Fluconazole side effects and contraindications. Fluconazole: instructions for use

Fluconazole with the same name INN is the most popular antifungal drug of the triazole group. Under this name, it is produced at once by several domestic manufacturers (Medisorb, East-Farm, Alvils, Drugs Technology, Veropharm, Pharmproject, Sintez, etc.) and a number of foreign companies specializing in the production of quality generics - Teva (Israel), Sandoz (Slovenia ), Hemofarm (Serbia), Zentiva (Czech Republic). According to statistics from the World Health Organization, certain fungal infections (skin, nail plates, mucous membranes oral cavity, Digestive tract, vagina, urethra) affects 20% of the world's population. Moreover: in last years, incl. and in our country there is a tendency to an increase in the incidence of mycoses. In this regard, the demand for antifungal drugs in medical practice is constantly growing. Fluconazole is one of the most commonly prescribed antimycotic drugs. Its pharmacological effect is based on the ability to suppress the activity of the enzymatic system of cytochrome P-450, which leads to a violation of the formation of ergosterol and an increase in the permeability of the cell wall of the fungus. If Ketoconazole inhibits the production of testosterone and cortisol, then Fluconazole does not have this property and does not interfere with the work endocrine system... The drug has fungistatic (stops growth and development) and fungicidal (destroys) activity against Candida, Blastomyces dermatitidis, Microsporum spp., Crypticoccus neoformans, Histoplasmacapsulatum, Trichophyton spp., Coccidioides immitis.

Fluconazole has a high bioavailability (90%) and, when taken orally, is well absorbed in the gastrointestinal tract.

It is important that the drug can be taken without regard to the diet, since food does not in any way affect its absorption in the gastrointestinal tract (which is another of its advantages in relation to other antifungal agents). Fluconazole solution and tablets have almost identical pharmacological characteristics. The half-life of the drug - 30 hours - allows you to take it once a day. The active substance has good penetrating ability and evenly spreads into all biological fluids and tissues of the body, which is confirmed by the measurement of the concentration of the drug in the blood, saliva, skin, sweat. Fluconazole secretes an unprecedented high ability to cross the blood-brain barrier, making it the drug of choice for fungal infection central nervous system: cerebrospinal fluid will reach 80% of the concentration of the active component in the blood. Elimination from the body is carried out mainly by the kidneys. The dosage regimen is determined individually, depending on the indications and the clinical situation. According to general recommendations, adults take from 50 to 400 mg once a day, children - from 3 to 12 mg once a day. In persons with chronic renal impairment, the dose is adjusted depending on the CC. The duration of the drug course is determined by the effectiveness of the treatment. As a summary: Fluconazole is by far one of the most effective antifungal drugs with relatively few side effects and is widely used in more than 60 countries around the world.

Pharmacology

Triazole derivative antifungal agent. It is a selective inhibitor of sterol synthesis in the fungal cell. Fluconazole is highly specific for cytochrome P450 dependent fungal enzymes.

Oral and intravenous administration fluconazole was active in various models of fungal infections in animals.

Fluconazole is active in opportunistic mycoses, incl. caused by Candida spp., including generalized candidiasis in animals with reduced immunity; Cryptococcus neoformans, including intracranial infections; Microsporum spp. and Trychoptyton spp. Active in models of endemic mycoses in animals, including infections caused by Blastomyces dermatitidis, Coccidioides immitis, including intracranial infections, and Histoplasma capsulatum in animals with normal and reduced immunity.

Pharmacokinetics

The pharmacokinetics of fluconazole are similar when administered intravenously and when taken orally.

After oral administration, fluconazole is well absorbed, its plasma levels (and overall bioavailability) exceed 90% of the plasma levels of fluconazole when administered intravenously. Concomitant food intake does not affect oral absorption. C max is reached within 0.5-1.5 hours after taking fluconazole on an empty stomach. Plasma concentration is proportional to dose.

90% C ss is achieved by the 4-5th day after the start of therapy (with repeated administration 1 time / day).

The introduction of a loading dose (on the 1st day), 2 times the average daily dose, makes it possible to achieve C ss 90% by the 2nd day. The apparent V d approaches the total body water content. Plasma protein binding is low (11-12%).

Fluconazole penetrates well into all body fluids. Fluconazole levels in saliva and sputum are similar to those in blood plasma. In patients with fungal meningitis, the levels of fluconazole in the cerebrospinal fluid are about 80% of its plasma levels.

In the stratum corneum, epidermis-dermis and sweat fluid, high concentrations are achieved, which exceed serum levels. Fluconazole accumulates in the stratum corneum. When taken in a dose of 50 mg 1 time / day, the concentration of fluconazole after 12 days was 73 μg / g, and 7 days after stopping treatment - only 5.8 μg / g. When used in a dose of 150 mg 1 time / 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.

Concentration of fluconazole in nails after 4 months of use at a dose of 150 mg 1 time / week. was 4.05 μg / g in healthy and 1.8 μg / g in affected nails; 6 months after completion of therapy, fluconazole was still detectable in the nails.

Fluconazole is excreted mainly by the kidneys; approximately 80% of the administered dose is found unchanged in the urine. The clearance of fluconazole is proportional to the CC. No circulating metabolites were found.

Prolonged T 1/2 from blood plasma allows you to take fluconazole once for vaginal candidiasis and 1 time / day or 1 time / week. with other indications.

Release form

7 pcs. - contour cell packaging (1) - cardboard packs.
7 pcs. - polymer bottles (1) - cardboard packs.
7 pcs. - polymer cans (1) - cardboard packs.
7 pcs. - dark glass jars (1) - cardboard packs.
4 things. - contour cell packaging (1) - cardboard packs.
4 things. - polymer bottles (1) - cardboard packs.
4 things. - polymer cans (1) - cardboard packs.
4 things. - dark glass jars (1) - cardboard packs.
10 pieces. - contour cell packaging (1) - cardboard packs.
10 pieces. - polymer bottles (1) - cardboard packs.
10 pieces. - polymer cans (1) - cardboard packs.
10 pieces. - dark glass jars (1) - cardboard packs.

Dosage

Individual. It is intended for oral administration and intravenous administration.

For adults, depending on the indications, treatment regimen and clinical situation, the daily dose is 50-400 mg, the frequency of use is 1 time / day.

For children, the dose is 3-12 mg / kg / day, the frequency of use is 1 time / day.

In patients with impaired renal function, the dose of fluconazole is reduced depending on the CC.

The duration of treatment depends on the clinical and mycological effect.

Interaction

With simultaneous use with warfarin, fluconazole increases prothrombin time (by 12%), and therefore may develop bleeding (hematomas, bleeding from the nose and gastrointestinal tract, hematuria, melena). In patients receiving coumarin anticoagulants, it is necessary to constantly monitor the prothrombin time.

After oral administration of midazolam, fluconazole significantly increases the concentration of midazolam and psychomotor effects, and this effect is more pronounced after taking fluconazole orally than when using it intravenously. If concomitant therapy with benzodiazepines is necessary, patients taking fluconazole should be monitored to reduce the dose of benzodiazepine accordingly.

With the simultaneous use of fluconazole and cisapride, adverse reactions from the heart are possible, incl. fibrillation / flutter of the ventricles (arrhythmia of the "pirouette" type). The use of fluconazole at a dose of 200 mg 1 time / day and cisapride at a dose of 20 mg 4 times / day leads to a pronounced increase in plasma concentrations of cisapride and an increase in the QT interval on the ECG. Concomitant use of cisapride and fluconazole is contraindicated.

In patients after kidney transplantation, the use of fluconazole at a dose of 200 mg / day leads to a slow increase in the concentration of cyclosporine. However, with repeated administration of fluconazole at a dose of 100 mg / day, changes in the concentration of cyclosporine were not observed in bone marrow recipients. With the simultaneous use of fluconazole and cyclosporine, it is recommended to monitor the concentration of cyclosporine in the blood.

Repeated use of hydrochlorothiazide simultaneously with fluconazole leads to an increase in plasma concentration of fluconazole by 40%. The effect of this degree of severity does not require a change in the dosage regimen of fluconazole in patients receiving concomitant diuretics, but this should be taken into account.

With the simultaneous use of a combined oral contraceptive with fluconazole at a dose of 50 mg, a significant effect on the level of hormones has not been established, while with a daily intake of 200 mg of fluconazole, the AUC of ethinylestradiol and levonorgestrel increase by 40% and 24%, respectively, and when taking 300 mg of fluconazole 1 time per week - AUC of ethinylestradiol and norethindrone increase 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.

