Diflucan powder for suspension 50 mg/5 ml 35 ml
Release form Powder for the preparation of suspension for oral administration
Compound
5 ml of ready-made suspension. contain fluconazole 50 mg;
excipients: sucrose, colloidal silicon, titanium dioxide, xanthan gum, sodium citrate, citric acid, sodium benzoate, natural orange supplement
Package
Bottle with a volume of 60 ml (volume of the finished suspension 35 ml).
pharmachologic effect
Diflucan, an antifungal drug, a representative of a new class of triazole antifungal agents, is a powerful selective inhibitor of sterol synthesis in fungal cells.
When administered orally and intravenously, fluconazole has been effective in various animal models of fungal infections. The activity of the drug in opportunistic mycoses has been demonstrated, incl. caused by Candida spp., including generalized candidiasis in animals with reduced immunity; Cryptococcus neoformans, including intracranial infections; Microsporum spp. and Trychoptyton spp. Fluconazole has also been shown to be active in animal models of endemic mycoses, including infections caused by Blastomyces dermatitides, Coccidioides immitis, including intracranial infections, and Histoplasma capsulatum in animals with normal and reduced immunity.
Treatment with fluconazole 50 mg/day for up to 28 days did not affect plasma testosterone concentrations in men or steroid concentrations 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 ACTH stimulation in healthy male volunteers.
There have been reports of cases of superinfection caused by Candida strains other than Candida albicans, which are often not sensitive to fluconazole (for example, Candida krusei). In such cases, alternative antifungal therapy may be required.
Indications
– cryptococcosis, including cryptococcal meningitis and infections of other sites (for example, lungs, skin). Treatment can be carried out in patients with a normal immune response and in patients with AIDS, organ transplant recipients and patients with other forms of immunodeficiency. Fluconazole can be used for maintenance therapy to prevent relapses of cryptococcosis in patients with AIDS;
– generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidiasis. These include infections of the peritoneum, endocardium, eyes, respiratory and urinary tracts. Treatment can be carried out in patients with malignant tumors, patients in intensive care units, patients receiving cytotoxic or immunosuppressive drugs, as well as in the presence of other factors predisposing to the development of candidiasis;
– candidiasis of the mucous membranes, incl. oral cavity and pharynx, esophagus, non-invasive bronchopulmonary infections, candiduria, mucocutaneous and chronic oral atrophic candidiasis (associated with wearing dentures). Treatment can be carried out in patients with normal and reduced immunity. Prevention of relapse of oropharyngeal candidiasis in patients with AIDS;
– genital candidiasis. Vaginal candidiasis, acute or recurrent. Prophylactic use to reduce the frequency of relapses of vaginal candidiasis (3 or more episodes per year). Candidal balanitis;
– prevention of fungal infections in patients with malignant tumors who are predisposed to their development as a result of cytotoxic chemotherapy or radiation therapy;
– mycoses of the skin, including mycoses of the feet, body, groin area, pityriasis versicolor, onychomycosis and skin candidal infections;
– deep endemic mycoses, coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immunity.
Contraindications
Concomitant use of cisapride; simultaneous use of terfenadine and astemizole; hypersensitivity to the drug or azole substances similar to it in chemical structure.
Use during pregnancy and breastfeeding
The use of fluconazole during pregnancy should be avoided, except in cases of severe and potentially life-threatening fungal infections when the expected benefit of treatment outweighs the possible risk to the fetus.
Fluconazole is found in breast milk in the same concentrations as in the blood, therefore the use of Diflucan during lactation (breastfeeding) is not recommended.
Directions for use and doses
Treatment can be started pending results of cultures and other laboratory tests. However, therapy will need to be modified accordingly when the results of these studies become known.
The daily dose of fluconazole depends on the nature and severity of the fungal infection.
For vaginal candidiasis, in most cases, a single dose of the drug is effective.
For infections requiring repeated administration of the antifungal drug, treatment should be continued until clinical or laboratory signs of the fungal infection disappear. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require supportive care to prevent recurrence of infection.
