other candidiasis infections of the mucous membranes, 50–100 mg per day is prescribed, the period of therapy is from 14 to 30 days.

In order to prevent the development of relapses of oropharyngeal candidiasis in people with AIDS , 150 mg once a week is indicated. If mucosal candidiasis develops in children, the dose should be taken at the rate of 3 mg of drugs per 1 kg of weight per day. On the first day, you can give your child a double dose.

Patients with cryptococcal infections and cryptococcal meningitis are usually prescribed 200–400 mg of drugs once a day. On the first day, 400 mg of the drug is indicated. The duration of treatment can be from 6 to 8 weeks. Children are prescribed a dose of 6–12 mg per 1 kg of weight per day.

People suffering from infectious skin diseases are recommended to prescribe 150 mg once a week or drink 50 mg of the drug once a day. Treatment should be continued for 2-4 weeks. For men and women with mycosis of the feet , longer therapy is sometimes required - up to 6 weeks.

Patients with pityriasis versicolor are recommended to take 300 mg once a week, the treatment period is 2 weeks. Depending on the intensity of your symptoms, your doctor may prescribe another dose of Fluconazole in the third week. It is possible to use another treatment regimen - 50 mg 1 time per day, the treatment period is two to four weeks.

Patients with onychomycosis are prescribed 150 mg once a week. Therapy should continue until a healthy nail grows in place of the diseased nail.

People suffering from deep endemic mycosis sometimes undergo a long course of treatment with the drug, which can last up to two years. The dose per day is 200–400 mg.

Instructions for the use of fluconazole for thrush stipulate that for vaginal candidiasis, a single dose of the drug is taken, its dose is 150 mg.

As a rule, Fluconazole for thrush is effective after a single dose. But your doctor will tell you more about how to take Fluconazole for thrush after an individual consultation. Before determining how to take any medicine for thrush if you have thrush, the specialist takes into account the causes of the disease and the individual characteristics of its course. For chronic thrush, Fluconazole Teva or other types of the drug are prescribed to prevent relapses at a dose of 150 mg once a month. The product should be used for 4-12 months. For the purpose of prevention, capsules are prescribed in a dose of 50–400 mg once a day, depending on how high the risk of the disease is. For children with thrush, Fluconazole tablets are prescribed at a dose of 3–12 mg of medication per 1 kg of weight per day. How much to drink depends on the severity of the infection.

For balanitis, the treatment regimen for men is as follows: the drug should be taken in a dose of 150 mg once.

Some patients are interested in whether it is possible to take pills or capsules during menstruation. According to experts, you can take Fluconazole at any time, regardless of your monthly cycle. How long it takes for the medicine to help depends on the intensity of the symptoms of the disease.

Nosological classification (ICD-10)

• B20.4 Disease caused by HIV, with manifestations of candidiasis
• B20.5 Disease caused by HIV, with manifestations of other mycoses
• B35.1 Mycosis of nails
• B35.3 Mycosis of the feet
• B35.4 Mycosis of the trunk
• B35.6 Athlete's foot
• B36.0 Tinea versicolor
• B37.0 Candidal stomatitis
• B37.1 Pulmonary candidiasis
• B37.2 Candidiasis of the skin and nails
• B37.3 Candidiasis of the vulva and vagina (N77.1*)
• B37.4 Candidiasis of other urogenital sites
• B37.6 Candidal endocarditis (I39.8*)
• B37.7 Candidal septicemia
• B37.8 Candidiasis of other sites
• B38 Coccidioidomycosis
• B39 Histoplasmosis
• B41 Paracoccidioidomycosis
• B42 Sporotrichosis
• B45 Cryptococcosis
• B45.0 Pulmonary cryptococcosis
• B45.1 Cerebral cryptococcosis
• B45.2 Cutaneous cryptococcosis
• N51.2 Balanitis in diseases classified elsewhere
• Y88.0 Consequences of adverse effects of drugs, medications and biological substances used for therapeutic purposes
• Z51.0 Radiotherapy course
• Z51.1 Chemotherapy for neoplasm

Interaction

Before starting treatment, it is important to know not only what Fluconazole in tablets and other forms helps with, but also about the interaction of drugs with other drugs.