Concomitant use of fluconazole and phenytoin may be clinically significant increase concentration of phenytoin. With this combination, the concentration of phenytoin should be monitored and its dose adjusted accordingly to ensure a therapeutic concentration in the serum.

Concomitant use of fluconazole and rifabutin can lead to an increase in serum concentrations of the latter. With the simultaneous use of fluconazole and rifabutin, cases of uveitis have been described. Patients receiving rifabutin and fluconazole concomitantly should be closely monitored.

The simultaneous use of fluconazole and rifampicin leads to a decrease in AUC by 25% and the duration of T 1/2 of fluconazole by 20%. In patients taking rifampicin at the same time, it is necessary to consider the advisability of increasing the dose of fluconazole.

Fluconazole, when taken simultaneously, leads to an increase in T 1/2 of oral sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide). Patients with diabetes mellitus can be co-administered with fluconazole and oral sulfonylureas, but the possibility of hypoglycemia should be taken into account.

The simultaneous use of fluconazole and tacrolimus leads to an increase in plasma concentrations of the latter. Cases of nephrotoxicity have been reported. With this combination, the patient's condition should be carefully monitored.

With the simultaneous use of azole antifungal agents 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 / day, an increase in the QT interval has not been established, however, the use of fluconazole at doses of 400 mg / day and above causes a significant increase in the plasma concentration of terfenadine. Concomitant administration of fluconazole at doses of 400 mg / day or more with terfenadine is contraindicated. Treatment with fluconazole at doses less than 400 mg / day in combination with terfenadine should be closely monitored.

With simultaneous use with fluconazole at a dose of 200 mg for 14 days, the average rate of plasma clearance of theophylline decreases by 18%. When prescribing fluconazole to patients taking high doses of theophylline, or patients with an increased risk of developing the toxic effect of theophylline, it is necessary to observe the appearance of symptoms of theophylline overdose and, if necessary, adjust the therapy accordingly.

With simultaneous use with fluconazole, an increase in zidovudine concentrations is noted, which is probably due to a decrease in the metabolism of the latter to its main metabolite. Before and after therapy with fluconazole at a dose of 200 mg / day for 15 days, patients with AIDS and ARC (AIDS-related complex) found a significant increase in the AUC of zidovudine (20%).

When zidovudine is used in HIV-infected patients at a dose of 200 mg every 8 hours for 7 days in combination with fluconazole at a dose of 400 mg / day or without it with an interval of 21 days between the two regimens, a significant increase in the AUC of zidovudine has been established (74%) with simultaneous use with fluconazole. Patients receiving this combination should be monitored for side effects of zidovudine.

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 serum concentrations of these drugs. With such combinations, the patient's condition should be carefully monitored.

Side effects

From the nervous system: headache, dizziness, convulsions, change in taste.

From the side digestive system: abdominal pain, diarrhea, flatulence, nausea, dyspepsia, vomiting, hepatotoxicity (including rare cases with fatal outcome), increased alkaline phosphatase, bilirubin, serum aminotransferase levels (ALT and AST), liver dysfunction, hepatitis, hepatocellular necrosis, jaundice ...

From the side of cardio-vascular system: increase in the QT interval on the ECG, fibrillation / flutter of the ventricles.

Dermatological reactions: rash, alopecia, exfoliative skin diseases including Stevens-Johnson syndrome and toxic epidermal necrolysis.

From the hematopoietic system: leukopenia, including neutropenia and agranulocytosis, thrombocytopenia.

From the side of metabolism: increased levels of cholesterol and triglycerides in plasma, hypokalemia.

Allergic reactions: anaphylactic reactions (including angioedema, facial edema, urticaria, itching).

Indications

Cryptococcosis, including cryptococcal meningitis and infections at other sites (eg, lungs, skin), incl. in patients with a normal immune response and in AIDS patients, organ transplant recipients and patients with other forms of immunodeficiency; maintenance therapy to prevent relapse of cryptococcosis in AIDS patients.

Generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidiasis, such as infections of the peritoneum, endocardium, eyes, respiratory and urinary tract, incl. in patients with malignant tumorswho are in the ICU and receiving cytotoxic or immunosuppressive drugs, as well as in patients with other factors predisposing to the development of candidiasis.

Candidiasis of the mucous membranes, including the mucous membranes of the oral cavity and pharynx, esophagus, non-invasive bronchopulmonary infections, candiduria, mucocutaneous and chronic atrophic oral candidiasis (associated with wearing dentures), incl. in patients with normal and suppressed immune function; prevention of recurrence of oropharyngeal candidiasis in AIDS patients.

Genital candidiasis; acute or recurrent vaginal candidiasis; prevention in order to reduce the frequency of relapses of vaginal candidiasis (3 or more episodes per year); candidal balanitis.

Mycoses of the skin, including mycoses of the feet, body, groin, pityriasis versicolor, onychomycosis and skin candidal infections.

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

Prevention of fungal infections in patients with malignant tumors predisposed to the development of such infections as a result of cytotoxic chemotherapy or radiation therapy.

Contraindications

Simultaneous use of terfenadine during repeated use of fluconazole at a dose of 400 mg / day or more; concomitant use of cisapride; hypersensitivity to fluconazole; hypersensitivity to azole derivatives with a structure similar to fluconazole.

Application features

Application during pregnancy and lactation

There have been no adequate and well-controlled studies of the safety of fluconazole in pregnant women. The use of fluconazole during pregnancy should be avoided, except in cases of severe and potentially life-threatening fungal infections, when the expected benefit of treatment exceeds possible risk for the fetus.

Women of childbearing age should use reliable contraception during treatment.

Fluconazole is determined in breast milk in concentrations close to plasma, therefore, use during lactation (breastfeeding) is not recommended.

Application for violations of liver function

Fluconazole should be used with caution in patients with severe liver dysfunction.

Application for impaired renal function

Fluconazole should be used with caution in patients with severe renal impairment. In case of impaired renal function, the dose of fluconazole should be reduced.

Application in children

Contraindicated in childhood up to 1 year.

special instructions

It is used with caution in case of violations of liver function indicators against the background of the use of fluconazole, with the appearance of a rash against the background of the use of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections, with the simultaneous use of terfenadine and fluconazole at a dose of less than 400 mg / day, with potentially proarrhythmic conditions in patients with multiple risk factors (organic heart disease, disorders electrolyte balance and concomitant therapy that promotes the development of such disorders).

The hepatotoxic effect of fluconazole was usually reversible; its signs disappeared after discontinuation of therapy. It is necessary to monitor the condition of patients whose liver function indicators are impaired during treatment with fluconazole in order to identify signs of more serious liver damage. When clinical signs or symptoms of liver damage that may be associated with fluconazole, it should be discontinued.

AIDS patients are more likely to develop severe skin reactions with many drugs. If a patient receiving treatment for a superficial fungal infection develops a rash that can be associated with the use of fluconazole, it should be discontinued. If a rash appears in patients with invasive / systemic fungal infections, they should be closely monitored and fluconazole should be discontinued if bullous lesions or erythema multiforme appear.

Concomitant use of fluconazole at doses less than 400 mg / day and terfenadine should be carefully monitored.

With the use of fluconazole, an increase in the QT interval and ventricular fibrillation / flutter have been observed very rarely in patients with multiple risk factors, such as organic heart disease, electrolyte imbalance, and concomitant therapy that contributes to the development of such disorders.

Therapy can be started pending culture and other laboratory test results. However, anti-infective therapy needs to be adjusted accordingly when the results of these studies become known.

There have been reports of cases of superinfection caused by strains of Candida other than Candida albicans, which often do not show sensitivity to fluconazole (for example, Candida krusei). In such cases, alternative antifungal therapy may be required.

Part preparation in the form of capsules contains 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, inside contains white or yellowish granular powder. Contained in blisters, which are placed in cardboard boxes. Also produced are Fluconazole tablets, syrup, gel, suppositories, solution for the introduction of Fluconazole IV.

pharmachologic effect

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

There is a specific effect on fungal enzymes, which depend on cytochrome P450 ... The active substance demonstrates activity against a variety of strains Candida spp. (including effective for 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 remedy pauses 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 demonstrate antiandrogenic activity.

