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Diflucan

Diflucan
The active substance of Diflucan, fluconazole, has been developed for the treatment of candidiasis and mycosis and other models of fungal infections in people of different ages. The effectiveness of the drug directly depends on the correctly selected dose, this information is contained in the Diflucan section of the instruction and requires careful study.

Brand: Fluconazole

Availability: In Stock
Average Delivery Time: 9 Days
Exp. Date: November 2023
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Diflucan 400 mg
270 pills - 400 mg
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$752.95 $2.79 $757.70 Add to cart
180 pills - 400 mg
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$521.53 $2.90 $485.57 Add to cart
120 pills - 400 mg
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$369.71 $3.08 $301.69 Add to cart
90 pills - 400 mg
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$291.55 $3.24 $212.00 Add to cart
60 pills - 400 mg
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$215.56 $3.59 $120.14 Add to cart
30 pills - 400 mg
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$137.99 $4.60 $29.86 Add to cart
10 pills - 400 mg $55.95 $5.60 No Add to cart
Diflucan 200 mg
270 pills - 200 mg
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$583.93 $2.16 $629.72 Add to cart
180 pills - 200 mg
+ 12 free Viagra 100 mg, 7% discount for future orders
$404.18 $2.25 $404.92 Add to cart
120 pills - 200 mg
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$285.99 $2.38 $253.41 Add to cart
90 pills - 200 mg
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$227.29 $2.53 $177.26 Add to cart
60 pills - 200 mg
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$166.91 $2.78 $102.79 Add to cart
30 pills - 200 mg
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$102.99 $3.43 $31.86 Add to cart
10 pills - 200 mg $44.95 $4.50 No Add to cart
Diflucan 150 mg
270 pills - 150 mg
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$347.91 $1.29 $488.82 Add to cart
180 pills - 150 mg
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$245.95 $1.37 $311.87 Add to cart
120 pills - 150 mg
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$175.99 $1.47 $195.89 Add to cart
90 pills - 150 mg
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$139.34 $1.55 $139.57 Add to cart
60 pills - 150 mg
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$101.80 $1.70 $84.14 Add to cart
30 pills - 150 mg $63.69 $2.12 $29.28 Add to cart
10 pills - 150 mg $30.99 $3.10 No Add to cart
Diflucan 100 mg
270 pills - 100 mg
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$285.99 $1.06 $442.74 Add to cart
180 pills - 100 mg
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$197.72 $1.10 $288.10 Add to cart
120 pills - 100 mg
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$139.54 $1.16 $184.34 Add to cart
90 pills - 100 mg
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$111.32 $1.24 $131.59 Add to cart
60 pills - 100 mg $79.99 $1.33 $81.95 Add to cart
30 pills - 100 mg $52.93 $1.76 $28.04 Add to cart
10 pills - 100 mg $26.99 $2.70 No Add to cart
Diflucan 50 mg
270 pills - 50 mg
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$213.56 $0.79 $380.17 Add to cart
180 pills - 50 mg
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$146.87 $0.82 $248.95 Add to cart
120 pills - 50 mg
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$103.45 $0.86 $160.43 Add to cart
90 pills - 50 mg $81.73 $0.91 $116.18 Add to cart
60 pills - 50 mg $59.25 $0.99 $72.69 Add to cart
30 pills - 50 mg $38.95 $1.30 $27.02 Add to cart
10 pills - 50 mg $21.99 $2.20 No Add to cart

Product description

Pharmacological action of Diflucan 

Fluconazole, a representative of the class of triazole antifungal agents, is a potent selective inhibitor of sterol synthesis in the fungal cell.

Fluconazole has demonstrated activity 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 against the following microorganisms in vitro, but the clinical significance of this is unknown: Candida dubliniensis, Candida guilliermondii, Candida kefyr, Candida lusitaniae.

When taken orally, fluconazole was active in various animal models of fungal infections. Demonstrated the activity of the drug in opportunistic mycoses, incl. caused by Candida spp. (including generalized candidiasis in immunosuppressed animals); Cryptococcus neoformans (including intracranial infections); Microsporum spp. and Trichophyton spp. The activity of fluconazole was also established in models of endemic mycoses in animals, including infections caused by Blastomyces dermatitides, Coccidioides immitis (including intracranial infections) and Histoplasma capsulatum in animals with normal and suppressed immunity.

Fluconazole is highly specific for cytochrome P450 dependent fungal enzymes. Fluconazole therapy at a dose of 50 mg / day for up to 28 days does not affect the concentration of testosterone in the blood plasma in men or the concentration of steroids in women of childbearing age. Fluconazole at a dose of 200-400 mg / day does not have a clinically significant effect on endogenous steroid levels and their response to adrenocorticotropic hormone (ACTH) stimulation in healthy male volunteers.

Mechanisms for the 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 for fluconazole (lanosteril 14-α-demethylase), reduced 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 the affinity for azoles. An increase in the expression of the ERG11 gene leads to the production of high concentrations of the target enzyme, which creates 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 elimination of fluconazole from the intracellular space through the activation of two types of transporters involved in the active elimination (efflux) of drugs from the fungal cell. These transporters include the main mediator encoded by the MDR (Multidrug Resistance) genes and the ATP-binding cassette transporter superfamily encoded by the CDR genes (genes for resistance of Candida fungi to azoles antimycotics).