When taking Warfarin , the prothrombin time of fluconazole becomes longer.

With simultaneous administration of hypoglycemic oral agents belonging to the group of sulfonylurea derivatives, the half-life of Fluconazole increases. As a result, there is a possibility of hypoglycemia.

With simultaneous administration of phenytoin, a clinically significant increase in phenytoin concentrations is observed.

With simultaneous repeated use of hydrochlorothiazide, an increase in the concentration of fluconazole in the blood is observed. There is no need to change the dosage.

With simultaneous treatment with Rifampicin, AUC decreases by 25%. The half-life is also reduced by 20%. In some cases, the doctor decides to increase its dose.

When treating with Fluconazole, monitoring the concentration of cyclosporine in the blood is recommended.

If the patient simultaneously receives high doses of Theophylline , it is important to consider the possibility of Theophylline overdose.

It is contraindicated to take a dose of more than 400 mg per day in combination with terfenadine .

When taking cisapride , negative side effects from blood vessels and the heart may occur, in particular, paroxysms of ventricular tachycardia .

If Fluconazole and Zidovudine , the patient should be monitored by a doctor, as the side effects of Zidovudine may increase.

If treatment with Astemizole , cisapride , Tacrolimus , Rifabutin , or any other drug that is metabolized by the cytochrome P450 system is simultaneously prescribed, the concentration of these drugs in the blood may increase.

The absorption of Fluconazole is not affected by simultaneous administration of Cimetidine or antacids.

Directions for use and doses

Inside.

For adults and children over 15 years of age (body weight over 50 kg) with cryptococcal meningitis and cryptococcal infections of other localizations, 400 mg (8 capsules of 50 mg each) is usually prescribed on the first day, and then treatment is continued at a dose of 200 mg (4 capsules of 50 mg each). 50 mg) – 400 mg (8 capsules of 50 mg each) 1 time per day. The duration of treatment for cryptococcal infections depends on clinical effectiveness confirmed by mycological examination; for cryptococcal meningitis, the course of treatment should be at least 6–8 weeks.

To prevent relapse of cryptococcal meningitis in patients with AIDS, after completing the 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 candidemia, disseminated candidiasis and other invasive candidal infections, on the first day the dose is 400 mg (8 capsules of 50 mg), and then 200 mg (4 capsules of 50 mg) per day. If clinical effectiveness is insufficient, the dose of the drug can be increased to 400 mg (8 capsules of 50 mg each) per day. The duration of therapy depends on clinical effectiveness.

For oropharyngeal candidiasis, the drug is usually prescribed at a dose of 150 mg 1 time / day, the duration of treatment is 7-14 days. If necessary, in patients with a pronounced decrease in immunity, treatment may be longer.

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

For atrophic oral candidiasis associated with wearing dentures - 50 mg once a day for 14 days in combination with local antiseptic drugs to treat the denture.

For other localizations of candidiasis (except genital), for example, esophagitis, non-invasive bronchopulmonary lesions, candiduria, candidiasis of the skin and mucous membranes, etc., the effective dose is usually 150 mg/day with a treatment duration of 14–30 days.

For vaginal candidiasis, fluconazole is taken orally once 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.

For balanitis caused by Candida, fluconazole is prescribed orally as a single dose of 150 mg/day.

For the prevention of candidiasis, the recommended dose is 50–400 mg 1 time per 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 developing a fungal infection. If there is a high risk of generalized infection, for example in patients with expected severe or long-lasting neutropenia, the recommended dose is 400 mg/day. Fluconazole is prescribed several days before the expected onset of neutropenia; after the number of neutrophils increases to more than 1 thousand/μl, treatment is continued for another 7 days.

For skin mycoses, including mycoses of the feet, skin of the groin area, and skin candidiasis, 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, however, with mycoses of the feet, longer therapy (up to 6 weeks) may be required.

For pityriasis versicolor - 300 mg (2 capsules of 150 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 to use 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 (the uninfected nail regrows). Fingernails and toenails normally take 3–6 months and 6–12 months to re-grow, respectively.

