Instructions for use of fluconazole tablets - composition, indications, side effects, analogues and price. Side effects of fluconazole Fluconazole symptoms

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The site provides reference information for informational purposes only. Diagnosis and treatment of diseases must be carried out under the supervision of a specialist. All drugs have contraindications. Consultation with a specialist is required!

Treatment with fluconazole 150 may cause a number of side effects.

Possible disruption of the functioning of the gastrointestinal tract, manifested in defecation disorders (constipation or diarrhea), bloating, vomiting, epigastric pain, toothache, and aversion to food. In isolated cases, liver dysfunction was noted, expressed in yellowing of the skin and mucous membranes, an increase in the amount of bilirubin in the blood, as well as activation of certain liver enzymes.

The functioning of the nervous system may also be disrupted. Such disturbances manifest themselves in migraine-like conditions, loss of coordination, weakness, and spontaneous muscle contraction.
The functioning of organs that produce blood may also be disrupted. This is expressed in thrombocytopenia, leukopenia, agranulocytosis, neutropenia.
Treatment with the drug often causes allergic manifestations, such as urticaria, very rarely various types of exudative erythema, Lyell's syndrome, and in isolated cases anaphylactic manifestations.

Sometimes treatment with fluconazole can cause deterioration in kidney function, a lack of potassium in the body, an increase in cholesterol levels in the blood, and an increase in triglycerides.
An overdose of the drug should not be allowed. This can trigger visions and paranoid states. In case of overdose, you need to do a gastric lavage and also drink a diuretic. Hemodialysis can also help for three hours.
You should not use fluconazole without consulting a physician or other doctor.

Before use, you should consult a specialist.

Reviews

I got sick with ARVI, throat and general condition. Apparently my immunity has dropped sharply.

After taking antibiotics, thrush worsened. I started using pimafucin suppositories and took fluconazole. I developed symptoms of poisoning - weakness, nausea, loose stools, loss of appetite. I'm unlikely to use fluconazole again

After taking fluconazole, the middle and index fingers are swollen and itchy. It’s not clear why! Why only these fingers and not all?

Good evening. I took fluconazole for thrush, it’s a real crap, it’s better not to drink it at all, the side effects from this medicine are that my upper lip is swollen and I can’t even put it into words, and two fingers on my right hand are so itchy and so swollen that I can’t bend my fingers.
So before you drink, think about whether it’s worth it!!

Good day. After using Fluconazole, 3 days later I began to experience itchy skin all over my body and redness. On the 4th or 5th day I went to a dermatologist, she prescribed me a hot injection for 5 days, she said it would go away within a month, but alas, after the hot injection these red redness darkened became brown (((didn’t know what to do, went to another dermatologist, she prescribed 10 days of hot injection, but there was no change. More than 1 year has passed since then and I still can’t get rid of it, because I’m a girl for me this a huge problem, and a simple disaster. I don’t even know what to do and who to contact, I’ve been suffering with this problem for a year, I tried whitening but the results were 0%.

Hello! After fluconozole, my face became very swollen and covered with red spots. After this, I’m afraid to even take nystatin. Please tell me what to do?

Hello! I suffer from thrush all the time; I recently completed a course of antibiotic treatment for another disease and it immediately worsened. I took Fluconazole at night. I suffered all night, a feeling of anxiety, discomfort.... In the morning I woke up all “bruised” with swelling on my face. Lips were so swollen that it was difficult to talk (((

A few months ago I had a mini-abortion. The period then was five weeks. After that, for two days it was a little smeared, and after the discharge intensified and became brown. Four weeks did not pass. They prescribed me hormonal drugs, herbs, fluconazole and a couple of other drugs, in addition to this and suppositories with indomethacin. It didn't help in four weeks. After that, I drank some more herbs and the cycle seemed to return to normal. As for fluconazole, I can say that it helped.

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Characteristics of the substance Fluconazole

An antifungal agent from the group of triazole derivatives.

White or almost white crystalline powder, odorless, with a characteristic taste, sparingly soluble in water and isopropyl alcohol, sparingly soluble in ethanol and chloroform, soluble in acetone and readily soluble in methanol (solution for infusion is isoosmotic). Molecular weight 306.3.

Pharmacology

Pharmacological action- antifungal.

Pharmacodynamics

Capsules, solution for infusion

Fluconazole, a triazole antifungal drug, is a powerful selective inhibitor of sterol synthesis in fungal cells.

Fluconazole has demonstrated activity under conditions in vitro and in clinical infections against most of 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 under conditions in vitro against the following microorganisms: Candida dubliniensis, Candida guilliermondii, Candida kefyr, Candida lusitaniae; however, the clinical significance of this is unknown.

When administered orally and intravenously, fluconazole exhibits activity in various models of fungal infections in animals. The activity of fluconazole has been demonstrated in opportunistic mycoses, incl. 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, including infections caused by Blastomyces dermatitidis, Coccidioides immitis(including intracranial infections) and Histoplasma capsulatum, in animals with normal and suppressed immunity.

Fluconazole has high specificity for fungal enzymes dependent on the cytochrome P450 system. Fluconazole therapy at a dose of 50 mg/day for up to 28 days does not affect plasma testosterone concentrations in men or plasma steroid concentrations in women of childbearing age. Fluconazole at a dose of 200-400 mg/day does not have a clinically significant effect on the concentrations of endogenous steroids and their response to ACTH stimulation in healthy male volunteers.

Mechanisms of development of resistance to fluconazole. Resistance to fluconazole can develop in the following cases: a qualitative or quantitative change in the enzyme that is the target of fluconazole (lanosteryl-14-α-demethylase), decreased 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. Increased expression of the ERG11 gene leads to the production of high concentrations of the target enzyme, which creates the 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. These transporters include the main messenger encoded by multidrug resistance genes (MDR), and the ATP-binding cassette transporter superfamily encoded by fungal resistance genes Candida to azole antimycotics (CDR).

Gene overexpression MDR leads to resistance to fluconazole, at the same time overexpression of genes CDR may lead to resistance to various azoles.

Resistance to Candida glabrata usually mediated by gene overexpression CDR, which leads to resistance to many azoles. For those strains in which the minimum inhibitory concentration is determined to be 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 effects of fluconazole.

Pharmacokinetics

Capsules, solution for infusion

The pharmacokinetics of fluconazole are similar when administered intravenously and orally. After oral administration, fluconazole is well absorbed, its plasma concentration (and overall bioavailability) exceeds 90% of those after intravenous administration. Concomitant food intake does not affect the absorption of fluconazole. The concentration in the blood plasma is proportional to the dose, and T max in the blood plasma is 0.5-1.5 hours after taking fluconazole on an empty stomach, and T 1/2 is about 30 hours. 90% C ss is achieved by the 4-5th day after start of therapy (with multiple doses of the drug once a day). When taken orally, Tmax is 4 hours.

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

Fluconazole penetrates well into all body fluids. The concentration of the drug in saliva and sputum is similar to its concentration in blood plasma. In patients with fungal meningitis, fluconazole concentrations in the cerebrospinal fluid are approximately 80% of its plasma concentrations.

In the stratum corneum, epidermis, dermis and sweat fluid, high concentrations are reached that exceed serum concentrations. Fluconazole accumulates in the stratum corneum. When taken at a dose of 50 mg 1 time per day, the concentration of fluconazole in the stratum corneum after 12 days is 73 mcg/g, and 7 days after stopping treatment - only 5.8 mcg/g. When used at a dose of 150 mg once a week, the concentration of fluconazole in the stratum corneum on the 7th day is 23.4 mcg/g, and 7 days after taking the second dose - 7.1 mcg/g.

The concentration of fluconazole in the nail plate after 4 months of use at a dose of 150 mg once a week is 4.05 mcg/g in healthy and 1.8 mcg/g in affected nail plates; 6 months after completion of therapy, fluconazole is still detectable in the nail plates.

The drug is excreted mainly by the kidneys, approximately 80% of the administered dose is found unchanged in the urine. Fluconazole clearance is proportional to creatinine clearance. No circulating metabolites were detected.

Long-term T1/2 from blood plasma allows you to take fluconazole once for vaginal candidiasis and once a day or once a week for other indications.

Pharmacokinetics in selected patient groups

Capsules solution for infusion

Children. Below are the obtained values ​​of T 1/2 (hours) and AUC (µg h/ml) depending on age and dose of fluconazole.

9 months-13 years: once orally 2 mg/kg - 25 hours and 94.7 mcg·h/ml.

9 months-13 years: once orally 8 mg/kg - 19.5 hours and 362.5 mcg·h/ml.

Average age 7 years: repeatedly orally 3 mg/kg - 15.5 hours and 41.6 mcg·h/ml.

11 days-11 months: once intravenously 3 mg/kg - 23 hours and 110.1 mcg·h/ml.

5-15 years: repeatedly intravenously 2 mg/kg - 17.4* h and 67.4* mcg·h/ml.

5-15 years: repeatedly intravenously 4 mg/kg - 15.2* h and 139.1* mcg·h/ml.

5-15 years: repeatedly intravenously 8 mg/kg - 17.6* h and 196.7* mcg·h/ml.

*Indicator recorded on the last day.