Overexpression of the MDR gene leads to resistance to fluconazole, while overexpression of the CDR genes can lead to resistance to various azoles.

Resistance to Candida glabrata is usually mediated by overexpression of the CDR gene, resulting in multiple azole resistance. For those strains in which the minimum inhibitory concentration (MIC) is defined as intermediate (16-32 μg / ml), it is recommended to use the maximum dose of fluconazole.

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

Pharmacokinetics

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

Absorption

After oral administration, fluconazole is well absorbed, its plasma concentrations (and overall bioavailability) exceed 90% of those for intravenous administration. Simultaneous food intake does not affect the absorption of fluconazole. Cmax is achieved within 0.5-1.5 hours after taking fluconazole on an empty stomach. Plasma concentration is proportional to dose.

The distribution of Diflucan

90% Css is achieved by the 4-5th day after the start of therapy (with repeated administration 1 time / day). The introduction of a loading dose (on the 1st day), 2 times the average daily dose, makes it possible to achieve Css 90% by the 2nd day. Vd approaches the total body water content. Plasma protein binding is low (11-12%).

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

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

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

In a pharmacokinetic study involving 10 women who temporarily or completely stopped breastfeeding, the concentration of fluconazole in blood plasma and breast milk was assessed within 48 hours after a single dose of 150 mg of Diflucan®. Fluconazole was found in breast milk at an average concentration of approximately 98% of the maternal plasma concentration of fluconazole. The average Cmax was 2.61 mg / l after 5.2 hours after taking the drug.

Metabolism and excretion

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

T1/2 from plasma is about 30 hours. Prolonged T1/2 from plasma allows you to take fluconazole once for vaginal candidiasis and 1 time / day or 1 time / week. with other indications.

It was found that with a single use of fluconazole at a dose of 50 mg orally in elderly patients aged 65 years and older, some of whom were simultaneously taking diuretics, Cmax was reached 1.3 hours after administration and was 1.54 μg / ml, average AUC values ​​were 76.4 ± 20.3 μg × h / ml, and the average T1/2 is 46.2 h. The values ​​of these pharmacokinetic parameters are higher than in young patients, which is probably due to the decreased renal function characteristic of the elderly. Simultaneous intake of diuretics did not cause a pronounced change in AUC and Cmax.

CC (74 ml / min), the percentage of fluconazole excreted by the kidneys unchanged (0-24 hours, 22%), and the renal clearance of fluconazole (0.124 ml / min / kg) in elderly patients is lower than in young patients.

Indications of the drug Diflucan®

Treatment of candidiasis with Diflucan

For the treatment of the following diseases in adults:

  • cryptococcal meningitis;

  • coccidioidomycosis;

  • invasive candidiasis;

  • mucous candidiasis, incl. oropharyngeal candidiasis, esophageal candidiasis, candiduria and chronic mucocutaneous candidiasis;

  • chronic atrophic oral candidiasis (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. dermatophytosis of the feet, dermatophytosis of the trunk, inguinal dermatophytosis, versicolor versicolor and cutaneous candidiasis, when systemic treatment is indicated;

  • dermatophytosis of the nails (onychomycosis), when treatment with other drugs is not acceptable.

For the prevention of the following diseases in adults:

  • relapse of cryptococcal meningitis in patients with a high risk of relapse;

  • recurrence of oropharyngeal candidiasis and esophageal candidiasis in HIV-infected patients with a high risk of recurrence;

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

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

Fluconazole is indicated for the treatment of children.

Fluconazole is used to treat mucous candidiasis (oropharyngeal and esophageal candidiasis), invasive candidiasis, cryptococcal meningitis, and the prevention of candidal infections in patients with weakened immune systems.

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

Dosing regimen of Diflucan

Packaging of tablets Diflucan

Inside. The capsules are swallowed whole.

Therapy can be started pending culture and other laboratory test results. However, antifungal therapy must be modified accordingly when the results of these studies become known.

When transferring a patient from intravenous to oral administration of the drug, or vice versa, no change in the daily dose is required.

The daily dose of Diflucan® depends on the nature and severity of the fungal infection. For infections requiring repeated administration of the drug, treatment should be continued until the disappearance of clinical or laboratory signs of active fungal infection. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require supportive care to prevent recurrent infection.

Adults

For cryptococcal meningitis and cryptococcal infections of other localization, 400 mg is usually used on the first day, and then treatment is continued at a dose of 200-400 mg 1 time / day. The duration of treatment for cryptococcal infections depends on the clinical and mycological effect; for cryptococcal meningitis, treatment is usually continued for at least 6-8 weeks. In cases of treatment of life-threatening infections, the daily dose can be increased to 800 mg.

To prevent the recurrence of cryptococcal meningitis in patients with a high risk of recurrence, after the completion of the full course of primary treatment, therapy with Diflucan® at a dose of 200 mg / day can be continued indefinitely.

