Fluconazole actavis. Fluconazole capsules "Vertex"

Attention! The information is provided for informational purposes only. This manual should not be used as a guide to self-medication. The need for appointment, methods and doses of the drug are determined solely by the attending physician.

general characteristics

international and chemical names: fluconazole; a-(2,4-difluorophenyl)-a-(1H-1,2,4-triazol-1-ylmethyl)-1-H-1,2,4-triazol-1-ethanol;

basic physical and chemical properties: hard gelatin capsules No. 2, white opaque body and white opaque cap (for a dosage of 50 mg), yellow opaque cap and yellow opaque body (for a dosage of 100 mg), green opaque body and green opaque cap (for a dosage of 150 mg). The contents of the capsules are a white powder with a yellowish tint. On the capsule it is allowed to apply the trademark of the enterprise;

compound: 1 capsule contains fluconazole in terms of 100% substance 50 mg, 100 mg or 150 mg;

Excipients: milk sugar (lactose), potato starch, medical low molecular weight polyvinylpyrrolidone, calcium stearate.

Release form. Capsules.

Pharmacotherapeutic group

Antifungal agents for systemic use. Fluconazole. ATC code J02A С01.

Pharmacological properties

Pharmacokinetics. After oral administration, it is well absorbed. Eating does not affect the absorption of fluconazole. Bioavailability (Bioavailability- an indicator of the degree and rate of entry into the blood of a medicinal substance from the total dose administered) the drug exceeds 90%. Concentration in plasma (Plasma- the liquid part of the blood, which contains formed elements (erythrocytes, leukocytes, platelets). Various diseases (rheumatism, diabetes mellitus, etc.) are diagnosed by changes in the composition of blood plasma. Medicines are prepared from blood plasma blood reaches its maximum value in 0.5-1.5 hours after taking the drug inside. Half-life (Half-life(T1 / 2, a synonym for the half-life) - the period of time during which the concentration of drugs in the blood plasma decreases by 50% of the initial level. Information about this pharmacokinetic indicator is necessary to prevent the creation of a toxic or, conversely, ineffective level (concentration) of drugs in the blood when determining the intervals between injections) is 30 hours. Fluconazole penetrates well into all body fluids. In the cerebrospinal fluid, the concentration of fluconazole reaches 80% of the level of its concentration in the blood plasma. In the stratum corneum of the skin epidermis (Epidermis- superficial layer of the skin, consisting of stratified squamous epithelium) and sweat fluid concentrations exceeding serum levels are reached; fluconazole accumulates in the stratum corneum, 6 months after completion therapy (Therapy- 1. The field of medicine that studies internal diseases, one of the oldest and main medical specialties. 2. Part of a word or phrase used to indicate a type of treatment (oxygen therapy\; hemotherapy - treatment with blood products)) the drug is determined in the nails.
It is excreted mainly by the kidneys; Approximately 80% of the administered dose is found in the urine unchanged. Clearance (Clearance(purification, purification) - a pharmacokinetic parameter that reflects the rate of purification of blood plasma from the drug and is denoted by the symbol C1) drug is proportional to creatinine clearance.

Indications for use

Capsules 50 mg and 100 mg - cryptococcosis (Cryptococcosis- a chronic infectious disease that is characterized by damage to the skin, bones and internal organs, the substance of the brain and meninges), systemic candidiasis, candidiasis of the mucous membranes, including the oral cavity, pharynx and esophagus; non-invasive bronchopulmonary infections; candiduria; prevention of fungal infections in patients with reduced immune system function, including patients receiving cytostatic or radiation therapy; pityriasis versicolor (Pityriasis versicolor Mycosis of the skin caused by the fungus Pityrosporum orbiculare. It is characterized by the appearance of yellowish-pink or brownish itchy spots on the neck, shoulders and torso) and skin candidal infections.
Capsules 150 mg - vaginal candidiasis, candidiasis balanitis (Balanitis- inflammation of the skin that covers the head of the penis. Most often occurs in childhood, especially with phimosis - narrow foreskin); mycoses of the skin, including mycoses of the feet, body, inguinal region, onychomycosis.

Dosage and administration

Inside, daily, 1 time per day. The daily dose of Fluconazole-Health depends on the nature and severity of the fungal infection and is determined individually. The duration of treatment depends on the clinical and mycological effect.
Adults:
for cryptococcal infections, 400 mg is usually prescribed on the first day, and then treatment is continued at a dose of 200-400 mg once a day. The duration of treatment is usually 6-8 weeks. To prevent recurrence of cryptococcal meningitis in patients AIDS (AIDS(Acquired Immune Deficiency Syndrome) is a condition that develops against the background of HIV infection and is characterized by a drop in the number of CD4 + lymphocytes, multiple infections that are not typical for people with normal immunity, non-infectious and neoplastic diseases. AIDS is the final stage of HIV infection)(after completion of the full course of primary treatment) therapy with Fluconazole-Health at a dose of 200 mg can be continued for a very long time;
for candidal infections, the dose is 400 mg on the first day, then 200 mg per day, if necessary, the dose can be increased to 400 mg per day. The duration of therapy depends on clinical efficacy;
with oropharyngeal candidiasis - 50-100 mg once a day for 7-14 days or, if necessary, for a longer time. In atrophic candidiasis of the oral mucosa, it is usually prescribed at a dose of 50 mg once a day for 14 days;
with vaginal candidiasis and balanitis, Fluconazole-Health is taken once at a dose of 150 mg;
for the prevention of fungal infections in patients with reduced function immunity (Immunity- immunity of the body to infectious agents and foreign substances. Provided by the protective properties of the skin and mucous membranes, cells of the immune system, etc.) the dose is 50 mg once a day while the patient is at risk;
for skin infections, including mycoses of the feet, skin of the groin and candidal infections, the recommended dose is 150 mg once a week or 50 mg once a day. The duration of therapy is usually 2-4 weeks, however, with mycoses of the feet, longer therapy (up to 6 weeks) may be required. With pityriasis versicolor, the recommended dose 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 replacement of the infected nail (growth of an uninfected nail).
Children from 5 years old:
with candidiasis of the mucous membranes - 3-6 mg per 1 kg of body weight per day, for at least 3 weeks;
with systemic candidiasis - 6-12 mg per 1 kg of body weight per day, for 10-12 weeks (until laboratory confirmation of the absence of the pathogen in the cerebrospinal fluid).
The daily dose for children should not exceed the dose for adults.
Elderly patients:
- in the absence of signs of renal failure, the drug is used in the usual dose.
Patients with renal insufficiency:
- with a single dose, a dose change is not required. With repeated administration, the drug is prescribed in the initial dose - from 50 to 400 mg. After that, the daily dose (depending on the indicators creatinine clearance (Creatinine clearance- an indicator characterizing the glomerular filtration rate. The level of creatinine in the blood is used to assess the efficiency of the kidneys. Creatinine clearance is the volume of blood plasma that is cleared of creatinine in 1 minute when passing through the kidneys)) is determined according to the table:

Side effect

Nausea, abdominal pain, diarrhea (Diarrhea- rapid excretion of liquid stools associated with the accelerated passage of intestinal contents due to increased peristalsis, impaired absorption of water in the large intestine and the release of a significant amount of inflammatory secretion by the intestinal wall), flatulence (Flatulence- accumulation of gases in the digestive tract with bloating, rumbling, belching, cramping pains), headache, dizziness. Allergic reactions: skin rash, anaphylactic reactions (Anaphylactic reaction- immediate type allergic reaction: anaphylactic shock, serum sickness, local inflammation, edema, tissue necrosis). Possible hepatotoxic effect.

Contraindications

Hypersensitivity to the drug or triazole compounds; pregnancy, lactation (Lactation- secretion of milk by the mammary gland; children's age up to 5 years.

Overdose

Symptoms: nausea, abdominal pain, diarrhea, flatulence, headache, dizziness. Skin rashes and anaphylactic reactions may also occur.

Treatment: symptomatic therapy (Symptomatic therapy- symptomatic treatment aimed at eliminating individual manifestations (symptoms) of the disease (for example, the appointment of painkillers))(gastric lavage, maintenance therapy); forced diuresis (Diuresis- the amount of urine excreted in a certain time. In humans, daily diuresis averages 1200-1600 ml) may accelerate the elimination of the drug.

Application features

The drug should be used with caution in patients with severe liver dysfunction. The use of the drug in children is possible only under the supervision of a physician. With caution appoint drivers of transport and persons whose work requires precise coordination of movements.

Interaction with other drugs

When used simultaneously with coumarin anticoagulants (Anticoagulants- drugs that reduce blood clotting) prothrombin time should be monitored; with hypoglycemic agents - development is possible hypoglycemia (hypoglycemia- a condition caused by low plasma glucose levels. It is characterized by signs of increased sympathetic activity and the release of adrenaline (sweating, anxiety, tremor, palpitations, hunger) and symptoms from the central nervous system (fainting, blurred vision, convulsions, coma)); when combined with rifampicin, the dose of Fluconazole-Health should be increased; with simultaneous use with cyclosporine, zidovudine, an increase in their concentrations in the blood is possible. Simultaneous intake of Fluconazole-Health with food, cimetidine, antacids does not affect its absorption.

Product General Information

Terms and conditions of storage. Store in a dry, dark place and out of the reach of children at a temperature not exceeding 25°C.
Shelf life - 2 years.

Holiday conditions. Without a prescription - capsules of 150 mg No. 1.
According to the prescription - capsules of 50 mg and 100 mg No. 10; capsules 150 mg No. 2, No. 3.

Package. Capsules 50 mg and 100 mg No. 10; capsules of 150 mg No. 1, No. 1x2, No. 1x3, No. 3 in blisters.

Manufacturer.LLC "Pharmaceutical company "Health".

Location. 61013, Ukraine, Kharkov, st. Shevchenko, 22.

Website. www.zt.com.ua

Preparations with the same active ingredient

Difluzol - "Arterium"
Fluconazole forte - "Health"

This material is presented in free form on the basis of the official instructions for the medical use of the drug.

Dosage form: cylindrical capsules with a turquoise cap and white body for a dosage of 50 mg, with a turquoise cap and body for a dosage of 150 mg .

Read the entire leaflet carefully before taking this medicine:

Do not throw away this leaflet. You may need to read it again.

If you have any questions, ask your doctor or pharmacist.

This medicine must be prescribed by your doctor. Do not pass it on to others. It can harm them even if their symptoms are the same as yours.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

What is Fluconazole and what it is used for: Each capsule of Fluconazole contains the active substance - fluconazole, 50 mg or 150 mg, and excipients: lactose, calcium hydrogen phosphate dihydrate, microcrystalline cellulose, talc. Fluconazole is a systemic antifungal drug. It is used to treat or prevent infections caused by fungi. ATC code J02AC01.

Fluconazole is used in the following cases:

Treatment in adult diseases caused by fungal microflora:

vaginal candidiasis (acute, recurrent),
candidal balanitis (when topical therapy is not suitable),
mucosal candidiasis (including oropharyngeal candidiasis, esophageal candidiasis, candiduria, chronic candidiasis of the skin and mucous membranes),
chronic oral atrophic candidiasis (candidiasis caused by dentures if oral hygiene or topical treatment is not enough),
dermatomycosis (including athlete's foot, athlete's foot, ringworm inguinal, versicolor and candidal infections of the skin when systemic therapy is not appropriate),
dermatophytic onychomycosis (when the use of other drugs is not appropriate).
cryptococcal meningitis, coccidioidomycosis, invasive candidiasis.

Prevention in adults in the following cases:

recurrent vaginal candidiasis (4 or more episodes per year) - to reduce the frequency of relapses,
high risk of recurrence of cryptococcal meningitis,
high risk of recurrence of candidiasis of the oropharynx or esophagus in patients with HIV,
prevention of candidiasis in patients with prolonged neutropenia.

Prevention and treatment of candidiasis in children:

treatment of candidiasis of the mucous membranes (oropharynx, esophagus),
invasive candidiasis, cryptococcal meningitis;
prevention of candidal infections in immunocompromised patients,
prevention of recurrence of cryptococcal meningitis in children at high risk of its development.

Do not take fluconazole if:

Hypersensitivity to fluconazole, other azole compounds or any of the excipients.

Simultaneous use of fluconazole and terfenadine, with multiple doses of fluconazole in a daily dose of more than 400 mg.

Simultaneous use of fluconazole and other drugs (cisapride, astemizole, pimozide, quinidine, erythromycin, etc.) that prolong the QT interval on the ECG and are metabolized by the CYP2A4 enzyme.

The combination of fluconazole and halofantrine (a treatment for malaria) is not recommended.

Pregnancy and lactation.

Be sure to tell your doctor if you suffer from diseases of the liver, kidneys, cardiovascular diseases (including changes in heart rhythm); have changes in the level of potassium, calcium or magnesium in the blood; there have been cases of severe allergic reactions; are planning a pregnancy.