For deep endemic mycoses, it may be necessary to use 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 for coccidioidomycosis, 2–17 months for paracoccidioidomycosis, 1–16 months for sporotrichosis, 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 (Table 1). In children, the drug should not be used in a daily dose that would exceed that in adults, i.e. no more than 400 mg/day. The drug is used daily, once a day.

Table 1

The use of Fluconazole capsules 50 mg in children from 4 to 15 years

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 in the absence of renal dysfunction, the usual dosage regimen of the drug should be followed. In patients with renal failure (Cl creatinine less than 50 ml/min), the dosage regimen should be adjusted as indicated below (Table 2).

Fluconazole is excreted mainly in the urine unchanged. For chronic renal failure, a loading dose of 50–400 mg is initially administered. If creatinine Cl (CC) is more than 50 ml/min, the usual dose of the drug is used (100% of the recommended dose). When CC is from 11 to 50 ml/min, 50% of the recommended dose or the usual dose is used 1 time every 2 days.

table 2

Use of the drug in patients with impaired renal function

For patients regularly on dialysis, one dose of the drug is administered after each hemodialysis session.

special instructions

If liver dysfunction is observed during treatment, constant monitoring by a physician is important. If signs of liver damage are observed, the medication should be discontinued.

When using the medicine topically for men and women, it should be taken into account that people with AIDS are more likely to develop a variety of skin reactions.

It is necessary to take into account not only how long it takes for Fluconazole to act, but also the fact that if treatment is stopped prematurely, relapses may develop. Therefore, it is important to completely complete the prescribed treatment regimen. It is important to take this into account when using Fluconazole for nail fungus, since reviews for nail fungus indicate that if treatment is stopped prematurely, a relapse of the disease may occur.

Many patients have a question about whether Fluconazole is an antibiotic or not? Please note that this is an antifungal agent, not an antibiotic.

Whether men can take this drug depends on the diagnosis. Fluconazole for men is prescribed for fungal infections; it must be taken exactly as prescribed.

Fluconazole analogs

Level 4 ATC code matches:
Medoflucon

Vfend

Itracon

Mikosist

Irunin

Mikomax

Orungal

Mycoflucan

Sporagal

Orungamin

Flucostat

Difluzol

Rumicosis

Futsis

Vero-Fluconazole

Kandizol

Kanditral

Itraconazole

Diflazon

Fluconazole analogues are products with a similar active ingredient. The price of analogues depends on the manufacturer and the form of release of the drug. There are a number of analogues of this drug:

• Diflazon
• Diflucan
• Vero-Fluconazole
• Mikomax
• Flucostat

Which is better: Fluconazole or Diflucan?

Often patients compare two drugs with antifungal action - Fluconazole and Diflucan . What is the difference between these medicines? Both drugs are based on the active substance fluconazole. Diflucan is available in tablets of 50 mg, 100 mg, 150 mg, and other forms. But the price of Diflucan is much higher.

Flucostat or Fluconazole - which is better?

Speaking about how Flucostat from Fluconazole, it should be noted that both drugs contain the same active substance. Flucostat is a more expensive medicine. What is the difference between these medications, and which one is best prescribed in a particular case, is determined by a specialist. As a rule, Fluconazole is more often prescribed when prophylaxis is necessary for cancer patients after radiation and chemotherapy.

Fluconazole or Nystatin - which is better?

Nystatin is an antifungal drug, an antibiotic, active against candida bacteria. Under the influence of Nystatin, the permeability of the membrane of fungal cells is disrupted, which contributes to disruption of their growth and reproduction. Which drug is preferred in a particular case depends on the diagnosis and the doctor’s prescription.

Fluconazole, 50 mg, capsules, 7 pcs.

Single or repeated use of fluconazole at a dose of 50 mg does not affect the metabolism of phenazone (Antipyrin) when used simultaneously.

