DIFLJuKAN

Active material: Fluconazole
When ATH: J02AC01
CCF: Antifungal agent
ICD-10 codes (testimony): B35.0, B35.1, B35.2, B35.3, B35.4, B35.6, B36.0, B37.0, B37.1, B37.2, B37.3, B37.4, B37.6, B37.7, B37.8, B38, B39, B41, B42, B45, H19.2, Z29.8
When CSF: 08.01.01
Manufacturer: PFIZER PGM (France)

Pharmaceutical form, composition and packaging

Capsules hard gelatin, №4, with turquoise and white shell cover, labeled as logo “Pfizer” and “Flu-50” black color; contents of capsules – powder from white to bledno-jeltogo color.

Excipients: lactose, corn starch, colloidal silicon dioxide, magnesium stearate, sodium lauryl.

The composition of the shell capsules: Titanium dioxide (E171), gelatin, patent blue dye (E131).
Ink composition: shellakovaja glaze, iron oxide black (E172), N-butyl alcohol, industrial methylated spirits 74 RR, soy lecithin, protivopennyj feature DC1510.

7 PC. – blisters (1) – packs cardboard.
7 PC. – blisters (4) – packs cardboard.

Capsules hard gelatin, №2, with white lid and casing, labeled as logo “Pfizer” and “Flu-100” black color; contents of capsules – powder from white to bledno-jeltogo color.

Excipients: lactose, corn starch, colloidal silicon dioxide, magnesium stearate, sodium lauryl.

The composition of the shell capsules: Titanium dioxide (E171), gelatin.
Ink composition: shellakovaja glaze, iron oxide black (E172), N-butyl alcohol, industrial methylated spirits 74 RR, soy lecithin, protivopennyj feature DC1510.

7 PC. – blisters (1) – packs cardboard.
7 PC. – blisters (4) – packs cardboard.

◊ Capsules hard gelatin, №1, with turquoise cover and enclosure, labeled as logo “Pfizer” and “Flu-150” black color; contents of capsules – powder from white to bledno-jeltogo color.

Excipients: lactose, corn starch, colloidal silicon dioxide, magnesium stearate, sodium lauryl.

The composition of the shell capsules: Titanium dioxide (E171), gelatin, patent blue dye (E131).
Ink composition: shellakovaja glaze, iron oxide black (E172), N-butyl alcohol, industrial methylated spirits 74 RR, soy lecithin, protivopennyj feature DC1510.

1 PC. – blisters (1) – packs cardboard.

Powder for oral suspension white or nearly white, free of visible dirt.

Excipients: Citric acid anhydrous, Sodium benzoate, Xanthan Gum, Titanium dioxide (E171), sucrose, Colloidal anhydrous silica, sodium citrate dihydrate, Orange flavoring *.

* contains Orange essential oil, maltodextrine and water.

Plastic Bottles (1) complete with measuring spoon – packs cardboard.

Powder for oral suspension white or nearly white, free of visible dirt.

Excipients: Citric acid anhydrous, Sodium benzoate, Xanthan Gum, Titanium dioxide (E171), sucrose, Colloidal anhydrous silica, sodium citrate dihydrate, Orange flavoring *.

* contains Orange essential oil, maltodextrine and water.

Plastic Bottles (1) complete with measuring spoon – packs cardboard.

The solution for the on / in the clear, colorless.

Excipients: sodium chloride, water d / and.

25 ml – colorless glass vials (1) – packs cardboard.

The solution for the on / in the clear, colorless.

Excipients: sodium chloride, water d / and.

50 ml – colorless glass vials (1) – packs cardboard.

The solution for the on / in the clear, colorless.

Excipients: sodium chloride, water d / and.

100 ml – colorless glass vials (1) – packs cardboard.

The solution for the on / in the clear, colorless.

Excipients: sodium chloride, water d / and.

200 ml – colorless glass vials (1) – packs cardboard.

Pharmacological action

Antifungal agent. Fluconazole - representative of the class of triazole antifungal agents, It is a potent selective inhibitor of sterol synthesis in the fungal cells.