When prescribing Fluconazole, be sure to inform your doctor if you are taking any of the following medicines:

Rifampicin, rifabutin - antibacterial agents for the treatment of tuberculosis;

Azithromycin - an antibacterial agent for the treatment of infections;

Alfentanil, fentanyl - drugs for general anesthesia;

Amitriptyline, nortriptyline - antidepressants;

Amphotericin B, voriconazole - antifungal drugs;

Medicines that reduce blood clotting and prevent the formation of blood clots (anticoagulants, including warfarin);

Benzodiazepines (midazolam, triazolam, etc.) - tranquilizers for the treatment of sleep disorders, anxiety;

Carbamazepine, phenytoin - anticonvulsants;

Nifedipine, isradipine, amlodipine, felodipine, losartan - drugs for the treatment of hypertension;

Cyclosporine, everolimus, sirolimus, tacrolimus - means to prevent transplant rejection;

Cyclophosphamide, vinca alkaloids (vincristine, vinblastine or similar drugs) - antitumor agents;

Statins (atorvastatin, simvastatin and fluvastatin or similar drugs) - drugs to lower cholesterol;

Methadone - a drug for pain relief and treatment of drug addiction;

Celecoxib, flurbiprofen, naproxen, ibuprofen, lornoxicam, meloxicam, diclofenac - non-steroidal anti-inflammatory drugs (NSAIDs);

oral contraceptives;

Prednisolone is a synthetic glucocorticoid hormone;

Zidovudine, saquinavir - drugs for the treatment of HIV infection;

Antidiabetic agents (chlorpropamide, glibenclamide, glipizide, tolbutamide);

Theophylline - a means for dilating the bronchi with difficulty breathing;

Vitamin A - food supplement;

The use of Fluconazole during pregnancy and lactation: Contraindicated.

The use of fluconazole in children: The drug in capsule form can be used in cases where children are able to swallow the capsule safely (usually over the age of 5 years). If it is necessary to take fluconazole in young children, it is necessary to prescribe a dosage form more suitable for children.

Influence on the ability to drive vehicles and control mechanisms: When driving vehicles and other mechanisms, one should be aware of the possibility of developing adverse reactions such as dizziness or convulsions.

How to take Fluconazole: The capsule is swallowed whole with a glass of water. It is advisable to take the capsules daily at the same time in the dose prescribed by the doctor.

Adults:

Treatment of cryptococcal meningitis: 400 mg on the first day, then from 200 mg to 400 mg once daily for 6 to 8 weeks or more as needed. The dose may be increased up to 800 mg.

Prevention of recurrence of cryptococcal meningitis: 200 mg once a day for a long time.

Treatment of coccidioidomycosis: 200 mg - 400 mg once a day, 11 - 24 months or more if necessary. The dose may be increased to 800 mg.

Treatment of internal candidal infections: 800 mg on the first day, then 400 mg once a day for a long time.

Treatment of candidal infections of the mucous membrane of the mouth, throat (including from wearing dentures): 200 mg - 400 mg on the first day, then 100 mg - 200 mg, until the symptoms disappear completely.

Treatment of candidal stomatitis: the dose depends on the localization of the infection: 50 mg - 400 mg once a day, 7 - 30 days until the symptoms disappear completely.

Prevention of recurrence of infections of the mucous membranes of the mouth, throat: 100 mg - 200 mg once a day or 200 mg 3 times a week until the risk of infection disappears.

Treatment of vaginal candidiasis: 150 mg once

Prevention of recurrence of vaginal candidiasis: 150 mg every three days, 3 doses (days 1, 4 and 7), then once a week for 6 months until the risk of infection disappears.

Treatment of fungal infections of the skin and nails: the dose depends on the location of the infection: 50 mg once a day, 150 mg - 400 mg once a week for 1 to 4 weeks (foot mycosis - up to 6 weeks, with damage to the nails - before replacing the infected nail).

Prevention of fungal infections in immunosuppressed patients: 200 mg - 400 mg once a day until the risk of infection disappears

Use in adolescents from 12 to 17 years: In most cases, the dosages correspond to those of adults.

Use in children under 11 years of age: The maximum dose for children is 400 mg per day.

Treatment of candidal infections of the mucous membrane of the mouth, throat: the dose and duration depend on the severity of the infection and on the place of its localization: 6 mg / kg of body weight on the first day, the subsequent dose is 3 mg / kg.

Cryptococcal meningitis or internal candidal infections: 6 mg - 12 mg/kg body weight.

Prevention of candidal infections in children with reduced immunity: 6 mg - 12 mg / kg of body weight.

Elderly patients: With normal renal function, dose adjustment is not required.

Patients with impaired renal function: With a single dose, dose adjustment is not needed. With multiple doses, on the first day of treatment, take 50 mg - 400 mg, depending on the indications. With creatinine clearance ≤ 50 ml / min - 50% of the indicated dose. Patients on regular dialysis should receive 100% of the recommended dose after each dialysis. On the day when dialysis is not carried out, the dose is adjusted depending on the creatinine clearance.

If you have taken more fluconazole than your doctor recommended: If the number of tablets per day that you have taken exceeds the number recommended by your doctor, or your child has swallowed the tablets, consult a doctor or call an ambulance! Stop taking the medicine! Overdose can be manifested by auditory, visual and sensory hallucinations (hallucinations and paranoid behavior). As a first aid, gastric lavage.

If you forget to take your next dose of Fluconazole on time: Take the capsule as soon as you remember. The total number of tablets taken during the day should not exceed that prescribed by the doctor. Do not take a double dose if you miss the next dose.

Possible adverse reactions: Like all medicines, fluconazole can cause side effects with varying frequency.

Common (1 in 10 to 100 cases): headache, abdominal pain, diarrhea, nausea, vomiting, rash, increased levels of liver enzymes (ALT, AST, alkaline phosphatase) in the blood,

Uncommon (1 in 100 to 1,000 cases): anemia, decreased appetite, insomnia, drowsiness, convulsions, dizziness, paresthesias, taste disturbances, vertigo, constipation, dyspepsia, flatulence, dry mouth, cholestasis, jaundice, increased bilirubin, pruritus , drug dermatitis, urticaria, increased sweating, muscle pain, fatigue, malaise, asthenia, fever.

Rare (1 in 1,000 to 10,000 cases): decreased blood cell count, anaphylaxis, increased blood lipids and cholesterol, decreased blood potassium, tremor, torsades de pointes, prolongation of the QT interval on ECG, liver failure , necrosis, hepatitis, toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, exfoliative dermatitis, facial edema, alopecia

If any of the following symptoms occur, stop taking the medicine immediately and seek medical attention: difficulty breathing, shortness of breath; swelling of the eyelids, face, or lips; itching, redness of the skin; skin rash; severe skin reactions!

Precautions and precautions while taking Fluconazole:

Dermatophytosis. Fluconazole is not used to treat this pathology due to low efficiency.

Cryptococcosis, deep endemic mycoses. Evidence of the effectiveness of fluconazole for these diseases is insufficient, and therefore there are no dosage recommendations.

hepatobiliary system. It is used with caution in violation of liver function. In rare cases, it is possible to develop severe hepatotoxicity, including deaths, against the background of a serious underlying disease. Usually, hepatotoxicity caused by fluconazole is reversible, and its manifestations disappear after cessation of therapy. Monitoring of liver function is recommended. If symptoms of asthenia, anorexia, persistent nausea, vomiting, jaundice appear, the drug should be discontinued.

The cardiovascular system. Very rare cases of QT interval prolongation and torsades de pointes have been reported in patients with severe comorbidities with a combination of many risk factors (structural heart disease, electrolyte disturbances, concomitant use of drugs that affect the QT interval). It is used with caution in patients at risk of developing arrhythmias.

Skin reactions. Fluconazole rarely causes severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis). HIV-positive patients are more likely to develop such reactions with many drugs. With the appearance of rashes associated with taking Fluconazole in this group of patients, the drug should be discontinued. It is recommended to monitor the patient's condition.

Excipients. Fluconazole is not taken in cases of congenital galactose intolerance and Lapp lactase deficiency or malabsorption of glucose and galactose (contains lactose).

Storage conditions: Store in a place protected from light, at a temperature not exceeding 25°C.

Keep out of the reach of children.

Best before date: 3 years. Do not use the medicinal product after the expiration date.

Leave conditions: The drug "Fluconazole, capsules 50 mg" by prescription.

The drug "Fluconazole, capsules 150 mg" without a doctor's prescription.

Release form:

Dosage 50 mg: 7 or 14 capsules in a polymer jar. Dosage 150 mg: 1 capsule in a blister pack or 1 capsule in a polymer jar. The sealing agent for the jar is medical cotton wool. Each can or one or two blister packs with package insert in secondary packaging.

Produced:“Belarusian-Dutch Joint Venture Limited Liability Company “Pharmland” (JV LLC “Pharmland”), Republic of Belarus, Nesvizh, st. Leninskaya,

Part drug in the form of capsules includes an active ingredient fluconazole . The capsules also contain additional components: potato starch, low molecular weight, calcium stearate or magnesium stearate.

fluconazole tablets contains a similar active ingredient, as well as sodium lauryl sulfate as an additional component.

Release form

This medicine is available in capsules Fluconazole 150 mg, 50 mg, 100 mg. These are blue capsules with a white or yellowish granular powder inside. Contained in blister packs, which are put into cardboard boxes. Fluconazole tablets, syrup, gel, suppositories, solution for intravenous administration of Fluconazole are also produced.

pharmachologic effect

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

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

The agent stops the transformation into ergosterol lanosterol fungal cells. 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 show antiandrogenic activity.

Pharmacokinetics and pharmacodynamics

Wikipedia indicates that after oral administration, the drug is actively absorbed in the human gastrointestinal tract. In plasma, the level of concentration of the active substance is more than 90% of the level that is noted if the intravenous route of 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 inside, the highest concentration in the blood occurs after 0.5–1.5 hours. The elimination half-life from the blood is 30 hours. That is, you can take the drug once a day. At 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 plasma proteins. When the drug begins to act depends on the treatment regimen. If you take the medicine once a day, then a stable concentration of the active ingredient in 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 in the body in all fluids. Excreted from the body through the kidneys, approximately 80% is excreted unchanged.

Indications for use

The following indications for the use of the drug are determined:

infectious diseases provoked by candida (disseminated candidiasis, generalized candidiasis, other forms of invasive candidiasis;
mucous (including 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 the recurrence of vaginal candidiasis (in the event that the disease develops from three times a year), candidal balanitis ;
cryptococcal infection, cryptococcal meningitis ;
dermatomycosis (including mycoses of the body, feet, groin area);
endemic mycoses deep ;
developmental prevention fungal infections in people who have undergone cytostatic or radiation therapy.

Contraindications

There are such contraindications for the use of this medication:

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

Caution should be taken with liver failure, also kidney failure, with the appearance of a rash in people suffering from a superficial fungal infection, with potentially proarrhythmogenic conditions in people with risk factors (organic heart disease, taking drugs that provoke the development , electrolyte imbalance). How to take Fluconazole in this case, you should definitely ask a specialist.

Side effects

During treatment with the drug, the patient may develop the following side effects:

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

How to drink the medicine with the manifestation of such effects, and whether it is worth continuing treatment, you should individually consult a doctor.

Instructions for use Fluconazole (Method and dosage)

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

The solution is administered by infusion 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.

Sick with disseminated candidiasis, candidemia on the first day, 400 mg is prescribed, then the dose should be reduced to 200 mg. children for treatment generalized candidiasis shows a daily intake of 6-12 mg per 1 kg of body weight.

Patients with oropharyngeal candidiasis shown from 50 mg to 100 mg of fluconazole once a day, the treatment period is 1-2 weeks.

People suffering atrophic candidiasis of the oral mucosa , shown at 50 mg once a day. The treatment is combined with the use of local means for the treatment of prostheses. In the treatment of other candidal infections of the mucous membranes, 50-100 mg per day is prescribed, the therapy period is from 14 to 30 days.

In order to prevent the development of relapses oropharyngeal candidiasis in people with coma, 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 body weight per day. On the first day, you can give the child a double dose.

Sick with cryptococcal infections and cryptococcal meningitis , as a rule, appoint 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 body weight per day.

People suffering skin infections , it is recommended to prescribe 150 mg once a week or drink 50 mg once a day. Treatment should be continued for 2-4 weeks. For men and women sick athlete's foot , sometimes longer therapy is required - up to 6 weeks.

Patients with pityriasis versicolor it is recommended to take 300 mg once a week, the therapy period is 2 weeks. Depending on the intensity of the symptoms, the 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 therapy period is two to four weeks.

Sick onychomycosis appoint 150 mg once a week. Therapy should continue until a healthy nail grows in place of the diseased nail.

People suffering 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 with provides that with vaginal candidiasis, a single dose of the drug is carried out, its dose is 150 mg.

As a rule, fluconazole with thrush is effective after a single dose. But the doctor will tell you more about how to take Fluconazole for thrush after an individual consultation. Before determining how to drink any medicine for thrush with thrush, the specialist takes into account the causes of the disease and the individual characteristics of its course. In chronic thrush, Fluconazole Teva or other types of the drug are prescribed to prevent relapse at a dose of 150 mg once a month. It is necessary to apply means for 4-12 months. For the purpose of prevention, capsules are prescribed at a dose of 50–400 mg once a day, depending on how high the risk of disease manifestation is. For children from thrush, fluconazole tablets are prescribed at a dose of 3-12 mg of the drug per 1 kg of body weight per day. How much to drink funds depends on the severity of the infection.

