Diflucan capsules 150 mg 1 pc
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Active ingredients
Fluconazole
Release form
Capsules
Composition
Active ingredient: Fluconazole (Fluconazole) Active ingredient concentration (mg): 150
Pharmacological effect
Antifungal drug of the triazole series, is a potent selective inhibitor of sterol synthesis in the fungal cell. Fluconazole activity in vitro and in clinical infections has been shown for most of the following microorganisms: Candida alhicans, Candida glabrata (many strains are moderately sensitive), Candida parapsilosis, Candida tropicalis, Cryptococcus neoforhora .In vitro fluconazole activity was shown in relation to the following microorganisms, however, its clinical significance is unknown: Candida dubliniensis, Candida guilliermondii, Candida kefyr, Candida lusitaniae. When taken orally and with a / in the introduction of f lukonazol was active in various models of fungal infections in animals. The activity of the drug was demonstrated in opportunistic mycoses, incl. caused by candida spp. (including generalized candidiasis in immunocompromised animals), Cryptococcus neoformans (including intracranial infections), Microsporum spp. and Trychoptyton spp. Fluconazole activity has also been established in models of endemic mycoses in animals, including infections caused by Blastomyces dermatitidis, Coccidioides immitis (including intracranial infections) and Histoplasma capsulatum in animals with normal and reduced immunity. Fluconazole has a high specificity for fungal enzymes, cell-dependent, cytotoxic, cell-dependent, cytotoxic, cell-dependent, cytotoxic, immune-dependent animals. . Fluconazole therapy at 50 mg / day for up to 28 days does not affect the plasma testosterone concentration in men or the concentration of steroids in women of childbearing age. Fluconazole at a dose of 200-400 mg / day did not have a clinically significant effect on the levels of endogenous steroids and their response to stimulation of ACTH in healthy male volunteers. Fluconazole resistance development mechanisms Fluconazole resistance may develop in the following cases: a qualitative or quantitative change in an enzyme that is target for fluconazole (lanosteril 14-α-demethylase), reducing access to the target of fluconazole or a combination of these mechanisms. Point mutations in the ERG11 gene encoding a target enzyme result in a target and decrease the azoles affinity. Increasing 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 lies in the active elimination of fluconazole from the intracellular space by activating two types of transporters,participating in the active elimination (efflux) of fungal cell preparations. These transporters include the main mediator encoded by the MDR genes (multidrug resistance) and the ATP-binding transporter cassette superfamily encoded by the CDR genes (Candida spp. Resistance genes to azole antimycotics). At the same time, overexpression of CDR genes can lead to resistance to various azoles. Resistance to Candida glabrata is usually mediated by overexpression of the CDR gene, which leads to resistance to many azoles. For those strains in which the MIC is defined as an intermediate (16-32 mcg / ml), it is recommended to use the maximum dose of fluconazole. Candida krusei should be considered as a pathogen resistant to fluconazole. The mechanism of resistance is associated with a reduced sensitivity of the target enzyme to the inhibitory effects of fluconazole.