The ingestion and when in/with the introduction of fluconazole has been active on various models of fungal infections in animals. Demonstrated activity of the preparation for opportunistic mikozah, incl. caused by Candida spp., including generalizovanny candidiasis in animals with reduced immunity; Cryptococcus neoformans, including intracranial infection; Microsporum spp. and Trychoptyton spp. There is also activity of fluconazole on models of endemic mycosis in animals, including infections, caused by Blastomyces dermatitidis, Merciless coccidioides, including intracranial infection, and Histoplasma capsulatum in animals with normal and with reduced immunity.

Fluconazole has high specificity against fungal enzymes, cytochrome P450-dependent. Therapy on flukonazolom 50 mg / day for up to 28 the day did not affect the concentration of plasma testosterone in males or steroid concentrations in women of childbearing age. Fluconazole at a dose 200-400 mg/day had no clinically significant effect on the levels of endogenous steroids and their response to stimulation of ACTH in healthy male volunteers.

Single or multiple receiving fluconazole at a dose 50 mg does not affect metabolism of antipyrine in their simultaneous admission.

There were reports of cases of superinfection, caused by other, than Candida albicans, strains of Candida, which often do not show sensitivity to fluconazole (eg, Candida krusei). In such cases, you may need an alternative antifungal therapy.

Pharmacokinetics

Pharmacokinetics of fluconazole is similar with on/in the introduction and ingestion.

Absorption

After oral administration fluconazole is well absorbed, levels in plasma (and the overall bioavailability) exceed 90% fluconazole levels in plasma in the on/in the introduction. Simultaneous food intake has no effect on absorption when administered. C_max achieved through 0.5-1.5 h after administration of fluconazole on an empty stomach. Concentration in plasma is proportional to dose.

Distribution

90% equilibrium concentration achieved the 4-5 day after the start of therapy (When multiple admission 1 time / day).

Bolus (1 day), in 2 times the average daily dose, allows you to achieve a C_ss 90% for the 2nd day. In Кажущийся_d It is approaching the total water content in the body. Linking blood plasma proteins is low (11-12%).

Fluconazole penetrates well into all body fluids. Fluconazole levels in saliva and sputum similar to the concentrations in blood plasma. In patients with fungal meningitis fluconazole levels in cerebrospinal fluid make up about 80% from its levels in plasma.

In the stratum corneum, the epidermis and the DermIS the sweat-fluid high concentrations are achieved, which exceed serum. Flukonazol accumulate in rogovom layer. When taken in the dose of 50 mg 1 times/day flukonazola concentration of via 12 days amounted to 73 g / g, and through 7 days after cessation of treatment – only 5.8 g / g. When applied in a dose of 150 mg 1 times / week. flukonazola concentration in rogovom layer on the 7th day was 23.4 g / g, and through 7 days after receiving the second dose- 7.1 g / g.

Concentration of fluconazole in nails after 4 months of use in dose 150 mg 1 times/week amounted to 4.05 µg/g in healthy and 1.8 µg/g in the affected nails; through 6 months after completion of therapy flukonazol still determined in nails.

Metabolism and excretion

Fluconazole is excreted, primarily, kidney; about 80% imposed dose found in the urine in an unmodified form. The clearance of fluconazole is proportional QC. Circulating metabolites not found.

Duration T_1/2 from blood plasma allows to take fluconazole once in waginalnom 4-8 and 1 time / day or 1 times / week. other testimony.

A comparison was made between concentration in saliva and plasma after a single dose of fluconazole at a dose 100 mg in the form of suspension for admission into (Rinse and save in your mouth during 2 mines and swallowing) and capsules. C_max fluconazole in the saliva after receiving suspensions was observed through 5 mines and 182 times the maximum concentration in saliva after taking capsules (achieved through 4 no). Approximately 4 h concentration of fluconazole in saliva were the same. Average AUC_0-96 in the saliva was significantly higher when taking suspensions, than capsules. Significant differences speed removal of saliva or indicators of pharmacokinetics in plasma using two forms of release not identified.

Pharmacokinetics in special clinical situations

Children identified the following pharmacokinetic parameters:

* – index, in the last day.

Premature babies (about 28 weeks of development) fluconazole injected in/in the dose 6 mg/kg every 3rd day prior to the imposition of a maximum 5 doses at a time, While the children remained in intensive care unit. Average T_1/2 made 74 no (within 44-185 no) 1 day, with the decrease of the 7-th day in average 53 no (within 30-131 no) and on the 13rd day in average 47 no (within 27-68 no).