Concomitant use of fluconazole with the following drugs is contraindicated:

Cisapride: with the simultaneous use of fluconazole and cisapride, adverse reactions from the heart are possible, including ventricular tachysystolic arrhythmia of the “pirouette” type (torsade de pointes). The use of fluconazole at a dose of 200 mg 1 time per day and cisapride at a dose of 20 mg 4 times a day leads to a marked increase in the plasma concentration of cisapride and an increase in the QT interval on the ECG. The simultaneous use of cisapride and fluconazole is contraindicated.

Terfenadine: When azole antifungals are used concomitantly with terfenadine, serious arrhythmias may occur as a result of prolongation of the QT interval. When using fluconazole at a dose of 200 mg/day, an increase in the QT interval has not been established, however, the use of fluconazole at doses of 400 mg/day and above causes a significant increase in the concentration of terfenadine in the blood plasma. Concomitant use of fluconazole in doses of 400 mg/day or more with terfenadine is contraindicated (see section “Contraindications”). Treatment with fluconazole in doses less than 400 mg/day in combination with terfenadine should be carried out under close monitoring.

Astemizole: simultaneous use of fluconazole with astemizole or other drugs metabolized by the cytochrome P450 system may be accompanied by an increase in serum concentrations of these drugs. Elevated concentrations of astemizole in blood plasma can lead to prolongation of the QT interval and, in some cases, to the development of ventricular tachysystolic arrhythmia of the “pirouette” type (torsade de pointes). The simultaneous use of astemizole and fluconazole is contraindicated.

Pimozide: Although adequate in vitro or in vivo studies have not been conducted, concomitant use of fluconazole and pimozide may result in inhibition of the metabolism of pimozide. In turn, an increase in plasma concentrations of pimozide can lead to a prolongation of the QT interval and, in some cases, to the development of ventricular tachysystolic arrhythmia of the “pirouette” type (torsade de pointes). The simultaneous use of pimozide and fluconazole is contraindicated.

Quinidine: Although adequate in vitro or in vivo studies have not been conducted, concomitant use of fluconazole and quinidine may also result in inhibition of quinidine metabolism. The use of quinidine is associated with prolongation of the QT interval and, in some cases, with the development of ventricular tachysystolic arrhythmia of the “torsade de pointes” type. The simultaneous use of quinidine and fluconazole is contraindicated.

Erythromycin: Concomitant use of fluconazole and erythromycin potentially leads to an increased risk of cardiotoxicity (QT prolongation, torsade de pointes) and, consequently, sudden cardiac death. The simultaneous use of fluconazole and erythromycin is contraindicated.

The following medications are not recommended:

Halofantrine: Fluconazole may increase plasma concentrations of halofantrine due to inhibition of CYP3A4. The development of ventricular tachysystolic arrhythmia of the “pirouette” type (torsade de pointes) is possible when used simultaneously with fluconazole, as well as with other azole antifungal drugs, so their combined use is not recommended.

Caution should be exercised when used simultaneously with fluconazole:

Amiodarone: Amiodarone use has been associated with prolongation of the OT interval. Caution should be exercised when using fluconazole and amiodarone simultaneously. especially when taking a high dose of fluconazole (800 mg).

Caution and possible dosage adjustments should be used when the following drugs are used concomitantly with fluconazole:

Drugs that affect fluconazole:

Hydrochlorothiazide: repeated use of hydrochlorothiazide concomitantly with fluconazole leads to an increase in fluconazole plasma concentrations by 40%. An effect of this magnitude does not require a change in the fluconazole dosage regimen in patients receiving concomitant diuretics, but the physician should take this into account.

Rifampicin: Concomitant use of fluconazole and rifampicin results in a 25% decrease in AUC and a 20% decrease in fluconazole half-life. In patients concomitantly taking rifampicin, the advisability of increasing the dose of fluconazole must be considered.

Drugs affected by fluconazole:

Fluconazole is a moderate inhibitor of cytochrome P450 (CYP) isoenzymes 2C9 and 3A4. Fluconazole is also an inhibitor of the CYP2C19 isoenzyme. In addition, in addition to the effects listed below, there is a risk of increased plasma concentrations of other drugs metabolized by the isoenzymes CYP2C9, CYP2C19 and CYP3A4 when used simultaneously with fluconazole. In this regard, caution should be exercised when using these drugs simultaneously, and if such combinations are necessary, patients should be under close medical supervision. It should be taken into account that the inhibitory effect of fluconazole persists for 4-5 days after discontinuation of the drug due to the long half-life.