Pharmacokinetics
The pharmacokinetics of fluconazole is similar with intravenous administration and oral administration. Absorption After oral administration, fluconazole is well absorbed, its plasma levels (and total bioavailability) exceed 90% of plasma levels of fluconazole when administered intravenously. Simultaneous ingestion does not affect absorption by ingestion. Cmax is achieved within 0.5-1.5 h after administration of fluconazole on an empty stomach. Plasma concentration is proportional to the dose. The distribution of 90% Css is achieved by the 4-5th day after the start of therapy (with repeated use of 1 time / day). The administration of the loading dose (on the 1st day), 2 times the average daily dose, allows you to reach a Css of 90% by the 2nd day. The Vd approaches the total water content in the body. Plasma protein binding is low (11-12%). Fluconazole penetrates well into all body fluids. Fluconazole levels in saliva and sputum are similar to its plasma concentrations. In patients with fungal meningitis, fluconazole levels in the cerebrospinal fluid make up about 80% of its plasma levels. In the stratum corneum, epidermis, dermis and sweat fluid, high concentrations are reached that exceed serum. Fluconazole builds up in the stratum corneum. When taken in a dose of 50 mg 1 time / day, the concentration of fluconazole after 12 days was 73 mcg / g, and 7 days after stopping treatment - only 5.8 mcg / 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 mcg / g, and 7 days after the second dose was taken - 7.1 mcg / g. The concentration of fluconazole in the nails after 4 months of use at a dose of 150 mg 1 time / week. amounted to 4.05 mcg / g in healthy and 1.8 mcg / g in affected nails; 6 months after completion of therapy, fluconazole was still detected in the nails. When comparing concentrations in saliva and blood plasma after a single dose of fluconazole in a dose of 100 mg in the form of a capsule and suspension for ingestion (rinsing and preserving in the mouth for 2 minutes and swallowing ) it was established that Cmax of fluconazole in saliva after taking the suspension was observed after 5 minutes and 182 times higher than Cmax in saliva after taking the capsule (reached after 4 hours). After about 4 hours, the concentrations of fluconazole in saliva were the same. The mean AUC0-96 in saliva was significantly higher when administered as a suspension than capsules. Significant differences in the rate of excretion from saliva or pharmacokinetics in plasma when using fluconazole in the form of two forms of release were not detected. Metabolism and excretion Fluconazole is excreted mainly by the kidneys; approximately 80% of the administered dose is detected in the urine unchanged. Clearance of fluconazole is proportional to QC. Circulating metabolites not found.
Indications
Cryptococcosis, including cryptococcal meningitis and infections of other localization (for example, lungs, skin), including in patients with a normal immune response and in patients with AIDS, recipients of transplanted organs and patients with other forms of immunodeficiency; supportive therapy to prevent the recurrence of cryptococcosis in AIDS patients - generalized candidiasis, including candidemia, disseminated candidiasis, and other forms of invasive candidal infection, such as infections of the peritoneum, endocardium, eyes, respiratory and urinary tract, including in patients with malignant tumors who are in ICUs and are receiving cytotoxic or immunosuppressive agents, as well as in patients with other factors predisposing to the development of candidiasis; mucocutaneous and chronic atrophic candidiasis of the oral cavity (associated with the wearing of dental prostheses), includingin patients with normal and suppressed immune function; prevention of recurrent oropharyngeal candidiasis in AIDS patients; genital candidiasis; acute or recurrent vaginal candidiasis; prevention to reduce the frequency of recurrences of vaginal candidiasis (3 or more episodes per year); candidal balanitis; prevention of fungal infections in patients with malignant tumors predisposed to the development of such infections as a result of cytotoxic chemotherapy or radiation therapy; endemic mycoses in patients with normal immunity, coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis.
Contraindications
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 isoenzyme CYP3A4, such as cisapride, astemizole, erythromycin, pimozide and quinidine; , fructose intolerance, glucose-galactose malabsorption (for powder for suspension); - galactose intolerance, lactase deficiency and impaired glucose / galactose absorption (for capsules); - children age up to 3 years (for capsules); - hypersensitivity to fluconazole, other components of the drug or azole substances with a structure similar to fluconazole.
Precautionary measures
Do not exceed the recommended dose. With caution, the drug is prescribed for impaired liver function, for renal dysfunction, when a rash appears when fluconazole is used in patients with surface fungal infection and invasive / systemic fungal infections, while simultaneous use of terfenadine and fluconazole is less than 400 mg / day, with potentially proarrhythmic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance and contributing p development of such disorders, concomitant therapy).
Use during pregnancy and lactation
Adequate and controlled studies of the safety of the drug in pregnant women have not been conducted.Cases of multiple congenital malformations in newborns whose mothers for 3 or more months received therapy with fluconazole in a high dose (400-800 mg / day) for coccidioidomycosis have been described. 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 these congenital disorders using low-dose fluconazole (150 mg once for treating vulvovaginal candidiasis) in the first trimester of pregnancy. Fluconazole should be avoided during pregnancy, except in cases of severe and potentially life-threatening fungal infections, when the expected benefit treatment exceeds the potential risk to the fetus. Therefore, women of childbearing age should use reliable means of contraception. Fluconazole is found in breast milk at concentrations close to plasma, therefore, it is not recommended to use Diflucan during lactation (breastfeeding).