Pharmacokinetics and pharmacodynamics

Wikipedia testifies that after oral administration, the agent is actively absorbed in the human gastrointestinal tract. In plasma, the concentration level of the active substance is more than 90% of the level that is observed if practiced intravenous route application. 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 half-life from the blood is 30 hours. That is, you can take the remedy once a day. When vaginal candidiasis a single dose of the drug is enough, for which one tablet or another form of the drug is used.

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

It penetrates into all fluids in the body. It is 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 the pharynx, mouth, 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 re-manifestation of vaginal candidiasis (in the event that the disease develops three times a year), candidal balanitis ;
• cryptococcal infection, cryptococcal meningitis ;
• dermatomycosis (including mycoses of the body, feet, groin area);
• deep endemic mycoses ;
• prevention of development fungal infections in people who have received cytostatic or radiation therapy.

Contraindications

There are such contraindications for the use of this medication:

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

It must be taken with caution in liver failure, also renal failure, when a rash appears in people suffering from a superficial fungal infection, with potentially proarrhythmogenic conditions in people with risk factors (organic heart disease, taking medications that provoke the development of , 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 such side effects:

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

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

Application instruction of Fluconazole (Way 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.

Patients with disseminated candidiasis, candidemia on the first day, 400 mg is prescribed, then the dose must be reduced to 200 mg. Children for the purpose of treatment generalized candidiasis shows a daily intake of 6–12 mg per 1 kg of body weight.

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

To people suffering atrophic candidiasis of the oral mucosa , shown at 50 mg once a day. Treatment is combined with local denture treatments. When treating other candidal infections of the mucous membranes, 50-100 mg per day are prescribed, the period of therapy is from 14 to 30 days.

In order to prevent the development of relapses oropharyngeal candidiasis in people with, 150 mg is shown once a week. 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 your child a double dose.

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

To people suffering infectious diseases skin , it is recommended to prescribe 150 mg once a week or drink 50 mg of the drug once a day. Treatment should be continued for 2-4 weeks. For men and women who are sick mycosis of the feet , 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 fluconazole dose in the third week. It is possible to use another treatment regimen - 50 mg once a day, the period of therapy is two to four weeks.

Sick onychomycosis appoint 150 mg once a week. The therapy should be continued until a healthy one grows on the site of the diseased nail.

People suffering deep endemic mycosis , sometimes they undergo a long course of drug treatment, which can last up to two years. The daily dose is 200-400 mg.

Instructions for the use of fluconazole when it provides that for vaginal candidiasis, a single dose of the drug is carried out, its dose is 150 mg.

As a rule, Fluconazole is effective for thrush 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. When chronic thrush Fluconazole Teva or other types of the drug are prescribed to prevent relapses at a dose of 150 mg once a month. You need to apply the product for 4-12 months. For the purpose of prophylaxis, capsules are prescribed at a dose of 50-400 mg once a day, depending on how high the risk of the disease is. For children from thrush Fluconazole tablets are prescribed in a dose of 3–12 mg of the drug per 1 kg of body weight per day. How much to drink depends on the severity of the infection.

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

If treatment is prescribed at the same time Astemizole , Cisapride , Tacrolimus , or any other drug that is metabolized by the cytochrome P450 system, an increase in the concentration of these drugs in the blood is possible.

Fluconazole absorption is not affected by simultaneous administration or antacids.

Terms of sale

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

Storage conditions

Store Fluconazole suppositories, Fluconazole ointment, cream, tablets and capsules in a dark place, drugs should be protected from the sun's rays.

Shelf life

special instructions

If liver dysfunctions are noted in the course of treatment, constant monitoring by a doctor is important. If there are signs of liver damage, the medication should be discontinued.

When applying the medicine topically for men and women, it should be borne in mind that people with AIDS often develop a variety of skin reactions.

It should be taken into account not only how much fluconazole acts, but also the fact that with premature termination of treatment, relapses may develop. Therefore, it is important to complete the prescribed treatment regimen completely. 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? It should be borne 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

Matching ATX level 4 code:

Fluconazole analogs are drugs with a similar active ingredient. The price of analogues depends on the manufacturer, the form of the drug release There are a number of analogues of this drug: Diflucan , Vero-Fluconazole , Flucostat , Fluconazole Tiwa , 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 in the form of tablets of 50 mg, 100 mg, 150 mg, as well as in 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 drug. What is the difference between these drugs, and which one is optimal to prescribe in a particular case, is determined by a specialist. As a rule, Fluconazole is more often prescribed when prophylaxis is required for cancer patients after radiation and chemotherapy.

Fluconazole or Nystatin - which is better?

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

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

When 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 in 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 of Fluconazole

Due to the high fungicidal activity of this drug, patient reviews and doctors' reviews about Fluconazole are mostly positive. Patients leaving feedback on Fluconazole Tevaas well as reviews about 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 tablets are relatively inexpensive, but at the same time they can completely get rid of nail fungus and other unpleasant diseases. Moreover, in some cases, it is enough to take Fluconazole 150 mg once to completely overcome the symptoms of diseases.

Very often women write positive reviews about Fluconazole when thrush ... It is noted that the medicine not only relieves thrush, but also helps prevent relapse 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 20 to 170 rubles. Capsules 150 mg (in a package of 1 pc.) Can be bought for an average of 30 rubles. 50 mg capsules can be purchased at a price of 30 rubles (7 pcs in a package). The cost of Fluconazole Teva 150 mg is 150-170 rubles per pack. (1 PC.).

The price of Fluconazole in Ukraine (Odessa, Kiev, etc.) is 17-20 hryvnia (capsules 100 mg, 7 pcs.). The price of Fluconazole 150 mg in Kharkov, Zaporozhye, Dnepropetrovsk, etc. - on average 10 hryvnia (in a package of 1 pc.). 150 mg tablets can be bought in Ukraine for an average of 20 hryvnia.

How much do thrush tablets cost in Kazakhstan, in Belarus, depends on the packaging, 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.

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

• Online pharmacies in RussiaRussia
• Online pharmacies of UkraineUkraine
• Internet pharmacies in KazakhstanKazakhstan

ZdravCity

Fluconazole caps. 150mg No. 4Vertex AO

Fluconazole capsules 150mg No. 1 CanonpharmKanonfarma Production CJSC

Fluconazole capsules 150mg No. 1 Production of medicinesProduction of medicines LLC

Fluconazole capsules 50mg No. 7 VertexVertex AO

Fluconazole-obl caps. 150mg No. 2JSC Obolenskoe Pharm. company

But also pathogenic fungi. In the event of fungal diseases, treatment is carried out using appropriate medications. One of the most effective antifungal agents is Fluconazole.

The substance Fluconazole is a Triazole derivative. The main property of this component is the ability to suppress the production of mycosterols contained in pathogenic fungi. Due to this, the drug is characterized by a pronounced antifungal effect. It is active against various groups of fungi, and therefore has a wide range of applications.

The drug is available in the form for oral administration and solution for intravenous use... Pharmacological and pharmacokinetic properties of different forms of Fluconazole do not differ. The medicine is available in 50 mg and 150 mg both in tablets and ampoules.

The active components of the drug are characterized by high absorbency. The bioavailability level is more than 90%, which affects the degree of effectiveness. Allowed to be consumed simultaneously with food, as this does not affect the absorption process. The maximum concentration in the blood is observed 30-90 minutes after ingestion.

Fluconazole has a low level of binding to. In this case, the active components of the drug are able to freely penetrate into all fluids inside the body, including saliva, phlegm. The concentration in these fluids is similar to the concentration in blood plasma.

A high concentration of Fluconazole is noted in the dermal layers, as well as in sweat. The accumulation of components occurs in the stratum corneum. Excretion from the body is carried out with (about 80%).

Overall, Fluconazole is an antifungal agent wide range action characterized by high level bioavailability and good absorption.

Indications and contraindications for taking Fluconazole

Due to its ability to suppress fungal activity, Fluconazole can be used for almost any fungal disease. Depending on the method of administration and dosages, it is used as an independent or auxiliary agent as part of complex drug therapy.

Indications for admission:

1. Cryptococcosis. A disease caused by pathogenic yeast cells, most often affecting the upper airways... It is most often observed in people with reduced immune properties of the body, mainly in men. If untreated, cryptococcosis causes complications in the form of meningoencephalitis. The main symptoms are intense in the back of the head, impaired consciousness, paralysis.