In preterm infants (around 28 weeks of development), fluconazole was administered IV at a dose of 6 mg/kg every 3rd day for a maximum of 5 doses while the infants remained in the NICU. The average T1/2 was 74 hours (range 44-185 hours) on day 1, decreasing on the 7th day to an average of 53 hours (range 30-131 hours) and on the 13th day on average up to 47 hours (within 27-68 hours).

The AUC value was 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 day and decreased to an average of 360 mcg·h/ml (range 167-566 mcg·h/ml) by the 13th day.

V d was 1183 ml/kg (range 1070-1470 ml/kg) on ​​day 1, then increased to an average of 1184 ml/kg (range 510-2130 ml/kg) on ​​day 7 and up to 1328 ml/kg (range 1040-1680 ml/kg) on ​​the 13th day.

Capsules, solution for infusion

Old age. With a single dose of fluconazole 50 mg orally in elderly patients 65 years of age and older (some of them were simultaneously taking diuretics), Tmax in blood plasma was 1.3 hours after administration and Cmax was 1.54 mcg/ml, average values AUC is (76.4±20.3) mcg h/ml, and the average half-life is 46.2 hours. The values ​​of these pharmacological parameters are higher than in young patients, which is likely due to decreased renal function, typical for elderly patients. The simultaneous use of diuretics did not cause a pronounced change in AUC and Cmax in blood plasma. Creatinine Cl (74 ml/min), the percentage of fluconazole excreted unchanged by the kidneys (0-24 hours, 22%), and renal clearance of fluconazole (0.124 ml/min/kg) are lower in elderly patients compared to young patients.

Use of the substance Fluconazole

Capsules

Treatment of diseases in adults: cryptococcal meningitis; coccidioidomycosis; invasive candidiasis; mucous candidiasis, incl. oropharyngeal candidiasis, esophageal candidiasis, candiduria and chronic mucocutaneous candidiasis; chronic atrophic candidiasis of the oral cavity (associated with wearing dentures), when oral hygiene or local treatment is not enough; vaginal candidiasis, acute or recurrent, when local therapy is not applicable; candidal balanitis, when local therapy is not applicable; dermatomycosis, incl. tinea pedis, dermatophytosis trunk, tinea inguinalis, lichen versicolor and cutaneous candidiasis when systemic treatment is indicated; dermatophytosis of the nails (onychomycosis), when treatment with other drugs is unacceptable.

Prevention of diseases in adults: relapse of cryptococcal meningitis in patients at high risk of relapse; relapse of oropharyngeal candidiasis and esophageal candidiasis in HIV-infected patients with a high risk of relapse; reduction in the frequency of relapses of vaginal candidiasis (4 or more episodes per year); candidal infections in patients with prolonged neutropenia (such as patients with hematologic malignancies undergoing chemotherapy or patients undergoing hematopoietic stem cell transplantation).

Treatment of diseases in children: mucous candidiasis (oropharyngeal candidiasis and esophageal candidiasis); invasive candidiasis; cryptococcal meningitis and prevention of candidal infections in patients with a weakened immune system. Fluconazole can be used as maintenance therapy to prevent recurrence of cryptococcal meningitis in children at high risk of recurrence.

Solution for infusion

Cryptococcosis, including cryptococcal meningitis and infections of other localizations (for example, lungs, skin), incl. in patients with a normal immune response and patients with AIDS, organ transplant recipients and patients with other forms of immunodeficiency, maintenance therapy to prevent relapses of cryptococcosis in patients with AIDS; 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 tumors who are in intensive care units and receiving cytotoxic and 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 mouth and pharynx, esophagus, non-invasive bronchopulmonary infections, candiduria, mucocutaneous and chronic atrophic candidiasis of the oral cavity (associated with wearing dentures), incl. in patients with normal and suppressed immune function, prevention of relapse of oropharyngeal candidiasis in patients with AIDS; prevention of fungal infections in patients with malignant tumors predisposed to such infections as a result of cytotoxic chemotherapy or radiation therapy; mycoses of the skin, including mycoses of the feet, body, groin area, pityriasis versicolor, onychomycosis and skin candidal infections; deep endemic mycoses in patients with normal immunity, coccidioidomycosis.

Contraindications

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Hypersensitivity to fluconazole, azole compounds with a structure similar to fluconazole; taking terfenadine during repeated use of fluconazole at a dose of 400 mg/day or more (see “Interaction”); simultaneous use with drugs that prolong the QT interval and are metabolized by the CYP3A4 isoenzyme, such as cisapride, astemizole, erythromycin, pimozide and quinidine (see “Interaction”).

Restrictions on use

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Liver dysfunction; renal dysfunction; the appearance of skin rash during 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 imbalances and concomitant therapy that contributes to the development of such disorders).

Use during pregnancy and breastfeeding

Capsules, solution for infusion

Adequate and controlled studies have not been conducted to study the use of fluconazole in pregnant women.

Several cases of multiple congenital malformations have been described in newborns whose mothers received high-dose fluconazole therapy (400-800 mg/day) for most or all of the first trimester. The following developmental disorders were noted: brachycephaly, impaired development of the facial part of the skull, impaired formation of the cranial vault, cleft palate, curvature of the femurs, thinning and elongation of the ribs, arthrogryposis and congenital heart defects. Currently, there is no evidence of a connection between the listed congenital anomalies and the use of low doses of fluconazole (150 mg once for the treatment of vulvovaginal candidiasis) in the first trimester of pregnancy. 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 outweighs the possible risk to the fetus.

Women of childbearing age should use contraception.

Fluconazole is found in breast milk in concentrations close to plasma concentrations, so its use in women during breastfeeding is not recommended.

Side effects of the substance Fluconazole

Capsules, solution for infusion

Fluconazole is usually very well tolerated.

In clinical and post-marketing* studies studying the use of fluconazole, the following adverse reactions were noted.

From the blood and lymphatic system*: leukopenia, including neutropenia and agranulocytosis, thrombocytopenia, anemia.

From the immune system*: anaphylaxis (including angioedema, facial swelling, urticaria, itching).

From the side of metabolism and nutrition*: increased concentrations of cholesterol and triglycerides in the blood plasma, hypokalemia.

From the nervous system: headache, dizziness*, convulsions*, change in taste*, paresthesia, insomnia, drowsiness, tremor.

From the gastrointestinal tract: abdominal pain, diarrhea, flatulence, nausea, dyspepsia*, vomiting*, dry mouth, constipation.

From the liver and biliary tract: hepatotoxicity, in some cases with a fatal outcome, increased concentration of bilirubin in the blood plasma, serum activity of ALT, AST, alkaline phosphatase, impaired liver function*, hepatitis*, hepatocellular necrosis*, jaundice*, cholestasis, hepatocellular damage.

For the skin and subcutaneous tissues: skin rash, alopecia*, exfoliative skin lesions*, including Stevens-Johnson syndrome and toxic epidermal necrolysis, acute generalized exanthematous pustulosis.

From the side of the heart*: prolongation of the QT interval on the ECG, ventricular tachycardia of the “pirouette” type (see “Precautions”).

From the musculoskeletal and connective tissue side: myalgia.

General disorders and disorders at the injection site: weakness, asthenia, increased fatigue, fever, increased sweating, vertigo.

In some patients, especially those with serious illnesses such as AIDS or cancer, changes in blood counts, renal and liver function have been observed during treatment with fluconazole and related drugs (see "Precautions"), but the clinical significance of these changes and their relationship to treatment is not installed.

Interaction

Capsules, solution for infusion

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

Concomitant use of fluconazole with the following drugs is contraindicated

Cisapride: with the simultaneous use of fluconazole and cisapride, adverse reactions from the heart are possible, incl. ventricular tachycardia of the “pirouette” type. The use of fluconazole at a dose of 200 mg 1 time per day and cisapride at a dose of 20 mg 4 times a day leads to a marked increase in plasma concentrations of cisapride and prolongation of the QT interval on the ECG. The simultaneous use of cisapride and fluconazole is contraindicated.

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

Astemizole: simultaneous use of fluconazole with astemizole or other drugs, the metabolism of which is carried out by the cytochrome P450 system, may be accompanied by an increase in serum concentrations of these drugs. Elevated plasma concentrations of astemizole may lead to prolongation of the QT interval on the ECG and, in some cases, to the development of torsade de pointes (TdP). The simultaneous use of astemizole and fluconazole is contraindicated.

Pimozide: in vitro or in vivo, simultaneous use of fluconazole and pimozide may lead to inhibition of pimozide metabolism. In turn, an increase in plasma concentrations of pimozide can lead to a prolongation of the QT interval on the ECG and, in some cases, to the development of ventricular tachycardia of the “pirouette” type. 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, simultaneous use of fluconazole and quinidine may also lead to inhibition of quinidine metabolism. The use of quinidine is associated with prolongation of the QT interval on the ECG and in some cases with the development of torsade de pointes (TdP). The simultaneous use of quinidine and fluconazole is contraindicated.

Erythromycin: simultaneous use of fluconazole and erythromycin potentially leads to an increased risk of cardiotoxicity (prolongation of the QT interval on the ECG, torsade de pointes) and, as a result, sudden cardiac death. The simultaneous use of fluconazole and erythromycin is contraindicated.

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

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

Rifampicin: simultaneous use of fluconazole and rifampicin leads to a decrease in the AUC value and half-life of fluconazole by 25 and 20%, respectively. In patients concomitantly taking rifampicin, the advisability of increasing the dose of fluconazole must be considered.