Dosage and administration
Treatment can begin before the results of seeding and other laboratory tests. However, therapy needs to be changed accordingly when the results of these studies become known. The daily dose of fluconazole depends on the nature and severity of the fungal infection. In vaginal candidiasis in most cases, a single dose of the drug is effective. For infections that require repeated use of an antifungal drug, treatment should be continued until the clinical or laboratory signs of a fungal infection disappear. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually need supportive therapy to prevent recurrence of infection. An adult with cryptococcal meningitis and cryptococcal infections of another location on the first day is prescribed an average of 400 mg, and then continue treatment at a dose of 200-400 mg 1 day / day . The duration of treatment of cryptococcal infections depends on the presence of clinical and mycological effect; with cryptococcal meningitis, treatment is usually continued for at least 6-8 weeks.
Side effects
Nervous system disorders: headache, dizziness *, cramps *, taste change *, paresthesia, insomnia, drowsiness, tremor. On the part of the digestive system: abdominal pain, diarrhea, flatulence, nausea, dyspepsia *, vomiting *, dry mucous membrane oral cavities, constipation, hepatotoxicity (in some cases with a fatal outcome), increased bilirubin concentration, serum ALT and AST, ALP, abnormal liver function *, hepatitis *, hepatocellular necrosis *, jaundice *, cholestasis, hepatocellular damage. On the side of the heart -with of the judicial system *: an increase in the QT interval on the ECG, arrhythmia, incl. ventricular tachysystolic type of pirouette. For the skin: rash, alopecia *, exfoliative skin diseases *, including Stevens-Johnson syndrome and toxic epidermal necrolysis, acute generalized exanthematoid pustules, sweating, drug rash. neutropenia and agranulocytosis, thrombocytopenia, anemia. On the side of metabolism *: increased plasma cholesterol and triglycerides, hypokalemia. On the part of the musculoskeletal system: myalgia Allergic reactions *: anaphylactic reactions (including angioedema, swelling of the face, urticaria, pruritus). Others: weakness, asthenia, fatigue, fever, vertigo. In some patients, especially with serious diseases (AIDS, malignant neoplasms), during treatment Diflucan and similar drugs were observed changes in blood parameters, kidney and liver function, but the clinical significance of these changes and their relationship to treatment has not been established. The tolerability of the drug is usually very good.
Overdose
In one of the cases of fluconazole overdose, a 42-year-old patient infected with HIV, after taking 8,200 mg of fluconazole, had hallucinations and paranoid behavior. The patient was hospitalized, his condition returned to normal within 48 hours. Treatment: in case of overdose, symptomatic therapy is carried out (including supporting measures and gastric lavage). Fluconazole is mainly excreted in the urine, therefore, forced diuresis can probably accelerate its excretion . A hemodialysis session lasting 3 hours reduces plasma levels of fluconazole by about 50%.
Interaction with other drugs
A single or multiple dose of fluconazole at a dose of 50 mg does not affect the metabolism of phenazone (antipyrine) when taken at the same time. Simultaneous use of fluconazole with the following drugs is contraindicated: with simultaneous use of fluconazole and cisapride, undesirable heart reactions may occur, including ventricular tachysystolic arrhythmia type pirouette. 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. Simultaneous use of cisapride and fluconazole is contraindicated. Terfenadine: with the simultaneous use of azole antifungal agents and terfenadine, serious arrhythmias may occur as a result of an increase in the QT interval. When taking fluconazole at a dose of 200 mg / day, an increase in the QT interval is not established, however, the use of fluconazole at doses of 400 mg / day and higher causes a significant increase in plasma terfenadine concentration. Simultaneous administration of fluconazole in doses of 400 mg / day or more with terfenadine is contraindicated. Fluconazole treatment in doses of less than 400 mg / day in combination with terfenadine should be carefully monitored. Astemizole: simultaneous use of fluconazole with astemizole or other drugs whose metabolism is carried out by cytochrome P450 isoenzymes, may be accompanied by an increase in serum concentrations of these agents. With increasing plasma concentrations of astemizol, prolongation of the QT interval is possible and in some cases the development of ventricular tachysystolic arrhythmia pirouette. Simultaneous use of astemizol