AUC values were 271 mcg x h / ml (within 173-385 mcg x h / ml) 1 day, then increased to 490 mcg x h / ml (within 292-734 mcg x h / ml) on the 7th day and fell to an average 360 mcg x h / ml (within 167-566 mcg x h / ml) the 13-day.

V_d made 1183 ml / kg (within 1070-1470 ml / kg) 1 day, then rose to an average 1184 ml / kg (within 510-2130 ml / kg) on the 7th day and to 1329 ml / kg (within 1040-1680 ml / kg) on the 13rd day.

In elderly patients (65 and older) the one-time use of fluconazole at a dose 50 mg orally (in some cases, with simultaneous application of diuretic effectively delivered) found, that C_max achieved through 1.3 hours after admission and was 1.54 ug / ml, the mean values of AUC 76.4 ± 20.3 µg. h/ml, Average T_1/2 sostaljal 46.2 no.

The values of these farmakokineticeskih parameters above, than in younger patients. Simultaneous use dioretikov not caused changes expressed the AUC and C_max. Creatinine clearance (74 ml / min), the percentage of drug, displayed with urine in an unmodified form (0-24 no, 22%) and kidney klirens fluconazole (0.124 ml / min / kg) older patients are lower compared to the young. Higher values farmakokineticeskih parameters in elderly patients, taking fluconazole, probably, associated with reduced renal function, characteristic for the elderly.

Testimony

- Kryptokokkoz, including chriptokokkovi meningitis and infections of other localization (eg, light, skin), incl. in patients with normal immune response and AIDS patients, recipients of transplanted organs and patients with other forms of immunodeficiency; supportive therapy to prevent recurrence of Cryptococcosis in AIDS patients;

- Generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive Candida infections, such as infection of the peritoneum, endokarda, eye, respiratory and urinary tract, incl. in patients with malignant tumors, are in intensive care units, patients, receiving cytotoxic or immunosuppressive agents, as well as patients with other factors, conducive to the development of candidiasis;

- Mucosal candidiasis, including the mucous membranes of the oral cavity and pharynx, esophagus, non-invasive bronchopulmonary infections, kandidurija, Mucocutaneous and atroficski chronic candidiasis of the oral cavity (associated with wearing dentures), incl. in patients with normal and suppressed immune function; prevention of relapse of oropharyngeal candidiasis in patients with AIDS;

- Genital candidiasis; acute or recurrent vaginal candidiasis; prophylaxis to reduce the frequency of relapses of vaginal candidiasis (3 or more episodes per year); kandidoznыj ʙalanit;

-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;

- Fungal infections of the skin, including tinea pedis, body, groin, chromophytosis, onihomikozy and skin severe Candida infection;

— deep endemic mikozy in patients with normal immunity, coccidioidomycosis, Paracoccidioidomycosis, Sporotrichosis and histoplasmosis.

Dosage regimen

Treatment can be started before receiving results of sowing and other laboratory studies. But therapy should change accordingly, When the results of these studies will be known.

Daily dose of fluconazole depends on the nature and severity of the fungal infection. In waginalnom 4-8 in most cases effective single dose drug. When infections, requiring readmitting antifungal drug, treatment should continue until the clinical or laboratory signs of fungal infection. AIDS and cryptococcal meningitis or recurrent invasive orofaringealnym for prevention of recurrence of infection usually requires supportive therapy.

Adults at kriptokokkovom meningitis and kriptokokkovyh infections Another localization in first day appoint an average 400 mg, and then continue treatment at a dose 200-400 mg 1 time / day. Duration of treatment kriptokokkovyh infections depends on the availability of clinical and mikologicheskogo effect; with kriptokokkovom meningitis treatment usually last at least 6-8 weeks.

To prevention of relapse of cryptococcal meningitis in patients with AIDS after completing a full course of primary treatment therapy fluconazole 200 mg / day can continue for a very long period of time.

At kandidemii, disseminirovannom 4-8 and other invasive kandidozhnykh infections dose averages 400 mg on the first day, and then 200 mg / day. Depending on the severity of clinical effect dose can be increased to 400 mg / day. The duration of therapy depends on the clinical effectiveness.