Concomitantly taken drugs that are affected by fluconazole. Fluconazole is a strong isoenzyme inhibitor CYP2C9 And CYP2C19 and a moderate inhibitor of the CYP3A4 isoenzyme. In addition, in addition to the effects listed below, there is a risk of increased plasma concentrations of other drugs metabolized by isoenzymes CYP2C9, CYP2C19 and CYP3A4 when used concomitantly with fluconazole. In this regard, caution should be exercised when using the listed drugs simultaneously, and if such combinations are necessary, patients should be under close medical supervision. It should be taken into account that the inhibitory effect of fluconazole persists for 4-5 days after its discontinuation due to the long half-life.

Alfentanil: there is a decrease in clearance and Vd, and an increase in T1/2 of alfentanil. This may be due to inhibition of the CYP3A4 isoenzyme by fluconazole. Alfentanil dosage adjustment may be required.

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

Amphotericin B: in studies on mice (including those with immunosuppression), the following results were noted - a small additive antifungal effect in systemic infection caused by Candida albicans, lack of interaction with intracranial infection caused by Cryptococcus neoformans, and antagonism in systemic infections caused by Aspergillus fumigatus. The clinical significance of these results is unclear.

Anticoagulants: like other antifungal drugs (azole derivatives), fluconazole, when used simultaneously with warfarin, increases PT (by 12%), and therefore bleeding may develop (hematomas, nasal and gastrointestinal bleeding, hematuria, melena). In patients receiving coumarin anticoagulants, PT should be continuously monitored during therapy and for 8 weeks after concomitant use. The advisability of adjusting the warfarin dose should also be assessed.

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

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

With simultaneous use of a single dose of triazolam, fluconazole increases the AUC of triazolam by approximately 50%, Cmax by 25-32% and T1/2 by 25-50% due to inhibition of triazolam metabolism. Triazolam dose adjustment may be necessary.

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

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

BKK: Some CCBs (nifedipine, isradipine, amlodipine, verapamil and felodipine) are metabolized by the CYP3A4 isoenzyme. Fluconazole increases the systemic exposure of CCBs. Monitoring for the development of side effects is recommended.

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

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

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

Halofantrine: Fluconazole may increase plasma concentrations of halofantrine due to inhibition of the CYP3A4 isoenzyme. When used simultaneously with fluconazole, as with other drugs of the azole series, the development of arrhythmia - ventricular tachycardia of the "pirouette" type - is possible. Therefore, combined use is not recommended.

HMG-CoA reductase inhibitors: with simultaneous use of fluconazole with HMG-CoA reductase inhibitors metabolized by the CYP3A4 isoenzyme (such as atorvastatin and simvastatin) or the isoenzyme CYP2D6(such as fluvastatin), the risk of developing myopathy and rhabdomyolysis increases. If simultaneous therapy with these drugs is necessary, patients should be monitored to identify symptoms of myopathy and rhabdomyolysis. It is necessary to monitor the concentration of CPK in the blood plasma. If a significant increase in the concentration of CPK in the blood plasma is diagnosed or the development of myopathy or rhabdomyolysis is 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 blood pressure monitoring is necessary.

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

NSAIDs: Cmax and AUC of flurbiprofen in blood plasma increase by 23 and 81%, respectively. Similarly: C max and AUC of the pharmacologically active isomer (S-(+)-ibuprofen) increased by 15 and 82%, respectively, when fluconazole was co-administered with racemic ibuprofen (400 mg).

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

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

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

Oral contraceptives: with simultaneous use of a combined oral contraceptive with fluconazole at a dose of 50 mg, a significant effect on the concentration of hormones in the blood plasma has not been established, while with daily use of 200 mg of fluconazole, the AUC of ethinyl estradiol and levonorgestrel in the blood plasma increases by 40 and 24%, respectively, and with use of 300 mg fluconazole once a week, the AUC of ethinyl estradiol and norethindrone in plasma increases by 24 and 13%, respectively. Thus, repeated use of fluconazole in the indicated doses is unlikely to affect the effectiveness of the combined oral contraceptive.

Phenytoin: simultaneous use of fluconazole and phenytoin may be accompanied by a clinically significant increase in the concentration of phenytoin in the blood plasma. If simultaneous use of both drugs is necessary, the concentration of phenytoin in the blood plasma should be monitored and its dose adjusted accordingly in order to ensure a therapeutic concentration in the blood serum.

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

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

Saquinavir: AUC of saquinavir in blood plasma increases by approximately 50%, C max by 55%, clearance of saquinavir decreases by approximately 50% due to inhibition of hepatic metabolism by the CYP3A4 isoenzyme and inhibition of P-gp. Dose adjustment of saquinavir may be necessary.

Sirolimus: an increase in the concentration of sirolimus in the blood plasma, presumably due to inhibition of the metabolism of sirolimus by the isoenzyme CYP3A4 and P-gp. This combination can be used with appropriate dose adjustment of sirolimus depending on the effect/concentration.

Sulfonylurea derivatives: fluconazole leads to a prolongation of half-life of sulfonylurea derivatives (chlorpropamide, glibenclamide, glipizide and tolbutamide) for oral administration. Patients with diabetes mellitus can be prescribed the simultaneous use of fluconazole and sulfonylurea derivatives for oral administration, but the possibility of hypoglycemia should be taken into account, in addition, regular monitoring of blood glucose is necessary and, if necessary, dose adjustment of sulfonylurea derivatives.

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

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

Tofacitinib: exposure of tofacitinib increases when used concomitantly with drugs that are both moderate inhibitors of the CYP3A4 isoenzyme and strong inhibitors of the isoenzyme CYP2C19(for example fluconazole). Dose adjustment of tofacitinib may be necessary.

Vinca alkaloids: Although targeted studies are lacking, it is suggested that fluconazole may increase plasma concentrations of vinca alkaloids (eg vincristine and vinblastine), etc. lead to neurotoxicity, which may be due to inhibition of the CYP3A4 isoenzyme.

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

Zidovudine: with simultaneous use with fluconazole, an increase in C max and AUC of zidovudine in blood plasma is observed by 84 and 74%, respectively. This effect is probably due to a slowdown in the metabolism of the latter to its main metabolite. Before and after therapy with fluconazole at a dose of 200 mg/day for 15 days in patients with AIDS and AIDS-associated complex, a significant increase in plasma AUC of zidovudine (20%) was found.

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

Voriconazole (isoenzyme inhibitor CYP2C9, CYP2C19 and CYP3A4): simultaneous use of voriconazole (400 mg 2 times a day on the first day, then 200 mg 2 times a day for 2.5 days) and fluconazole (400 mg on the first day, then 200 mg/day for 4 days) leads to an increase in Cmax and AUC of voriconazole in blood plasma by 57 and 79%, respectively. This effect persists when the dose is reduced and/or the frequency of administration of any of the drugs is reduced. Concomitant use of voriconazole and fluconazole is not recommended.

Interaction studies of fluconazole (for oral administration) when taken concomitantly with food, cimetidine, antacids, and after total body irradiation in preparation for bone marrow transplantation showed that these factors do not have a clinically significant effect on the absorption of fluconazole.

The listed interactions were established with repeated use of fluconazole; interactions with drugs as a result of a single dose of fluconazole are unknown.

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

The substance Fluconazole is a derivative of Triazole. 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. The pharmacological and pharmacokinetic properties of different forms of Fluconazole do not differ. The medicine is available in 50 mg and 150 mg doses, both in tablets and ampoules.

The active components of the drug are characterized by high absorption capacity. The level of bioavailability is more than 90%, which affects the degree of effectiveness. It is 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 administration.

Fluconazole has a low level of binding to. At the same time, the active components of the drug are able to freely penetrate into all fluids inside the body, including saliva and sputum. The concentration in these liquids is similar to the concentration in blood plasma.

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

In general, Fluconazole is a broad-spectrum antifungal agent that is characterized by a high level of 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 dosage, it is used as an independent or auxiliary agent as part of complex drug therapy.

Indications for use:

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





• Individual hypersensitivity to Fluconazole or other substances included in the drug
• Age limit (up to 16 years old)
• Concomitant use of drugs containing terfenadine
• Severe liver dysfunction
• Late stages of kidney failure
• Concomitant use with alcohol
• Diseases of the cardiovascular system
• Hormonal disorders

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

Rarely, Fluconazole can be used in the early stages if the intended benefit outweighs the potential harm to the mother or child. In this case, the maximum dose of the drug is 150 mg, which is taken once.

It is not recommended for use during breastfeeding due to its high penetrating ability. The concentration of the active substance in breast milk and blood plasma is almost identical, which is why if it enters a child’s body it can cause an overdose, severe poisoning with a high probability of death.

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

Method of use of the drug

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

Admission is strictly contraindicated for children under 1 year of age. At the age of 1-16 years, Fluconazole can be used only for fungal diseases that can cause irreversible damage to the body or death. In this case, the dosage is no more than 50-100 mg once a 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. Every day you need to take 50 mg of the drug, that is, one tablet.
• Dermatomycosis. For deep skin lesions, it is necessary to take 200-400 mg daily. Diseases from this group, as a rule, are difficult to treat, 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 breaks for diagnostic procedures to assess the effectiveness and prevent the negative consequences of taking it.
• Cryptococcal meningitis. On the first day after diagnosis, the patient is prescribed 400 mg of Fluconazole. In subsequent days, the daily dosage varies from 200 to 400 mg. The duration of drug therapy is determined depending on the clinical effect. The maximum duration of treatment for meningitis is 8 weeks.
• Prevention of fungal diseases. For preventive purposes, Fluconazole is used no more than once a week. If there have been cases of the disease in the past, it is necessary to take 100 mg of the drug (2 tablets) to prevent relapse. In the absence of cases of fungal diseases, it is enough to take 1 tablet (50 mg) weekly.