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

For candidemia, disseminated candidiasis and other invasive candidal infections, the saturating dose is 800 mg on the first day, followed by 400 mg / day. The duration of therapy depends on the clinical effectiveness. The general recommendation for duration of treatment for candidemia is 2 weeks after the first negative blood culture result and the disappearance of the signs and symptoms of candidemia.

Treatment of mucous candidiasis

In oropharyngeal candidiasis, the saturating dose is 200-400 mg on the first day, the subsequent dose is 100-200 mg 1 time / day for 7-21 days. If necessary, in patients with severe suppression of immune function, treatment can be continued for a longer time. In case of atrophic candidiasis of the oral cavity associated with wearing dentures, the drug is usually used at a dose of 50 mg 1 time / day for 14 days in combination with local antiseptic agents for processing the denture.

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

In chronic mucocutaneous candidiasis, 50-100 mg / day are used for up to 28 days of treatment. Longer periods of therapy may be used depending on the severity of the infection or concomitant immune system disorder and infection.

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

For the prevention of recurrence of oropharyngeal candidiasis in HIV-infected patients with a high risk of recurrence, the drug is used at 100-200 mg / day or 200 mg 3 times / week. for an indefinite period of time in patients with chronically lowered immunity.

To prevent recurrence of esophageal candidiasis in HIV-infected patients with a high risk of recurrence, the drug is used at 100-200 mg / day or 200 mg 3 times / week. for an indefinite period of time in patients with chronically lowered immunity.

In chronic atrophic candidiasis of the oral cavity associated with the interconnection of dentures, the drug is usually used at a dose of 50 mg 1 time / day for 14 days in combination with local antiseptic agents for processing the denture.

In acute vaginal candidiasis, candidal balanitis, the drug is used once orally at a dose of 150 mg. To reduce the frequency of relapses of vaginal candidiasis, the drug can be used at a dose of 150 mg every three days - only 3 doses (on the 1st, 4th and 7th day), then a maintenance dose of 150 mg 1 time / week. A maintenance dose can be used for up to 6 months.

Treatment of dermatomycosis

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

With multi-colored lichen, the recommended dose is 300-400 mg 1 time / week. within 1-3 weeks. An alternative treatment regimen is the use of the drug at 50 mg 1 time / day for 2-4 weeks.

With onychomycosis, the recommended dose is 150 mg 1 time / week. Treatment should be continued until the infected nail is replaced (an uninfected nail grows out). Re-growth of nails on fingers and toes usually takes 3-6 months and 6-12 months, respectively. However, the growth rate can vary widely from person to person, as well as age. After successful treatment of persistent chronic infections, nail shape changes are sometimes observed.

For the prevention of candidiasis in patients with malignant tumors, the recommended dose of Diflucan® is 200-400 mg 1 time / day, depending on the degree of risk of developing a fungal infection. For patients at high risk of generalized infection, for example, with severe or long-term neutropenia, the recommended dose is 400 mg 1 time / day. Diflucan® is used a few days before the expected development of neutropenia, after an increase in the number of neutrophils more than 1000 mm3, the treatment is continued for another 7 days.

Children

As with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. For children, the daily dose of the drug should not exceed that for adults. Diflucan® is used daily 1 time / day.

For candidiasis of the mucous membranes, the recommended dose of Diflucan® is 3 mg / kg 1 time / day. On the first day, in order to more quickly reach the equilibrium concentration, a loading dose of 6 mg / kg / day can be used.

For the treatment of invasive candidiasis and cryptococcal meningitis, the recommended dose is 6-12 mg / kg 1 time / day, depending on the severity of the disease.

To suppress the recurrence of cryptococcal meningitis in children with AIDS, the recommended dose of Diflucan® is 6 mg / kg / day.

For the prevention of fungal infections in children with suppressed immunity, in whom the risk of developing an infection is associated with neutropenia, which develops as a result of cytotoxic chemotherapy or radiation therapy, the drug is used at 3-12 mg / kg 1 time / day, depending on the severity and duration of preservation of induced neutropenia (see dose for adults; for children with renal failure - see dose for patients with renal failure).

If the correct use of the dosage form of the drug Diflucanin children is impossible® in the form of capsules, the possibility of replacing it with other dosage forms of the drug (powder for preparation of a suspension for oral administration or solution for intravenous administration) in equivalent doses should be considered.

In elderly patients with no signs of renal failure Diflucan® is used in the usual dose. In patients with renal insufficiency (CC <50 ml / min), the dose of the drug is adjusted as described below.

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

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


Contraindications to the use of

  • simultaneous use of terfenadine during repeated use of fluconazole at a dose of 400 mg / day or more;

  • simultaneous use with drugs that increase the QT interval and are metabolized by the CYP3A4 isoenzyme, such as cisapride, astemizole, erythromycin, pimozide and quinidine;

  • lactase deficiency, galactose intolerance, glucose-galactose malabsorption;

  • children under 3 years of age (for this dosage form);

  • hypersensitivity to fluconazole, other components of the drug, or azole substances with a structure similar to fluconazole.

With care: liver failure; renal failure; the appearance of a rash against the background of the use of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections; simultaneous use of terfenadine and fluconazole at a dose of less than 400 mg / day; potentially proarrhythmic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance and concomitant therapy that promotes the development of such disorders).