At orofaringealьnom kandidoze the drug is prescribed an average of 50-100 mg 1 times/day on 7-14 days. If necessary,, in patients with severe depression of immunity, treatment may continue for a longer time. Atroficescom in 4-8 of the oral cavity, associated with wearing dentures, the drug is prescribed in high doses 50 mg 1 times / day for 14 days in combination with local antiseptic agents for treatment of prosthesis.

At other Candida infections of the mucous membranes (for isklyucheniem genitalynogo candidiasis), such as esophagitis, non-invasive bronchopulmonary infections, kandidurii, candidiasis of the skin and mucous membranes, effective dose averages 50-100 mg / day when the duration of treatment 14-30 days.

To prevention of relapse of oropharyngeal candidiasis in patients with AIDS after completing a full course of primary therapy, fluconazole may be appointed by 150 mg 1 times / week.

At vaginal candidiasis fluconazole take a single oral dose 150 mg.

To reduce the frequency of recurrence of vaginal candidiasis the drug can be applied at a dose 150 mg 1 times / month. The duration of therapy is determined individually; it ranges from 4 to 12 Months. Some patients may require more frequent use of. Use of the drug in single dose in children under the age of 18 years and older patients 60 years without a doctor's prescription is not recommended.

At ʙalanite, caused by Candida, Fluconazole prescribe a single dose 150 mg orally.

To preventions candidiasis The recommended dose of fluconazole 50-400 mg 1 times / day depending on the degree of risk of fungal infection. If you have a high risk of generalized infection, for example in patients with pronounced or the long-term persistence of neutropenia, The recommended dose is 400 mg 1 time / day. Fluconazole is prescribed for a few days before the anticipated emergence of neutropenia and after the increase in the number of Klebsiella over 1000/l treatment continued for 7 d.

At infections of the skin, including tinea pedis, smooth skin, groin and Candidal infections, The recommended dose is 150 mg 1 times / week. or 50 mg 1 time / day. Duration of therapy in conventional cases is 2-4 Sun., however athlete's foot may require longer therapy (to 6 Sun.).

At pityriasis versicolor The recommended dose is 300 mg 1 times / week. during 2 weeks; some patients required a third dose 300 mg / Sun., While some patients satisfied with the single drug dose 300-400 mg. Alternative treatment is the use of the drug 50 mg 1 times / day for 2-4 Sun.

At onixomikoze The recommended dose is 150 mg 1 times / week. Treatment should be continued until infected nail replacement (sprouting uninfected nail). For re-growth of the nails on the fingers of the hands and feet usually required 3-6 months and 6-12 months, respectively. However, the growth rate can vary widely for different people, and depending on the age. After successful treatment, long stubbornly chronic infections sometimes seen changing shape nails.

At Deep endemic mycoses may be required drug dose 200-400 mg / day for up to 2 years. The duration of therapy is determined individually; It is at kokcidioidomikoze – 11-24 Months, when paracoccidioidomycosis – 2-17 Months, when sporotrichosis – 1-16 months and at gistoplazmoze – 3-17 Months.

In children, as in the similar infections in adults, the duration of treatment depends on the clinical and mycological effect. Daily dose for children should not exceed that for adults. Fluconazole used daily 1 time / day.

At mucosal candidiasis The recommended dose of fluconazole 3 mg / kg / day. The first day can be assigned to the loading dose 6 mg / kg in order to more quickly achieve permanent equilibrium concentrations.

For the treatment of generalizovannogo candidiasis infections and kriptokokkovoy The recommended dose is 6-12 mg / kg / day, depending on the severity of the disease.

To Prevention of fungal infections in patients with low immunity, in which the risk of infection associated with neutropenia, developing as a result of cytotoxic chemotherapy or radiotherapy, the drug is prescribed for 3-12 mg / kg / day, depending on the severity and duration of neutropenia induced by conservation.

In applying the drug in children 4 weeks or less it should be understood, that infants fluconazole is excreted slowly. First 2 weeks of life, the drug is prescribed in the same dose (in mg / kg), and that older children, but the intervals 72 no. For children 3 and 4 weeks of life the same dose administered at intervals of 48 no.

In elderly patients in the absence of signs of kidney failure drug appointed dose of medium.

Patients with renal insufficiency (CC<50 ml / min) requires correction mode.