For adults with cryptococcal meningitis and cryptococcal infections of other localization, an average of 400 mg is prescribed 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 presence of clinical and mycological effect; for cryptococcal meningitis it is usually continued for at least 6-8 weeks.
To prevent relapse of cryptococcal meningitis in patients with AIDS, after completing the full course of primary treatment, therapy with fluconazole at a dose of 200 mg/day can be continued for a very long period.
For candidemia, disseminated candidiasis and other invasive candidal infections, the dose averages 400 mg on the first day, and then 200 mg/day. Depending on the severity of the clinical effect, the dose can be increased to 400 mg/day. The duration of therapy depends on clinical effectiveness.
For oropharyngeal candidiasis, the drug is prescribed on average 50-100 mg 1 time/day for 7-14 days. If necessary, in patients with a pronounced decrease in immunity, treatment can be continued for a longer time. For atrophic candidiasis of the oral cavity associated with wearing dentures, the drug is prescribed at an average dose of 50 mg 1 time / day for 14 days in combination with local antiseptics for treating the denture.
For other candidiasis infections of the mucous membranes (with the exception of genital candidiasis), for example, esophagitis, non-invasive bronchopulmonary infections, candiduria, candidiasis of the skin and mucous membranes, the effective dose averages 50-100 mg/day with a treatment duration of 14-30 days.
To prevent relapses of oropharyngeal candidiasis in patients with AIDS after completing the full course of primary therapy, fluconazole can be prescribed 150 mg once a week.
For vaginal candidiasis, fluconazole is taken orally once 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 1 time/month. The duration of therapy is determined individually; it varies from 4 to 12 months. Some patients may require more frequent use.
For balanitis caused by Candida, fluconazole is prescribed as a single dose of 150 mg orally.
For the prevention of candidiasis, the recommended dose of fluconazole is 50-400 mg 1 time / day, depending on the degree of risk of developing a fungal infection. If there is a high risk of generalized infection, for example, in patients with expected severe or long-lasting neutropenia, the recommended dose is 400 mg 1 time / day. Fluconazole is prescribed several days before the expected onset of neutropenia; after the number of neutrophils increases to more than 1000/μl, treatment is continued for another 7 days.
For skin infections, including mycoses of the feet, smooth skin, groin area and candidal infections, the recommended dose is 150 mg 1 time/week. or 50 mg 1 time/day. The duration of therapy in normal cases is 2-4 weeks, however, with mycoses of the feet, longer therapy may be required (up to 6 weeks).
For pityriasis versicolor, the recommended dose is 300 mg once a week. within 2 weeks; some patients require a third dose of 300 mg/week, while in some cases a single dose of 300-400 mg is sufficient. An alternative treatment regimen is the use of the drug 50 mg 1 time / day for 2-4 weeks.
For onychomycosis, the recommended dose is 150 mg once a week. Treatment should be continued until the infected nail is replaced (the uninfected nail regrows). It normally takes 3-6 months and 6-12 months for fingernails and toenails to re-grow, respectively. However, growth rate can vary widely between individuals and also depending on age. After successful treatment of long-standing chronic infections, a change in the shape of the nails is sometimes observed.
For deep endemic mycoses, it may be necessary to use the drug at a dose of 200-400 mg/day for up to 2 years. The duration of therapy is determined individually; it is 11-24 months for coccidioidomycosis, 2-17 months for paracoccidioidomycosis, 1-16 months for sporotrichosis and 3-17 months for histoplasmosis.
In children, as with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. In children, the drug should not be used in a daily dose higher than that in adults. Fluconazole is used daily 1 time/day.
For candidiasis of the mucous membranes, the recommended dose of fluconazole is 3 mg/kg/day. On the first day, a loading dose of 6 mg/kg may be prescribed in order to more quickly achieve constant equilibrium concentrations.
For the treatment of generalized candidiasis and cryptococcal infection, the recommended dose is 6-12 mg/kg/day, depending on the severity of the disease.
For the prevention of fungal infections in patients with reduced immunity, in whom the risk of developing infection is associated with neutropenia developing as a result of cytotoxic chemotherapy or radiation therapy, the drug is prescribed at 3-12 mg/kg/day, depending on the severity and duration of persistence of induced neutropenia.