Application during pregnancy and lactation There are no

adequate and well-controlled studies of the use of fluconazole in pregnant women. During pregnancy, the use of fluconazole should be avoided, except in cases of severe and potentially life-threatening fungal infections, when the expected benefit of treatment to the mother outweighs the possible risk to the fetus.

It is necessary to consider effective methods of contraception in women of childbearing age during the entire period of treatment and for about a week (5-6 half-lives) after taking the last dose of the drug.

Cases of spontaneous abortion and the development of congenital anomalies were reported in infants whose mothers received fluconazole at a dose of 150 mg once or repeatedly in the first trimester of pregnancy. 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, malformation of the facial part of the skull, malformation of the cranial vault, cleft palate, curvature of the femur, thinning and lengthening of the ribs, arthrogryposis, and congenital heart defects.

Fluconazole is found in breast milk in concentrations close to plasma levels. T1/2 of the drug from breast milk is approximately equal to T1/2 from plasma - 30 hours The estimated dose of fluconazole absorbed by the infant (taking into account the fact that the average amount of milk consumed is 150 ml / kg daily), and calculated in accordance with the average The Cmax of the drug in breast milk is 0.39 mg / kg / day, which is approximately 40% of the recommended neonatal dose (for children under 2 weeks of age) or 13% of the recommended infant dose for the treatment of mucosal candidiasis.

Breastfeeding can be continued after a single 150 mg dose of fluconazole. It is not recommended to breastfeed after repeated or high dose fluconazole. When deciding on the appointment of the drug Diflucan® against the background of breastfeeding, the following factors should be taken into account: the benefits of breastfeeding for the health and development of the infant, together with the clinical indications for prescribing the drug Diflucan® and the possibility of any potential side effects in the infant or the effect of concomitant pathology of the mother on the health of the baby.

Application for violations of liver function

Precautions: liver failure.

Application for impaired renal function

Precautions: renal failure.

Use in children

Use in children under 3 years of age is contraindicated (for this dosage form).

Use in elderly patients

In elderly patients in the absence of signs of renal failure, the drug is used in the usual dose.

Specific guidance

Cases of superinfection have been reported with non-Candida albicans strains of Candida, which are often naturally resistant to fluconazole (eg Candida krusei). In such cases, alternative antifungal therapy may be required.

During pregnancy, the use of fluconazole should be avoided, except in cases of severe and potentially life-threatening fungal infections, when the expected benefit of treatment to the mother outweighs the possible risk to the fetus. It is necessary to consider effective methods of contraception in women of childbearing age during the entire period of treatment and for about a week (5-6 half-lives) after taking the last dose of the drug.

In rare cases, the use of fluconazole was accompanied by toxic liver changes, incl. with a fatal outcome, mainly in patients with serious concomitant diseases. In the case of hepatotoxic effects associated with the use of fluconazole, there was no clear dependence on the total daily dose of the drug, the duration of therapy, gender and age of the patient. The hepatotoxic effect of the drug was usually reversible; its signs disappeared after discontinuation of therapy. Patients whose liver function indicators are disturbed during treatment with the drug should be monitored for signs of more serious liver damage. If clinical signs or symptoms of liver damage appear, which may be associated with the use of fluconazole, the drug should be discontinued.

As with other azoles, fluconazole in rare cases can cause anaphylactic reactions.

Exfoliative skin lesions such as Stevens-Johnson syndrome and toxic epidermal necrolysis developed in rare cases during treatment with fluconazole. AIDS patients are more likely to develop severe skin reactions with many drugs. If a rash appears in a patient during treatment with a superficial fungal infection, which can be associated with the use of fluconazole, the drug should be canceled. If a rash appears in patients with invasive or systemic fungal infections, they should be carefully observed and the drug should be discontinued if bullous lesions or erythema multiforme appear.

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

Like other azoles, fluconazole can cause an increase in the QT interval on the ECG. Fluconazole causes an increase in the QT interval by inhibiting the current of potassium channels in the IV rectification. An increase in the QT interval caused by other drugs (such as amiodarone) can be enhanced by inhibitors of the cytochrome P450 isoenzyme 3A4 (CYP). With the use of fluconazole, an increase in the QT interval and fibrillation or flutter of the ventricles were observed very rarely in patients with severe diseases with multiple risk factors, such as organic heart disease, electrolyte imbalance and concomitant therapy that promotes the development of such disorders. Patients with hypokalemia and progressive heart failure may be at increased risk of developing life-threatening ventricular arrhythmias and polymorphic ventricular tachycardia. Therefore, such patients with potentially proarrhythmic conditions should use fluconazole with caution.

Patients with diseases of the liver, heart and kidneys are recommended to consult a doctor before using the drug. When using fluconazole 150 mg for vaginal candidiasis, patients should be warned that symptoms usually improve after 24 hours, but sometimes it takes several days for them to completely disappear. If symptoms persist for several days, see your doctor.