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

If treatment is given at the same time Astemizole , cisapride , Tacrolimus , or any other drug that is metabolized by the cytochrome P450 system, it is possible to increase the concentration of these blood drugs.

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

Terms of sale

In pharmacies, they are sold by prescription, a specialist gives a prescription in Latin.

Storage conditions

Fluconazole suppositories, Fluconazole ointment, cream, tablets and capsules should be stored in a dark place, drugs should be protected from sunlight.

Best before date

special instructions

If in the process of treatment there is a violation of the liver, constant monitoring of the doctor is important. If there are signs of liver damage, the medication should be discontinued.

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

It should be taken into account not only how long Fluconazole acts, but also the fact that if treatment is stopped prematurely, relapses may develop. Therefore, it is important to fully 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 is possible.

Many patients have a question about whether Fluconazole is an antibiotic or not? Keep in mind 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 according to the prescribed scheme.

Fluconazole's analogs

Coincidence in the ATX code of the 4th level:

Fluconazole analogues are products with a similar active ingredient. The price of analogues depends on the manufacturer, the form of release of the drug. There are a number of analogues of this drug:, Diflucan , Vero-Fluconazole , Flucostat , Fluconazole Teva ,Fluconazole Stada and etc.

Which is better: Fluconazole or Diflucan?

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

Flucostat or Fluconazole - which is better?

Talking about what's different 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 drugs, and which one is best to prescribe in a particular case, the specialist determines. As a rule, Fluconazole is more often prescribed if prophylaxis is necessary for cancer patients after radiation and chemotherapy.

Fluconazole or Nystatin - which is better?

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

For kids

The instructions indicate that the drug is prescribed to children after they reach 5 years of age. The dosage for children is determined depending on the disease. As a rule, it is determined at the rate of 6-12 mg per 1 kg of the child's weight. For children under 5 years of age, the medicine is prescribed strictly according to indications and under the supervision of a specialist.

fluconazole and alcohol

Discussing compatibility with alcohol, Fluconazole, doctors do not recommend drinking alcohol during treatment. This combination is very dangerous for the liver. In addition, alcohol during treatment can provoke the development of unpleasant side effects from the gastrointestinal tract, blood vessels, and the heart.

Fluconazole during pregnancy and lactation

Fluconazole is rarely prescribed during pregnancy, especially in the 1st trimester and the 2nd trimester. The only exceptions are those cases when a woman is diagnosed with a severe fungal infection. During lactation, the drug is not prescribed, since the substance passes into breast milk.

Reviews about Fluconazole

Due to the high fungicidal activity of this drug, patient reviews and doctors' reviews of Fluconazole are mostly positive. Patients leaving feedback on Fluconazole Teva, as well as reviews of Fluconazole Stada on the forums, they write that the drug helps to quickly and effectively eliminate the symptoms of fungal diseases. Users mention that the pills 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 a single dose of Fluconazole 150 mg to completely overcome the symptoms of the disease.

Very often, women write positive reviews about Fluconazole with 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 a price of 10 to 290 rubles. Capsules 150 mg (packed 1 pc.) Can be bought for 10-200 rubles. Capsules 50 mg can be bought at a price of 25 rubles (pack of 7 pcs.) The cost of the drug Fluconazole Teva 150 mg is 190-220 rubles per pack. (1 PC.).

The price of Fluconazole in Ukraine (Odessa, Kyiv, etc.) is 17-20 hryvnias (capsules 50 mg, 7 pcs.). The price of Fluconazole 150 mg in Kharkiv, in Zaporozhye, in Dnepropetrovsk, etc. is an average of 30 hryvnias (2 pcs in a package). Tablets of 150 mg can be bought in Ukraine for an average of 20 hryvnia.

How much do tablets for thrush cost in Kazakhstan, in Belarus, depends on the packaging, the manufacturer. In Minsk, you can buy 150 mg capsules at a price of 10,000 - 103,000 rubles, depending on the number of tablets in the package and the manufacturer.

How much other forms of release of the drug with fluconazole (suppositories, ointment, cream) cost also depends on the manufacturer.

Internet pharmacies in Russia Russia
Internet pharmacies in Ukraine Ukraine
Internet pharmacies in Kazakhstan Kazakhstan

ZdravCity

Fluconazole capsules 150mg 1 pc. CanonpharmaCJSC Canonpharma Production

Fluconazole capsules 150mg CJSC Biokom

Fluconazole-OBL capsules 150mg 2 pcs.JSC Obolenskoye pharm. company

Fluconazole-Teva capsules 50mg 7 pcs.Teva Pharmaceutical Works Private Limited Company

Fluconazole medisorb capsules 150mg 2 pcs. JSC Medisorb

Pharmacy Dialog

Fluconazole (caps. 50mg №7) Vertex

Description

Capsules hard gelatinous cylindrical shape with hemispherical ends, white.

Compound

One capsule contains: active ingredient- fluconazole - 150 mg; Excipients- lactose monohydrate, povidone K-17, sodium lauryl sulfate, magnesium stearate, potato starch.
Capsule composition: gelatin, methyl parahydroxybenzoate E 218, titanium dioxide E 171, propyl parahydroxybenzoate E 216.

Pharmacotherapeutic group

Antifungal drugs for systemic use.
ATX code: J02AC01.

Pharmacological properties

Pharmacodynamics
Mechanism of action
Fluconazole is an antifungal drug of the triazole group. The main mechanism of action of fluconazole is to inhibit the reaction of 14α-lanosterol-demethylation mediated by cytochrome P450, which is an integral step in the biosynthesis of fungal ergosterol. The accumulation of 14α-methylsterols correlates with the subsequent loss of ergosterol by the fungal cell membrane. This process may underlie the antifungal activity of fluconazole. Fluconazole is more selective for fungal cytochrome P450 enzymes than for various mammalian cytochrome P450 enzyme systems.
The use of fluconazole at a dose of 50 mg / day for 28 days had no effect on plasma testosterone levels in men or plasma steroid levels in women of reproductive age. Fluconazole at a dose of 200-400 mg / day does not show a clinically significant effect on the level of endogenous steroids or response to ACTH stimulation in healthy male volunteers. Interaction studies with antipyrine have shown that the use of fluconazole at a dose of 50 mg single or multiple does not affect the metabolism of antipyrine.
Sensitivity in vitro.
Fluconazole in vitro exhibits antifungal activity against the most common types of fungus of the genus Candida(including FROM.albicans, C. parapsilosis, C. tropicalis).C. glabrata shows a wide range of sensitivity to fluconazole, while C. krusei is resistant to it.
Fluconazole is also active in vitro with respect to C ryptococcus neoformans and Cryptococcus gattii, as well as endemic mold fungi Blastomyces dermatitis, Coccidioides immitis, Histoplasma capsulatum and Paracoccidioides brasiliensis.
Dependence of parameters of pharmacokinetics and pharmacodynamics
According to the results of experimental studies on animals, there is a correlation between the values of the minimum inhibitory concentration (MIC) and efficacy against experimental models of mycoses caused by fungi of the genus Candida. According to clinical studies, there is an almost linear (almost 1:1) relationship between AUC and the dose of fluconazole. There is also a direct but not sufficient relationship between AUC or dose and positive clinical response to oral candidiasis and, to a lesser extent, candidemia. Similarly, the treatment of infections caused by strains for which fluconazole shows a higher MIC is less effective.
Mechanisms of resistance development
Fungi of the genus Candida implement numerous mechanisms for the development of resistance to antifungal agents from the azole group. It is known that fungal strains using 1 or more resistance mechanisms show a high MIC of fluconazole, which has a negative impact on the effectiveness of the drug. in vivo and in clinical practice.
There have been reports of cases of superinfection caused by fungi of the genus Candida besides C. albicans, which are often inherently insensitive to fluconazole (for example, Candida krusei). In such cases, alternative antifungal therapy is required.
Limit values (according to EUCAST)
Based on the analysis of pharmacokinetic/pharmacodynamic (PK/PD) data, in vitro susceptibility and clinical response, EUCAST-AFST (European Committee for Antibacterial Susceptibility Testing - Subcommittee for Antifungal Susceptibility Testing) developed fluconazole susceptibility breakpoints for fungi of the genus Candida(“Rationale for the use of fluconazole EUCAST (2007)” - revision 2). These breakpoints were divided into non-species-specific breakpoints (which were largely determined by PK/PD data and were independent of MIC species distribution) and species-specific breakpoints (which are the most common pathogens in humans). These limit values are presented in the table below:

Antifungals

Boundary values associated with a particular type of pathogen (P≤/P˃)

Limit values not associated with a specific type of pathogen A (P≤/P˃)

candida albicans

Candida

glabrata

Candida

krusei

Candida

parapsilosis

Candida

tropical

Fluconazole

H = sensitive;
P = resistant;
A = Non-species-specific breakpoints that were largely determined by PK/PD data and did not depend on MIC allocation to specific species. They are used only for microorganisms for which no specific breakpoints exist;
“–” - it is not recommended to conduct sensitivity tests, since this type of microorganism is difficult to treat with this drug;
ND - there is insufficient evidence that this type of organism responds well to therapy with this drug.
Pharmacokinetics
The pharmacokinetics of fluconazole is similar when administered intravenously and when taken orally.
Suction
After oral administration, fluconazole is well absorbed and its plasma concentration (and total bioavailability) is more than 90% of its plasma concentration after intravenous administration. Simultaneous food intake does not affect the absorption of the drug when taken orally. The maximum plasma concentration is reached 0.5-1.5 hours after taking the drug on an empty stomach. Plasma concentrations of fluconazole are proportional to the dose of the drug taken. Equilibrium concentration (at the level of 90%) is achieved by 4-5 days of treatment with multiple doses of the drug 1 time per day. Taking the drug on the first day at a loading dose twice the average daily dose allows reaching an equilibrium concentration (at the level of 90%) by the second day of treatment.
Distribution
The apparent volume of distribution approaches the total body water content. The binding of fluconazole to plasma proteins is low (11-12%).
Fluconazole penetrates well into all studied body fluids. Fluconazole concentrations in saliva and sputum are similar to those in plasma. In patients with fungal meningitis, fluconazole levels in the cerebrospinal fluid are approximately 80% of its plasma levels.
In the stratum corneum, epidermis, dermis and sweat fluid, high concentrations of the drug are achieved, which exceed serum values. Fluconazole accumulates in the stratum corneum. When taking the drug at a dose of 50 mg once a day, the concentration of fluconazole after 12 days was 73 mcg / g, and after 7 days after stopping treatment - 5.8 mcg / g. When using the drug at a dose of 150 mg once a week, the concentration of fluconazole in the stratum corneum on the 7th day was 23.4 μg / g, and 7 days after taking the second dose - 7.1 μg / g.
The concentration of fluconazole in the nails after 4 months of using the drug at a dose of 150 mg once a week was 4.05 µg/g in healthy and 1.8 µg/g in affected nails; fluconazole was detected in nail samples 6 months after the end of therapy.
Biotransformation
Fluconazole is slightly metabolized. With the introduction of a dose labeled with radioactive isotopes, only 11% of fluconazole is excreted in the urine in an altered form. Fluconazole is a selective inhibitor of CYP2C9 and CYP3A4 isoenzymes (with see the section “Reciprocallyactions with other drugs), as well as an inhibitor of the CYP2C19 isoenzyme.
breeding
The plasma half-life of fluconazole is approximately 30 hours. The main route of elimination of the drug is renal excretion, with approximately 80% of the dose taken unchanged in the urine. Fluconazole clearance is proportional to creatinine clearance. No circulating metabolites were found.
The long half-life of the drug from blood plasma allows you to take fluconazole once for the treatment of vaginal candidiasis and once a day or once a week for the treatment of other diseases.
Pharmacokinetics in impaired renal function
In patients with severe renal insufficiency (GFR< 20 мл/мин) период полувыведения препарата увеличивался с 30 ч до 98 ч. В связи с чем, этой категории пациентов необходимо снижать дозу препарата. Флуконазол удаляется путем гемодиализа и в меньшей степени – перитонеального диализа. Сеанс гемодиализа продолжительностью 3 ч снижает уровень флуконазола в плазме крови приблизительно на 50 %.
Pharmacokinetics in children
Pharmacokinetics were evaluated in 113 children in 5 studies: 2 single dose studies, 2 multiple dose studies, and one study in preterm infants. Data from one study were not subject to interpretation due to a change in the way the drug was taken during the course of the study. During the charitable trial use of the drug, additional information was obtained.
After administration of fluconazole at a dose of 2–8 mg/kg to children aged 9 months to 15 years, the AUC of fluconazole was about 38 µg h/ml per 1 mg/kg dose. After repeated administration of fluconazole, the mean plasma half-life of fluconazole ranged from 15 hours to 18 hours, and the volume of distribution was approximately 880 ml/kg. A longer plasma half-life of the drug (approximately 24 hours) was observed after a single dose of the drug, which is comparable to the plasma half-life of fluconazole after its single intravenous administration to children aged 11 days to 11 months at a dose of 3 mg / kg . The volume of distribution of the drug in patients of this age group was approximately 950 ml/kg.
Experience with fluconazole in neonates is limited to pharmacokinetic studies involving 12 preterm infants with a gestational age of approximately 28 weeks. The mean age of the child at the first dose was 24 hours (range 9 hours to 36 hours); mean birth weight was 0.9 kg (range 0.75 to 1.10 kg). Seven patients completed the study according to the protocol. A maximum of 5 intravenous injections of fluconazole at a dose of 6 mg/kg was given every 72 hours. h) and on the thirteenth day on average up to 47 hours (within 27–68 hours). AUC values were 271 µg h/mL (range 173-385 µg h/mL) on day 1, then increased to 490 µg h/mL (range 292-734 µg h/mL) on day 7 and decreased to a median of 360 mcg h/ml (range 167–566 mcg h/ml) by day thirteen. The volume of distribution was 1183 ml/kg (range 1070–1470 ml/kg) on day 1, then increased over time to a mean of 1184 ml/kg (range 510–2130 ml/kg) on day 7 and to 1328 ml/kg. kg (range 1040–1680) on the thirteenth day.
Pharmacokinetics in elderly patients
Pharmacokinetic studies were performed in 22 patients aged 65 years and older who took fluconazole once orally at a dose of 50 mg. Ten patients were simultaneously taking diuretics. C max was 1.54 µg/ml and reached 1.3 hours after taking the drug. The mean AUC was 76.4±20.3 µg h/mL, and the mean terminal half-life was 46.2 hours. These pharmacokinetic parameters are higher than those found in younger, healthy male volunteers. The simultaneous use of diuretics did not significantly affect the values of AUC and Cmax. In addition, creatinine clearance (74 ml/min), the percentage of fluconazole excreted in the urine unchanged (0–24 h, 22%), and renal clearance of fluconazole (0.124 ml/min/kg) were generally lower in the elderly. than those in younger volunteers. Thus, changes in the pharmacokinetics of fluconazole in elderly patients are probably associated with reduced renal function characteristic of the elderly.