and fluconazole is contraindicated. Pimozide: although no appropriate in vitro or in vivo studies have been conducted, the simultaneous use of fluconazole and pimozide may lead to inhibition of pimozide metabolism. In turn, an increase in plasma concentrations of pimozide can lead to a prolongation of the QT interval and in some cases to the development of ventricular tachysystolic arrhythmias such as pirouette. The simultaneous use of pimozide and fluconazole is contraindicated. Quinidine: although no appropriate in vitro or in vivo studies have been conducted, the simultaneous use of fluconazole and quinidine can also lead to inhibition of quinidine metabolism.Application quinidine associated with lengthening QT interval, and, in some cases with the development of ventricular arrhythmias tachysystolic type piruet.Odnovremennoe application protivopokazano.Eritromitsin quinidine and fluconazole: fluconazole and simultaneous application of erythromycin potentially leads to increased risk of cardiotoxicity (prolongation of the interval QT, ventricular arrhythmia type pirouette) and, consequently, sudden cardiac death. Simultaneous use of fluconazole and erythromycin is contraindicated. Care should be taken and, possibly, dose adjustment with simultaneous use of the following drugs and fluconazole. Preparations affecting fluconazole / hydrochlorothiazide: repeated use of hydrochlorothiazide simultaneously with fluconazole leads to an increase in the concentration of fluconazole in the blood plasma on the blood plasma. The effect of this severity does not require a change in the dosage regimen of fluconazole in patients receiving diuretics at the same time, but the physician should take this into account. Rifampicin: the simultaneous use of fluconazole and rifampicin reduces AUC by 25% and decreases T1 / 2 of fluconazole by 20%. In patients taking rifampicin at the same time, it is necessary to take into account the feasibility of increasing the dose of fluconazole. Preparations that are affected by fluconazole Fluconazole is a potent inhibitor of CYP2C9 and CYP2C19 isoenzymes and a moderate inhibitor of the CYP3A4 isoenzyme. In addition, in addition to the effects listed below, there is a risk of increased concentrations in blood plasma and other drugs metabolized by the isoenzymes CYP2C9, CYP2C19 and CYP3A4 when taken concurrently with fluconazole. In this regard, caution should be exercised with the simultaneous use of these drugs, and if necessary - like combinations. Patients should be under close medical supervision. It should be noted that the inhibitory effect of fluconazole persists for 4-5 days after discontinuation of the drug due to prolonged T1 / 2.Alfentanil: a decrease in clearance and Vd, an increase in T1 / 2 of Alfentanil. Perhaps this is due to inhibition of the CYP3A4 isoenzyme by fluconazole. Dosage adjustment of Alfentanil may be required. Amitriptyline, nortriptyline: increased effect.The concentration of 5-nortriptyline and / or S-amitriptyline can be determined at the start of combination therapy with fluconazole and one week after the start. If necessary, the dose of amitriptyline / nortriptilin should be adjusted. Amphotericin B: In studies on mice (including immunosuppression), the following results were noted: a small additive antifungal effect during systemic infection caused by Сandida albicans, the lack of interaction during intracranial infection caused by Cryptococcus neoformans and antagonism in systemic infections caused by A. fumigatus. The clinical significance of these results is not clear. Anti-coagulants: like other antifungal agents - azole derivatives, fluconazole, when used simultaneously with warfarin, increases the prothrombin time (by 12%), and therefore bleeding can develop (hematomas, hemorrhages from the nose and gastrointestinal tract, hematuria melena). In patients receiving coumarin anticoagulants, it is necessary to constantly monitor the prothrombin time. You should also evaluate the feasibility of adjusting the dose of warfarin. Azitromycin: with simultaneous oral administration of fluconazole in a single dose of 800 mg with azithromycin in a single dose of 1200 mg, pronounced pharmacokinetic interaction has not been established. Benzodiazepines (short-acting): after oral administration of midazolam, fluconazole significantly increases the concentration of midazolam and moths: effects, and this effect is more pronounced after taking fluconazole inside than with its use in /. If necessary, concomitant benzodiazepine therapy of patients taking fluconazole should be monitored to assess the feasibility of appropriately reducing the dose of benzodiazepine. When taking triazolam in a single dose, fluconazole increases the AUC of triazolam by about 50%, C max by 