• Individual hypersensitivity to Fluconazole or other substances that make up the drug
• Age limit (up to 16 years old)
• Concomitant use of drugs containing Terfenadine
• Severe liver dysfunctions
• Late stages of renal failure
• Simultaneous reception with alcohol
• Diseases of the cardiovascular system
• Hormonal disorders

Contraindicated for use during pregnancy. Taking the drug can provoke pathological changes in the fetus, which will lead to the development congenital anomalies... In particular, cases of deformation of the facial part of the skull, developmental disorders of the musculoskeletal system, congenital heart muscle defects are described.

Rarely, early fluconazole may be used if the intended benefit outweighs potential harm for the body of the mother or child. In this case, the maximum dose of the drug is 150 mg, which is taken once.

During the period of breastfeeding, it is not recommended for admission due to its high penetrating ability. The concentration of the active substance in breast milk and blood plasma is almost identical, which is why ingestion of a child can provoke an overdose, severe poisoning with a high probability of death.

Fluconazole is used as part of a complex antifungal therapy or as an independent agent. Before taking it, you must read the list in order to prevent negative consequences for the body.

Method of drug administration

The flunazole regimen differs depending on the type of disease and the age of the patients. The drug can be taken orally in tablet form or intravenously using a solution. The dosage for different forms of release does not differ.



Due to the fact that the drug is characterized by a pronounced antifungal activity and a long period of elimination from the body, it is enough to take 1 dose per day. The dosage ranges from 200-400 mg per day, and depends on the severity of the disease. The duration of the course of treatment is from 7 to 30 days.

Reception is categorically contraindicated in children under 1 year old. At the age of 1-16 years, the use of Fluconazole can be carried out only in case of fungal diseases that can provoke irreversible for the body or death. In this case, the dosage is no more than 50-100 mg 1 time per day.

Application for various diseases:

• Lichen. For the treatment of pityriasis versicolor, small doses of fluconazole are used. The course of treatment is 14 days. You need to take 50 mg of the drug daily, that is, one tablet.
• Dermatomycosis. For deep cutaneous lesions, it is necessary to take from 200-400 mg daily. Diseases from this group, as a rule, do not respond well to treatment, and therefore the duration of use of Fluconazole can be up to two years. The course of treatment lasts up to 30 days with minor interruptions for diagnostic procedures in order to assess the effectiveness and prevent the negative consequences of admission.
• Cryptococcal meningitis. On the first day after the diagnosis, the patient is prescribed 400 mg of Fluconazole. On the following days, the daily dosage varies from 200 to 400 mg. The duration of drug therapy is determined depending on the clinical effect. The maximum admission period for meningitis is 8 weeks.
• Prevention of fungal diseases. For preventive purposes, Fluconazole is used no more than 1 time per week. If you have a history of illness, you need to take 100 mg of the drug (2 tablets) to prevent recurrence. In the absence of cases of fungal diseases, it is sufficient to take 1 tablet (50 mg) weekly.

Fluconazole treatment is effective only if the prescribed dosages are observed and the specialist is observed.

Application for thrush

Fluconazole is the main medication treatment of candidiasis. This disease is provoked by yeast-like fungi that affect the mucous membranes of the external genital and internal organs. The development of thrush occurs with a significant increase in the number of fungal organisms.






Exists various analogues Fluconazole, used as a replacement for this drug in the treatment of fungal diseases.

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Classmates

Antifungal drug. Effectively suppresses the vital activity of many types of fungi, including malignant neoplasms. Dispensed according to the recipe.

Diseases for which fluconazole is used

• Generalized candidiasis.
• Cryptococcosis. Including as part of maintenance therapy in the treatment of AIDS.
• Candidiasis of the mucous membranes.
• Prevention of fungal infections in malignant neoplasms.
• Genital candidiasis. Treatment and prevention to reduce the risk of relapse.
• Deep endemic mycosis, paracoccidioidomycosis, coccidioidomycosis, histoplasmosis, sporotrichosis.
• Skin fungal infections.

Fluconazole varieties

Capsules:

• 50 mg AB (active substance).
• 100 mg AB.
• 150 mg AB.
• 200 mg AB.

Suspension:

Infusion solution:

Side effects of fluconazole

• Nervous system. Convulsions, dizziness, headache.
• Digestive system. Nausea, vomiting, pain in the stomach, dyspepsia, flatulence, diarrhea, digestive disorders.
• Skin. Hyperemia, rash, toxic epidermal necrolysis, alopecia, Stevens-Johnson syndrome.
• The cardiovascular system. Paroxysmal ventricular tachycardia, prolongation of the QT interval.
• Hematopoietic system. Granulocytosis, neutropenia, leukopenia, thrombocytopenia.
• Liver and gallbladder. Hepatic failure, toxic liver damage, hepatocellular necrosis, hepatitis, jaundice, increased aspartate aminotransferase levels, alkaline phosphatase, alanine aminotransferase, bilirubin.
• Others. Hypertriglyceridemia, hypercholesterolemia, deterioration of taste, hypokalemia.

Contraindications for fluconazole

• Age up to 5 years (for injections - up to 16 years).
• Hypersensitivity.
• Pregnancy, lactation.
• Simultaneous reception of terfenadine (with a dosage of fluconazole more than 400 mg / day) and cisapride.

Reception with extreme caution:

• Impaired digestibility of lactose.
• Concomitant use of terfenadine (when the dosage of fluconazole is more than 400 mg / day, the combination with terfenadine is contraindicated).
• Elevated liver enzymes.
• Renal failure

Fluconazole during pregnancy

During pregnancy, taking the drug is permissible only if the benefits outweigh the potential harm to the fetus. Fluconazole passes into breast milk. If necessary, treatment during lactation is recommended to refuse breastfeeding.

Pharmacological properties of the drug Fluconazole

Antifungal agent of the triazole class. Fluconazole has a pronounced antifungal effect, specifically inhibits the synthesis of fungal sterols. Has a specific effect on fungal enzymes dependent on cytochrome P450. Active against various strains Candida spp. (including visceral candidiasis), Cryptococcus neoformans Microsporum spp. and Trichophytum spp. Fluconazole is active against the causative agents of endemic mycoses: Blastomyces dermatitidis, Coccidioides immitis (including intracranial infections), Hystoplasma capsulatum.
After oral administration, it is well absorbed into digestive tract; the concentration in the blood plasma exceeds 90% of the concentration level achieved with the on / in the introduction. Food intake does not affect the absorption of fluconazole. The maximum concentration in blood plasma is reached within 0.5-1.5 hours after ingestion. The half-life of the drug from blood plasma is 30 hours, which allows using the drug once a day during the course of treatment with fluconazole and provides a therapeutic effect in vaginal candidiasis after a single dose of the drug. The concentration of the active substance in the blood plasma is directly proportional to the dose taken. 11-12% of fluconazole binds to blood plasma proteins.
With a single daily dose of fluconazole on days 4–5, a stable plasma concentration is achieved in 90% of patients. When a shock (double daily) dose is administered on the 1st day of treatment, the above effect is achieved by the 2nd day of treatment.
The pharmacokinetics of fluconazole for intravenous administration is similar to that for oral administration.
Fluconazole penetrates well into all body fluids. In the cerebrospinal fluid, the concentration of fluconazole reaches 80% of the level of its concentration in blood plasma.
Fluconazole is excreted from the body in the urine, and 80% is excreted unchanged. Fluconazole clearance is directly proportional to creatinine clearance.

Indications for the use of the drug Fluconazole

Infections caused by candidiasis, including generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidiasis (infections of the peritoneum, endocardium, eyes, respiratory and urinary tract); candidiasis of the mucous membranes, including the oral cavity and pharynx, esophagus; non-invasive bronchopulmonary infections; candiduria; mucocutaneous and chronic atrophic candidiasis of the oral mucosa (associated with wearing dentures); genital candidiasis - vaginal candidiasis (acute or recurrent), prevention of recurrence of vaginal candidiasis (with an incidence of 3 times or more per year), as well as candidal balanitis.
Flucanosol is used for cryptococcal meningitis and cryptococcal infections of other localization; dermatomycosis, including mycoses of the feet, body, groin, pityriasis versicolor; onychomycosis; deep endemic mycoses, including coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis; as well as for the prevention of fungal infections in patients receiving cytostatic or radiation therapy.