Treatment with Fluconazole is effective only if the prescribed dosages are followed and followed by a specialist.

Use for thrush

Fluconazole is the main drug treatment for 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.






There are various analogs of Fluconazole that are used as a replacement for this drug in the treatment of fungal diseases.

Pharmacological action - antifungal.

Blocks a number of cytochrome P450-dependent enzymes and highly selectively inhibits the synthesis of sterols in fungal cell membranes. Effective against infections caused by fungi of the genus Candida spp., Cryptococcus neoformans, Microsporum spp., Trichophyton spp., as well as infections caused by pathogens Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum.

The pharmacokinetic characteristics of fluconazole are similar when administered intravenously and when administered orally.

After oral administration, it is well absorbed from the gastrointestinal tract. Bioavailability is 90%; food intake does not affect absorption. Plasma protein binding - 11–12%. Cmax and AUC are proportional to dose. Cmax is achieved 1–2 hours after administration. Equilibrium concentration - within 5–10 days of treatment (when taking 50–400 mg 1 time per day). Administration of a loading dose on the first day of treatment, 2 times the usual daily dose, allows one to achieve a level close to the equilibrium concentration by the second day. The apparent volume of distribution approaches the total body water content. Penetrates well into all biological fluids of the body and passes through the BBB. In meningitis caused by fungi, the level of fluconazole in the cerebrospinal fluid reaches approximately 80% of the level in plasma. In healthy volunteers, the concentration of fluconazole in saliva was equal to or slightly higher than its plasma level, regardless of the dose, route and duration of administration. In patients with bronchiectasis, sputum fluconazole concentrations 4 and 24 hours after a single oral dose of 150 mg were similar to plasma concentrations. After a single oral dose of 150 mg, the fluconazole vaginal tissue/plasma concentration ratio was 0.94–1.14 during the first 48 hours (n=27), the vaginal fluid/plasma ratio was 0.36–0.71 during the first 72 h (n=14). The ratio of fluconazole concentrations in urine/plasma and normal skin/plasma reached 10.

It is excreted mainly by the kidneys; in healthy volunteers, 80% of fluconazole is excreted unchanged, about 11% in the form of metabolites. T1/2 - about 30 hours (in the range of 20–50 hours). The pharmacokinetics of fluconazole depends significantly on renal function. T1/2 is inversely proportional to creatinine clearance.

When fluconazole was administered to healthy volunteers in doses of 200 to 400 mg once for 14 days, little effect was observed on the concentrations of testosterone, endogenous corticosteroids and ACTH-stimulated cortisol response. When taken 50 mg per day, fluconazole did not change the concentration of testosterone in the blood in men and the level of steroids in women of childbearing age.

Fig. 1 Formula of the fluconazole molecule

Carcinogenicity, mutagenicity, effect on fertility

There was no evidence of the carcinogenicity of fluconazole in studies in mice and rats receiving it orally for 24 months at doses of 2.5; 5 and 10 mg/kg/day (approximately 2–7 times the recommended human dose). In male rats, at doses of 5 and 10 mg/kg/day, an increase in the incidence of hepatocellular adenomas was noted.

Fluconazole was not found to be mutagenic in a number of in vitro and in vivo tests.

There was no effect on fertility in male or female rats with daily oral doses of 5, 10 or 20 mg/kg or parenteral doses of 5, 25 or 75 mg/kg, although a slight delay in the onset of labor was observed with oral doses of 20 mg/kg. In perinatal studies with intravenous fluconazole doses of 5, 20, and 40 mg/kg in rats, labor was difficult and prolonged in several females receiving doses of 20 and 40 mg/kg (approximately 5 to 15 times the human recommended dose). This effect was not observed at doses of 5 mg/kg. Disturbances in labor were associated with a slight increase in the incidence of stillbirths and a decrease in neonatal survival. The effect on parturition in rats is consistent with the specific estrogen-lowering effect caused by high doses of fluconazole. Similar hormonal changes were not found in women receiving fluconazole.

Pregnancy

Teratogenic effects. In two studies, oral administration of fluconazole to pregnant rabbits during organogenesis at doses of 5, 10, 20, 25 and 75 mg/kg resulted in impaired weight gain at all doses and miscarriages at 75 mg/kg (approximately 20–60 years). times higher than recommended doses for humans), and no adverse fetal abnormalities were observed. In several studies in which fluconazole was administered orally to pregnant rats during organogenesis, disturbances in body weight gain and placental weight were increased at a dose of 25 mg/kg. No fetal abnormalities were noted at doses of 5 or 10 mg/kg; at doses of 25 and 50 mg/kg and higher, an increase in the number of anatomical changes in the fetus (additional ribs, expansion of the renal pelvis), and delayed ossification were noted. At doses ranging from 80 mg/kg (approximately 20 to 60 times the recommended human dose) to 320 mg/kg in rats, embryo lethality and fetal abnormalities, including ruffled ribs, cleft palate, and craniofascial ossification abnormalities, were increased. These effects are consistent with suppression of estrogen synthesis in rats and may result from the known effects of reduced estrogen levels on pregnancy, organogenesis, and parturition.

Use of the drug Fluconazole

Cryptococcosis: cryptococcal meningitis, skin and lung infections; prevention of relapses of cryptococcosis in patients; generalized: candidemia, disseminated candidiasis and other forms of invasive candidal infections (damage to the peritoneum, endocardium, eyes, respiratory and urinary tract); candidiasis of the mucous membranes of the oral cavity and pharynx, esophagus, bronchopulmonary candidiasis, candiduria, candidiasis of the skin and mucous membranes, atrophic candidiasis of the oral cavity (associated with wearing dentures), prevention of relapse of oropharyngeal candidiasis in patients with AIDS; genital candidiasis: vaginal (acute or recurrent), including prevention of relapses, candidal balanitis; prevention and treatment of fungal infections in malignant neoplasms (treatment with cytostatics and/or radiation therapy), antibiotic therapy, treatment with immunosuppressants, after transplantation; mycoses of the skin (feet, body, groin area), pityriasis versicolor, onychomycosis, skin candidiasis; deep endemic mycoses (coccidioidomycosis, paracoccidioidomycosis, sporotrichosis, histoplasmosis) in patients with unimpaired immunity.

Contraindications

Hypersensitivity, simultaneous use of terfenadine with repeated use of doses of fluconazole 400 mg or higher; combined use with drugs that prolong the QT interval and are metabolized via CYP3A4 (such as cisapride, astemizole, quinidine).

Restrictions on use

Known hypersensitivity to other azole derivatives, because There is no information regarding cross-hypersensitivity between fluconazole and other azole antifungals (caution should be exercised).

Use during pregnancy and breastfeeding

During pregnancy, it is possible only with life-threatening severe infections, if the expected effect of therapy exceeds the potential risk to the fetus (adequate and strictly controlled studies of the safety of use in pregnant women have not been conducted). There are reports of various congenital disorders in infants whose mothers were treated for 3 months or more with high doses of fluconazole - 400-800 mg / day for coccidioidomycosis, although the causal relationship of these cases with fluconazole is unclear.

During treatment, breastfeeding should be stopped (concentrations of fluconazole in breast milk are comparable to plasma concentrations).

Side effects of the drug Fluconazole

In patients receiving a single dose for vaginal candidiasis

In a comparative clinical study in the United States in patients with vaginal candidiasis (n=448) receiving a single dose of 150 mg fluconazole, the overall incidence of possibly drug-related side effects was 26%; in patients receiving the comparator drug (n=448) – 16%. The most common side effects associated with fluconazole were: (13%), nausea (7%), (6%), (3%), dyspepsia (1%), dizziness (1%), taste disturbance (1%). ). Most side effects were mild or moderate. Very rarely, angioedema and anaphylactic reactions were observed in marketing studies.

In patients receiving multiple doses for other infections

In clinical trials, approximately 16% of 4048 patients treated with fluconazole for 7 days or more experienced adverse reactions. Treatment was discontinued due to adverse effects in 1.5% of patients and due to abnormal laboratory tests in 1.3% of patients.

During treatment with fluconazole, clinically significant side effects were more often observed in HIV-infected patients (21%), in contrast to non-HIV-infected patients (13%). The number of patients who discontinued treatment due to adverse effects was similar in both groups (1.5%).

Side effects that were observed in clinical trials when treated with fluconazole for 7 days or more in more than 1% of cases and were associated with the drug (n = 4048): nausea (3.7%), headache (1.9% ), skin rash (1.8%), vomiting (1.7%), abdominal pain (1.7%) and diarrhea (1.5%).

Side effects that are likely to be associated with fluconazole treatment: hepatotoxicity, immunological reactions.