The evidence for the efficacy of fluconazole in the treatment of other types of endemic mycoses, such as paracoccidioidomycosis, sporotrichosis and histoplasmosis, is limited, which does not allow for specific dosage recommendations. Fluconazole is a moderate inhibitor of the CYP2C9 isoenzyme and a moderate inhibitor of the CYP3A4 isoenzyme. Fluconazole is also an inhibitor of the CYP2C19 isoenzyme. With simultaneous therapy with drugs with a narrow therapeutic profile, metabolized by isoenzymes CYP2C9, CYP2C19 and CYP3A4, caution is recommended.

It has been reported about the development of adrenal cortex insufficiency in patients receiving therapy with other azoles (eg, ketoconazole). Reversible cases of adrenal cortex insufficiency have been observed in patients receiving fluconazole.

Influence on the ability to drive vehicles and control mechanisms

When using the drug, it is necessary to take into account the possibility of dizziness and seizures.

Overdose

In one case of an overdose of fluconazole, a 42-year-old patient infected with HIV developed hallucinations and paranoid behavior after taking 8200 mg of fluconazole. The patient was hospitalized, his condition returned to normal within 48 hours.

Treatment: in case of overdose, symptomatic therapy is performed (including supportive measures and gastric lavage). Fluconazole is excreted mainly in the urine, so forced diuresis is likely to accelerate its excretion. A 3-hour hemodialysis session reduces plasma fluconazole levels by about 50%.

Drug Interactions

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

The simultaneous 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. arrhythmia ventricular tachysystolic type "pirouette" (torsade de pointes). The use of fluconazole at a dose of 200 mg 1 time / day and cisapride at a dose of 20 mg 4 times / day leads to a pronounced increase in plasma concentrations of cisapride and an increase in the QT interval on the ECG. The simultaneous use of cisapride and fluconazole is contraindicated.

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

Astemizole: the 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 can lead to lengthening of the QT interval and, in some cases, to the development of arrhythmias of the ventricular tachysystolic type "pirouette" (torsade de pointes). The simultaneous use of astemizole and fluconazole is contraindicated.

Pimozide: despite the fact that there have been no relevant studies in vitro or in vivo, the simultaneous use of fluconazole and pimozide can lead to inhibition of the metabolism of pimozide. In turn, an increase in plasma concentrations of pimozide can lead to a prolongation of the QT interval and, in some cases, to the development of arrhythmias of the ventricular tachysystolic type "pirouette" (torsade de pointes). The simultaneous use of pimozide and fluconazole is contraindicated.

Quinidine: despite the fact that there have been no relevant studies in vitro or in vivo, the simultaneous use of fluconazole and quinidine can also lead to inhibition of quinidine metabolism. The use of quinidine is associated with prolongation of the QT interval and, in some cases, with the development of arrhythmias of the ventricular tachysystolic type "pirouette" (torsade de pointes). The simultaneous use of quinidine and fluconazole is contraindicated.

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

The following medicines are not recommended

Halofantrine: fluconazole may increase the concentration of halofantrine in blood plasma due to inhibition of the isoenzyme CYP3A4. It is possible to develop arrhythmias of the ventricular tachysystolic type "pirouette" (torsade de pointes) when used simultaneously with fluconazole, as well as with other azole antifungal drugs, so their combined use is not recommended.

Caution should be exercised when used concomitantly with fluconazole

Amiodarone: the use of amiodarone was associated with prolongation of the QT interval. Caution should be exercised with the simultaneous use of fluconazole and amiodarone, especially when taking a high dose of fluconazole (800 mg).

Care should be taken and, possibly, dose adjustments should be made while using the following drugs and fluconazole

Drugs affecting fluconazole

Hydrochlorothiazide: repeated use of hydrochlorothiazide simultaneously with fluconazole leads to an increase in the concentration of fluconazole in blood plasma by 40%. The effect of this degree of severity does not require a change in the dosage regimen of fluconazole in patients receiving diuretics at the same time, but the doctor should take this into account.

Rifampicin: the simultaneous use of fluconazole and rifampicin leads to a decrease in AUC by 25% and the duration of T1/2 of fluconazole by 20%. In patients taking rifampicin at the same time, it is necessary to consider the advisability of increasing the dose of fluconazole.

Drugs affected by fluconazole

Fluconazole is a moderate inhibitor of cytochrome P450 isoenzymes 2C9 and 3A4 (CYP). Fluconazole is also an inhibitor of the CYP2C19 isoenzyme. In addition, in addition to the effects listed below, there is a risk of an increase in plasma concentrations of other drugs metabolized by isoenzymes CYP2C9, CYP2C19 and CYP3A4, when used simultaneously with fluconazole. In this regard, caution should be exercised with the simultaneous use of the listed drugs, and if necessary, such combinations, patients should be under close medical supervision. It should be borne in mind that the inhibitory effect of fluconazole persists for 4-5 days after discontinuation of the drug due to prolonged T1/2.

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

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

Amphotericin B: In studies in mice (including those with immunosuppression), the following results were noted: a small additive antifungal effect in systemic infection with Candida albicans, no interaction with intracranial infection with Cryptococcus neoformans, and antagonism with systemic infection with Aspergillus fumigatus. The clinical significance of these results is not clear.