Application of the drug Fluconazole

Inside or in / in infusion at a rate of no more than 10 ml / min; the choice of route of administration depends on clinical condition sick. When replacing intravenous administration with oral administration of the drug or, conversely, changes in the daily dose are not required. It depends on the nature and severity of the course of the fungal infection. The duration of treatment depends on the clinical and mycological effect. The daily dose for children should not exceed that for adults. Fluconazole is used daily 1 time per day.
For candidemia, disseminated candidiasis and other invasive candidal infections, the dose is usually 400 mg on the 1st day, and then 200 mg / day. Depending on the severity of the clinical effect, the therapy can be prolonged and the dose increased to 400 mg / day. For the treatment of generalized candidiasis, the dose of fluconazole for children is 6–12 mg / kg per day, depending on the severity of the disease.
With oropharyngeal candidiasis, adults are usually prescribed 50-100 mg of fluconazole 1 time per day for 7-14 days. In patients with severe suppression of immunity, treatment, if necessary, is continued for a longer time. In case of atrophic candidiasis of the oral mucosa caused by wearing dentures, the drug is usually prescribed at a dose of 50 mg once a day for 14 days in combination with local antiseptic agents for processing the denture. For other candidiasis infections of the mucous membranes (with the exception of genital candidiasis, such as esophagitis, non-invasive bronchopulmonary infections, candiduria, candidiasis of the skin and mucous membranes, etc.), the effective dose is usually 50-100 mg / day with a duration of treatment of 14-30 days. For the prevention of recurrence of oropharyngeal candidiasis in AIDS patients, after the completion of the course of primary therapy, fluconazole is prescribed at a dose of 150 mg once a week. For candidiasis of the mucous membranes, the recommended dose of fluconazole for children is 3 mg / kg / day. On the 1st day, a loading dose of 6 mg / kg can be prescribed to more quickly achieve a stable equilibrium concentration.
For vaginal candidiasis, fluconazole is taken once orally at a dose of 150 mg. To reduce the frequency of relapses of the disease, the drug is taken at a dose of 150 mg once a month. The duration of therapy is determined individually; it varies from 4 to 12 months. In some cases, the frequency of receptions is increased. With balanitis caused Candida, fluconazole is prescribed as a single oral dose of 150 mg.
For the prevention of candidiasis, the recommended dose of fluconazole is 50–400 mg once a day, depending on the degree of risk of developing a fungal infection. In the presence of a high risk of generalized infection, for example, in patients with suspected severe or long-term neutropenia, the recommended dose is 400 mg 1 time per day. Fluconazole is prescribed several days before the expected appearance of neutropenia; after an increase in the number of neutrophilic granulocytes more than 1000 per 1 mm3, treatment is continued for another 7 days. For children, fluconazole is prescribed at 3–12 mg / kg / day, depending on the severity and duration of the persistence of induced neutropenia.
With cryptococcal meningitis and cryptococcal infections of other localization, 400 mg is usually prescribed on the 1st 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 clinical and mycological effect achieved; with cryptococcal meningitis, it is usually continued for at least 6-8 weeks. For the prevention of recurrence of cryptococcal meningitis in AIDS patients (after completion of the course primary treatment) therapy with fluconazole at a dose of 200 mg / day can be continued for a sufficiently long period. In the treatment of cryptococcal infection, the recommended dose of fluconazole for children is 6–12 mg / kg per day, depending on the severity of the disease.
For skin infections, including mycoses of the feet, smooth skin, groin area, 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, but with mycosis of the feet, longer treatment (up to 6 weeks) may be required. With pityriasis versicolor, the recommended dose is 300 mg once a week for 2 weeks; some patients need a third dose of fluconazole - 300 mg, while in some cases a single dose of 300-400 mg of the drug is sufficient. An alternative treatment regimen is the use of the drug at a dose of 50 mg 1 time per day for 2-4 weeks. For onychomycosis (tinea unguium), the recommended dose is 150 mg once a week. Treatment should be continued until the affected nail is completely replaced with a healthy one. Regrowth of nails on fingers and toes usually takes 3–6 and 6–12 months, respectively, but the growth rate of nails can vary widely in different peopleas well as depending on age. After successful treatment of difficult to treat chronic infections, the shape of the nails is sometimes observed.
With deep endemic mycosis, long-term (up to 2 years) use of the drug at a dose of 200-400 mg / day may be required. The duration of therapy is determined individually; usually it is 11-24 months with coccidioidomycosis, 2-17 months - with paracoccidioidomycosis, 1-16 months - with sporotrichosis and 3-17 months - with histoplasmosis.
In newborns, fluconazole is excreted slowly. In the first 2 weeks of life, the drug is prescribed in the same dose as for older children, but with an interval of 72 hours. For children aged 2-4 weeks, the same dose is administered with an interval of 48 hours.
In the elderly, in the absence of signs of renal failure, the drug is used in the usual dose. For patients with renal insufficiency (creatinine clearance 11-50 ml / min), the initial loading dose is 50-400 mg, the daily dose of fluconazole for subsequent injections is reduced by 2 times. Patients who are constantly on dialysis receive fluconazole after each dialysis session.

Contraindications to the use of the drug Fluconazole

Hypersensitivity to fluconazole or azole compounds close to it in chemical structure; concomitant use of terfenadine in patients receiving fluconazole therapy at a dose of 400 mg / day or higher.

Fluconazole side effects

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

Special instructions for the use of the drug Fluconazole

patients whose liver function parameters are impaired during treatment with fluconazole should be under medical supervision. If clinical signs of liver damage appear, fluconazole should be discontinued.
AIDS patients are more likely to develop severe skin reactions with many drugs. When a rash appears in a patient receiving treatment for a superficial fungal infection, which may be caused by the use of fluconazole, the drug should be canceled. When a rash appears in patients with invasive / systemic fungal infections, their condition should be monitored, with the development of bullous lesions or polymorphic erythema, fluconazole is canceled.
The use of fluconazole in pregnant women should be avoided, except in cases of severe and potentially life-threatening fungal infections, when the intended benefit to the woman outweighs the potential risk to the fetus. Fluconazole is detected in breast milk at the same concentration as in the blood, therefore its use during breastfeeding is not recommended.

Fluconazole drug interactions

Simultaneous administration of warfarin and fluconazole increases prothrombin time; fluconazole and oral hypoglycemic drugs of the sulfonylurea group of derivatives (chlorpropamide, glibenclamide, glipizide and tolbutamide) - lengthens their half-life (the possibility of hypoglycemia should be taken into account); fluconazole and phenytoin - clinically significantly increases the concentration of phenytoin (monitoring of concentration and dose selection is necessary).
Repeated use of hydrochlorothiazide increases the plasma concentration of fluconazole, but changes in the dosage regimen of fluconazole are usually not required.
Fluconazole at a dose of 50-200 mg does not significantly affect the effectiveness of combined oral contraceptives.
The simultaneous use of fluconazole and rifampicin led to a decrease in AUC by 25% and the half-life of fluconazole by 20%. In patients using the specified combination of drugs, it is necessary to consider the advisability of increasing the dose of fluconazole.
During the use of fluconazole, it is recommended to monitor the concentration of cyclosporine in the blood.
When treating with fluconazole in patients receiving high doses of theophylline, or in patients with an increased risk of theophylline toxicity, it is necessary to control the symptoms of theophylline overdose; when they appear, therapy should be changed accordingly.
Given the occurrence of severe arrhythmias due to lengthening of the interval Q – T, in patients receiving azole antifungal agents in combination with terfenadine, concomitant administration of fluconazole at a dose of 400 mg / day or higher with terfenadine is contraindicated. Treatment with fluconazole at a dose below 400 mg / day in combination with terfenadine must be carried out under the strict supervision of a physician.
With the simultaneous use of fluconazole and cisapride, adverse reactions from the cardiovascular system are possible, including paroxysms ventricular tachycardia.
The condition of patients who are prescribed a combination of fluconazole and zidavudine should be monitored for early detection of side effects of zidavudine, the AUC of which in this case increases significantly.
The use of fluconazole in patients simultaneously receiving cisapride, astemizole, rifabutin, tacrolimus or others medicines, metabolized by the cytochrome P450 system, may be accompanied by an increase in the concentration of these drugs in the blood serum.
Concomitant administration of cimetidine or antacids does not have a clinically significant effect on the absorption of fluconazole.
Fluconazole for intravenous administration is compatible with the following solutions: 20% glucose solution, Ringer's solution, Hartmann's solution, potassium chloride solution in glucose, 4.2% sodium bicarbonate solution, aminofusine, 0.9% sodium chloride solution.

Fluconazole overdose, symptoms and treatment

Manifested by hallucinations and paranoid behavior. Treatment is symptomatic (including supportive therapy and gastric lavage). Fluconazole is excreted mainly in the urine, so forced diuresis can accelerate the elimination of the drug. A hemodialysis session lasting 3 hours reduces the plasma level of fluconazole by about 50%.