Hepatotoxicity

Combined data from clinical trials and marketing experience indicate that fluconazole treatment is associated with rare cases of serious liver toxicity, including death. There was no obvious relationship between fluconazole-associated hepatotoxicity and the total daily dose, duration of therapy, gender, or age of patients. The hepatotoxic effect of fluconazole is usually (but not always) reversible, with symptoms disappearing after discontinuation of therapy. To avoid serious liver reactions, patients who exhibit abnormal liver function tests during fluconazole therapy should be carefully monitored. Fluconazole treatment should be discontinued if clinically significant symptoms of developing liver disease occur that may be associated with fluconazole treatment.

Reactions from the liver can have different severity: from a slight transient increase in the level of liver transaminases to clinically significant hepatitis, cholestasis, fulminant liver failure, including death. Cases of fatal hepatic reactions occurred mainly in patients suffering from a severe underlying disease (tumor diseases) and often receiving multidrug therapy.

Two comparative trials evaluating the effectiveness of fluconazole in preventing relapses of cryptococcal meningitis found a statistically significant increase in median AST levels from baseline. Elevations of serum transaminases greater than 8 times the upper limit of normal have been observed in approximately 1% of patients treated with fluconazole. These cases were observed in patients with severe underlying disease (AIDS, malignancy), most of whom were receiving multiple concomitant drug therapy, including many drugs with known hepatotoxicity. The incidence of transaminase elevations was higher in patients receiving one or more of the following drugs concomitantly with fluconazole: rifampin, phenytoin, isoniazid, valproic acid, oral sulfonylurea hypoglycemic agents.

Immunological reactions: Rare cases of anaphylaxis have been reported.

Side effects whose relationship with fluconazole treatment has not been established.

From the side of the central nervous system: convulsions.

Dermatological: exfoliative skin diseases, including Stevens-Johnson syndrome and toxic epidermal necrolysis; alopecia. Exfoliative skin diseases rarely developed during treatment with fluconazole; in patients with serious underlying diseases (AIDS, tumor diseases), they rarely had a fatal outcome. If skin symptoms appear during treatment with fluconazole, careful monitoring of the patient is required and if symptoms increase, treatment with fluconazole should be discontinued.

Hematopoietic and lymphatic: leukopenia, including neutropenia and agranulocytosis, thrombocytopenia.

Metabolic: hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Side effects observed in children

In Phase 2 and 3 clinical trials in the United States and Europe in 577 patients aged 1 day to 17 years treated with fluconazole at doses up to 15 mg/kg/day for up to 1616 days, adverse events in children were observed in 13% of cases; in patients receiving a comparison drug (n=451) - in 9% of cases. The most common side effects reported were: vomiting (5.4%), abdominal pain (2.8%), nausea (2.3%), diarrhea (2.1%). Treatment was discontinued due to adverse effects in 2.3% of patients, and due to abnormal laboratory tests (in most cases, increased levels of transaminases and alkaline phosphatase) in 1.4% of patients.

Interaction with other drugs

Fluconazole increases plasma T1/2 of oral hypoglycemic drugs - sulfonylurea derivatives (clinically significant hypoglycemia is possible). Increases phenytoin concentrations (if simultaneous use of both drugs is necessary, the concentration of phenytoin should be monitored and its dose adjusted accordingly to ensure therapeutic serum concentrations). Against the background of fluconazole, serum concentrations of theophylline increase (biotransformation slows down) (the concentration of theophylline in the blood should be carefully monitored and, if necessary, therapy should be adjusted accordingly). With simultaneous use of zidovudine with fluconazole, there is an increase in Cmax of zidovudine by 84%, AUC by 74%, T1/2 is prolonged by approximately 128%; an increase in the side effects of zidovudine is possible (a dose reduction of zidovudine may be required). Fluconazole increases saquinavir AUC by approximately 50%, Cmax by approximately 55%, and decreases saquinavir clearance by approximately 50% (saquinavir dose adjustment may be required).

Fluconazole increases plasma concentrations of sirolimus, presumably due to inhibition of sirolimus metabolism mediated by CYP3A4 and P-glycoprotein (dose adjustment of sirolimus may be required when used concomitantly).
Fluconazole may significantly increase blood levels of cyclosporine in kidney transplant patients with or without renal impairment (monitoring of cyclosporine concentrations and blood creatinine levels is necessary).

With the combined use of fluconazole and coumarin-type anticoagulants, the PT may be prolonged, which may result in the development of bleeding (hematomas, bleeding from the nose and gastrointestinal tract, hematuria and melena); Close monitoring of PT is recommended, and warfarin dosage adjustments may be required. Rifampicin increases the metabolism of fluconazole: AUC decreases by 25%, T1/2 - by 20% (the possibility of increasing the dose of fluconazole should be considered).

When taking fluconazole (100 mg) together with hydrochlorothiazide (50 mg) for 10 days, the level of fluconazole in the blood plasma of healthy volunteers (n=13) increased by approximately 40%, and renal clearance decreased by 30%.

With simultaneous use of fluconazole and rifabutin, serum concentrations of rifabutin increase. There are reports of the development of uveitis. Patients receiving rifabutin and fluconazole concomitantly should be monitored closely.
Fluconazole may increase the systemic exposure of NSAIDs that are metabolized by CYP2C9 (including naproxen, lornoxicam, meloxicam, diclofenac); Frequent monitoring of patients is recommended for timely detection of side effects and NSAID-mediated toxicity; NSAID dose adjustment may be necessary.

When taking fluconazole (200 mg daily) and (200 mg) simultaneously, Cmax increased by 68%, AUC by 134%; When administered together, it may be necessary to reduce the dose of celecoxib by half.

The use of fluconazole simultaneously with drugs that are metabolized with the participation of the cytochrome P450 enzyme system (including cisapride, astemizole, quinidine) may lead to an increase in serum levels of these drugs (in the absence of accurate information, caution must be exercised and the patients' condition must be carefully monitored). Given the occurrence of serious arrhythmias in patients receiving other azole antifungals in combination with terfenadine, careful monitoring of patients is necessary when using fluconazole and terfenadine simultaneously.

Against the background of fluconazole, the biotransformation of cisapride slows down, increasing the risk of cardiovascular disorders, incl. fatal (paroxysmal ventricular tachycardia). Controlled studies have shown that the use of fluconazole at a dose of 200 mg 1 time per day and cisapride at a dose of 20 mg 4 times a day for 5 days leads to a marked increase in plasma concentrations of cisapride and an increase in the QT interval on the ECG. Concomitant use of cisapride and fluconazole is contraindicated.

Fluconazole may increase the systemic exposure of some CCBs (nifedipine, isradipine, amlodipine, felodipine), which are metabolized by CYP3A4. Patients receiving fluconazole and nifedipine simultaneously are recommended to be closely monitored due to the increased risk of side effects.

Fluconazole inhibits the metabolism of carbamazepine and increases the level of carbamazepine in the blood serum (by 30%), increasing the risk of carbamazepine toxicity; The dose of carbamazepine may need to be adjusted.
Fluconazole may increase serum concentrations of orally administered tacrolimus (risk of nephrotoxicity); If coadministered together, a dosage adjustment of tacrolimus may be required. There were no significant pharmacokinetic changes observed with IV tacrolimus.

Following oral administration of midazolam, fluconazole significantly increases midazolam concentrations and psychomotor effects; this effect is more pronounced after taking fluconazole orally than when using it intravenously. If concomitant therapy with short-acting benzodiazepines is necessary in patients taking fluconazole, a dose reduction of the benzodiazepine may be necessary.

Fluconazole increases the effect of amitriptyline; It is advisable to measure the level of amitriptyline/nortriptyline at the beginning of combination therapy and after 1 week; if necessary, the dose of amitriptyline should be adjusted.

There is a report of the development of acute adrenal insufficiency in a patient receiving prednisone after liver transplantation 3 months after the end of fluconazole therapy. Presumably, the end of therapy with fluconazole (a CYP3A4 inhibitor) caused an increase in the activity of this isoenzyme, which led to an increase in the metabolism of prednisone. In patients on long-term therapy with fluconazole and prednisone, adrenal function should be carefully monitored after completion of fluconazole therapy.

Antacids do not affect the absorption of fluconazole.

The solution for infusion is compatible with solutions of 20% glucose, Ringer, Hartmann, potassium chloride in glucose, sodium bicarbonate 4.2%, isotonic sodium chloride solution.

Overdose

Symptoms: nausea, vomiting, diarrhea, and in severe cases, convulsions.

Treatment: gastric lavage, forced diuresis, hemodialysis (three-hour hemodialysis reduces the concentration of the drug in plasma by approximately 50%), symptomatic therapy.

There is one report of an overdose of fluconazole (8200 mg orally) in a 42-year-old HIV-infected patient with the development of hallucinations and paranoid behavior. The patient was hospitalized and his condition returned to normal within 48 hours.

Directions for use and doses

Inside, intravenously. The dose, route of administration, and duration of treatment are determined individually depending on the indications, the patient’s condition, clinical and mycological effect. The daily dose depends on the nature and severity of the infection. In children, the daily dose should not exceed the maximum daily dose for adults. When transferring a patient from intravenous administration of fluconazole to oral administration and vice versa, there is no need to change the daily dose.

Adults with cryptococcosis and generalized candidiasis - intravenously, orally, 400 mg on the 1st day, then 200–400 mg per day; for oropharyngeal candidiasis - orally, 50–100 mg per day for 7–14 days; for vaginal candidiasis - orally, 150 mg once, for the chronic form - 150 mg once a month for 4–12 months; for mycoses - 150 mg once a week.
For children with generalized candidiasis - 6-12 mg/kg/day, for candidiasis of the mucous membranes - 3-6 mg/kg/day, for the prevention of fungal infections - 3-12 mg/kg/day.