Indications for use

The use of the drug Fluconazole, capsules 150 mg is indicated for the fungal infections listed below ( see section "Pharmacodynamics").
Fluconazole, capsules 150 mg (in package No. 1×1):
acute vaginal candidiasis when topical therapy is not appropriate;
candidal balanitis when topical therapy is not appropriate.
Fluconazole, capsules 150 mg (in package No. 1 × 2):
dermatomycosis, including tinea pedis, tinea corporis, tinea cruris, tinea versicolor and candidal infections of the skin, if necessary, systemic therapy;
tinea unguium(onychomycosis) in the case when the prescription of other drugs is not acceptable.
Therapy can begin before the results of the culture method and other laboratory methods are known. However, after these results become known, an appropriate correction in anti-infective therapy should be made.
When using this drug, you must follow official recommendations for the proper use of antifungal medicines.

Contraindications

Hypersensitivity to the active substance, azole substances close to it in chemical structure, or to any of the excipients that make up the drug, indicated in the "Composition" section.
According to a study of drug interactions with multiple doses of drugs, the simultaneous use of terfenadine during repeated use of fluconazole at a dose of 400 mg per day and above is contraindicated. Patients taking fluconazole are contraindicated in the simultaneous administration of drugs that prolong the QT interval and are metabolized by cytochrome P450 isoenzyme CYP3A4, such as cisapride, astemizole, pimozide, quinidine and erythromycin ( see sections "Precautions" and "Interaction with other drugs").

Dosage and administration

Adult patients

Indications		Dosing regimen	Duration of treatment
Acute vaginal candidiasis when topical therapy is not appropriate Candida balanitis when topical therapy is not appropriate		150 mg once
genital candidiasis	Treatment and prevention of recurrence of vaginal candidiasis (4 or more episodes per year)	150 mg once every three days for a total of 3 doses (on days 1, 4 and 7), followed by a maintenance dose of 150 mg once a week		Maintenance dose 6 months
Dermatomycosis	- tinea pedis -tinea corporis -tinea cruris - Candida infection	150 mg once a week or 50 mg once a day		2-4 weeks, but treatment for tinea pedis may require therapy for up to 6 weeks
	Tinea versicolor	300-400 mg once a week		1-3 weeks
	tinea unguium (onychomycosis)	150 mg once a week		The course of treatment should be continued until the infected nail is completely replaced (until a healthy nail grows back). It usually takes 3 to 6 months and 6 to 12 months to regenerate fingernails and toenails, respectively.

Special categories of patients
Elderly patients
In the absence of signs of impaired renal function, the usual dose of the drug should be used to treat this category of patients.
Impaired kidney function
Fluconazole is excreted mainly in the urine unchanged. With a single use, dose adjustment of the drug is not required.
Impaired liver function
Since there is insufficient information on the use of fluconazole in patients with hepatic impairment, fluconazole should be used with caution in this category of patients ( see sections "Precautions" and "Side effects").
Children and teenagers
The safety and efficacy of fluconazole for the treatment of genital candidiasis in children have not been established. Currently available data on the safety of the drug for other indications in children are given in the "Side effect" section. If it is necessary to use the drug for the treatment of genital candidiasis in adolescents (aged 12 to 17 years), the dosage should be the same as for adults.
Mode of application
Capsules are taken orally, without opening or chewing, regardless of the meal.

Side effect

The most commonly reported adverse reactions (≥1/10) were headache, abdominal pain, diarrhea, nausea, vomiting, elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated blood alkaline phosphatase, and rash.
When taking the drug, the development of the following adverse reactions was observed with the following frequency: very often (≥1/10), often (from ≥1/100 to<1/10), нечасто (от ≥1/1000 до <1/100), редко (от ≥1/10 000 до < 1/1000), очень редко (<1/10 000) и неизвестно (невозможно установить по имеющимся данным).

Class of organ systems	Often	Infrequently	Rarely
Blood and lymphatic system disorders			Agranulocytosis, leukopenia, thrombocytopenia, neutropenia
Immune System Disorders			Anaphylaxis
Metabolic and nutritional disorders		Decreased appetite	Hypercholesterolemia, hypertriglyceridemia, hypokalemia
Mental disorders		Drowsiness, insomnia
Nervous System Disorders	Headache	Convulsions, paresthesias, dizziness, taste perversion
Hearing and labyrinth disorders
Heart disorders			Paroxysmal torsades de pointes, prolongation of the QT interval (see Precautions section)
Gastrointestinal disorders	Abdominal pain, vomiting, diarrhea, nausea	Constipation, dyspepsia, flatulence, dry mouth
Liver and biliary tract disorders	Elevated alanine aminotransferase, elevated aspartate aminotransferase, elevated blood alkaline phosphatase, rash (see Precautions section)	Cholestasis, jaundice, elevated bilirubin (see Precautions section)	Liver failure, hepatocellular necrosis, hepatitis, hepatocellular damage (see Precautions section)
Skin and subcutaneous tissue disorders	Rash (see Precautions section)	Drug rash, hives, itching, increased sweating (see Precautions section)	Toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis (see Precautions section), exfoliative dermatitis, angioedema, facial edema, alopecia
Musculoskeletal and connective tissue disorders
General disorders and disorders at the injection site		Fatigue, malaise, asthenia, fever

Children and teenagers
The nature and frequency of adverse reactions, as well as deviations in the results of laboratory research methods, recorded in children and adolescents during clinical studies, with the exception of genital candidiasis, were comparable to those in adult patients.
Providing information about suspected adverse reactions
Providing data on suspected adverse reactions after registration of the medicinal product is of great importance. This allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions using the national adverse reaction reporting system.