When using the drug in children aged 4 weeks or less, it should be borne in mind that fluconazole is excreted slowly in newborns. In the first 2 weeks of life, the drug is prescribed at the same dose (in mg/kg) as for older children, but with an interval of 72 hours. For children aged 3 and 4 weeks of life, the same dose is administered with an interval of 48 hours.
In elderly patients in the absence of signs of renal failure, the drug is used in an average dose.
Diflucan can be taken orally or administered intravenously by infusion at a rate of no more than 10 ml/min; the choice of route of administration depends on the clinical condition of the patient. When transferring a patient from intravenous administration to oral administration of the drug or vice versa, no change in the daily dose is required.
Capsules should be swallowed whole.
When preparing a suspension for oral administration, you should first shake the bottle to loosen the powder, then add 24 ml of water, then shake the bottle thoroughly again. Immediately before use, the suspension should be shaken. Side effects
The most common side effects that were reported in clinical studies of fluconazole.
From the side of the central nervous system: headache.
Dermatological reactions: rash.
From the digestive system: abdominal pain, diarrhea, flatulence, nausea, toxic effects on the liver (including rare cases with fatal outcome), increased levels of alkaline phosphatase, bilirubin, increased serum levels of aminotransferases (ALT and AST).
In some patients, especially with serious diseases (AIDS, malignant neoplasms), changes in blood counts, kidney and liver function were observed during treatment with fluconazole and similar drugs, but the clinical significance of these changes and their relationship with treatment have not been established.
During widespread use, the following side effects have been additionally registered.
From the central nervous system and peripheral nervous system: dizziness, convulsions.
Dermatological reactions: alopecia, exfoliative skin diseases, including Stevens-Johnson syndrome, Lyell's syndrome (toxic epidermal necrolysis).
From the digestive system: dyspepsia, vomiting, liver dysfunction, hepatitis, hepatocyte necrosis, jaundice, increased serum levels of ALT and AST.
From the hematopoietic system: leukopenia, including neutropenia and agranulocytosis, thrombocytopenia.
From the side of metabolism: increased levels of cholesterol and triglycerides in plasma, hypokalemia.
Allergic reactions: anaphylactic reactions, angioedema, facial swelling, itching.
Other: change in taste.
special instructions
In rare cases, the use of fluconazole was accompanied by toxic changes in the liver, incl. with a fatal outcome, mainly in patients with serious concomitant diseases. There was no obvious dependence of the incidence of hepatotoxic effects of fluconazole on the total daily dose, duration of therapy, gender and age of the patient. The hepatotoxic effects of fluconazole were usually reversible; its signs disappeared after cessation of therapy. Patients whose liver function tests are impaired during treatment with fluconazole should be monitored for signs of more serious liver damage. If clinical signs of liver damage that may be associated with fluconazole appear, the drug should be discontinued.
During treatment with fluconazole, patients have rarely developed exfoliative skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. People with AIDS are more likely to develop severe skin reactions when taking many drugs. If a patient receiving treatment for a superficial fungal infection develops a rash that can be associated with fluconazole, the drug should be discontinued. If a rash appears in patients with invasive/systemic fungal infections, they should be closely monitored and fluconazole should be discontinued if bullous lesions or erythema multiforme appear.
It should be borne in mind that anaphylactic reactions have been observed in rare cases when using the drug.
Impact on the ability to drive vehicles and operate machinery
Experience with the use of fluconazole suggests that deterioration in the ability to drive a car and operate machinery associated with the drug is unlikely.
Storage conditions
The drug should be stored at a temperature not exceeding 30°C, out of the reach of children.