Precautions when using the drug Fluconazole

In patients with impaired renal function (with creatinine Cl less than 50 ml/min), the dosage regimen should be adjusted; with a single dose, no dose change is required.

Newborns in the first 2 weeks of life are prescribed the same dose (mg/kg) as for older children, but with an interval of 72 hours; at the age of 3–4 weeks - at the same dose with an interval of 48 hours.

During treatment, it is necessary to carefully monitor peripheral blood counts and liver function. If signs of hepatotoxicity, rash, bullous changes, or erythema multiforme appear, therapy should be discontinued.

Special instructions

Treatment with fluconazole may be initiated pending the results of cultures and other laboratory tests, but therapy should be adjusted accordingly once the results of these tests are available.

Treatment should be continued until clinical/hematological remission occurs (an exception is acute vaginal candidiasis). Premature cessation of treatment leads to relapses.

Most antifungal drugs are widely advertised on television and radio. However, not everyone knows that there are cheaper analogues of these medications. In particular, the active ingredient in most medicines against fungus and thrush is fluconazole. Reviews say that it is really effective. The drug "Fluconazole" is produced in the form of a solution for intravenous administration and in the form of capsules and film-coated tablets. The solution for infusion contains 2 mg of the drug in 1 ampoule. Tablets and capsules come in 50, 100 and 150 mg. Below we will talk specifically about capsules and tablets.

Description and effect of the drug

The drug "Fluconazole" is an antifungal drug with intense action. It prevents the development of fungal cells by inhibiting their development. The advantage of Fluconazole tablets over other drugs is that this medication does not inhibit beneficial enzymes in the human body and does not inhibit androgenic activity. The effect of the drug applies to many types of fungi, which include Cryptococcus neoformans, Histoplasma capsulatum, Trichophyton spp and Candida spp.

Indications for use

The drug is widely used for cryptococcal infections, regardless of the patient’s immune system. Also used to prevent cryptococcosis in patients with HIV infection or AIDS. The drug is effective in the fight against all diseases caused by fungi of the genus Candidia. This includes generalized candidiasis (including lesions of the abdominal cavity, intestines, respiratory tract), candidiasis of the mucous membranes, for example, the oral cavity, pharynx or esophagus, also fungal infections of the skin, genital and vaginal candidiasis (for prevention, treatment, reducing the number of relapses, etc.). d.). The drug "Fluconazole" is actively used in the fight against fungal infections in people suffering from malignant tumors (for prevention), as well as for various mycoses, even deep ones.

The drug "Fluconazole": instructions, reviews, method of application and dosage

The dosage and frequency of use of the drug depend on the purpose of its use and the disease. For cryptococcal infections (including meningitis), the dosage is quite large. On the first day of treatment, and then depending on the severity of the disease. The drug is used once a day. The course of treatment is determined individually; for meningitis, it lasts on average a day. Prevention of cryptococcal infection in patients with AIDS includes a single dose of 200 mg of the drug per day for a very long period of time. The drug “Fluconazole” for thrush is used once a day, regardless of the patient’s gender, at a dosage of 150 mg. For frequently recurrent thrush, it is possible to use the drug two or three times. A preventive course is also taken - 1 capsule (150 mg) once a month. Ease of administration is a big advantage of the drug Fluconazole. Reviews from patients confirm this. Particular care should be taken with the dosage of the drug in children. It is calculated by multiplying the required amount of medication by the child’s body weight. However, the daily dose should not exceed 400 mg. Thus, for cryptococcal infections in children, the dosage is calculated using the formula 6 mg per 1 kg. Course duration: weeks. For candidiasis of the mucous membranes, skin, esophagus, etc., the drug is prescribed in an amount of 3 mg per 1 kg. Sometimes the dose is increased to 6 mg.

Contraindications

A complete contraindication to the use of Fluconazole tablets is the period of lactation and individual intolerance to the drug. It should be used with caution during pregnancy. The positive effect for the mother must outweigh the possible risk to the fetus. Fluconazole is prescribed only in extreme cases. Also, people suffering from liver failure, kidney disease, and regular alcohol consumption should approach the use of the drug with caution.

Features of treatment

Treatment with Fluconazole must be continued until all symptoms disappear. Untreated disease leads to frequent relapses. The drug can be prescribed until culture results are obtained, but treatment should be adjusted (if necessary) afterwards. When using the drug, it is necessary to monitor blood tests, kidney and liver function. If the functions of these organs are impaired, treatment should be discontinued. The drug "Fluconazole" (reviews of experts often contain information about this) has a hepatotoxic effect. However, most often it is reversible: when treatment is stopped, everything is restored. But when a clinical picture appears, the drug is discontinued. It is noted that the drug affects the ability to drive and perform quick actions that require a good reaction. Therefore, during the treatment period, it is not recommended to drive or engage in activities that involve risk and require great concentration.

Side effects

Like other medications, the drug Fluconazole also has a number of side effects. Reviews from patients and doctors contain information that when using the drug, sometimes abdominal pain, bloating, and, less often, diarrhea or vomiting occur. From the nervous system - dizziness, pain, increased fatigue. Sometimes - convulsions. In this case, treatment is stopped. From the skin - rash, urticaria, alopecia. Some side effects of the drug occur when it is used together with other drugs, so treatment should not be prescribed independently. The drug should only be taken under the supervision of a doctor, especially if the person is at risk for contraindications or regularly takes any medications.

Genital (vaginal) candidiasis: symptoms, treatment

Every woman has at least once encountered this disease, which is also called thrush. Men are less likely to suffer from this type of candidiasis. Symptoms of vaginal candidiasis are itching, burning, and discomfort in the perineal area. Most often, thrush is accompanied by cheesy discharge or deposits on the mucous membrane. However, in some cases, the discharge may be non-pathological or completely transparent, however, as a rule, it is profuse, irritates the mucous membrane, causing itching and redness, and has an unpleasant odor. Thrush can be caused by a basic lack of hygiene, wearing uncomfortable or artificial underwear for too long, in which the skin does not breathe, as well as poor nutrition, taking antibiotics, or a sharp decrease in immunity (due to stress, illness). Fluconazole is widely used for thrush. Feedback from patients about it is the most positive: it helps no worse than other means, the effect is felt on the second day, it is easy to use (only 1 time), etc. In addition to using the antifungal agent, it is necessary to maintain a special diet: do not consume sour and dairy products, very spicy or spicy. It is also recommended to use decoctions of chamomile and calendula for washing, which have a calming and anti-inflammatory effect. In case of recurrent candidiasis, it is necessary to increase the frequency of taking the drug Fluconazole (consult your doctor before use).

Fluconazole

Use of fluconazole

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

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.

Types of fluconazole

Side effects of fluconazole

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

Contraindications for fluconazole

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

Use with extreme caution:

• Impaired absorption of lactose.
• Simultaneous use of terfenadine (at a fluconazole dosage of more than 400 mg/day, combination with terfenadine is contraindicated).
• Elevated levels of liver enzymes.
• Kidney failure.

Fluconazole during pregnancy

During pregnancy, taking the drug is permissible only if the benefit from it outweighs the potential harm to the fetus. Fluconazole passes into breast milk. If treatment is necessary during lactation, it is recommended to stop breastfeeding.

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Is it worth experimenting with fluconazole and alcohol?

Alcohol and fluconazole are two substances that have a toxic effect on the liver. Yes, other systems and organs may suffer from this combination. Or, in extreme cases, treatment of the fungus with fluconazole will not have results if alcohol is consumed during this period. So, you shouldn’t experiment with your own health. To prove this, read this article.

Effects of fluconazole on the liver

• Changes in laboratory data (increase in bilirubin in the blood, excessive activity of liver enzymes).
• The skin and sclera acquire a yellowish tint.
• Hepatitis.
• Necrosis of liver cells.
• All side effects can last either for a short time or have serious consequences, causing irreversible changes in the organ.

Double harm to the liver

Harm to other organs and tissues

The role of alcohol in the treatment of fungus

Ethyl alcohol or alcohol when taken orally is characterized by rapid absorption into the blood and a significant effect on cellular metabolism. This disrupts the functioning of all active substances important in metabolic processes. And this, in turn, leads to leveling the effect of fluconazole and reducing its effect. Fluconazole is an effective drug in the fight against fungal infections. But at the same time, it has a number of side effects, including a detrimental effect on brain and liver cells. To avoid irreversible consequences, alcohol consumption is prohibited during treatment with fluconazole. This is indicated in the instructions for use of the drug and you should not skip these lines, arguing that fluconazole is not a “strong” medicine!

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Fluconazole effect on the liver

Alcohol and fluconazole are two substances that have a toxic effect on the liver. Yes, other systems and organs may suffer from this combination. Or, in extreme cases, treatment of the fungus with fluconazole will not have results if alcohol is consumed during this period. So, you shouldn’t experiment with your own health. To prove this, read this article.

The effect of fluconazole on the liver The effect of fluconazole and alcohol on brain cells The role of alcohol in the treatment of fungus

Fluconazole is an effective medical antifungal drug that has a wide spectrum of action. The work of the product is directly related to the destruction of biologically active substances necessary for the construction of membranes in fungal cells. Consequently, if there are not enough of these substances, then the vital activity of fungi is disrupted and their cells die.