Interaction with other drugs

Co-administration of fluconazole and the following drugs is contraindicated:
Cisapride: in patients taking fluconazole and cisapride at the same time, the development of adverse reactions from the heart was observed, including paroxysmal ventricular tachycardia of the pirouette type ( torsade de pointes). In a controlled study, the simultaneous 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 led to a significant increase in plasma concentrations of cisapride and a prolongation of the QTc interval. Co-administration of fluconazole and cisapride is contraindicated ( see section "Contraindications").
Terfenadine: in connection with the development of severe cardiac arrhythmias caused by prolongation of the QTc interval in patients who used antifungal drugs from the azole group simultaneously with terfenadine, interaction studies of these drugs were conducted. In one study, no prolongation of the QTc interval was found with fluconazole 200 mg/day. In another study using fluconazole at a dose of 400 mg / day and 800 mg / day, it was demonstrated that fluconazole at doses of 400 mg / day or higher significantly increases the level of terfenadine in blood plasma while using these drugs. The combined use of fluconazole at doses of 400 mg or higher with terfenadine is contraindicated When using fluconazole at a dose of less than 400 mg / day simultaneously with terfenadine, careful monitoring of the patient's condition should be carried out.
Astemizol: the combined use of fluconazole and astemizole may lead to a decrease in the clearance of astemizole. The resulting increase in the concentration of astemizole in the blood plasma can, in turn, lead to a prolongation of the QT interval and, in rare cases, to the development of paroxysmal ventricular tachycardia of the pirouette type (torsade de pointes). Simultaneous use of fluconazole and astemizole is contraindicated (see section "Contraindications").
Pimozide: Although no relevant in vitro or in vivo studies have been conducted, it is believed that the combined use of fluconazole and pimozide may lead to inhibition of the metabolism of pimozide. In turn, an increase in the concentration of pimozide in the blood plasma can lead to a prolongation of the QT interval and, in rare cases, to the development of paroxysmal ventricular tachycardia of the pirouette type ( torsade de pointes). Co-administration of fluconazole and pimozide is contraindicated (see section "Contraindications").
Quinidine: despite the fact that no relevant in vitro or in vivo studies have been conducted, it is believed that the combined use of fluconazole and quinidine may lead to inhibition of the metabolism of the latter. The use of quinidine was accompanied by prolongation of the QT interval and, in rare cases, the development of paroxysmal ventricular tachycardia of the pirouette type ( torsade de pointes). The simultaneous use of fluconazole and quinidine is contraindicated (see section "Contraindications").
Erythromycin: the simultaneous use of erythromycin and fluconazole increases the risk of developing cardiotoxicity (prolongation of the QT interval, development of paroxysmal ventricular tachycardia of the pirouette type ( torsade de pointes)) and, consequently, sudden coronary death. The simultaneous use of fluconazole and erythromycin is contraindicated (see section "Contraindications").
The simultaneous use of fluconazole and the following drugs is not recommended:
Halofantrine: fluconazole may increase plasma concentrations of halofantrine by inhibiting CYP3A4. The simultaneous use of fluconazole and halofantrine may increase the risk of developing cardiotoxicity (prolongation of the QT interval, the development of paroxysmal ventricular tachycardia of the torsade de pointes type) and, as a result, sudden coronary death. The combination of these drugs should be avoided (See Precautions section).
Simultaneous use with the following medicinal products you require caution and dose adjustment:
Effect of other medicinal products on fluconazole
Rifampicin: the simultaneous use of fluconazole and rifampicin resulted in a 25% decrease in AUC and a 20% reduction in the half-life of fluconazole. In patients taking rifampicin, an increase in the dose of fluconazole should be considered.
Interaction studies have shown that oral administration of fluconazole during a meal, in conjunction with cimetidine, antacids, or after total body irradiation (in preparation for bone marrow transplantation) does not have a clinically significant effect on the absorption of fluconazole.
Effect of fluconazole on other medicinal products
Fluconazole is a potent inhibitor of cytochrome P450 isoenzyme CYP2C9 and a moderate inhibitor of CYP3A4. In addition, fluconazole is an inhibitor of the CYP2C19 isoenzyme. In addition to the identified / established interactions (listed below), there is a risk of increasing plasma concentrations of other drugs that are metabolized by CYP2C9, CYP2C19 and CYP3A4 when they are used simultaneously with fluconazole. Therefore, such drug combinations should be used with caution; while it is necessary to carefully monitor the condition of patients. Due to the long half-life of fluconazole, its inhibitory effect on enzymes persists for 4–5 days after the end of treatment. (see section "Contraindications").
Alfentanil: in healthy volunteers, the simultaneous use of fluconazole (at a dose of 400 mg) and alfentanil (at a dose of 20 μg / kg intravenously) led to a two-fold increase in the AUC10 of alfentanil (probably due to inhibition of the CYP3A4 isoenzyme). Dose adjustment of alfentanil may be required.
Amitriptyline, nortriptyline: fluconazole enhances the effect of amitriptyline and nortriptyline. It is recommended that 5-nortriptyline and/or S-amitriptyline concentrations be measured at the start of combination therapy and after the first week of treatment. If necessary, the dose of amitriptyline/nortriptyline should be adjusted.
Amphotericin B: with the simultaneous use of fluconazole and amphotericin B in infected mice with normal and reduced immunity, the following results were obtained: a small additive antifungal effect in systemic infection caused by C. albicans; no interaction with intracranial infection caused by Cryptococcus neoformans; and antagonism of two drugs in systemic infection caused by Aspergillus fumigatus. The clinical significance of the results obtained in these studies is unknown.
Anticoagulants: during the period of post-registration observation, there were reports of the development of bleeding (formation of hematomas, epistaxis, gastrointestinal bleeding, hematuria and melena) due to prolongation of the prothrombin time with the simultaneous use of warfarin and fluconazole. Similar phenomena were observed with the use of other antifungal agents from the azole group. With the simultaneous use of fluconazole and warfarin, a two-fold increase in prothrombin time was noted, probably due to inhibition of warfarin metabolism mediated by the CYP2C9 isoenzyme. In patients taking coumarin anticoagulants in conjunction with fluconazole, it is recommended to carefully monitor the prothrombin time. If necessary, the dose of warfarin should be adjusted.
Short-acting benzodiazepines such as midazolam and triazolam: after oral administration of midazolam and fluconazole, a significant increase in the concentration of midazolam in the blood serum and an increase in psychomotor effects were observed. The simultaneous use of fluconazole at a dose of 200 mg and midazolam at a dose of 7.5 mg orally led to an increase in AUC and a prolongation of the half-life of midazolam by 3.7 and 2.2 times, respectively. The simultaneous use of fluconazole at a dose of 200 mg / day and triazolam at a dose of 0.25 mg orally led to an increase in AUC and a prolongation of the half-life of triazolam by 4.4 and 2.3 times, respectively. With the simultaneous use of fluconazole and triazolam, potentiation and prolongation of the effects of triazolam were noted. If patients receiving fluconazole require concomitant benzodiazepine therapy, consideration should be given to reducing the dosage of the latter and establishing appropriate monitoring of the patient's condition.
Carbamazepine: fluconazole inhibits the metabolism of carbamazepine and increases the concentration of carbamazepine in plasma by 30%, which, in turn, may be accompanied by the development of toxic effects of carbamazepine. It may be necessary to adjust the dose of carbamazepine depending on the level of its concentration in the blood and the severity of the therapeutic effect.
Calcium channel blockers: some calcium channel blockers (nifedipine, isradipine, amlodipine, verapamil and felodipine) are metabolized by the CYP3A4 isoenzyme. Fluconazole is able to increase the systemic exposure of calcium channel blockers. Careful monitoring for adverse reactions is recommended.
Celecoxib: with the simultaneous use of fluconazole (at a dose of 200 mg / day) and celecoxib (at a dose of 200 mg), there was an increase in the maximum concentration and AUC of celecoxib by 68% and 134%, respectively. Co-administration of celecoxib and fluconazole may require a halving of the celecoxib dose.
Cyclophosphamide: the simultaneous use of cyclophosphamide and fluconazole leads to an increase in the level of bilirubin and creatinine in the blood serum. These drugs can be used simultaneously, taking into account the possible risk of increasing the concentration of bilirubin and creatinine in the blood serum.
Fentanyl: One case of fatal fentanyl intoxication has been reported due to a possible interaction between fentanyl and fluconazole. In addition, in a study on healthy volunteers, it was demonstrated that fluconazole significantly slowed down the elimination of fentanyl. Increasing the concentration of fentanyl can lead to respiratory depression. Patients should be carefully monitored to identify potential risk of respiratory depression. Dose adjustment of fentanyl may be required.
HMG-CoA reductase inhibitors: the simultaneous use of fluconazole and HMG-CoA reductase inhibitors metabolized by CYP3A4 (such as atorvastatin and simvastatin), or HMG-CoA reductase inhibitors metabolized by CYP2C9 (such as fluvastatin), increases the risk of myopathy and rhabdomyolysis. If it is necessary to use these drugs simultaneously, the patient's condition should be carefully monitored for symptoms of myopathy and rhabdomyolysis and creatine kinase levels should be monitored. With a pronounced increase in the level of creatine kinase, as well as with suspicion or detection of myopathy / rhabdomyolysis, you should stop taking HMG-CoA reductase inhibitors.
Immunosuppressants (eg, cyclosporine, everolimus, sirolimus, and tacrolimus):
Cyclosporine: fluconazole significantly increases the concentration and AUC of cyclosporine. With the simultaneous use of fluconazole at a dose of 200 mg / day and cyclosporine (at a dose of 2.7 mg / kg / day), an increase in the AUC of cyclosporine by 1.8 times was noted. These drugs can be used simultaneously, provided that the dose of cyclosporine is reduced depending on its concentration.
Everolimus: Although no relevant in vivo and in vitro studies have been conducted, fluconazole is believed to be able to increase everolimus serum concentrations by inhibiting CYP3A4.
Sirolimus: fluconazole increases plasma concentrations of sirolimus, probably by inhibiting the metabolism of sirolimus CYP3A4 and P-glycoprotein. This combination can be used subject to adjustment of the dose of sirolimus, depending on the level of concentration and the severity of the therapeutic effect.
Tacrolimus: fluconazole is able to increase serum concentrations of tacrolimus up to 5-fold when administered orally by inhibiting the metabolism of tacrolimus by the CYP3A4 enzyme in the intestine. With intravenous use of tacrolimus, significant changes in pharmacokinetics were noted. An increase in the concentration of tacrolimus in the blood serum was associated with the development of nephrotoxicity. The dose of tacrolimus for oral administration should be reduced depending on its concentration in the blood.
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 when taking losartan. It is recommended to carry out continuous monitoring of blood pressure in patients during the entire period of treatment.
Methadone: fluconazole is able to increase the concentration of methadone in the blood serum. Dose adjustment of methadone may be required.
Non-steroidal anti-inflammatory drugs (NSAIDs): when used simultaneously with fluconazole C max and AUC of flurbiprofen increased by 23% and 81%, respectively, compared with similar indicators when using only flurbiprofen. Similarly, with the simultaneous use of fluconazole and racemic ibuprofen (at a dose of 400 mg), Cmax and AUC of the pharmacologically active isomer S-(+)-ibuprofen increased by 15% and 82%, respectively, compared with similar indicators when using only racemic ibuprofen.
Despite the lack of targeted studies, it is known that fluconazole is able to increase the systemic exposure of other NSAIDs that are metabolized by the CYP2C9 isoenzyme (for example, naproxen, lornoxicam, meloxicam, diclofenac). In the case of the joint use of these drugs, it is recommended to conduct frequent monitoring to identify adverse reactions and toxic manifestations associated with the use of NSAIDs. Dose adjustment of NSAIDs may be required.
Phenytoin: fluconazole inhibits the metabolism of phenytoin in the liver. Simultaneous repeated use of fluconazole at a dose of 200 mg and phenytoin at a dose of 250 mg intravenously led to an increase in AUC24 and C min of phenytoin by 75% and 128%, respectively. With the simultaneous use of these drugs, the concentration of phenytoin in the blood plasma should be monitored to exclude the development of the toxic effect of phenytoin.
Prednisone: there is a report on the development of acute adrenal insufficiency in a patient after liver transplantation against the background of fluconazole withdrawal after a 3-month course of therapy. Presumably, the cessation of fluconazole therapy caused an increase in the activity of the CYP3A4 isoenzyme, which led to an increase in the metabolism of prednisone. Patients receiving long-term combination therapy with prednisone and fluconazole should be under close medical supervision when fluconazole is discontinued in order to detect adrenal insufficiency.
Rifabutin: fluconazole increases the concentration of rifabutin in the blood serum, which leads to an increase in the AUC of rifabutin up to 80%. With the simultaneous use of fluconazole and rifabutin, cases of uveitis have been described. When using this combination of drugs, it is necessary to take into account the symptoms of the toxic effect of rifabutin.
Saquinavir: fluconazole increases the AUC and Cmax of saquinavir by approximately 50% and 55%, respectively, due to inhibition of the metabolism of saquinavir in the liver by the CYP3A4 isoenzyme and inhibition of P-glycoprotein. Interaction studies between fluconazole and saquinavir/ritonavir have not been conducted, so interactions may be even more pronounced. Dose adjustment of saquinavir may be required.
Sulfonylureas: Studies in healthy volunteers have shown that the concomitant use of fluconazole with oral sulfonylureas (eg, chlorpropamide, glibenclamide, glipizide, tolbutamide) resulted in a prolongation of their half-life. With simultaneous use with fluconazole, regular monitoring of blood glucose levels and, if necessary, a timely reduction in the dose of sulfonylurea drugs is necessary.
Theophylline: in a placebo-controlled drug interaction study when taking fluconazole at a dose of 200 mg for 14 days, the average plasma clearance rate of theophylline was reduced by 18%. When prescribing fluconazole to patients using high doses of theophylline or at an increased risk of developing toxic manifestations of theophylline, it is necessary to monitor the appearance of symptoms of theophylline toxic effect. If signs of toxicity appear, an appropriate correction of therapy should be carried out.
Vinca alkaloids: despite the lack of targeted studies, it is believed that fluconazole is able to increase the concentration of vinca alkaloids in plasma (for example, vincristine and vinblastine) and, thus, lead to the development of neurotoxicity, which may possibly be associated with inhibition of the CYP3A4 isoenzyme.
Vitamin A: there is a report of one case of the development of adverse reactions from the side of the central nervous system in the form of a pseudotumor of the brain with the simultaneous use of all-trans retinoic acid (the acid form of vitamin A) and fluconazole, which resolved after fluconazole was discontinued. The use of this combination is possible, but one should be aware of the possibility of developing adverse reactions from the central nervous system.
Voriconazole (an inhibitor of CYP2C9, CYP2C19 and CYP3A4 isoenzymes): Simultaneous oral administration of voriconazole (400 mg every 12 hours on the first day, then 200 mg every 12 hours for 2.5 days) and fluconazole (400 mg on the first day, then 200 mg every 24 hours for 4 days) in 8 healthy male volunteers resulted in an increase in Cmax and AUC of voriconazole by an average of 57% (90% CI: 20%, 107%) and 79% (90% CI: 40%, 128%), respectively. It is not known whether reducing the dose and/or frequency of voriconazole or fluconazole will eliminate this effect. When using voriconazole together with fluconazole, it is recommended to monitor the condition of patients for the development of adverse events associated with the use of voriconazole.
Zidovudine: when administered orally, fluconazole reduces the clearance of zidovudine by approximately 45% and increases the Cmax and AUC of zidovudine by 84% and 74%, respectively. In addition, with simultaneous use with fluconazole, an increase in the half-life of zidovudine by about 128% was noted. Patients receiving this combination of drugs should be monitored for adverse reactions associated with the use of zidovudine. If necessary, it is possible to reduce the dose of zidovudine.
Azithromycin: To establish the effect of a single dose of azithromycin at a dose of 1200 mg on the pharmacokinetics of fluconazole at a single dose of 800 mg, as well as the effect of fluconazole on the pharmacokinetics of azithromycin, an open, randomized, tripartite crossover study was conducted involving 18 healthy volunteers. There was no significant pharmacokinetic interaction between fluconazole and azithromycin.
Oral contraceptives: Two pharmacokinetic studies have been conducted on the use of a combined oral contraceptive against the background of multiple doses of fluconazole. When using fluconazole at a dose of 50 mg, a significant effect on hormone levels was not established, while with daily intake of fluconazole at a dose of 200 mg, the AUC of ethinylestradiol and levonorgestrel increased by 40% and 24%, respectively. Thus, repeated use of fluconazole at the indicated doses is unlikely to affect the effectiveness of combined oral contraceptives.
Ivacaftor: simultaneous use with ivacaftor, a potentiator of the transmembrane conductance regulator gene in cystic fibrosis (CFTR), increased the exposure of ivacaftor by 3 times, and hydroxymethyl-ivacaftor (Ml) by 1.9 times. Patients concomitantly taking moderate CYP3A inhibitors such as fluconazole and erythromycin are advised to reduce the dose of ivacaftor to 150 mg once daily.

Pregnancy and breastfeeding

Pregnancy
The results of an observational study showed an increased risk of spontaneous abortion in women taking fluconazole during the first trimester of pregnancy.
Cases of multiple congenital malformations in newborns (including brachycephaly, auricular dysplasia, excessive enlargement of the anterior fontanel, hip curvature, humeroulnar synostosis) have been described, whose mothers took high doses of fluconazole (400-800 mg / day) for three or more months for treatment of coccidioidomycosis, although the causal relationship of these cases with fluconazole is unclear.
Animal studies have shown reproductive toxicity of the drug.
Fluconazole at standard doses and for short-term treatment should not be used during pregnancy unless the expected benefit substantially outweighs the risk.
Fluconazole at high doses and/or for long-term use should not be used during pregnancy, except in cases of potentially life-threatening infections.
Breast-feeding
Fluconazole passes into breast milk, while its concentration in breast milk is lower than in blood plasma. You can continue breastfeeding after a single dose of fluconazole at a standard dose of 200 mg or less. It is not recommended to breastfeed with repeated use of fluconazole or when it is used in high doses.
Fertility
Fluconazole had no effect on the fertility of female and male rats.

Influence on the ability to drive vehicles and maintain mechanical equipment

Studies of the effect of the drug Fluconazole, capsules 150 mg on the ability to drive vehicles and maintain mechanical equipment have not been conducted.
However, patients should be informed about the possibility of developing dizziness or convulsions when using the drug (see the section "Side Effects") and advised not to drive a car or work with mechanical equipment if any of these symptoms develop.