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

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

Benzodiazepines (short-acting): after oral administration of midazolam, fluconazole significantly increases the concentration of midazolam and psychomotor effects, and this effect is more pronounced after taking fluconazole orally than when using it intravenously. If concomitant therapy with benzodiazepines is necessary, patients taking fluconazole should be monitored to assess the appropriateness of a corresponding reduction in the dose of benzodiazepine. With the simultaneous use of a single dose of triazolam, fluconazole increases the AUC of triazolam by approximately 50%, Cmax by 20-32% and T1/2 by 25-50% due to inhibition of the metabolism of triazolam. Dose adjustment of triazolam may be necessary.

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

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

Nevirapine: Concomitant use of fluconazole and nevirapine increases the exposure of nevirapine by approximately 100% compared to control data for nevirapine alone. Due to the risk of increased nevirapine excretion with concomitant drug use, some precautions and close patient monitoring are necessary.

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. However, with repeated use of fluconazole at a dose of 100 mg / day, changes in the concentration of cyclosporine in bone marrow recipients were not observed. With the simultaneous use of fluconazole and cyclosporine, it is recommended to control the concentration of cyclosporine in the blood.

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

Fentanyl: there has been a report of one death, possibly associated with the simultaneous use of fentanyl and fluconazole. The disorders are thought to be related to fentanyl intoxication. It has been shown that fluconazole significantly prolongs the elimination time of fentanyl. It should be borne in mind that an increase in the concentration of fentanyl can lead to respiratory depression.

HMG-CoA reductase inhibitors: while the use of fluconazole with HMG-CoA reductase inhibitors, metabolized by the CYP3A4 isoenzyme (such as atorvastatin and simvastatin) or the CYP2D6 isoenzyme (such as fluvastatin), the risk of developing myopathies increases. If simultaneous therapy with these drugs is necessary, patients should be observed in order to identify symptoms of myopathy and rhabdomyolysis. It is necessary to control the concentration of creatinine kinase. In the case of a significant increase in the concentration of creatinine kinase or if myopathy or rhabdomyolysis is diagnosed or suspected, therapy with HMG-CoA reductase inhibitors should be discontinued.

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

Methadone: Fluconazole can increase the plasma methadone concentration. Dose adjustment of methadone may be necessary.

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

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

Despite the lack of targeted studies, fluconazole may increase the systemic exposure of other NSAIDs metabolized by the CYP2C9 isoenzyme (for example, naproxen, lornoxicam, meloxicam, diclofenac). Dose adjustment of NSAIDs may be necessary.

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

Olaparib: Moderate inhibitors of the CYP3A4 isoenzyme, such as fluconazole, increase the plasma concentration of olaparib. Their simultaneous use is not recommended. If it is impossible to avoid simultaneous use, it is necessary to reduce the dose of olaparib to 200 mg 2 times / day.

Oral contraceptives: with the simultaneous use of a combined oral contraceptive with fluconazole at a dose of 50 mg, a significant effect on the level of hormones has not been established, whereas with daily use of 200 mg of fluconazole, the AUC of ethinyl estradiol and levonorgestrel increase by 40% and 24%, respectively, and with the use of 300 mg of fluconazole Once a week, the AUC of ethinylestradiol and norethindrone increase by 24% and 13%, respectively. Thus, repeated use of fluconazole at the indicated doses is unlikely to affect the efficacy of the combined oral contraceptive.

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

Ivacaftor: when used simultaneously with ivacaftor, a stimulant of the cystic fibrosis transmembrane conductance regulator (CFTR), an increase in the exposure of ivacaftor was observed by 3 times and the exposure of hydroxymethyl ivacaftor (M1) by 1.9 times. Patients concurrently taking moderate inhibitors of the isoenzyme CYP3A, such as fluconazole and erythromycin, are recommended to reduce the dose of ivacaftor to 150 mg 1 time / day.

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

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

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

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

Sulfonylurea preparations: fluconazole, when used simultaneously, leads to an increase in T1/2 of oral sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide). Patients with diabetes mellitus can be prescribed the combined use of fluconazole and oral sulfonylurea preparations, but the possibility of hypoglycemia should be taken into account, in addition, regular monitoring of blood glucose and, if necessary, dose adjustment of sulfonylurea preparations is required.

Tacrolimus: the simultaneous use of fluconazole and tacrolimus (by mouth) leads to an increase in serum concentrations of the latter by 5 times due to inhibition of the metabolism of tacrolimus, which occurs in the intestine through the isoenzyme CYP3A4. No significant changes in the pharmacokinetics of the drugs were noted with the use of tacrolimus IV. Cases of nephrotoxicity have been reported. Patients taking oral tacrolimus and fluconazole at the same time should be closely monitored. The dose of tacrolimus should be adjusted depending on the degree of increase in its concentration in the blood.

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

Tofacitinib: the exposure of tofacitinib is increased when it is used together with drugs that are simultaneously moderate inhibitors of CYP3A4 and CYP2C19 isoenzymes (for example, fluconazole). Dose adjustment of tofacitinib may be necessary.

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

Vitamin A: there is a report of one case of development of adverse reactions from the central nervous system in the form of pseudotumor of the brain with the simultaneous use of completely transretinoic acid and fluconazole, which disappeared after the discontinuation of fluconazole. The use of this combination is possible, but you should remember about the possibility of adverse reactions from the central nervous system.