Fluconazole, like other active medications, can cause many side effects. Central to this list is the detrimental effect on liver cells (hepatotoxicity).

It is noteworthy that the liver suffers from the toxic effect to the greatest extent when there is some kind of disturbance in the functioning of this organ. A healthy liver experiences virtually no negative effects.

Unfortunately, few patients are aware of the presence of this or that liver disease. The reason for this is the absence of symptoms, which are noticeable only in advanced cases. When prescribing an antifungal agent, a doctor must force the patient to check the functioning of the liver. In reality, such a procedure is not performed often, so the hepatotoxic effect of fluconazole cannot be excluded.

Impaired liver function when treated with this drug manifests itself in the following form:

Changes in laboratory data (increase in bilirubin in the blood, excessive activity of liver enzymes). The skin and sclera acquire a yellowish tint. Hepatitis. Necrosis of liver cells. All side effects can last either for a short time or have serious consequences, causing irreversible changes in the organ.

The prescription for the drug states that while taking fluconazole, it is prohibited to use other medications or hepatotoxic substances. Of course, alcohol is no exception, since it directly has a toxic effect on liver cells (hepatocytes), destroying and replacing them with fat cells or connective tissue cells. For minor liver ailments, the medicine may not have any effect, but combining it with alcohol will cause irreparable harm to the organ.

The effect of fluconazole and alcohol on brain cells

Fluconazole can also negatively affect neurons (brain cells). This side effect is rare and manifests itself as:

seizures; loss of performance; fatigue; dizziness; headache.

In case of overdose, hallucinations and delusions occur.

Alcohol affects brain cells in the same way as it affects hepatocytes. And the combination of alcohol intake with fluconazole treatment will increase the neurotoxic effect several times. Moreover, the induced condition is difficult to predict.

The antifungal drug also affects the circulatory system. All this is reflected in the activity of the heart, even causing ventricular flutter and atrial fibrillation.

Alcoholic drinks, especially strong ones, first simply dilate blood vessels, and then sharply narrow them.

It’s no wonder that chronic alcoholics experience increased blood pressure. All this puts a lot of stress on the heart and leads to various disorders of its functions. The combination of alcohol and fluconazole can cause a severe attack of arrhythmia.

Ethyl alcohol or alcohol when taken orally is characterized by rapid absorption into the blood and a significant effect on cellular metabolism. This disrupts the functioning of all active substances important in metabolic processes. And this, in turn, leads to leveling the effect of fluconazole and reducing its effect. Fluconazole is an effective drug in the fight against fungal infections. But at the same time, it has a number of side effects, including a detrimental effect on brain and liver cells. To avoid irreversible consequences, alcohol consumption is prohibited during treatment with fluconazole. This is indicated in the instructions for use of the drug and you should not skip these lines, arguing that fluconazole is not a “strong” medicine!

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Fluconazole is a fairly serious antifungal drug that has a number of possible side effects, contraindications and drug interactions. Applies 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.

It is well absorbed from the intestine (bioavailability 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. Excreted by the kidneys (mainly). Partially affects hormonal levels in men.

High doses of fluconazole negatively affect 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 amounts of fluconazole administered to the animal weight, no negative effects from the fetus or mother were identified. The existing negative effects when prescribing high doses are attributed to the moderate effect of the drug on hormonal levels.

For pregnant women, fluconazole is indicated only for severe infections that threaten the life of the mother and/or fetus. Only the attending physician can take responsibility, 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 fairly 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 to the fetus is assessed as C, i.e. speculative.

During the mother's therapy, breastfeeding should be stopped, because... Fluconazole is found in breast milk in the same concentrations as in the blood (as already mentioned, it penetrates perfectly into all liquids).

Side effects of the drug

In the USA, a fairly serious study was conducted on 448 patients taking fluconazole in a standard therapeutic dosage, i.e. 150 mg once for the treatment of vaginal candidiasis (thrush). Every fourth person experienced the following side effects while taking the drug:

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

The rest felt some poorly differentiated negative sensations. In isolated cases, fluconazole causes a severe 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 and cytostatics was in HIV patients. The main side effects were the same as in the first group of subjects.

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

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

This may be due to the parallel use of heavy specific antibiotics: isoniazid, rifampicin, phenytoin, pyrazinamide.

A side effect differs from a side effect in that the connection between the event and the use of a specific drug has not been proven. However, manufacturing companies are required to record everything that happens to the patient (control group) during treatment and include it in the instructions:

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

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

Decreased potassium levels.

The studies were conducted in the USA and Europe and included 577 children from one day old to 17 years old inclusive. The dosage for all was 15 mg/kg body weight/day for a long 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.

This medicine may cause harm in the following conditions:

Overdose and first aid

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

Skin rashes

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

There is information about one patient who, with an overdose of fluconazole, experienced symptoms of paranoid delusions and hallucinations. Considering that this was a 42-year-old HIV patient (drug addict), such side effects may not be considered typical for an 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, and do not drink alcohol during this period. Particular attention should be paid to elderly relatives who are taking many different medications at the same time, since this significantly increases the risk of side effects while taking fluconazole.

General practitioner at a city clinic. Eight years ago I graduated from Tver State Medical University with honors.

The antifungal agent Fluconazole is a synthetic antimycotic that belongs to the group of triazole derivatives. The action of the drug is based on the inhibition of fungal cytochrome P450 enzymes.

In the human body, Fluconazole inhibits the cytochrome P450 enzyme CYP2C9, which is involved in the metabolism of anticoagulants - drugs that reduce blood clotting and prevent the formation of blood clots.

Fluconazole does not inhibit the main group of cytochrome P450-dependent enzymes in humans, which makes it safer for the liver than other classes of antifungals.

The antimycotic Fluconazole is used in the treatment of a wide range of fungal diseases; it is used in the treatment of:

candidiasis – skin, genitals, mouth, lungs; microsporia; trichophytosis; blastomycosis.

An antifungal agent is prescribed during treatment with antibiotics, chemotherapy, and organ transplantation to prevent fungal diseases.

The drug is available in tablets, capsules, and powders for injection. When taking capsules, the maximum concentration in the blood is created after 1.5 hours. The time during which the concentration of Fluconazole in the blood plasma decreases by 2 times is 30 hours.

The antimycotic easily penetrates into all body fluids and is maintained in a therapeutic dose throughout the day. The medicine is found in saliva, breast milk, cerebrospinal fluid, sputum, vaginal secretions, sweat fluid.

“Can alcoholism be cured? Yes! Use an effective home remedy..."

The drug is excreted from the body by the kidneys; the duration of the half-life depends on their functional state. In case of renal failure, the elimination of the drug slows down.

An absolute contraindication for the antimycotic is an allergy to the drug, breastfeeding, and age under 4 years. It is prescribed with caution to elderly people, persons suffering from renal failure, liver diseases, and during pregnancy.

A relative contraindication is the simultaneous use of drugs with hepatotoxic effects and alcohol. In this case, when prescribing a medicine, the possible benefits or harm that it may have on human health are assessed.

The most pronounced side effects are observed in the digestive tract. Taking an antimycotic causes:

pain in the stomach; nausea, vomiting; perversion of taste, lack of appetite; jaundice, hepatonecrosis.

Fluconazole causes dysfunction of the nervous system. Long-term treatment with this antifungal agent can cause dizziness, fatigue, convulsions, and in case of overdose, hallucinations and changes in behavior.

Dangerous changes occur when the body reacts adversely to Fluconazole from the heart. Changes in the cardiogram are noted (prolongation of the Q-T interval), atrial fibrillation. Less commonly, there is a decrease in potassium in the blood, damage to the hematopoietic system and kidneys.

In the video, information about the drug Fluconazole:

The danger of compatibility between Fluconazole and ethyl alcohol lies in their effect on the liver and heart. Simultaneous use of the drug and ethanol can cause severe allergic reactions - anaphylactic shock, angioedema.

In addition, if you take alcohol together with Fluconazole, dysfunction of the balance organs is possible with the development of true vertigo - a disease in which dizziness can last for several hours.

Alcohol, like antimycotics, negatively affects the electrocardiogram (ECG). These toxic compounds, when used together, make changes to the ECG that threaten sudden death.

One of the possible side effects of taking Fluconazole is prolongation of the Q-T interval on the ECG. Alcohol, especially with long-term abuse, causes a similar ECG change.

The cardiotoxic effect of Fluconazole and ethanol is manifested by dizziness and loss of consciousness. The asymptomatic course of this disorder is especially dangerous. With a hidden, asymptomatic form of long QT interval syndrome, the risk of sudden death increases.

Both alcohol and Fluconazole have a toxic effect on the liver and cause an increase in bilirubin in the blood, a breakdown product of red blood cells.

Liver dysfunction is accompanied by:

yellowing of the skin, whites of the eyes; darkening of urine and feces; irritability, weakness; drowsiness, fainting.

Like alcohol, Fluconazole can increase the level of the liver enzyme alkaline phosphatase, causing nausea, abdominal pain, and fever.

The use of antimycotics and alcohol affects the liver in a similar way:

activates the enzymes alanine aminotransferase, aspartate aminotransferase; increases the risk of liver failure.

The most likely consequence of the simultaneous interaction of Fluconazole and alcohol is hepatonecrosis of the liver. Moreover, the alcohol itself will change the effect of the drug on the body.