Fluconazole is a fairly serious antifungal drug that has a number of possible side effects, contraindications and drug interactions... Refers to prescription drugs, i.e. can only be prescribed by a doctor, taking into account the individual characteristics of the patient and the disease.

The severity of side effects does not depend on the route of administration of the drug, but on the dose per kg of body weight per day.

Pharmacokinetic properties of fluconazole

It is perfectly absorbed from the intestines (bioavailability is more than 90%), food intake does not affect absorption. The maximum concentration in the blood appears within an hour after administration. Penetrates into all tissues, including the brain. It is excreted by the kidneys (mainly). Partially affects hormones in men.

Studies of the effect of the drug on pregnant women

High doses of fluconazole have a negative effect on weight gain in rabbits and increase the frequency of miscarriages. This applies to dosages similar to 20 times therapeutic dose for a person. With adequate weight of the animals, the amounts of fluconazole administered, no negative effects on the part of the fetus or mother were detected. The existing negative effects when prescribing high doses are attributed to the moderate effect of the drug on the hormonal background.

For pregnant women, fluconazole is indicated only for severe infections that threaten the life of the mother and / or fetus. Responsibility can only be assumed by the attending physician, with a clear comparison of the risks and the expected effect. There are no direct studies of the use of fluconazole in pregnant and lactating women.

There is evidence of developmental abnormalities in children whose mothers were treated with sufficiently high doses of the drug (for severe fungal diseases), although a direct connection between these facts has not been proven. According to FDA standards, the risk of exposure to the fetus is assessed as C, i.e. conjectural.

Breastfeeding should be discontinued during maternal therapy. fluconazole is found in breast milk in the same concentrations as in the blood (as already mentioned, it perfectly penetrates into all liquids).

Direct contraindications to the appointment

Individual intolerance to the active substance or components dosage form; Simultaneous appointment with terfenadine; Combination with quinidine, cisapride, astemizole.

Side effects of the remedy

In the USA, a rather serious study was carried out on 448 patients who took fluconazole at a standard therapeutic dosage, i.e. 150 mg once for the treatment of vaginal candidiasis (thrush). Every fourth person, while taking the drug, had the following side effects:

13% headache; 7% nausea; 6% abdominal pain; 3% diarrhea; 1% dyspepsia; 1% dizziness; 1% violation of taste perception.

The rest felt some weakly differentiated negative sensations. In isolated cases, fluconazole causes a pronounced allergic reaction.

In a larger study (4048 patients), the incidence of complications was observed when fluconazole was combined with other drugs and diseases. The worst combination of fluconazole with cytostatics in HIV patients. The main side effects were the same as in the first group of subjects.

Effect of fluconazole on the liver (hepatotoxicity)

Sometimes fluconazole causes serious complications from the liver, up to and including death. When the drug is discontinued, the symptoms of liver damage subside. For this reason, with long courses of treatment with fluconazole, the doctor should periodically prescribe liver tests (AST, ALT, etc.).

In severe cases, the hepatotoxic effect is manifested in the form of hepatitis, impaired bile outflow (cholestasis), acute liver failure. All these sad outcomes were observed mainly in HIV patients, malignant neoplasms, severe forms of tuberculosis.

Perhaps this is due to the concurrent use of heavy specific antibiotics: isoniazid, rifampicin, phenytoin, pyrazinamide.

Side effects, sometimes observed while taking the drug

A side effect differs from a side effect in that the relationship between what happened with the intake of a specific drug has not been proven. Nevertheless, manufacturing companies are obliged to record everything that happens to the patient (control group) during treatment, and to include this in the instructions:

Convulsions; Skin rashes, Stevenas-Johnson syndrome, toxic skin lesions (epidermal necrolysis); Exfoliative dermatitis in patients with AIDS and malignant tumors; Violation of the composition of the cellular elements of the blood: leukopenia (decrease in the number of leukocytes), thrombocytopenia (decrease in the number of platelets);

Fat metabolism disorders: increased cholesterol levels (hypercholesterolemia), triglycerides;

Decreased potassium levels.

Side effects from taking fluconazole in children

The studies were conducted in the United States and Europe and included 577 children from one day to 17 years old inclusive. The dosage for all was 15 mg / kg bw / day for an extended period. In total, side effects were identified in 13% of cases:

5.4% vomiting; 2.8% abdominal pain; 2.3% nausea; 2.1% diarrhea.

In 2.3%, treatment was discontinued due to severe side effects.

Interaction with other medications

Increases the half-life of sugar-reducing tablets (sulfonylurea-based), which can lead to hypoglycemia. Those. at diabetes insipidus the elderly - hypoglycemic drugs are much stronger; Slows down the excretion of theophylline and zidovudine, saquinavir, increases the concentration of sirolimus, which may require an additional titer of the dose of these substances; Increases the concentration of cytostatics, which is important for patients with transplanted internal organs; In combination with anticoagulants (clexane, rivaroxaban, warfarin), it can provoke different types bleeding. If a sign of any bleeding is found while taking fluconazole, the drug is immediately canceled; When combined with hydrochlorothiazide, which is part of many drugs for pressure (Enap-N, etc.), the concentration of fluconazole increases sharply (one and a half times), which must be taken into account, since the risks of side effects also increase, incl. renal failure; Increases the toxicity of drugs of the NSAID group - diclofenac, meloxicam, naproxen, etc. Given that all these drugs are routine (and many are over-the-counter), the patient should exercise increased caution when using NSAIDs during treatment with fluconazole; May cause cardiac arrhythmias when combined with quinidine, cisapride, astemizole and other antifungal agents; May cause renal failure when taken with tacrolimus; When combined with midazolam, it can cause mental abnormalities; Enhances the action of amitriptyline.

The drug can be harmful under the following conditions

Overdose and first aid

The main symptoms: diarrhea, nausea up to vomiting, there may be convulsions.

Skin rashes

Treatment: gastric lavage with parallel administration of diuretics. Hospitalization is required. An admitted patient is sent for a three-hour hemodialysis (allows to reduce the concentration of the drug by almost 50%), otherwise the doctors act according to the circumstances, depending on the type of interaction. As a rule, a similar situation occurs in an elderly patient with a large number of concomitant prescriptions.

There is information about one patient who, with an overdose of fluconazole, gave a clinic of paranoid delusions and hallucinations. Considering that it was a 42-year-old HIV patient (drug addict), such side effects may not be considered typical for overdose.

If you or your loved ones have been prescribed fluconazole for a long course, try to eliminate the risk of drug interactions, carefully listen to the recommendations of your doctor, do not use during this period alcoholic drinks... Particular attention should be paid to elderly relatives who are taking many different drugs at the same time, as this significantly increases the risk of side effects while taking fluconazole.

Video about the consequences of six-month fluconazole therapy

Therapist of the city polyclinic. Eight years ago she graduated from Tver State Medical University with honors.

In general, fluconazole is well tolerated - both with intravenous and oral administration... In some cases, when taking the drug, changes in the functioning of the kidneys and liver were observed - mainly in patients with such serious underlying diseases as AIDS and cancer. The clinical significance of such changes and their relationship with fluconazole intake is still unclear.

In clinical trials, side effects were observed in 26% of patients who took one dose of fluconazole during the course of treatment. Among patients taking drugs similar in properties, side effects were noted in 16% of cases. The most common side effects in female patients who took single dose fluconazole (150 mg) for the treatment of vaginal infections, there were headaches, nausea and abdominal pain. In most cases, the side effects were mild to moderate.

Some side effects appeared in 16% of patients taking more than one dose of fluconazole. Side effects were more common in HIV-positive patients than in people not infected with HIV (21% and 13%, respectively). At the same time, the nature of side effects in both groups of patients was almost the same.

From the nervous system

In rare cases, seizures began in patients taking fluconazole, although it was not possible to establish a direct relationship between the drug and this side effect. However, it should be borne in mind that convulsions are possible after taking at least 100 mg of fluconazole. Other side effects from the nervous system are dizziness, headaches (observed in about 13% of cases), paresthesia, insomnia, drowsiness, tremors.

Side effects from the gastrointestinal tract

Among the side effects from the gastrointestinal tract in patients taking fluconazole, nausea (approximately 7% of patients), abdominal pains are observed Abdominal pain: types and symptoms (6%), diarrhea (3%), vomiting (1.7%) , dyspepsia (1%), taste disturbances (1%), lack of appetite and general abdominal discomfort.