Alfentanil: There is a decrease in clearance and volume of distribution, and an increase in the half-life of alfentanil. This may be due to inhibition of the CYP3A4 isoenzyme by fluconazole. Alfentanil dosage adjustment may be required.

Amitriptyline, nortriptyline: increased effect. Concentrations of 5-nortriptyline and/or S-amitriptyline can be measured at the start of combination therapy with fluconazole and one week after initiation. If necessary, the dose of amitriptyline/nortriptyline should be adjusted.

Amphotericin B: In studies in mice (including immunosuppressed mice), the following results were observed: a small additive antifungal effect in systemic C. albicans infection, no interaction in intracranial Cryptococcus neoformans infection, and antagonism in systemic C. albicans infection. A. fumigatus. The clinical significance of these results is unclear.

Anticoagulants: like other antifungal agents (azole derivatives), fluconazole, when used simultaneously with warfarin, increases prothrombin time (by 12%), and therefore bleeding may develop (hematomas, bleeding from the nose and gastrointestinal tract, hematuria , melena). In patients receiving coumarin and indanedione anticoagulants and fluconazole, it is necessary to constantly monitor prothrombin time during therapy and for 8 days after simultaneous use. The feasibility of adjusting the dose of these anticoagulants should also be assessed.

Azithromycin: with simultaneous oral use of fluconazole in a single dose of 800 mg with azithromycin in a single dose of 1200 mg, no pronounced pharmacokinetic interaction has been established between both drugs.

Benzodiazepines (short-acting): After oral administration of midazolam, fluconazole significantly increases midazolam concentrations and psychomotor effects, and this effect is more pronounced after fluconazole is administered orally than when fluconazole is administered intravenously. If concomitant therapy with benzodiazepines is necessary, patients taking fluconazole should be monitored to assess the appropriateness of an appropriate reduction in the benzodiazepine dose.

With the simultaneous use of a single dose of triazolam, fluconazole increases the AUC of triazolam by approximately 50%, Cmax by 20-32% and half-life by 25-50% due to inhibition of triazolam metabolism. Triazolam dose adjustment may be necessary.

Carbamazepine: Fluconazole inhibits the metabolism of carbamazepine and increases the serum concentration of carbamazepine by 30%. The risk of carbamazepine toxicity must be taken into account. The need for carbamazepine dose adjustment based on concentration/effect should be assessed.

Calcium channel blockers: Some calcium channel antagonists (nifedipine, isradipine, amlodipine, verapamil and felodipine) are metabolized by CYP3A4. Fluconazole increases the systemic exposure of calcium channel antagonists. Monitoring for the development of side effects is recommended.

Nevirapine: Coadministration of fluconazole and nevirapine increased nevirapine exposure by approximately 100% compared with control data for nevirapine alone. Due to the risk of increased excretion of nevirapine during concomitant use of drugs, some precautions and careful monitoring of patients are necessary.

Cyclosporine: In patients with a kidney transplant, the use of fluconazole at a dose of 200 mg/day leads to a slow increase in cyclosporine concentrations. However, with repeated use of fluconazole at a dose of 100 mg/day, no changes in cyclosporine concentrations were observed in bone marrow recipients. When using fluconazole and cyclosporine simultaneously, it is recommended to monitor the concentration of cyclosporine in the blood.

Cyclophosphamide: with simultaneous use of cyclophosphamide and fluconazole, an increase in serum concentrations of bilirubin and creatinine is observed. This combination is acceptable given the risk of increased bilirubin and creatinine concentrations.

Fentanyl: There has been a report of one death possibly related to the concomitant use of fentanyl and fluconazole. The disturbances are believed to be related to fentanyl intoxication. Fluconazole has been shown to significantly prolong the clearance time of fentanyl. It should be borne in mind that an increase in the concentration of fentanyl can lead to depression of respiratory function.