DIFLUCAN powder for the preparation of suspension for oral administration 50 mg/5 ml bottle 35 ml No. 1
Single or multiple doses of fluconazole at a dose of 50 mg do not affect the metabolism of phenazone (antipyrine) when taken 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. ventricular tachysystolic ari. 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 marked increase in plasma concentrations of cisapride and an increase in the QT interval on the ECG. Concomitant use of cisapride and fluconazole is contraindicated. Terfenadine: When azole antifungals are used concomitantly with terfenadine, serious arrhythmias may occur as a result of prolongation of the QT interval. When taking fluconazole at a dose of 200 mg/day, an increase in the QT interval has not been established, however, the use of fluconazole at doses of 400 mg/day and above causes a significant increase in the concentration of terfenadine in the blood plasma. Concomitant use of fluconazole in doses of 400 mg/day or more with terfenadine is contraindicated. Treatment with fluconazole in doses less than 400 mg/day in combination with terfenadine should be carried out under close monitoring. Astemizole: simultaneous use of fluconazole with astemizole or other drugs whose metabolism is carried out by isoenzymes of the cytochrome P450 system may be accompanied by an increase in serum concentrations of these drugs. With an increase in the concentration of astemizole in the blood plasma, a prolongation of the QT interval and, in some cases, the development of ventricular tachysystolic arrhythmia are possible. The simultaneous use of astemizole and fluconazole is contraindicated. Pimozide: Although adequate in vitro or in vivo studies have not been conducted, concomitant use of fluconazole and pimozide may result in 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 ventricular tachysystolic arrhythmias. The simultaneous use of pimozide and fluconazole is contraindicated. Quinidine: Although adequate in vitro or in vivo studies have not been conducted, concomitant use of fluconazole and quinidine may also result in inhibition of quinidine metabolism. Quinidine use is associated with QT prolongation and, in some cases, torsade de pointes (TdP). The simultaneous use of quinidine and fluconazole is contraindicated. Erythromycin: Concomitant use of fluconazole and erythromycin potentially leads to an increased risk of cardiotoxicity (QT prolongation, torsade de pointes) and consequently sudden cardiac death. The simultaneous use of fluconazole and erythromycin is contraindicated. Caution and possible dosage adjustments should be used when the following drugs are used concomitantly with fluconazole Drugs affecting fluconazole Hydrochlorothiazide: Repeated use of hydrochlorothiazide concomitantly with fluconazole results in an increase in fluconazole plasma concentrations by 40%. An effect of this severity does not require a change in the fluconazole dosage regimen in patients receiving concomitant diuretics, but the doctor should take this into account. Rifampicin: simultaneous use of fluconazole and rifampicin leads to a decrease in AUC by 25% and a decrease in T1/2 of fluconazole by 20%. In patients concomitantly taking rifampicin, it is necessary to consider the advisability of increasing the dose of fluconazole. Drugs Affected by Fluconazole Fluconazole is a potent inhibitor of CYP2C9 and CYP2C19 and a moderate inhibitor of CYP3A4. In addition, in addition to the effects listed below, there is a risk of increased plasma concentrations of other drugs metabolized by the isoenzymes CYP2C9, CYP2C19 and CYP3A4 when taken simultaneously with fluconazole. In this regard, caution should be exercised when using these drugs simultaneously, and, if necessary, similar combinations. Patients should be under close medical supervision. It should be taken into account that the inhibitory effect of fluconazole persists for 4-5 days after discontinuation of the drug due to the long T1/2. Alfentanil: there is a decrease in clearance and Vd, an increase in T1/2 of alfentanil. This may be due to inhibition of the CYP3A4 isoenzyme by fluconazole. Alfentanil dosage adjustment may be required. Amitriptyline, nortriptyline: increased effect. The concentration of 5-nortriptyline and/or S-amitriptyline can be determined 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 observed: a small additive antifungal effect in systemic infection with Candida albicans, no interaction in intracranial infection with Cryptococcus neoformans and antagonism in systemic infection with A .fumigatus. The clinical significance of these results is unclear. Anticoagulants: like other antifungal agents - azole derivatives, fluconazole, when used simultaneously with warfarin, increases the prothrombin time (by 12%), and therefore the development of bleeding (hematomas, bleeding from the nose and gastrointestinal tract, hematuria, melena) is possible. In patients receiving coumarin anticoagulants, prothrombin time must be constantly monitored. The advisability of adjusting the warfarin dose should also be assessed. 