Precautionary measures

kidneys
In patients with impaired renal function, Fluconazole 150 mg capsules should be used with caution (see section "Dosage and method of administration").
Hepatobiliary system
In rare cases, the use of fluconazole may be accompanied by the development of serious toxic reactions from the liver, including fatal. The risk of developing such reactions increases if the patient has severe concomitant diseases. In cases where the development of hepatotoxicity was associated with the use of fluconazole, no correlation was found between the patient's condition and the daily dose of the drug, the duration of treatment, the age and gender of the patient. The hepatotoxic effect of fluconazole was usually reversible.
Patients who experience abnormal liver function tests during treatment with fluconazole should be monitored for signs of more severe liver damage.
Patients should be informed about symptoms that may indicate serious liver damage (severe weakness, anorexia, persistent nausea, vomiting and jaundice). If you experience the above symptoms, you should immediately stop using fluconazole and consult a doctor.
The cardiovascular system
Some azoles, including fluconazole, have been associated with prolongation of the QT interval on the electrocardiogram. During the period of post-marketing follow-up in patients treated with fluconazole, there were very rare cases of prolongation of the QT interval and the development of paroxysmal ventricular tachycardia of the pirouette type (torsade de pointes). These cases were recorded in patients with severe diseases with a combination of many risk factors, such as structural heart disease, electrolyte imbalance, as well as with the simultaneous use of other drugs that could also cause the development of these complications.
Fluconazole 150 mg capsules should be used with caution in patients with proarrhythmic conditions. Simultaneous use with fluconazole of other drugs that prolong the QT interval and are metabolized using the CYP3A4 isoenzyme of cytochrome P450 is contraindicated (see sections "Contraindications" and "Interaction with other drugs").
Halofantrine
It has been established that halofantrine is a substrate of the CYP3A4 isoenzyme and prolongs the QTc interval when used at recommended therapeutic doses. In this connection, the simultaneous use of halofantrine and fluconazole is not recommended. (see section "Interaction with other drugs").
Dermatological reactions
In rare cases, when using fluconazole, patients developed exfoliative skin reactions of the type of Stevens-Johnson syndrome and toxic epidermal necrolysis.
AIDS patients are more likely to develop severe skin reactions with many drugs. If a skin rash develops in a patient with a superficial fungal infection while taking fluconazole, further use of the drug should be discontinued. If a patient with an invasive / systemic fungal infection develops a skin rash, his condition should be carefully monitored, and in the event of bullous rashes or erythema multiforme, fluconazole should be discontinued.
Hypersensitivity
In rare cases, anaphylactic reactions have been reported (see section "Contraindications").
Cytochrome P450
Fluconazole is a potent inhibitor of the CYP2C9 isoenzyme and a moderate inhibitor of the CYP3A4 isoenzyme. In addition, fluconazole is an inhibitor of the CYP2C19 isoenzyme. In this regard, the condition of patients simultaneously taking Fluconazole, 150 mg capsules and drugs with a narrow therapeutic window, which are metabolized with the participation of CYP2C9, CYP2C19 and CYP3A4 isoenzymes, should be carefully monitored (see section "Interaction with other drugs").
Terfenadine
The patient's condition should be carefully monitored while the use of terfenadine and fluconazole in doses<400 мг в сутки (see sections "Contraindications" and "Interactions with other drugs").
Excipients
Fluconazole 150 mg capsules contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Instructions for use

Fluconazole instructions for use

Dosage form

No. 3 hard gelatin capsules with a white body and an orange cap. The contents of the capsules are a powder or compacted mass of white or white with a yellowish tint, disintegrating when pressed.

Compound

1 capsule contains:

Active ingredient: fluconazole - 50.0 mg;

Excipients: lactose monohydrate - 69.5 mg; corn starch - 25.0 mg; povidone K-17 (polyvinylpyrrolidone low molecular weight) - 3.0 mg; calcium stearate - 1.5 mg; colloidal silicon dioxide - 0.7 mg; sodium lauryl sulfate - 0.3 mg;

Hard gelatin capsules No. 3:

Case: [titanium dioxide - 2.0%, gelatin - up to 100%];

Lid: [titanium dioxide - 2.0%, azorubine dye - 0.0328%, sunset yellow dye - 0.219%, gelatin - up to 100%].

Pharmacodynamics

Fluconazole is a triazole antifungal agent that is a powerful selective inhibitor of sterol synthesis in the fungal cell.

Fluconazole has shown activity against the following microorganisms: Candida albicans, Candida glabrata (many strains are moderately sensitive), Candida parapsilosis, Candida tropicalis, Cryptococcus neoformans.

Fluconazole has been shown to be active in vitro against the following microorganisms, but its clinical significance is unknown: Candida dubliniensis, Candida guilliermondii, Candida kefyr, Candida lusitaniae.

When administered orally, fluconazole is active in various models of fungal infections in animals. Fluconazole is effective in opportunistic mycoses, including those caused by Candida spp. (including generalized candidiasis in immunosuppressed animals), Cryptococcus neoformans (including intracranial infections), Microsporum spp. and Trychophyton spp. The activity of fluconazole has also been established in models of endemic mycoses in animals, including infections caused by Blastomyces dermatitides, Coccidioides immitis (including intracranial infections) and Histoplasma capsulatum in animals with normal and suppressed immunity.

Fluconazole has a high specificity for fungal enzymes dependent on the cytochrome P450 system. Therapy with fluconazole at a dose of 50 mg per day for up to 28 days does not affect the concentration of testosterone in the blood plasma in men or the concentration of steroids in women of childbearing age. Fluconazole at a dose of 200-400 mg per day has no clinically significant effect on endogenous steroid concentrations and their response to adrenocorticotropic hormone (ACTH) stimulation in healthy male volunteers.

Mechanisms of development of resistance to fluconazole

Fluconazole resistance can develop in the following cases: a qualitative or quantitative change in the enzyme that is the target of fluconazole (lanosteril 14-α-demethylase), a decrease in access to the target of fluconazole, or a combination of these mechanisms. Point mutations in the ERG11 gene encoding the target enzyme lead to a modification of the target and a decrease in affinity for azoles. An increase in the expression of the ERG11 gene leads to the production of high concentrations of the target enzyme, which creates a need to increase the concentration of fluconazole in the intracellular fluid to suppress all enzyme molecules in the cell.

The second significant mechanism of resistance is the active removal of fluconazole from the intracellular space through the activation of two types of transporters involved in the active removal (efflux) of drugs from the fungal cell. Such transporters include the main mediator encoded by the MDR genes (multidrug resistance - multiple drug resistance), and the superfamily of the ATP-binding transporter cassette encoded by the CDR genes (Candida resistance genes to azole antimycotics).

Overexpression of the MDR gene leads to resistance to fluconazole, while overexpression of the CDR genes can lead to resistance to various azoles. Resistance in Candida glabrata is usually mediated by overexpression of the CDR gene, resulting in resistance to many azoles. For those strains in which the minimum inhibitory concentration (MIC) is defined as intermediate (16-32 μg / ml), it is recommended to use the maximum dose of fluconazole.

Candida krusei should be considered resistant to fluconazole. The mechanism of resistance is associated with reduced sensitivity of the target enzyme to the inhibitory effect of fluconazole.

Pharmacokinetics

Suction

After oral administration, fluconazole is well absorbed, its bioavailability is 90%. The maximum concentration (Cmax) after ingestion on an empty stomach of 150 mg is 90% of the content in blood plasma when administered intravenously at a dose of 2.5-3.5 mg / kg. Simultaneous food intake does not affect the absorption of fluconazole taken orally. Plasma concentration reaches a maximum after 0.5-1.5 hours (TCmax) after administration. Plasma concentration is directly proportional to the dose.

90% of the equilibrium concentration is reached by the fourth or fifth day after the start of therapy (with multiple doses of the drug once a day).

The use on the first day of a dose that is 2 times the usual daily dose allows reaching a plasma concentration of fluconazole equal to 90% of the equilibrium concentration by the second day. The apparent volume of distribution (Vd) approaches the total volume of water in the body. Plasma protein binding is low

Distribution

Fluconazole penetrates well into all body fluids, including cerebrospinal fluid. Fluconazole concentrations 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 concentration in blood plasma.

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

Metabolism

Less than 5% of fluconazole is metabolized during the primary passage through the liver. The half-life (T1 / 2) of fluconazole is about 30 hours. Long-term plasma T1 / 2 allows you to take fluconazole once for vaginal candidiasis and once a day or once a week for other indications.

breeding

Fluconazole is excreted mainly by the kidneys. Approximately 80% of the administered dose is excreted by the kidneys unchanged. Fluconazole clearance is proportional to creatinine clearance. Fluconazole metabolites were not detected in peripheral blood.

Pharmacokinetics in children

In children, the following values of pharmacokinetic parameters were obtained:

Age Dose Half-life (hours) Area under

Concentration-Time Curve (AUC) (mcg h/mL)

9 months - 13 years Single dose - orally 2 mg/kg 25.0 94.7

9 months - 13 years Single dose - orally 8 mg/kg 19.5 362.5

Mean age 7 years Repeated oral dose 3 mg/kg 15.5 41.6

Pharmacokinetics in special groups of patients

Patients with renal insufficiency

In patients with severe renal insufficiency (glomerular filtration rate

< 20 мл/мин) Т1/2 возрастал от 30 до 98 часов. Поэтому в дальнейшем необходимо снижение дозы препарата.

Elderly patients

It was found that with a single dose of fluconazole at a dose of 50 mg orally in elderly patients aged 65 years and older, some of whom were simultaneously taking diuretics, Cmax was 1.54 μg / ml and was reached 1.3 hours after taking the drug. Mean AUC values were 76.4±20.3 µg∙h/ml, mean terminal T1/2 was 46.2 hours. These pharmacokinetic parameters are higher than those described in healthy young volunteers. Co-administration of diuretics did not significantly alter AUC or Cmax. Creatinine clearance (74 ml/min), fluconazole concentration found unchanged in the urine (0-24 hours, 22%), and fluconazole renal clearance (0.124 ml/min/kg) in elderly patients were generally lower than in young volunteers. Therefore, the change in the distribution of fluconazole in elderly patients seems to be associated with reduced renal function in this age group.

Side effects

Classification of the incidence of side effects according to the recommendations of the World Health Organization (WHO):

Very common ≥ 1/10;

Often ≥ 1/100 to< 1/10;

Uncommon ≥ 1/1000 to< 1/100;

Rare ≥ 1/10000 to< 1/1000;

Very rarely< 1/10000, включая отдельные сообщения;

The frequency is unknown - according to the available data, it is not possible to establish the frequency of occurrence.

Nervous system disorders:

Often - headache;

Infrequently - dizziness, convulsions, taste changes, paresthesia, insomnia, drowsiness;

Rarely - tremor.

Sensory disturbances:

Infrequently - vertigo.

Gastrointestinal disorders:

Often - abdominal pain, diarrhea, nausea, vomiting;

Infrequently - dryness of the oral mucosa, flatulence, dyspepsia, constipation, loss of appetite.

Liver and biliary tract disorders:

Often - increased activity of "liver" transaminases, increased activity of alkaline phosphatase;

Infrequently - an increase in the concentration of bilirubin, stagnation of the biliary tract, jaundice;

Rarely - liver failure, hepatocellular necrosis, hepatitis, hepatotoxicity, in some cases fatal, impaired liver function, hepatocellular damage.

Skin disorders:

Often - rash;

Infrequently - increased sweating, drug rash;

Rarely - alopecia, exfoliative skin lesions, including syndrome

Stevens-Johnson and toxic epidermal necrolysis, acute generalized exanthematous pustulosis.

Immune system disorders:

Rarely - anaphylaxis (including angioedema, swelling of the face, urticaria, itching).

Blood and lymphatic system disorders:

Infrequently - anemia;

Rarely - leukopenia, including neutropenia and agranulocytosis, thrombocytopenia.

Cardiovascular disorders:

Often - an increase in the QT interval on the ECG, ventricular tachysystolic arrhythmia of the "pirouette" type (torsade de pointes).

Metabolic and nutritional disorders:

Rarely - an increase in the concentration of cholesterol and triglycerides in the blood plasma, hypokalemia.

Musculoskeletal and connective tissue disorders:

Infrequently - myalgia.

Infrequently - weakness, asthenia, fatigue, fever, excessive sweating.

In some patients, especially those suffering from serious diseases such as AIDS or cancer, changes in blood parameters, kidney and liver function have been observed during treatment with fluconazole and similar drugs, but the clinical significance of these changes and their relationship to treatment has not been established.

Selling Features

Released without a prescription

Special conditions

Treatment may be initiated if culture or other laboratory results are not available, but appropriate adjustment of fungicidal therapy is recommended if available.

Since fluconazole is excreted primarily by the kidneys, caution should be exercised in patients with renal insufficiency. With long-term treatment with fluconazole, dosing should be based on creatinine clearance.

Caution should be exercised when prescribing fluconazole to patients with impaired liver function. In rare cases, the use of fluconazole was accompanied by toxic changes in the liver, including fatal, mainly in patients with serious concomitant diseases. In the case of hepatotoxic effects associated with the use of fluconazole, there was no obvious dependence on the total daily dose of the drug, duration of therapy, sex and age of the patient.