Zidovudine: with simultaneous use with fluconazole, there is an increase in Cmax and AUC of zidovudine by 84% and 74%, respectively. This effect is probably due to a decrease in the metabolism of the latter to its main metabolite. Before and after therapy with fluconazole at a dose of 200 mg / day for 15 days, patients with AIDS and ARC (AIDS-related complex) found a significant increase in the AUC of zidovudine (20%). Patients receiving this combination should be monitored for side effects of zidovudine.

Voriconazole (inhibitor of isoenzymes CYP2C9, CYP2C19 and CYP3A4): simultaneous use of voriconazole (400 mg 2 times / day on the first day, then 200 mg 2 times / day for 2.5 days) and fluconazole (400 mg on the first day, then 200 mg / day for 4 days) in 8 healthy male subjects led to an increase in Cmax and AUC of voriconazole by 57% and 79%, respectively. It has been shown that this effect persists with decreasing the dose and / or decreasing the frequency of administration of any of the drugs. Concomitant use of voriconazole and fluconazole is not recommended.

Studies of the interaction of oral forms of fluconazole while taking it with food, cimetidine, antacids, as well as after total body irradiation to prepare for bone marrow transplantation have shown that these factors do not have a clinically significant effect on the absorption of fluconazole.

The listed interactions have been established with repeated use of fluconazole; drug interactions resulting from a single dose of fluconazole are not known.

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

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. However, with repeated administration of fluconazole at a dose of 100 mg / day, changes in the concentration of cyclosporine were not observed in bone marrow recipients. With the simultaneous use of fluconazole and cyclosporine, it is recommended to control the concentration of cyclosporine in the blood.

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

Fentanyl: there has been a report of one death, possibly associated with the simultaneous administration of fentanyl and fluconazole. The disorders are thought to be related to fentanyl intoxication. It has been shown that fluconazole significantly prolongs the elimination time of fentanyl. It should be borne in mind that an increase in the concentration of fentanyl can lead to respiratory depression.

Halofantrine: Fluconazole may increase the plasma concentration of halofantrine due to inhibition of the CYP3A4 isoenzyme.

HMG-CoA reductase inhibitors: with the simultaneous use of fluconazole with HMG-CoA reductase inhibitors metabolized by the CYP3A4 isoenzyme (such as atorvastatin and simvastatin) or the CYP2D6 isoenzyme (such as fluvastatin and rhabdomyolysis), the risk of myopathy increases. If simultaneous therapy with these drugs is necessary, patients should be observed in order to identify symptoms of myopathy and rhabdomyolysis. It is necessary to control the concentration of creatine kinase. In the case of a significant increase in the concentration of creatine kinase or if myopathy or rhabdomyolysis is diagnosed or suspected, therapy with HMG-CoA reductase inhibitors should be discontinued.

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

Methadone: Fluconazole can increase the plasma methadone concentration. Dose adjustment of methadone may be necessary.

NSAIDs: Cmax and AUC of flurbiprofen increase by 23% and 81%, respectively. Similarly, the Cmax and AUC of the pharmacologically active isomer [S - (+) - ibuprofen] increased by 15% and 82%, respectively, with the simultaneous use of fluconazole with racemic ibuprofen (400 mg). With the simultaneous use of fluconazole at a dose of 200 mg / day and celecoxib at a dose of 200 mg, the Cmax and AUC of celecoxib increase by 68% and 134%, respectively. In this combination, it is possible to reduce the dose of celecoxib by half.

Despite the lack of targeted studies, fluconazole may increase the systemic exposure of other NSAIDs metabolized by the CYP2C9 isoenzyme (for example, naproxen, lornoxicam, meloxicam, diclofenac). Dose adjustment of NSAIDs may be necessary.

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

Oral contraceptives: with the simultaneous use of a combined oral contraceptive with fluconazole at a dose of 50 mg, a significant effect on the level of hormones has not been established, whereas with a daily intake of 200 mg of fluconazole, the AUC of ethinyl estradiol and levonorgestrel increases by 40% and 24%, respectively, and when taking 300 mg of fluconazole 1 time / week AUC of ethinylestradiol and norethindrone increases by 24% and 13%, respectively. Thus, repeated use of fluconazole at the indicated doses is unlikely to affect the efficacy of the combined oral contraceptive.

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

Prednisone: there is a report on the development of acute adrenal cortex insufficiency in a patient after liver transplantation while discontinuing fluconazole after a 3-month course of therapy. Presumably, the cessation of fluconazole therapy caused an increase in the activity of the isoenzyme CYP3A4, which led to an increase in the metabolism of prednisone.

Patients receiving combination therapy with prednisone and fluconazole should be under close medical supervision when discontinuing fluconazole in order to assess the state of the adrenal cortex.

Rifabutin: The simultaneous use of fluconazole and rifabutin can lead to an increase in the plasma concentration of the latter up to 80%. With the simultaneous use of fluconazole and rifabutin, cases of uveitis have been described.

Patients receiving rifabutin and fluconazole concomitantly should be closely monitored.