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 has been established. Benzodiazepines (short-acting): After oral administration of midazolam, fluconazole significantly increases midazolam concentrations and psychomotor effects, and this effect is more pronounced after oral administration of fluconazole than with intravenous administration. If concomitant therapy with benzodiazepines is necessary, patients taking fluconazole should be monitored to assess the appropriateness of an appropriate reduction in the benzodiazepine dose. When taking triazolam simultaneously in a single dose, fluconazole increases the AUC of triazolam by approximately 50%, Cmax by 25-32% and T1/2 by 25-50% due to inhibition of triazolam metabolism. Triazolam dose adjustment may be necessary. Carbamazepine: Fluconazole inhibits the metabolism of carbamazepine and increases plasma concentrations of carbamazepine by 30%. The risk of carbamazepine toxicity must be taken into account. The need for carbamazepine dose adjustment based on concentration/effect should be assessed. Calcium channel blockers: Some calcium channel antagonists (nifedipine, isradipine, amlodipine, verapamil and felodipine) are metabolized by CYP3A4. Fluconazole increases the systemic exposure of calcium channel antagonists. Monitoring for the development of side effects is recommended. Cyclosporine: In patients with a kidney transplant, the use of fluconazole at a dose of 200 mg/day leads to a slow increase in cyclosporine concentrations. However, with repeated doses of fluconazole at a dose of 100 mg/day, no changes in cyclosporine concentrations were observed in bone marrow recipients. When using fluconazole and cyclosporine simultaneously, 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 observed. This combination is acceptable given the risk of increased bilirubin and creatinine concentrations. Fentanyl: There has been a report of one death possibly related to the concomitant use of fentanyl and fluconazole. The disturbances are believed to be related to fentanyl intoxication. Fluconazole has been shown to significantly prolong the clearance time of fentanyl. It should be borne in mind that an increase in the concentration of fentanyl can lead to depression of respiratory function. Halofantrine: Fluconazole may increase plasma concentrations of halofantrine due to inhibition of CYP3A4. HMG-CoA reductase inhibitors: When fluconazole is used concomitantly with HMG-CoA reductase inhibitors metabolized by the CYP3A4 isoenzyme (such as atorvastatin and simvastatin) or the CYP2D6 isoenzyme (such as fluvastatin), the risk of developing myopathy and rhabdomyolysis increases. If simultaneous therapy with these drugs is necessary, patients should be monitored to identify symptoms of myopathy and rhabdomyolysis. It is necessary to monitor the concentration of creatinine kinase. If there is a significant increase in creatinine kinase concentrations 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 blood pressure monitoring is necessary. Methadone: Fluconazole may increase plasma concentrations of methadone. Methadone dose adjustment may be necessary. NSAIDs: Cmax and AUC of flurbiprofen increase by 23% and 81%, respectively. Similarly, the Cmax and AUC of the pharmacologically active isomer [S-(+)-ibuprofen] increased by 15% and 82%, respectively, when fluconazole was co-administered with racemic ibuprofen (400 mg). With simultaneous use of fluconazole at a dose of 200 mg/day and celecoxib at a dose of 200 mg, 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. Although there are no targeted studies, fluconazole may increase the systemic exposure of other NSAIDs metabolized by CYP2C9 (eg, naproxen, lornoxicam, meloxicam, diclofenac). NSAID dose adjustment may be necessary. When using NSAIDs and fluconazole concomitantly, patients should be under close medical supervision to identify and monitor NSAID-related adverse reactions and toxicities. Oral contraceptives: with simultaneous use of a combined oral contraceptive with fluconazole at a dose of 50 mg, no significant effect on hormone levels has been established, while with daily administration of 200 mg of fluconazole, the AUC of ethinyl estradiol and levonorgestrel increases by 40% and 24%, respectively, and with 300 mg of fluconazole 1 time/week The AUC of ethinyl estradiol and norethindrone increased 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: Concomitant use of fluconazole and phenytoin may be accompanied by a clinically significant increase in phenytoin concentrations. If simultaneous use of both drugs is necessary, phenytoin concentrations should be monitored and the dose adjusted accordingly to ensure therapeutic plasma concentrations. Prednisone: there is a report of the development of acute adrenal insufficiency in a patient after liver