Liver side effects

Side effects in this category include disorders such as hepatitis Hepatitis - the scourge of our time, cholestasis and liver failure, which can sometimes lead to the death of the patient. There have also been cases of liver necrosis. Fatal liver dysfunctions have been observed extremely rarely, and have been observed mainly in patients with AIDS or cancer. As a rule, these patients were taking several medications at the same time, and it is impossible to say with certainty whether the development of severe complications was associated precisely with taking fluconazole. A case is known when an AIDS patient developed acute liver necrosis approximately three weeks after starting fluconazole administration.

An increase in the level of transaminase in the blood was also observed in patients with severe diseases who took, in addition to fluconazole, other drugs during the course of treatment, mostly hepatotoxic.

In patients without severe underlying diseases, temporary liver dysfunctions were observed. In all these cases, liver function returned to normal soon after the patients stopped taking fluconazole.

Dermatologic side effects

The most common dermatological side effects of fluconazole are skin rash (which occurs in about 1.8% of patients taking this medication) and hair loss that stops after treatment ends. In some cases, exanthematous pustulosis also develops and more intense sweating begins.

Hair loss is most common in people who have been taking fluconazole for two months or more.

In patients with severe illnesses, serious disorders affecting the skin may develop while taking the drug; in very rare cases, as a rule, in combination with the influence of other factors, they lead to the death of the patient.

Hypersensitivity

In clinical trials, a fifty-two-year-old female patient who took a single dose of fluconazole (400 mg) developed drug-fixated erythema. Within 12 hours after taking the drug, three oval, painful spots appeared on her torso, each with a diameter of 3-4 cm. The diagnosis was confirmed when the patient was given another 25 mg of the drug. Fixed drug erythema is just one example of how drug hypersensitivity can manifest.

In much more rare cases, patients with hypersensitivity can develop side effects such as anaphylactic shock and angioedema. In addition, the development of exfoliative dermatitis and a significant decrease in blood pressure are possible.

Side effects from the cardiovascular system

In most cases, side effects in this category when taking fluconazole occur in patients with additional risk factors, such as structural heart disease and electrolyte disturbances. Many of them have also taken drugs that can contribute to cardiovascular problems. The most common cardiovascular side effects are palpitations of the heart and prolongation of the QT interval.

Hematologic side effects

Cases are known when patients developed anemia, eosinophilia, leukopenia, neutropenia while taking fluconazole. Neutropenia - immunity under attack and thrombocytopenia. Typically, these patients had severe fungal infections or other serious illnesses.

Spontaneous development of anemia was most often observed in patients over the age of 65 years, however, in normal elderly people anemia occurs much more often than in people under 65 years of age. It is not yet clear whether there is a direct link between the development of anemia and taking fluconazole.

Kidney side effects

A fifty-eight-year-old woman in a clinical trial with a history of hypertension and cervical cancer Cervical cancer: Possible cure, developed membrane nephropathy while taking fluconazole. The patient presented with generalized edema, nausea, and indigestion; these symptoms persisted for three weeks. In addition to fluconazole, she took amlodipine, hydrochlorothiazide, metoclopramide, and levosulpiride. After the patient stopped taking fluconazole, she was in remission.

Cases of acute renal failure were most often observed among patients over the age of 65 years taking fluconazole. However, this disorder is generally more common in elderly people, so it cannot be said with certainty that it is associated with taking fluconazole.

Metabolic side effects

Among the metabolic side effects of fluconazole were hypercholesterolemia, hypertriglyceridemia and hypokalemia.

Side effects from the musculoskeletal system

Some patients taking fluconazole complained of back pain and joint pain, as well as stiff finger joints. Somewhat less often, when taking fluconazole, muscle pain... The relationship between taking this medication and the occurrence of such side effects has not yet been established.

Other side effects

In addition to the above side effects, fluconazole can cause fever, weakness, general malaise, and asthenia.

Request immediately medical helpif you develop any of the following signs of an allergic reaction to fluconazole: extensive skin rash, difficulty breathing, swelling on the face, tongue, lips, swelling of the throat. You should consult your doctor as soon as possible if fluconazole has caused symptoms such as lack of appetite, jaundice (yellowish skin and whites of the eyes), flu-like symptoms, and seizures.

Fluconazole is a fairly serious antifungal drug that has a number of possible side effects, contraindications and drug interactions. Refers to prescription drugs, i.e. can only be prescribed by a doctor, taking into account the individual characteristics of the patient and the disease.

The severity of side effects does not depend on the route of administration of the drug, but on the dose per kg of body weight per day.

Pharmacokinetic properties of fluconazole

It is perfectly absorbed from the intestines (bioavailability is more than 90%), food intake does not affect absorption. The maximum concentration in the blood appears within an hour after administration. Penetrates into all tissues, including the brain. It is excreted by the kidneys (mainly). Partially affects hormones in men.

Studies of the effect of the drug on pregnant women

High doses of fluconazole have a negative effect on weight gain in rabbits and increase the frequency of miscarriages. This applies to dosages similar to 20 times the therapeutic dose for humans. With adequate weight of the animals, the amounts of fluconazole administered, no negative effects on the part of the fetus or mother were detected. The existing negative effects when prescribing high doses are attributed to the moderate effect of the drug on the hormonal background.

Pregnancy

For pregnant women, fluconazole is indicated only for severe infections that threaten the life of the mother and / or fetus. Responsibility can only be assumed by the attending physician, with a clear comparison of the risks and the expected effect. There are no direct studies of the use of fluconazole in pregnant and lactating women.

There is evidence of developmental abnormalities in children whose mothers were treated with sufficiently high doses of the drug (for severe fungal diseases), although a direct connection between these facts has not been proven. According to FDA standards, the risk of exposure to the fetus is assessed as C, i.e. conjectural.

Breastfeeding should be discontinued during maternal therapy. fluconazole is found in breast milk in the same concentrations as in the blood (as already mentioned, it perfectly penetrates into all liquids).

Direct contraindications to the appointment

Individual intolerance to the active substance or components of the dosage form; Simultaneous appointment with terfenadine; Combination with quinidine, cisapride, astemizole.

Side effects of the remedy

In the USA, a rather serious study was carried out on 448 patients who took fluconazole at a standard therapeutic dosage, i.e. 150 mg once for the treatment of vaginal candidiasis (thrush). Every fourth person, while taking the drug, had the following side effects:

13% headache; 7% nausea; 6% abdominal pain; 3% diarrhea; 1% dyspepsia; 1% dizziness; 1% violation of taste perception.

The rest felt some weakly differentiated negative sensations. In isolated cases, fluconazole causes a pronounced allergic reaction.

In a larger study (4048 patients), the incidence of complications was observed when fluconazole was combined with other drugs and diseases. The worst combination of fluconazole with cytostatics in HIV patients. The main side effects were the same as in the first group of subjects.

Effect of fluconazole on the liver (hepatotoxicity)

Sometimes fluconazole causes serious complications from the liver, up to and including death. When the drug is discontinued, the symptoms of liver damage subside. For this reason, with long courses of treatment with fluconazole, the doctor should periodically prescribe liver tests (AST, ALT, etc.).

In severe cases, the hepatotoxic effect is manifested in the form of hepatitis, impaired bile outflow (cholestasis), acute liver failure. All these sad outcomes were observed mainly in patients with HIV, malignant neoplasms, and severe forms of tuberculosis.

Perhaps this is due to the concurrent use of heavy specific antibiotics: isoniazid, rifampicin, phenytoin, pyrazinamide.

Side effects, sometimes observed while taking the drug

A side effect differs from a side effect in that the relationship between what happened with the intake of a specific drug has not been proven. Nevertheless, manufacturing companies are obliged to record everything that happens to the patient (control group) during treatment, and to include this in the instructions:

Convulsions; Skin rashes, Stevenas-Johnson syndrome, toxic skin lesions (epidermal necrolysis); Exfoliative dermatitis in patients with AIDS and malignant tumors; Violation of the composition of the cellular elements of the blood: leukopenia (decrease in the number of leukocytes), thrombocytopenia (decrease in the number of platelets);

Increased cholesterol

Fat metabolism disorders: increased cholesterol levels (hypercholesterolemia), triglycerides;

Decreased potassium levels.