The most dangerous changes in cardiac activity are:

heart rhythm disturbance; cardiac ischemia; heart attack

The most dangerous consequences of taking the drug and large doses of alcohol are cirrhosis of the liver, sudden death due to cardiac arrest.

Doctors note that you should not drink even small doses of alcohol when taking antimycotics. The substances are not compatible with each other. But is it possible to drink alcohol 30 hours after Fluconazole, after the half-life of the drug has passed?

In this case, you need to remember that the half-life corresponds to a halving of the therapeutic concentration, and not to the complete elimination of the drug from the body.

In case of liver failure, in old age, this antimycotic remains in the body for a long time, which is taken into account when prescribing the dosage - in this case it is reduced by 2 times.

A certain amount of Fluconazole is present in the blood plasma even after 30 hours. And with concomitant kidney diseases, the half-life interval itself may increase.

So how long before you can drink alcohol? For the body to completely clear Fluconazole, 3 days or more must pass if the patient has kidney disease. Trace levels of this antimycotic can be detected within 5 days.

You can drink alcohol after Fluconazole no earlier than 3 days later. It is advisable to extend this period to 5 days to allow the liver and kidneys to completely rid the body of the presence of the antimycotic.

Fluconazole - description, indications and side effects

Fluconazole is a triazole antifungal drug intended for the treatment and prevention of superficial and systemic fungal infections. In bulk form, it is a white crystalline powder, slightly soluble in water and soluble in alcohol. Typically sold under the trade names Diflucan and Trican (Pfizer).

Mechanism of action of fluconazole

Similar to the imidazole and triazole class antifungals, fluconazole inhibits the fungal cytochrome 14α-demethylase P450 enzyme. Mammalian demethylase activity is much less sensitive to fluconazole than fungal demethylase. This inhibition prevents the conversion of lanosterol to ergosterol, an important component of the fungal cytoplasmic membrane, and the subsequent accumulation of 14α-methyl sterols. Fluconazole is primarily fungistatic, however, depending on the dose, it can be fungicidal against some microorganisms, in particular Cryptococcus.

It is interesting to note that when fluconazole was in development at Pfizer, a decision was made early in the process to avoid any chiral centers in the drug. Therefore, subsequent synthesis and purification did not encounter difficulties in separating enantiomers and associated changes in biological effect. A number of related compounds have proven to be extremely potent teratogens and have subsequently been discarded.

Video about fluconazole

Microbiology

Fluconazole is active against:

• Blastomyces dermatitidis
• Candida spp. (except C. krusei and C. glabrata)
• Coccidioides immitis
• Cryptococcus neoformans
• Epidermophyton spp.
• Histoplasma capsulatum
• Microsporum spp.
• Trichophyton spp.

Sustainability

Fungal resistance to drugs in the azole class tends to develop gradually over long-term drug treatment, leading to clinical failure in immunocompromised patients (eg, patients with advanced HIV who are being treated for thrush or esophageal Candida infections).

In C. albicans, resistance occurs through mutations in the ERG11 gene, which encodes 14α-demethylase. These mutations prevent binding of the azole drug, although they allow binding of the enzyme's natural substrate, lanosterol. Development of resistance to one azole will thus confer resistance to all anti-TB drugs in the class. Another resistance mechanism used by both C. albicans and C. glabrata increases the rate of azole drug efflux from the cell via the ATP-binding cassette and essential messenger superfamily transporters. Other gene mutations are known to promote resistance.

The full spectrum of fungal susceptibility and resistance to fluconazole can be found in the TOKU-E product data sheet.

Pharmacokinetics

After oral administration, fluconazole is almost completely absorbed within two hours. The absence of stomach acid does not significantly affect bioavailability. Concentrations measured in urine, tears and skin are approximately 10 times higher than plasma concentrations, while concentrations in saliva, sputum and vaginal secretions are approximately equal to plasma concentrations after a standard dose ranging from 100 mg to 400 mg per day. The half-life of fluconazole follows zero-order kinetics, and only 10% of elimination is due to metabolism, with the rest being excreted through urine and sweat. Patients with impaired renal function should be wary of overdose.

Indications for use of fluconazole

Fluconazole is indicated for the treatment and prevention of fungal infections when other antifungal agents have failed or are not tolerated (eg, due to adverse effects), including:

• Candidiasis caused by sensitive strains of Candida
• Ringworm, tinea groin, or tinea pedis
• Onychomycosis
• Cryptococcal meningitis
• Fluconazole can be used as first-line therapy for the following indications:
• Coccidioidomycosis
• Cryptococcosis
• Histoplasmosis
• Preventing candidiasis in people with suppressed immune systems
• Auto-brewing syndrome

Dosage

Dosage varies with indication and between patient groups, ranging from a two-week course of 150 mg/day for vulvovaginal candidiasis to once weekly for persistent skin infections or some prophylactic indications. Dosages of mg/day can be used for systemic or serious infections, and in case of emergency infections such as meningitis caused by yeast, a dose of 800 mg/day has been used. In children, doses are estimated at 6-12 mg/kg/day. The loading dose will be indicated when entering the daily dosage schedule, for example, a loading dose of 200 mg on the first day and then 150 mg/day is usually used.

Contraindications

Fluconazole is contraindicated in patients who:

• Have known hypersensitivity to another azole drug.
• Terfenadine is taken if a multidose of fluconazole 400 mg per day is administered.
• Fluconazole (especially in high doses) and quinidine are taken at the same time.
• Pregnant.
• Take selective serotonin reuptake inhibitors.

Precautions while taking fluconazole

Fluconazole is secreted in human milk in concentrations similar to plasma. Therefore, the use of fluconazole in nursing mothers is not recommended.

Fluconazole therapy is associated with QT prolongation, which can lead to serious cardiac arrhythmias. Therefore, it is used with caution in patients with risk factors for QT prolongation, such as electrolyte imbalance or use of other medications that may prolong the QT interval (especially cisapride and pimozide).

Fluconazole has also rarely been associated with severe or fatal hepatotoxicity, so liver function tests are usually performed routinely during long-term fluconazole therapy. Additionally, it is used with caution in patients with pre-existing liver disease.

Some people are allergic to azoles, so those who are allergic to other azole drugs may be allergic to fluconazole. That is, some azole drugs have unwanted side effects. Some azole drugs may interfere with estrogen production during pregnancy, affecting pregnancy outcome.

Fluconazole 150 mg is classified as pregnancy category C by the FDA. However, high doses (mg/day) have been associated with a rare and specific set of birth defects in infants. When taken at these doses, pregnancy category C changes to pregnancy category D. This indicates that there is positive evidence of risk to the human fetus based on human data. In some cases, such as if a pregnant woman has a serious or life-threatening condition, the potential benefits of a drug may be acceptable despite the risks. Fluconazole should not be taken during pregnancy or if you may become pregnant during treatment without first consulting your doctor. Oral fluconazole is not associated with a significant increase in the risk of birth defects overall, although it does increase the tetralogy of Fallot ratio, but the absolute risk remains low.

Fluconazole should not be taken with cisapride (Propulsid) due to the possibility of serious, even fatal, heart problems. In rare cases, serious allergic reactions, including anaphylactic shock, may occur.

Side effects

Adverse drug reactions associated with fluconazole treatment include:

• Common (≥1% of patients): rash, dizziness, headache, vomiting, nausea, abdominal pain, diarrhea and/or increased liver enzymes.
• Uncommon (0.1–1% of patients): anorexia, fatigue, constipation.
• Rare (<0.1% пациентов): олигурия, гипокалиемия, алопеция, парестезия, судороги, синдром Стивенса-Джонсона, тромбоцитопения, другие патологические изменения крови, серьезная гепатотоксичность, включая печеночную недостаточность, анафилактические/анафилактоидные реакции.
• Very rare: prolonged QT interval, torsade de pointes.

According to the FDA, treatment with high-dose (mg/day) chronic fluconazole in the first trimester of pregnancy may be associated with a rare and specific set of birth defects in infants.

Fluconazole drug interactions

Fluconazole is an inhibitor of the human cytochrome P450 system, in particular the CYP2C9 isoenzyme (CYP3A4 to a lesser extent). In theory, therefore, fluconazole decreases metabolism and increases the concentration of any drug metabolized by these enzymes. In addition, its potential effect on the QT interval increases the risk of cardiac arrhythmia if used concomitantly with other drugs that prolong the QT interval. Berberine has been shown to have a synergistic effect with fluconazole even in drug-resistant Candida albicans infections.

Synthesis

Fluconazole can be synthesized from a halogenated acetophenone derivative.

Brands

Fluconazole is sold as a single dose of 150 mg without a prescription in Canada under the brand names Monicure and Canesten. In Mexico it is sold over the counter as Alfumet, Afungil or Dofil. It is sold under the brand name Candivast in the Gulf region. In Colombia it is sold as Batén by Laboratorios Bussié. In Panama it is sold under the name Ibarin from various manufacturers. In Egypt it is sold under the names Diflucan, Flucoral, Fungican, Triconal. India's No. 1 brand Zocon comes in the form of tablets, lotion, powder, transgel and eye drops.

Recommendations and opinions published on the site are for reference or popular information and are provided to a wide range of readers for discussion. The information provided does not replace qualified medical care based on medical history and diagnostic results. Be sure to consult your doctor.