25-32% and T1 / 2 by 25 -50% due to inhibition of triazolam metabolism. You may need a dose adjustment of triazolam. Carbamazepine: fluconazole inhibits carbamazepine metabolism and increases plasma carbamazepine concentration by 30%. The risk of carbamazepine toxicity must be considered. The need to adjust the dose of carbamazepine depending on the concentration / effect should be assessed. Calcium channel blockers: some calcium channel antagonists (nifedipine, isradipine, amlodipine, verapamil and felodipine) are metabolized by CYP3A4 isoenzyme. Fluconazole increases the systemic exposure of calcium channel antagonists.Controlling the development of side effects is recommended. Cyclosporin: 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, no change in the concentration of cyclosporin in bone marrow recipients was observed. With simultaneous use of fluconazole and cyclosporine, it is recommended to monitor the concentration of cyclosporine in the blood. Cyclophosphamide: with simultaneous use of cyclophosphamide and fluconazole, an increase in serum concentrations of bilirubin and creatinine is noted. This combination is acceptable given the risk of increasing concentrations of bilirubin and creatinine. Fentanyl: there is a report of one lethal outcome, possibly associated with simultaneous intake of fentanyl and fluconazole. It is assumed that the violations are associated with intoxication with fentanyl. Fluconazole has been shown to significantly prolong fentanyl elimination time. It should be noted that increasing the concentration of fentanyl can lead to inhibition of respiratory function. Halofantrine: fluconazole may increase the concentration of halofantrine in the blood plasma due to inhibition of the CYP3A4 isoenzyme. HMG-CoA reductase inhibitors: while using fluconazole with HMG-CoA reductase inhibitors, metabolized by CYP3A4 isoenzyme (such as atorvastatin and simvastatin) or CYP2D6 isoenzyme (such as fluvastatin), the risk of myopathy and rhabdomyolysis increases. If necessary, simultaneous therapy with these drugs, patients should be monitored to identify symptoms of myopathy and rhabdomyolysis. It is necessary to control the concentration of creatinine kinase. If there is a significant increase in creatinine kinase concentration, or if myopathy or rhabdomyolysis is diagnosed or suspected, therapy with HMG-CoA reductase inhibitors should be stopped. 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 needed. Metadone: fluconazole may increase the plasma concentration of methadone.Methadone dose adjustment may be necessary. NVPP: Cmax and AUC of flurbiprofen are increased by 23% and 81%, respectively. Similarly, Cmax and AUC of the pharmacologically active isomer [S - (+) - ibuprofen] increased by 15% and 82%, respectively, with simultaneous use of fluconazole 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 celecoxib are increased by 68% and 134%, respectively. In this combination, the dose of celecoxib may be halved. Despite the lack of targeted research, fluconazole may increase the systemic exposure of other NSAIDs metabolized by the CYP2C9 isoenzyme (eg, naproxen, lornoxicam, meloxicam, diclofenac). Dose adjustment of NSAIDs may be necessary. When NSAIDs and fluconazole are used at the same time, patients should be carefully monitored to detect and control adverse reactions and toxicity associated with NSAIDs. Oral contraceptives: while using a combined oral contraceptive with fluconazole 50 mg is essential effect on hormone levels has not been established, whereas with daily intake of 200 mg of fluconazole, AUC of ethinyl estradiol and levonorgestrel increases and 40% and 24%, respectively, while receiving 300 mg of fluconazole 1 time / week. AUC of ethinyl estradiol and norethindrone 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: the simultaneous use of fluconazole and phenytoin can be accompanied by a clinically significant increase in the concentration of phenytoin. If necessary, the simultaneous use of both drugs should monitor the concentration of phenytoin and adjust its dose accordingly to ensure therapeutic plasma concentrations. Prednison: there is a message about the development of acute adrenal insufficiency in a patient after liver transplantation amid the withdrawal of fluconazole after a 3-month course therapy. Presumably, cessation of therapy with fluconazole caused an increase in the activity of the CYP3A4 isoenzyme, which led to an increase in the metabolism of prednisone. Patientsreceiving 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: simultaneous use of fluconazole and rifabutin can lead to an increase in plasma concentration of the latter up to 80%. With simultaneous use of fluconazole and rifabutin, cases of uveitis are described. Patients