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

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


Sulfonylurea preparations: fluconazole, when taken simultaneously, leads to an increase in T1/2 of oral sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide). Patients with diabetes mellitus can be simultaneously prescribed fluconazole and sulfonylureas for oral administration, but the possibility of hypoglycemia should be taken into account, in addition, regular monitoring of blood glucose levels and, if necessary, dose adjustment of sulfonylureas are required.

Tacrolimus: the simultaneous use of fluconazole and tacrolimus (by mouth) leads to an increase in serum concentrations of the latter up to 5 times due to inhibition of the metabolism of tacrolimus, which occurs in the intestine through the isoenzyme CYP3A4. No significant changes in the pharmacokinetics of the drugs were noted with the use of tacrolimus IV. Cases of nephrotoxicity have been reported. Patients receiving oral tacrolimus and fluconazole at the same time require careful monitoring. The dose of tacrolimus should be adjusted depending on the degree of increase in its concentration in the blood.

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

Tofacitinib: The exposure of tofacitinib is increased when it is used together with drugs that are both moderate inhibitors of the CYP3A4 isoenzyme and potent inhibitors of the CYP2C19 isoenzyme (for example, fluconazole). Dose adjustment of tofacitinib may be necessary.

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

Vitamin A: there is a report of one case of development of adverse reactions from the central nervous system in the form of pseudotumor of the brain with the simultaneous use of completely transretinoic acid and fluconazole, which disappeared after the discontinuation of fluconazole. The use of this combination is possible, but you should remember about the possibility of adverse reactions from the central nervous system.

Zidovudine: with simultaneous use with fluconazole, there is an increase in Cmax and AUC of zidovudine by 84% and 74%, respectively. This effect is probably due to a decrease in the metabolism of the latter to its main metabolite. Before and after therapy with fluconazole at a dose of 200 mg / day for 15 days, patients with AIDS and ARC (AIDS-related complex) found a significant increase in the AUC of zidovudine (20%). Patients receiving this combination should be monitored for side effects of zidovudine.

Voriconazole (inhibitor of isoenzymes CYP2C9, CYP2C19 and CYP3A4): simultaneous use of voriconazole (400 mg 2 times / day on the first day, then 200 mg 2 times / 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 the concentration and AUC of voriconazole by 57% and 79%, respectively. It has been shown that this effect persists with decreasing the dose and / or decreasing the frequency of administration of any of the drugs. Concomitant use of voriconazole and fluconazole is not recommended.

Studies of the interaction of oral forms of fluconazole while taking it with food, cimetidine, antacids, as well as after total body irradiation to prepare for bone marrow transplantation have shown that these factors do not have a clinically significant effect on the absorption of fluconazole.

The above interaction was established with repeated use of fluconazole; drug interactions resulting from a single dose of fluconazole are unknown.

It should be borne in mind that interaction with other drugs has not been specifically studied, but it is possible.

Side effect

Frequency assessment criteria: very often (≥10%); often (≥1% and <10%); infrequently (≥0.1% and <1%); rarely (≥0.01% and <0.1%); very rare (<0.01%); the frequency is unknown (cannot be determined from the available data).

The drug is usually very well tolerated.

In clinical and post-marketing (*) studies of the drug Diflucan®, the adverse reactions presented below were noted.

From the nervous system: often - headache; infrequently - dizziness *, convulsions *, taste changes *, paresthesia, insomnia, drowsiness; rarely - tremor.

From the digestive system: often - abdominal pain, diarrhea, nausea, vomiting *; infrequently - flatulence, dyspepsia *, dryness of the oral mucosa, constipation.

On the part of the hepatobiliary system: often - increased serum activity of aminotransferases (ALT and AST), alkaline phosphatase; infrequently - cholestasis, jaundice *, increased bilirubin concentration; rarely - hepatotoxicity, in some cases fatal, liver dysfunction *, hepatitis *, hepatocellular necrosis *, hepatocellular damage.

From the side of the skin: often - a rash; infrequently - itchy skin, hives, increased sweating, drug rash (including persistent drug rash); rarely - exfoliative skin lesions *, including Stevens-Johnson syndrome and toxic epidermal necrolysis, acute generalized exanthematous pustulosis, facial edema, alopecia *; frequency unknown - drug rash with eosinophilia and systemic symptoms (DRESS syndrome).

From the hematopoietic system *: rarely - leukopenia, including neutropenia and agranulocytosis, thrombocytopenia, anemia.

From the immune system *: anaphylaxis (including angioedema).

From the side of the cardiovascular system *: rarely - an increase in the QT interval on the ECG, ventricular tachysystolic arrhythmia of the "pirouette" type (torsade de pointes).

From the side of metabolism *: rarely - an increase in the concentration of cholesterol and triglycerides in the blood plasma, hypokalemia.

From the musculoskeletal system: infrequently - myalgia.

Others: infrequently - weakness, asthenia, increased fatigue, fever, vertigo.

In some patients, particularly those with serious diseases such as AIDS or cancer, the treatment of drug Diflucan® and similar drugs have been observed changes in blood counts, kidney and liver, but the clinical significance of these changes and their relationship to treatment is not established.