Side effects from taking fluconazole in children

The studies were conducted in the United States and Europe and included 577 children from one day to 17 years old inclusive. The dosage for all was 15 mg / kg bw / day for an extended period. In total, side effects were identified in 13% of cases:

5.4% vomiting; 2.8% abdominal pain; 2.3% nausea; 2.1% diarrhea.

In 2.3%, treatment was discontinued due to severe side effects.

Interaction with other medications

Increases the half-life of sugar-reducing tablets (sulfonylurea-based), which can lead to hypoglycemia. Those. with diabetes insipidus of the elderly - hypoglycemic drugs are much stronger; Slows down the excretion of theophylline and zidovudine, saquinavir, increases the concentration of sirolimus, which may require an additional titer of the dose of these substances; Increases the concentration of cytostatics, which is important for patients with transplanted internal organs; In combination with anticoagulants (clexane, rivaroxaban, warfarin), it can provoke different types of bleeding. If a sign of any bleeding is found while taking fluconazole, the drug is immediately canceled; When combined with hydrochlorothiazide, which is part of many drugs for pressure (Enap-N, etc.), the concentration of fluconazole increases sharply (one and a half times), which must be taken into account, since the risks of side effects also increase, incl. renal failure; Increases the toxicity of drugs of the NSAID group - diclofenac, meloxicam, naproxen, etc. Given that all these drugs are routine (and many are over-the-counter), the patient should exercise increased caution when using NSAIDs during treatment with fluconazole; May cause cardiac arrhythmias when combined with quinidine, cisapride, astemizole and other antifungal agents; May cause renal failure when taken with tacrolimus; When combined with midazolam, it can cause mental abnormalities; Enhances the action of amitriptyline.

The drug can be harmful under the following conditions

Overdose and first aid

The main symptoms: diarrhea, nausea up to vomiting, there may be convulsions.

Skin rashes

Treatment: gastric lavage with parallel administration of diuretics. Hospitalization is required. An admitted patient is sent for a three-hour hemodialysis (allows to reduce the concentration of the drug by almost 50%), otherwise the doctors act according to the circumstances, depending on the type of interaction. As a rule, a similar situation occurs in an elderly patient with a large number of concomitant prescriptions.

There is information about one patient who, with an overdose of fluconazole, gave a clinic of paranoid delusions and hallucinations. Considering that it was a 42-year-old HIV patient (drug addict), such side effects may not be considered typical for overdose.

If you or your loved ones have been prescribed fluconazole for a long course, try to eliminate the risk of drug interactions, carefully listen to the recommendations of your doctor, do not consume alcoholic beverages during this period. Particular attention should be paid to elderly relatives who are taking many different drugs at the same time, as this significantly increases the risk of side effects while taking fluconazole.

Video about the consequences of six-month fluconazole therapy

Therapist of the city polyclinic. Eight years ago she graduated from Tver State Medical University with honors.

More details

In general, fluconazole is well tolerated, both for intravenous and oral administration. In some cases, when taking the drug, changes in the functioning of the kidneys and liver were observed - mainly in patients with such serious underlying diseases as AIDS and cancer. The clinical significance of such changes and their relationship with fluconazole intake is still unclear.

In clinical trials, side effects were observed in 26% of patients who took one dose of fluconazole during the course of treatment. Among patients taking drugs similar in properties, side effects were noted in 16% of cases. The most common side effects in patients who took a single dose of fluconazole (150 mg) to treat vaginal infections were headaches, nausea, and abdominal pain. In most cases, the side effects were mild to moderate.

Some side effects appeared in 16% of patients taking more than one dose of fluconazole. Side effects were more common in HIV-positive patients than in people not infected with HIV (21% and 13%, respectively). At the same time, the nature of side effects in both groups of patients was almost the same.

From the nervous system

In rare cases, seizures began in patients taking fluconazole, although it was not possible to establish a direct relationship between the drug and this side effect. However, it should be borne in mind that convulsions are possible after taking at least 100 mg of fluconazole. Other side effects from the nervous system are dizziness, headaches (observed in about 13% of cases), paresthesia, insomnia, drowsiness, tremors.

Side effects from the gastrointestinal tract

Side effects from the gastrointestinal tract in patients taking fluconazole include nausea (in about 7% of patients), abdominal pain Abdominal pain: types and symptoms (6%), diarrhea (3%), vomiting (1.7%), dyspepsia (1%), taste disturbances (1%), lack of appetite and general abdominal discomfort.

Liver side effects

Side effects in this category include disorders such as hepatitis Hepatitis is the scourge of our time , cholestasis and liver failure, which can sometimes lead to patient death. There have also been cases of liver necrosis. Fatal liver dysfunctions have been observed extremely rarely, and have been observed mainly in patients with AIDS or cancer. As a rule, these patients were taking several medications at the same time, and it is impossible to say with certainty whether the development of severe complications was associated precisely with taking fluconazole. A case is known when an AIDS patient developed acute liver necrosis approximately three weeks after starting fluconazole administration.

An increase in the level of transaminase in the blood was also observed in patients with severe diseases who took, in addition to fluconazole, other drugs during the course of treatment, mostly hepatotoxic.

In patients without severe underlying diseases, temporary liver dysfunctions were observed. In all these cases, liver function returned to normal soon after the patients stopped taking fluconazole.

Dermatologic side effects

The most common dermatological side effects of fluconazole are skin rash (which occurs in about 1.8% of patients taking this medication) and hair loss that stops after treatment ends. In some cases, exanthematous pustulosis also develops and more intense sweating begins.

Hair loss is most common in people who have been taking fluconazole for two months or more.

In patients with severe illnesses, serious disorders affecting the skin may develop while taking the drug; in very rare cases, as a rule, in combination with the influence of other factors, they lead to the death of the patient.

Hypersensitivity

In clinical trials, a fifty-two-year-old female patient who took a single dose of fluconazole (400 mg) developed drug-fixated erythema. Within 12 hours after taking the drug, three oval, painful spots appeared on her torso, each with a diameter of 3-4 cm. The diagnosis was confirmed when the patient was given another 25 mg of the drug. Fixed drug erythema is just one example of how drug hypersensitivity can manifest.

In much more rare cases, patients with hypersensitivity can develop side effects such as anaphylactic shock and angioedema. In addition, the development of exfoliative dermatitis and a significant decrease in blood pressure are possible.

Side effects from the cardiovascular system

In most cases, side effects in this category when taking fluconazole occur in patients with additional risk factors, such as structural heart disease and electrolyte disturbances. Many of them have also taken drugs that can contribute to cardiovascular problems. The most common cardiovascular side effects are palpitations of the heart and prolongation of the QT interval.

Hematologic side effects

There are cases when patients developed anemia, eosinophilia, leukopenia, neutropenia while taking fluconazole Neutropenia - immunity is under attack and thrombocytopenia. Typically, these patients had severe fungal infections or other serious illnesses.

Spontaneous development of anemia was most often observed in patients over the age of 65 years, however, in normal elderly people anemia occurs much more often than in people under 65 years of age. It is not yet clear whether there is a direct link between the development of anemia and taking fluconazole.

Kidney side effects

A fifty-eight-year-old woman in a clinical trial with a history of hypertension and cervical cancer Cervical cancer: a cure , while taking fluconazole, membrane nephropathy developed. The patient presented with generalized edema, nausea, and indigestion; these symptoms persisted for three weeks. In addition to fluconazole, she took amlodipine, hydrochlorothiazide, metoclopramide and levosulpiride. After the patient stopped taking fluconazole, she was in remission.

Cases of acute renal failure were most often observed among patients over the age of 65 years taking fluconazole. However, this disorder is generally more common in elderly people, so it cannot be said with certainty that it is associated with taking fluconazole.

Metabolic side effects

Among the metabolic side effects of fluconazole were hypercholesterolemia, hypertriglyceridemia and hypokalemia.

Side effects from the musculoskeletal system

Some patients taking fluconazole complained of back pain and joint pain, as well as stiff finger joints. Muscle pains are observed somewhat less frequently when taking fluconazole. The relationship between taking this medication and the occurrence of such side effects has not yet been established.

Other side effects

In addition to the above side effects, fluconazole can cause fever, weakness, general malaise, and asthenia.

Get immediate medical attention if you develop any of the following signs of an allergic reaction to fluconazole: extensive skin rash, difficulty breathing, swelling of the face, tongue, lips, and swelling of the throat. You should consult your doctor as soon as possible if fluconazole causes symptoms such as lack of appetite, jaundice (yellowish skin and whites of the eyes), flu-like symptoms, and seizures.