The hepatotoxic effect of the drug was usually reversible, its signs disappeared after cessation of therapy. Patients who develop liver dysfunction during therapy should be monitored for signs of more severe liver damage. With the appearance of clinical signs and symptoms of liver damage, which may be associated with the use of fluconazole, the drug should be discontinued.

As with other azoles, fluconazole can rarely cause anaphylactic reactions.

During treatment with fluconazole, patients have rarely developed exfoliative skin lesions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

HIV-infected patients are more likely to develop severe skin reactions with many drugs. In cases where a rash develops in patients with a superficial fungal infection and is regarded as definitely related to fluconazole, the drug should be discontinued. If a rash occurs in patients with invasive / systemic fungal infections, they should be carefully monitored and fluconazole should be discontinued if bullous changes or erythema multiforme appear.

It is necessary to control the prothrombin time in patients simultaneously receiving fluconazole and coumarin anticoagulants.

Cases of superinfection caused by strains of Candida other than Candida albicans, which often have natural resistance to fluconazole (for example, Candida krusei), have been reported. In such cases, alternative antifungal therapy may be required.

Like other azoles, fluconazole can cause an increase in the QT interval on the ECG. When using fluconazole, an increase in the QT interval and ventricular fibrillation or flutter was observed very rarely in patients with severe diseases with multiple risk factors, such as organic heart disease, electrolyte imbalance and concomitant therapy that contributes to the development of such disorders. Therefore, fluconazole should be used with caution in these patients with potentially proarrhythmic conditions. Patients with diseases of the liver, heart and kidneys are advised to consult a doctor before using the drug. When using fluconazole 150 mg for vaginal candidiasis, patients should be warned that improvement in symptoms is usually observed after 24 hours, but sometimes it takes several days for them to disappear completely. If symptoms persist for several days, you should consult a doctor.

The simultaneous use of fluconazole at doses less than 400 mg / day and terfenadine should be carefully monitored (see section "Interaction with other drugs").

With simultaneous therapy with drugs with a narrow therapeutic profile, metabolized by isoenzymes CYP2C9, CYP2C19, CYP3A4, caution is recommended.

Treatment should be continued until the appearance of clinical and microbiological remission. Premature termination of treatment leads to relapses.

The dye azorubine, which is part of the drug, can cause allergic reactions, including bronchial asthma. Allergic reactions are more common in patients with intolerance to acetylsalicylic acid.

Influence on the ability to drive vehicles and mechanisms

The experience of using fluconazole indicates that the violation of the ability to drive vehicles and mechanisms associated with the use of the drug is unlikely. However, if the patient develops dizziness, drowsiness and convulsions while taking the drug, you should stop engaging in potentially hazardous activities.

Indications

Fluconazole is indicated for the treatment of the following disorders in adults:

Cryptococcal meningitis;

coccidioidomycosis;

invasive candidiasis;

Mucous candidiasis, including oropharyngeal candidiasis, esophageal candidiasis, candiduria, and chronic mucocutaneous candidiasis;

Chronic atrophic candidiasis of the oral cavity (associated with the wearing of dentures), when oral hygiene or topical treatment is not enough;

Vaginal candidiasis, acute or recurrent when topical therapy is not applicable;

Candidal balanitis when topical therapy is not applicable;

Dermatomycosis, including tinea pedis, dermatophytosis of the trunk, tinea groin, versicolor versicolor, and skin candidal infections, when systemic treatment is indicated;

Dermatophytosis of the nails (onychomycosis) when treatment with other drugs is not acceptable.

Fluconazole is indicated for the prevention of the following diseases in adults:

Recurrent cryptococcal meningitis in patients at high risk of relapse;

Relapses of oropharyngeal candidiasis and esophageal candidiasis in

HIV-infected patients at high risk of relapse;

To reduce the frequency of recurrence of vaginal candidiasis (4 or more episodes per year);

For the prevention of candidal infections in patients with prolonged neutropenia (such as patients with hemoblastoses undergoing chemotherapy or patients undergoing hematopoietic stem cell transplantation).

Fluconazole is indicated for the treatment of the following conditions in children:

Mucous candidiasis (oropharyngeal candidiasis and esophageal candidiasis);

invasive candidiasis;

Cryptococcal meningitis.

Fluconazole is indicated for the prevention of the following diseases in children:

Candida infections in immunocompromised patients.

Fluconazole can be used as maintenance therapy to prevent recurrence of cryptococcal meningitis in children at high risk of relapse.

Contraindications

Hypersensitivity to fluconazole, other components of the drug or azole substances with a structure similar to fluconazole;

Simultaneous administration of terfenadine during repeated use of fluconazole at a dose of 400 mg / day or more (see section "Interaction with other drugs");

Simultaneous use with drugs that can prolong the QT interval and are metabolized by the CYP3A4 isoenzyme, such as cisapride, astemizole, erythromycin, pimozide, quinidine, amiodarone (see section "Interaction with other drugs");

Lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

The period of breastfeeding;

Children's age up to 3 years (for this dosage form).

Carefully

Liver failure;

kidney failure;

The appearance of a rash against the background of the use of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections;

Simultaneous use of terfenadine and fluconazole at a dose of less than 400 mg / day;

Potentially proarrhythmic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance and concomitant therapy that contributes to the development of such disorders).

Use during pregnancy and during breastfeeding

Pregnancy

Adequate and well-controlled studies of the use of fluconazole in pregnant women have not been conducted. Several cases of multiple congenital malformations have been described in newborns whose mothers received high-dose fluconazole therapy for most or all of the first trimester of pregnancy.

(400-800 mg per day).

The following developmental disorders were noted: brachycephaly, developmental disorders of the facial part of the skull, malformation of the cranial vault, cleft palate, curvature of the femur, thinning and lengthening of the ribs, arthrogryposis and congenital heart defects. Currently, there is no evidence of an association of these congenital anomalies with the use of low doses of fluconazole (150 mg once for the treatment of vulvovaginal candidiasis) in the first trimester of pregnancy.

During pregnancy, the use of fluconazole should be avoided, except for severe or life-threatening forms of fungal infections, if the expected benefit to the mother outweighs the possible risk to the fetus.

Women of childbearing age should use contraception.

breastfeeding period

Fluconazole is found in breast milk at the same concentration as in blood plasma, so its appointment during breastfeeding is contraindicated.

drug interaction

A single or multiple dose of fluconazole at a dose of 50 mg does not affect the metabolism of phenazone when they are taken simultaneously.

Simultaneous use of fluconazole with the following drugs is contraindicated:

Amiodarone: Co-administration of fluconazole and amiodarone may result in inhibition of amiodarone metabolism. The use of amiodarone has been associated with prolongation of the QT interval. The simultaneous use of fluconazole and amiodarone is contraindicated (see section "Contraindications").

Cisapride: with the simultaneous use of fluconazole and cisapride, adverse reactions from the heart are possible, including ventricular arrhythmia tachysystolic type "pirouette" (torsade de pointes). Dose of fluconazole

200 mg 1 time per day and cisapride at a dose of 20 mg 4 times a day leads to a pronounced increase in the plasma concentration of cisapride and an increase in the QT interval on the ECG. Co-administration of cisapride and fluconazole is contraindicated.

Terfenadine: With the simultaneous use of azole antifungals and terfenadine, serious arrhythmias may occur as a result of an increase in the QT interval. When taking fluconazole at a dose of 200 mg per day, an increase in the QT interval was not established, however, the use of fluconazole at doses of 400 mg per day and above causes a significant increase in the concentration of terfenadine in blood plasma. Simultaneous administration of fluconazole in doses of 400 mg per day or more with terfenadine is contraindicated. Treatment with fluconazole at doses less than 400 mg per day in combination with terfenadine should be carefully monitored.

Astemizole: the simultaneous use of fluconazole with astemizole or other drugs, the metabolism of which is carried out by isoenzymes of the cytochrome P450 system, may be accompanied by an increase in plasma concentrations of these agents. An increased concentration of astemizole in the blood plasma 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 astemizole and fluconazole is contraindicated.

Pimozide: Although no appropriate in vitro or in vivo studies have been conducted, the simultaneous use of fluconazole and pimozide may lead to inhibition of the metabolism of pimozide. In turn, an increase in the plasma concentration 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: Despite the fact that no relevant studies have been conducted in vitro or in vivo, the simultaneous use of fluconazole and quinidine can also lead to inhibition of the metabolism of quinidine. The use of quinidine is associated with prolongation of the QT interval and, in some cases, with the development of ventricular tachysystolic arrhythmias of the "pirouette" type (torsade de pointes). The simultaneous use of quinidine and fluconazole is contraindicated.

Erythromycin: the simultaneous use of fluconazole and erythromycin potentially leads to an increased risk of cardiotoxicity (prolongation of the QT interval, the development of arrhythmia of the ventricular tachysystolic type "pirouette") and, consequently, to sudden cardiac death. The simultaneous use of fluconazole and erythromycin is contraindicated.

Caution should be exercised and dose adjustments possible when the following drugs are co-administered with fluconazole:

Hydrochlorothiazide: repeated use of hydrochlorothiazide simultaneously with fluconazole leads to an increase in the concentration of fluconazole in blood plasma by

40%. The effect of this degree of severity does not require a change in the dosing regimen of fluconazole in patients receiving diuretics at the same time, but the doctor should take this into account.

Rifampicin: The simultaneous use of fluconazole and rifampicin leads to a decrease in AUC by 25% and the duration of the half-life of fluconazole by 20%. In patients concomitantly taking rifampicin, it is necessary to consider the advisability of increasing the dose of fluconazole.

Fluconazole is a potent inhibitor of cytochrome P450 isoenzymes CYP2C9 and CYP2C19 and a moderate inhibitor of CYP3A4 isoenzyme. In addition, in addition to the effects listed below, there is a risk of increasing plasma concentrations of other drugs metabolized by CYP2C9, CYP2C19 and CYP3A4 isoenzymes while taking fluconazole. In this regard, caution should be exercised with the simultaneous use of these drugs, and if necessary, such combinations, patients should be under close medical supervision. It should be borne in mind 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, an increase in the half-life of alfentanil. This may be due to the inhibition of the CYP3A4 isoenzyme by fluconazole. Dose adjustment of alfentanil may be required. Amitriptyline, nortriptyline: Fluconazole enhances the effect of amitriptyline and nortriptyline. The concentration of 5-nortriptyline and / or S-amitriptyline can be measured at the beginning of combination therapy with fluconazole and one week after the start. If necessary, the dose of amitriptyline/nortriptyline should be adjusted.

Amphotericin B: small additive antifungal effect in systemic C. albicans infection, no interaction in intracranial Cryptococcus neoformans infection, and antagonism in systemic A. fumigatus infection. The clinical significance of these results is not clear.

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

Azithromycin: With the simultaneous use of oral fluconazole in a single dose of 800 mg with azithromycin in a single dose of 1200 mg, a pronounced pharmacokinetic interaction between both drugs has not been established.

Benzodiazepines (short-acting): After oral administration of midazolam, fluconazole significantly increases midazolam concentrations and psychomotor effects. If concomitant therapy with benzodiazepines is required, patients taking fluconazole should be observed to assess the appropriateness of an appropriate dose reduction of the benzodiazepine.

With the simultaneous administration of a single dose of triazolam, fluconazole increases triazolam AUC by approximately 50%, Cmax by 25-50% and half-life by

25-50% due to inhibition of triazolam metabolism. Dose adjustment of triazolam may be necessary.

Carbamazepine: fluconazole inhibits the metabolism of carbamazepine and increases the plasma concentration of carbamazepine by 30%. The risk of carbamazepine toxicity must be considered. The need to adjust the dose of carbamazepine depending on the concentration / effect should be evaluated.

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

Nevirapine: Co-administration of fluconazole and nevirapine increases the exposure of nevirapine by approximately 100% compared with controls for nevirapine alone. Due to the risk of increased excretion of nevirapine with concomitant use of drugs, some precautions and careful monitoring of patients are necessary.

Cyclosporine: In patients with a transplanted kidney, the use of fluconazole at a dose of 200 mg per day leads to a slow increase in the concentration of cyclosporine. However, with repeated administration of fluconazole at a dose of 100 mg per day, no change in the concentration of cyclosporine in bone marrow recipients was observed. With the simultaneous use of fluconazole and cyclosporine, it is recommended to control the concentration of cyclosporine in the blood plasma.

Cyclophosphamide: With the simultaneous use of cyclophosphamide and fluconazole, an increase in plasma concentrations of bilirubin and creatinine is noted. This combination is acceptable, taking into account the risk of increasing the concentrations of bilirubin and creatinine.

Fentanyl: There has been a report of one death possibly related to the concomitant use of fentanyl and fluconazole. It is assumed that the violations are associated with fentanyl intoxication. Fluconazole has been shown to significantly prolong the elimination time of fentanyl. It should be borne in mind that an increase in the concentration of fentanyl can lead to respiratory depression.