HMG-CoA reductase inhibitors: When fluconazole is used concomitantly with HMG-CoA reductase inhibitors metabolized by the CYP3A4 isoenzyme (such as atorvastatin and simvastatin) or the CYP2D6 isoenzyme (such as fluvastatin), the risk of developing myopathy and rhabdomyolysis increases. If concomitant therapy with these drugs is necessary, patients should be monitored for symptoms of myopathy and rhabdomyolysis. It is necessary to monitor the concentration of creatinine kinase. If there is a significant increase in creatinine kinase concentrations, or if myopathy or rhabdomyolysis is diagnosed or suspected, therapy with HMG-CoA reductase inhibitors should be discontinued.

Losartan: Fluconazole inhibits the metabolism of losartan to its active metabolite (E-3174), which is responsible for most of the effects associated with angiotensin II receptor antagonism. Regular monitoring of blood pressure is necessary.

Methadone: Fluconazole may increase plasma concentrations of methadone. Methadone dose adjustment may be necessary.

Nonsteroidal anti-inflammatory drugs (NSAIDs): Cmax and AUC of flurbiprofen increase by 23% and 81%, respectively. Similarly, the Cmax and AUC of the pharmacologically active isomer [S-(+)-ibuprofen] increased by 15% and 82%, respectively, when fluconazole was administered simultaneously with racemic ibuprofen (400 mg).

With simultaneous use of fluconazole at a dose of 200 mg/day and celecoxib at a dose of 200 mg, the Cmax and AUC of celecoxib increase by 68% and 134%, respectively. In this combination, it is possible to reduce the dose of celecoxib by half.

Although there are no targeted studies, fluconazole may increase the systemic exposure of other NSAIDs metabolized by CYP2C9 (eg, naproxen, lornoxicam, meloxicam, diclofenac). NSAID dose adjustment may be necessary.

When NSAIDs and fluconazole are used concomitantly, patients should be closely monitored medically to identify and monitor NSAID-related adverse events and toxicities.

Olaparib: Moderate CYP3A4 inhibitors, such as fluconazole, increase plasma concentrations of olaparib. Their simultaneous use is not recommended. If concomitant use cannot be avoided, reduce the dose of olaparib to 200 mg twice daily.

Oral contraceptives: with simultaneous use of a combined oral contraceptive with fluconazole at a dose of 50 mg, no significant effect on hormone levels has been established, while with daily administration of 200 mg of fluconazole, the AUC of ethinyl estradiol and levonorgestrel increases by 40% and 24%, respectively, and with 300 mg of fluconazole once weekly administration, the AUCs of ethinyl estradiol and norethindrone increased by 24% and 13%, respectively. Thus, repeated use of fluconazole at the indicated doses is unlikely to affect the effectiveness of the combined oral contraceptive.

Phenytoin: Concomitant use of fluconazole and phenytoin may be accompanied by a clinically significant increase in phenytoin concentrations. If concomitant use of both drugs is necessary, phenytoin concentrations should be monitored and the dose adjusted accordingly to ensure therapeutic serum concentrations.

Ivacaftor: When coadministered with ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) stimulator, there was a 3-fold increase in ivacaftor exposure and a 1.9-fold increase in hydroxymethyl-ivacaftor (M1) exposure. For patients concomitantly taking moderate CYP3A inhibitors such as fluconazole and erythromycin, a dose reduction of ivacaftor to 150 mg once daily is recommended.

Prednisone: there is a report of the development of acute adrenal insufficiency in a patient after liver transplantation when fluconazole was discontinued after a three-month course of therapy. Presumably, discontinuation of fluconazole therapy caused an increase in the activity of the CYP3A4 isoenzyme, which led to increased metabolism of prednisone. Patients receiving combination therapy with prednisone and fluconazole should be under close medical supervision when discontinuing fluconazole to evaluate the condition of the adrenal cortex.