receiving rifabutin and fluconazole at the same time must be carefully monitored. Saquinavir: AUC increases by approximately 50%, Cmax - by 55%, clearance of saquinavir decreases by approximately 50% due to inhibition of hepatic metabolism CYP3A4 isoenzyme and inhibition of P-glycoprotein. A dose adjustment of saquinavir may be necessary. Sirolimus: an increase in plasma sirolimus concentration, presumably due to inhibition of sirolimus metabolism through inhibition of the CYP3A4 isoenzyme and P-glycoprotein. This combination can be used with an appropriate dose adjustment of sirolimus depending on the effect / concentration. Sulfonylurea preparations: fluconazole, when administered simultaneously, leads to an increase in T1 / 2 oral sulfonylurea preparations (chlorpropamide, glibenclamide, glipizide and tolbutamide). Patients with diabetes mellitus can be prescribed both fluconazole and sulfonylurea for oral administration, but the possibility of developing hypoglycemia should be considered, in addition, regular monitoring of blood glucose and, if necessary, dose adjustment of sulfonylurea are necessary. Tacrolimus: simultaneous use of fluconazole and tacrolimus (inside) leads to an increase in serum concentrations of the latter up to 5 times due to inhibition of tacrolimus metabolism, which occurs in the intestine through th isoenzyme CYP3A4. Significant changes in the pharmacokinetics of drugs were not observed when using tacrolimus in / in. Cases of nephrotoxicity are described. Patients receiving tacrolimus and fluconazole simultaneously must be carefully monitored. The dose of tacrolimus should be adjusted depending on the degree of increase of its concentration in the blood. Theophylline: when used simultaneously with fluconazole at a dose of 200 mg for 14 days, the average plasma clearance rate of theophylline is reduced by 18%.When fluconazole is prescribed to patients taking theophylline in high doses or patients with an increased risk of the toxic action of theophylline, the symptoms of the theophylline overdose should be observed and, if necessary, the therapy should be adjusted accordingly. Tofacitinib: tofacitinib exposure increases when it is used together with drugs they are both moderate inhibitors of CYP3A4 isoenzyme and powerful inhibitors of CYP2C19 isoenzyme (for example, fluconazole). It may be necessary to adjust the dose of tofacitinib. Vinca alkaloid: despite the lack of targeted research, it is assumed that fluconazole may increase the concentration of vinca alkaloids (for example, vincristine and vinblastine) in the blood plasma and, thus, lead to neurotoxicity, which may to be associated with inhibition of CYP3A4 isoenzyme. Vitamin A: there is a message about one case of undesirable CNS reactions in the form of a brain pseudotumor with simultaneous use of a complete trans etinoevoy acid and fluconazole, which disappeared after withdrawal of fluconazole. The use of this combination is possible, but one should be aware of the possibility of undesirable reactions from the CNS.Zidovudin: with simultaneous use with fluconazole, Cid and AUC of zidovudine increase 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) showed a significant increase in zidovudine AUC (20%). Patients receiving this combination should be monitored to detect side effects. effects of zidovudine. Vorikonazol (inhibitor of CYP2C9, CYP2C19 and CYP3A4 isoenzymes): 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 concentration ation and voriconazole AUC by 57% and 79% respectively. It was shown that this effect persists with decreasing the dose and / or decreasing the frequency of administration of any of the drugs. Simultaneous use of voriconazole and fluconazole is not recommended. Studies of the interaction of oral forms of fluconazole with its simultaneous intake with food, cimetidine, antacids, as well as after total body irradiation to prepare for bone marrow transplants showedthat these factors do not have a clinically significant effect on the absorption of fluconazole. The listed interaction has been established with repeated use of fluconazole; interaction with drugs as a result of a single dose of fluconazole is unknown. Doctors should be aware that interaction with other drugs has not been specifically studied, but it is possible. Pharmaceutical interaction Disflucan® - solution for iv administration is compatible with the following solutions: 20% glucose solution, Ringer's solution, Hartmann solution, potassium chloride solution in glucose, 4.2% sodium bicarbonate solution, aminofuzin, isotonic saline. Diflucan® can be administered into the infusion system along with one of the above solutions. Although cases of specific incompatibility of fluconazole with other means are not described, nevertheless