Halofantrine: fluconazole may increase plasma concentrations of halofantrine due to inhibition of the CYP3A4 isoenzyme. With simultaneous use with fluconazole, as with other antifungal drugs of the azole series, it is possible to develop arrhythmia of the ventricular tachysystolic type "pirouette", so their combined use is not recommended.

HMG-CoA reductase inhibitors: With the simultaneous use of fluconazole 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. In case of need for simultaneous therapy with these drugs, patients should be observed in order to detect symptoms of myopathy and rhabdomyolysis. It is necessary to control the concentration of creatinine kinase. In the event of a significant increase in the concentration of creatinine kinase 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 the plasma concentration of methadone. You may need to adjust your methadone dose.

Non-steroidal anti-inflammatory drugs (NSAIDs): Flurbiprofen Cmax and AUC increased by 23% and 81%, respectively. Similarly, the Cmax and AUC of the pharmacologically active isomer increased by 15% and 82%, respectively, when fluconazole was co-administered with racemic ibuprofen (400 mg).

With the simultaneous use of fluconazole at a dose of 200 mg per day and celecoxib at a dose of 200 mg, 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.

Despite the lack of targeted studies, fluconazole may increase the systemic exposure of other NSAIDs metabolized by the CYP2C9 isoenzyme (eg, naproxen, lornoxicam, meloxicam, diclofenac). You may need to adjust the dose of NSAIDs.

With the simultaneous use of NSAIDs and fluconazole, patients should be under close medical supervision in order to identify and control adverse events and manifestations of toxicity associated with NSAIDs.

Oral contraceptives: with the simultaneous use of a combined oral contraceptive with fluconazole at a dose of 50 mg, no significant effect on hormone concentrations has been established, while with daily intake of 200 mg of fluconazole, the AUC of ethinylestradiol and levonorgestrel increase by 40% and 24%, respectively, and with 300 mg of fluconazole once a week AUC of ethinylestradiol 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: The simultaneous use of fluconazole and phenytoin may be accompanied by a clinically significant increase in the concentration of phenytoin. If it is necessary to use both drugs simultaneously, the concentration of phenytoin should be monitored and its dose adjusted accordingly in order to ensure therapeutic plasma concentrations.

Ivacaftor: When co-administered with ivacaftor, a cystic fibrosis transmembrane conductance regulator (CFTR) stimulant, there was a 3-fold increase in ivacaftor exposure and a 1.9-fold increase in hydroxymethyl-ivacaftor exposure. Patients concomitantly taking moderate CYP3A inhibitors such as fluconazole and erythromycin are advised to reduce the dose of ivacaftor to 150 mg once daily.

Prednisone: There is a report of the development of acute adrenal insufficiency in a patient after liver transplantation against the background of fluconazole withdrawal after a three-month course of therapy. Presumably, the cessation of fluconazole therapy caused an increase in the activity of the CYP3A4 isoenzyme, which led to an increased metabolism of prednisone. Patients receiving combination therapy with prednisone and fluconazole should be under close medical supervision when fluconazole is discontinued in order to assess the state of the adrenal cortex.

Rifabutin: the simultaneous use of fluconazole and rifabutin can lead to an increase in plasma concentrations of the latter up to 80%. With the simultaneous use of fluconazole and rifabutin, cases of uveitis have been described. Patients receiving rifabutin and fluconazole concomitantly should be closely monitored.

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

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

Sulfonylureas: when taken concomitantly, fluconazole leads to an increase in the half-life of oral sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide). Patients with diabetes mellitus can be given the combined use of fluconazole and oral sulfonylurea preparations, but the possibility of hypoglycemia should be considered. In addition, regular monitoring of the concentration of glucose in the blood plasma and, if necessary, dose adjustment of sulfonylurea drugs is necessary.

Tacrolimus: The simultaneous use of fluconazole and tacrolimus (orally) leads to an increase in the plasma concentration of the latter by 5 times due to inhibition of the metabolism of tacrolimus that occurs in the intestine through the CYP3A4 isoenzyme. Significant changes in the pharmacokinetics of drugs were observed when tacrolimus was administered intravenously. Cases of nephrotoxicity have been described. Patients taking oral tacrolimus and fluconazole concomitantly should be closely monitored. The dose of tacrolimus should be adjusted depending on the degree of increase in its concentration in blood plasma.

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

Vinca alkaloids: Despite the lack of targeted studies, it is assumed that fluconazole may increase the concentration of drugs containing vinca alkaloids (for example, vincristine and vinblastine) in blood plasma and, thus, lead to neurotoxicity, which may be associated with inhibition of the isoenzyme CYP3A4.

Vitamin A: There is a report of one case of the development of an adverse reaction from the central nervous system (CNS) in the form of a pseudotumor of the brain with the simultaneous use of all-trans retinoic acid and fluconazole, which disappeared after fluconazole was discontinued. The use of this combination is possible, but one should be aware of the possibility of unwanted reactions from the central nervous system.

Zidovudine: when used simultaneously with fluconazole, there is an increase in Cmax and AUC of zidovudine 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 per day for 15 days in

In HIV-infected patients with an 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 (an inhibitor of CYP2C9, CYP2C19 and CYP3A4 isoenzymes): concomitant use of voriconazole (400 mg twice a day on the first day, then 200 mg twice a day for 2.5 days) and fluconazole (400 mg on the first day, then 200 mg per day for 4 days) leads to an increase in the concentration and AUC of voriconazole by

57% and 79% respectively. This effect has been shown to persist with dose reduction and/or reduction in the frequency of administration of any of the drugs. Co-administration of voriconazole and fluconazole is not recommended.

Tofacitinib: Exposure to tofacitinib is increased when co-administered with drugs that are both moderate inhibitors of the CYP3A4 isoenzyme and potent inhibitors of the CYP2C19 isoenzyme (for example, fluconazole). Dose adjustment of tofacitinib may be necessary.

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

These interactions have been established with repeated use of fluconazole. Drug interactions resulting from a single dose of fluconazole are not known.

Physicians should be aware that interactions with other drugs have not been specifically studied, but they are possible.

Prices for Fluconazole in other cities

Buy fluconazole,, Fluconazole in Voronezh,Fluconazole in Krasnodar,Fluconazole in Saratov,Fluconazole in Tyumen

Mode of application

Dosage

inside. The capsules are swallowed whole.

Therapy can be initiated before culture and other laboratory results are available. However, antifungal therapy should be changed accordingly when the results of these studies become known.

When transferring a patient from intravenous to oral administration of the drug or vice versa, changes in the daily dose are not required.

The daily dose of fluconazole depends on the nature and severity of the fungal infection. For infections requiring repeated administration of the drug, treatment should be continued until the disappearance of clinical or laboratory signs of an active fungal infection. HIV-infected patients with cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require maintenance therapy to prevent recurrence of the infection.

Use in adults

With cryptococcal meningitis and cryptococcal infections of other localization, the drug is usually used at a dose of 400 mg on the first day, and then treatment is continued at a dose of 200-400 mg once a day. The duration of treatment for cryptococcal infections depends on the presence of a clinical and mycological effect; in cryptococcal meningitis, treatment is usually continued for at least 6-8 weeks. In cases of treatment of life-threatening infections, the daily dose can be increased to 800 mg. To prevent recurrence of cryptococcal meningitis in patients at high risk of relapse, fluconazole 200 mg daily may be continued indefinitely after completion of the full course of primary treatment.

With coccidioidomycosis, it may be necessary to use the drug at a dose

200-400 mg per day. For some infections, especially those involving the meninges, a dose of 800 mg per day may be considered. The duration of therapy is determined individually; it can be up to 2 years, namely, 11-24 months - with coccidioidomycosis, 2-17 months - with paracoccidioidomycosis, 1-16 months - with sporotrichosis and 3-17 months - with histoplasmosis.

For candidaemia, disseminated candidiasis and other invasive candidal infections, the loading dose is 800 mg on the first day, the subsequent dose

400 mg per day. The duration of therapy depends on clinical efficacy. The general recommendation for duration of treatment for candidemia is 2 weeks after the first negative blood culture and the disappearance of signs and symptoms of candidemia.

Treatment of mucous candidiasis:

1) in oropharyngeal candidiasis, the loading dose is 200-400 mg on the first day, followed by a dose of 100-200 mg once a day for 7-21 days. If necessary, in patients with severe suppression of immune function, treatment can be continued for a longer time;

2) with candiduria, the effective dose is usually 200-400 mg per day with a duration of treatment of 7-21 days. In patients with severely impaired immune system function, longer periods of therapy may be used;

3) in chronic mucocutaneous candidiasis, 50-100 mg per day is used for up to 28 days of treatment. Depending on the severity of the infection or concomitant impairment of the immune system and infection, longer periods of therapy may be used;

4) in case of esophageal candidiasis, the loading dose is 200-400 mg on the first day, the subsequent dose is 100-200 mg per day. The course of treatment is 14-30 days (until remission of esophageal candidiasis is achieved). If necessary, in patients with severe suppression of immune function, treatment can be continued for a longer time;

5) for the prevention of recurrence of oropharyngeal candidiasis in

In HIV-infected patients with a high risk of relapse, fluconazole is used at 100-200 mg per day or 200 mg 3 times a week for an indefinite period in patients with chronically reduced immunity;

6) to prevent recurrence of esophageal candidiasis in HIV-infected patients with a high risk of relapse, fluconazole is used at 100-200 mg per day or 200 mg 3 times a week for an indefinite period of time in patients with chronically reduced immunity.

In chronic atrophic candidiasis of the oral cavity associated with the wearing of dentures, the drug is usually used at a dose of 50 mg once a day for 14 days in combination with local antiseptic agents for the treatment of the prosthesis.

In acute vaginal candidiasis, candidal balanitis, fluconazole is used once orally at a dose of 150 mg. To reduce the frequency of recurrence of vaginal candidiasis, the drug can be used at a dose of 150 mg every three days - a total of 3 doses (on the first, fourth and seventh days), then a maintenance dose of 150 mg once a week. The maintenance dose can be used up to 6 months.

Treatment of dermatomycosis:

1) for skin infections, including dermatophytosis of the feet, dermatophytosis of the body, groin dermatophytosis and candidal infections, the recommended dose is 150 mg once a week or 50 mg once a day. The duration of therapy is usually 2-4 weeks, with mycoses of the feet, longer therapy up to 6 weeks may be required;

For onychomycosis, the recommended dose is 150 mg once a week. Treatment should be continued until replacement of the infected nail (growth of an uninfected nail). Fingernail and toenail regrowth usually takes 3-6 months and 6-12 months, respectively. However, the rate of growth can vary widely from person to person and also according to age. After successful treatment of long-standing chronic infections, a change in the shape of the nails is sometimes observed.

For the prevention of candidiasis in patients with malignant tumors, the recommended dose of fluconazole is 200-400 mg once a day, depending on the degree of risk of developing a fungal infection. For patients at high risk of generalized infection, such as severe or long-lasting neutropenia, the recommended dose is 400 mg once daily. Fluconazole is used a few days before the expected development of neutropenia and, after an increase in the number of neutrophils over 1000 mm3, treatment is continued for another 7 days.

Use in children

As with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. For children, the daily dose of the drug should not exceed that for adults.

Fluconazole is used daily once a day.

3 mg/kg/day. On the first day, a loading dose of 6 mg/kg can be used to reach steady state more quickly.

For the treatment of invasive candidiasis and cryptococcal meningitis, the recommended dose is 6-12 mg/kg/day, depending on the severity of the disease.

To suppress the recurrence of cryptococcal meningitis in HIV-infected children, the recommended dose of fluconazole is 6 mg/kg/day.

For the prevention of fungal infections in immunosuppressed children in whom the risk of infection is associated with neutropenia that develops as a result of cytotoxic chemotherapy or radiation therapy, the drug is used according to

3-12 mg / kg / day, depending on the severity and duration of induced neutropenia (see dose for adults; for children with renal insufficiency - see dose for patients with renal insufficiency).

If it is not possible to properly use the dosage form of the drug Fluconazole in the form of capsules in children, consideration should be given to replacing it with other dosage forms of the drug (powder for oral suspension or solution for intravenous administration) in equivalent doses.

Use in elderly patients

In the absence of signs of renal failure, fluconazole is used at the usual dose. Patients with renal insufficiency (creatinine clearance< 50 мл/мин) дозу препарата корректируют, как описано ниже.

Use in patients with renal insufficiency

With a single dose, dose changes are not required. In patients (including children) with impaired renal function with repeated use of the drug, a loading dose of 50 mg to 400 mg should be initially administered, after which the daily dose (depending on the indication) is set according to the following table:

≤ 50 (without dialysis) 50%

Regular dialysis 100% after each dialysis

Patients on regular dialysis should receive 100% of the recommended dose after each dialysis session. On the day when dialysis is not performed, patients should receive a reduced (depending on creatinine clearance) dose of the drug.

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

Overdose

Symptoms

Nausea, vomiting, diarrhea. In severe cases, convulsions, hallucinations, and paranoid behavior may occur.

Symptomatic, gastric lavage. Since fluconazole is excreted by the kidneys, forced diuresis is recommended. Hemodialysis for 3 hours reduces plasma concentration by 2 times.