Rifabutin: Concomitant use of fluconazole and rifabutin can lead to an increase in serum concentrations of the latter by up to 80%. Cases of uveitis have been described with the simultaneous use of fluconazole and rifabutin. Patients receiving rifabutin and fluconazole concomitantly should be monitored closely.

Saquinavir: AUC increases by approximately 50%, Cmax by 55%, clearance of saquinavir decreases by approximately 50% due to inhibition of hepatic metabolism of the CYP3A4 isoenzyme and inhibition of P-glycoprotein. Dose adjustment of saquinavir may be necessary.

Sirolimus: increased plasma concentrations of sirolimus, presumably due to inhibition of sirolimus metabolism through inhibition of the CYP3A4 isoenzyme and P-glycoprotein. This combination can be used with appropriate dose adjustment of sirolimus depending on the effect/concentration.

Sulfonylureas: Fluconazole, when used concomitantly, results in an increase in the half-life of oral sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide). Patients with diabetes mellitus can be prescribed the combined use of fluconazole and oral sulfonylureas, but the possibility of hypoglycemia should be taken into account, in addition, regular monitoring of blood glucose is necessary and, if necessary, dose adjustment of sulfonylureas.

Tacrolimus: simultaneous use of fluconazole and tacrolimus (orally) leads to an increase in serum concentrations of the latter by 5 times due to inhibition of the metabolism of tacrolimus occurring in the intestine through the CYP3A4 isoenzyme. No significant changes in the pharmacokinetics of the drugs were observed when tacrolimus was administered intravenously. Cases of nephrotoxicity have been described. Patients receiving oral tacrolimus and fluconazole concomitantly should be monitored closely. The dose of tacrolimus should be adjusted depending on the degree of increase in its concentration in the blood.

Theophylline: when used simultaneously with fluconazole at a dose of 200 mg for 14 days, the average rate of plasma clearance of theophylline is reduced by 18%. When prescribing fluconazole to patients taking high doses of theophylline or to patients at increased risk of theophylline toxicity, monitor for symptoms of theophylline overdose and, if necessary, adjust therapy accordingly.

Tofacitinib: The exposure of tofacitinib is increased when coadministered with drugs that are both moderate inhibitors of CYP3A4 and CYP2C19 (eg, fluconazole). Dose adjustment of tofacitinib may be necessary.

Vinca alkaloids: Although focused studies are lacking, it is suggested that fluconazole may increase plasma concentrations of vinca alkaloids (e.g., vincristine and vinblastine) and thus lead to neurotoxicity, which may be due to inhibition of CYP3A4.

Vitamin A: There has been a report of one case of an adverse reaction from the central nervous system (CNS) in the form of pseudotumor cerebri with the simultaneous use of all-trans retinoic acid and fluconazole, which disappeared after discontinuation of fluconazole. The use of this combination is possible, but one should remember the possibility of adverse reactions from the central nervous system.

Zidovudine: when used simultaneously with fluconazole, an increase in the Cmax and AUC of zidovudine is observed by 84% and 74%, respectively. This effect is probably due to a decrease in the metabolism of the latter to its main metabolite. Before and after therapy with fluconazole at a dose of 200 mg/day for 15 days in patients with AIDS and ARC (AIDS-related complex), a significant increase in the AUC of zidovudine (20%) was found.

Patients receiving this combination should be monitored for side effects of zidovudine.

Voriconazole (inhibitor of CYP2C9, CYP2C19 and CYP3A4 isoenzymes): simultaneous use of voriconazole (400 mg twice daily on the first day, then 200 mg twice daily for 2.5 days) and fluconazole (400 mg on the first day, then 200 mg per day for 4 days) in 8 healthy male subjects resulted in an increase in Cmax and AUC of voriconazole by 57% and 79%, respectively. It has been shown that this effect persists when the dose is reduced and/or the frequency of administration of any of the drugs is reduced. Concomitant use of voriconazole and fluconazole is not recommended.

Studies of the interaction of oral forms of fluconazole when taken simultaneously with food, cimetidine, antacids, as well as after total body irradiation in preparation for bone marrow transplantation showed that these factors do not have a clinically significant effect on the absorption of fluconazole.