transplantation while fluconazole was discontinued after a 3-month course of therapy. Presumably, cessation of fluconazole therapy caused an increase in the activity of the CYP3A4 isoenzyme, which led to increased metabolism of prednisone. Patients receiving combination therapy with prednisone and fluconazole should be under close medical supervision when discontinuing fluconazole to assess the condition of the adrenal cortex. Rifabutin: simultaneous use of fluconazole and rifabutin can lead to an increase in plasma concentrations of the latter by up to 80%. Cases of uveitis have been described with the simultaneous use of fluconazole and rifabutin. Patients receiving rifabutin and fluconazole concomitantly should be monitored closely. Saquinavir: AUC increases by approximately 50%, Cmax by 55%, 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: increased plasma concentrations of sirolimus, presumably due to inhibition of sirolimus metabolism through inhibition of the CYP3A4 isoenzyme and P-glycoprotein. This combination can be used with appropriate dose adjustment of sirolimus depending on the effect/concentration. Sulfonylureas: Fluconazole, when taken concomitantly, leads to an increase in T1/2 of oral sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide). Patients with diabetes mellitus can be prescribed fluconazole and sulfonylureas for oral administration simultaneously, 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 necessary. Tacrolimus: simultaneous use of fluconazole and tacrolimus (orally) leads to an increase in serum concentrations of the latter up to 5 times due to inhibition of the metabolism of tacrolimus occurring in the intestine through the CYP3A4 isoenzyme. No significant changes in the pharmacokinetics of the drugs were observed when tacrolimus was used intravenously. Cases of nephrotoxicity have been described. Patients receiving oral tacrolimus and fluconazole simultaneously 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 is reduced by 18%. When prescribing fluconazole to patients taking high doses of theophylline or to patients at increased risk of developing theophylline toxicity, monitor for symptoms of theophylline overdose and, if necessary, adjust therapy accordingly. Tofacitinib: Tofacitinib exposure is increased when coadministered with drugs that are both moderate CYP3A4 inhibitors and strong CYP2C19 inhibitors (eg, fluconazole). Dose adjustment of tofacitinib may be necessary. Vinca alkaloid: Although focused studies are lacking, it is suggested that fluconazole may increase plasma concentrations of vinca alkaloids (e.g., vincristine and vinblastine) and thus lead to neurotoxicity, possibly due to inhibition of CYP3A4. Vitamin A: There has been a report of one case of the development of adverse reactions from the central nervous system in the form of pseudotumor cerebri with the simultaneous use of all-trans retinoic acid and fluconazole, which disappeared after discontinuation of fluconazole. The use of this combination is possible, but one should remember the possibility of adverse reactions from the central nervous system. Zidovudine: when used simultaneously with fluconazole, an increase in the Cmax and AUC of zidovudine is observed 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 in patients with AIDS and ARC (AIDS-related complex), a significant increase in the AUC of zidovudine (20%) was found. Patients receiving this combination should be monitored for side effects of zidovudine. Voriconazole (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 voriconazole concentration and AUC by 57% and 79%, respectively. It has been shown that this effect persists when the dose is reduced and/or the frequency of administration of any of the drugs is reduced. Concomitant use of voriconazole and fluconazole is not recommended. Studies of the interaction of oral forms of fluconazole when taken simultaneously with food, cimetidine, antacids, as well as after total body irradiation in preparation for bone marrow transplantation showed that these factors do not have a clinically significant effect on the absorption of fluconazole. The listed interaction was established with repeated use of fluconazole; Drug interactions resulting from a single dose of fluconazole are unknown. Doctors should note that interactions with other drugs have not been specifically studied, but are possible. Pharmaceutical interaction Diflucan® - solution for intravenous administration is compatible with the following solutions: 20% glucose solution, Ringer's solution, Hartmann's solution, potassium chloride solution in glucose, 4.2% sodium bicarbonate solution, aminofusin, isotonic saline solution. Diflucan® can be administered into the infusion system together with one of the solutions listed above. Although cases of specific incompatibility of fluconazole with other drugs have not been described, it is nevertheless not recommended to mix it with any other drugs before infusion.