The listed interactions were established with repeated use of fluconazole; interactions with drugs as a result of a single dose of fluconazole are not known.

Doctors should note that interactions with other drugs have not been specifically studied, but are possible.

Reviews about Fluconazole

Due to the high fungicidal activity of this drug, patient reviews and doctors' reviews of Fluconazole are mostly positive. Patients, leaving reviews about Fluconazole Teva, as well as reviews about Fluconazole Stada on the forums, write that the drug helps to quickly and effectively eliminate the symptoms of fungal diseases. Users mention that the tablets are relatively inexpensive, but at the same time they allow you to completely get rid of nail fungus and other unpleasant diseases. In some cases, it is enough to take Fluconazole 150 mg once to completely overcome the symptoms of the disease.

Very often, women write positive reviews about Fluconazole for thrush . It is noted that the medicine not only relieves thrush, but also helps prevent relapses of the disease.

Fluconazole price, where to buy

The price of Fluconazole tablets depends on the packaging and manufacturer. You can buy Fluconazole in Moscow at prices ranging from 40 to 140 rubles. Capsules 150 mg (1 piece in a package) can be purchased for 140 rubles. Capsules 50 mg can be purchased for 60 rubles (pack of 7 pieces)

• Online pharmacies in RussiaRussia
• Online pharmacies in UkraineUkraine
• Online pharmacies in KazakhstanKazakhstan

ZdravCity

• Fluconazole capsules 150 mg 4 pcs.
  OzonOzon LLC/Ozon Pharm LLC 97 RUR order
• Fluconazole capsules 150 mg 2 pcs. Ozon LLC

  48 RUR order

• Fluconazole capsules 150 mg 1 pc. KanonpharmaZAO Kanonpharma Production

  42 RUR order

• Fluconazole Medisorb capsules 150 mg 2 pcs. JSC Medisorb

  182 RUR order

• Fluconazole Medisorb capsules 150 mgAO Medisorb

  125 rub. order

Pharmacy Dialogue

• Fluconazole-Teva capsules 150 mg No. 1Teva

  RUB 137 order

• Fluconazole-Teva capsules 50 mg No. 7Teva

  RUB 308 order

• Fluconazole-OBL (caps. 150 mg No. 1) Obolenskoye pharmaceutical pred.

  35 rub. order

• Fluconazole Stada (caps. 150 mg No. 1) Hemofarm LLC

  62 RUR order

• Fluconazole (caps. 50 mg No. 7) Ozon LLC

  65 rub. order

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Pharmacy24

• Fluconazole-Darnitsa 0.15g N2 capsules PrAT" Pharmaceutical company "Darnitsa", Ukraine
  28 UAH. order
• Fluconazole-KR 50 mg No. 7 capsules PAT"Khimpharmzavod"Chervona Zirka", Kharkov, Ukraine

  15 UAH order

• Fluconazole-Darnitsa 150 mg No. 3 capsules PrAT" Pharmaceutical company "Darnitsa", Ukraine

  40 UAH order

• Fluconazole 200 mg 100 ml No. 1 solution Eurolife Healthcare Pvt. Ltd., India

  83 UAH order

• Fluconazole 100 mg N10 tablets PrAT "Technolog", Uman, Cherkasy region, Ukraine

  32 UAH order

PaniPharmacy

• FLUCONAZOL capsule Fluconazole capsules 0.15g No. 2 Ukraine, Zdorovye LLC

  33 UAH order

• Fluconazole caps. 150mg №2

  31 UAH order

• FLUCONAZOL tablets Fluconazole tablets 150 mg No. 2 Ukraine, Tekhnolog ChAO

  29 UAH order

• FLUCONAZOLE capsule Fluconazole forte caps. 200 mg No. 2 Ukraine, Health LLC

  47 UAH order

• FLUCONAZOL capsule Fluconazole capsules 0.05g No. 10 Ukraine, Darnitsa ChAO

  28 UAH order

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Composition and release form

in a blister 7 (50 mg) or 1 (150 mg) pcs.; 1 blister in a cardboard pack.