Fluconazole is derived mainly from the urine in unchanged form. When a single admission dose not required. Patients (including children) with kidney function with repeated use of the drug should initially enter a shock dose of 50 mg 400 mg, then the daily dose (depending on the evidence) determined according to the following table.

Fluconazole can be taken orally (in the form of capsules and suspension) or/386/1989 (in the form of solution for the on/in the introduction) by infusion at a rate of not more than 10 ml / min; the choice of the route of Administration depend on the clinical condition of the patient. When transferring a patient with on/in the introduction to the reception of the drug inside or vice versa changes the daily dose is not required.

The capsules should be swallowed whole.

When preparing for the reception inside the contents of one vial should add 24 ml of water and shake carefully. Before each use, suspension should stir.

Preparation solution for the on/in the introduction contains 0.9% sodium chloride solution; in every 200 mg (vial 100 ml) contains 15 mmol of Na⁺ and Cl^–, Consequently, patients, who need to limit sodium intake or liquid, You must take into account the speed of fluid.

Side effect

The most frequent side effects, which have been registered in clinical and postmarketingovyh (*) studies of fluconazole.

From the central and peripheral nervous system: headache, Dizzy *, cramps *, changing taste *.

From the digestive system: abdominal pain, diarrhea, flatulence, nausea, indigestion *, vomiting *, gepatotoksichnostь (including rare cases of fatal), increase in AP, bilirubin, serum aminotransferase levels (ALT IS), the liver *, Hepatitis *, Hepatocellular necrosis *, jaundice *.

From the circulatory system *: increase the QT interval on the ECG, flicker / ventricular flutter.

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

Blood system *: leukopenia, including neutropenia and agranulocytosis, thrombocytopenia.

Metabolism *: increased cholesterol and triglyceride levels in plasma, kaliopenia.

Allergic reaction *: anaphylactic reactions (including angioedema, swelling of the face, hives, itch).

In some patients,, especially with serious diseases (AIDS, malignant neoplasms), in the treatment flukonazolom and similar drugs were observed changes in blood, kidney and liver function, However, the clinical significance of these changes and their relationship with treatment not installed.

Contraindications

-the simultaneous use of cisapride;

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

- Hypersensitivity to fluconazole, other components of the drug or azolnym substances with similar flukonazolom structure.

FROM caution shall mean disorders in the liver with the use of fluconazole, When you see the scars on the background of the use of fluconazole in patients with superficial fungal infection and invasive/systemic fungal infections, together with the use of terfenadine and fluconazole at a dose of less than 400 mg / day, When potentially proaritmicheskih conditions in patients with multiple risk factors (organic heart disease, violations elektrolitnogo balance and contributing to the development of such violations accompanying therapy).

Pregnancy and lactation

Adequate and controlled studies safety of the drug in pregnant women has been carried out. Describes cases of multiple birth defects in newborns, for mothers 3 months or more received therapy in the high dose flukonazolom (400-800 mg / day) about kokcidioidomikoza. The relationship between those violations and receiving fluconazole is not installed.

Fluconazole should be avoided during pregnancy, except in cases of severe and potentially life-threatening fungal infections, when the expected benefit of treatment exceeds potential risk for the fetus. Therefore, women of childbearing age should use reliable methods of contraception.

Fluconazole found in breast milk in concentrations, close to plasma, so apply Diflucan^® lactation (breast-feeding) do not recommend.

Cautions

In rare cases, fluconazole was accompanied by toxic changes in the liver, incl. fatal, mainly in patients with severe concomitant diseases. Not observed explicit dependence of hepatotoxic effects of fluconazole on the total daily dose, duration of therapy, sex and age of the patient. Gepatotoksicescoe the flukonazola usually reversible; its signs disappeared after cessation of therapy. It is necessary to observe patients, which at the time of treatment flukonazolom violated the liver, with a view to detecting signs of more serious liver damage. With the appearance of clinical signs or symptoms of liver damage, that may be associated with fluconazole, the drug should be discontinued.

During treatment flukonazolom in patients in rare cases evolved jeksfoliativnye skin reactions, such as Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis. AIDS patients are more prone to the development of severe skin reactions in the application of many drugs. When the patient, receiving treatment for superficial fungal infections, rash, that can be associated with the use of fluconazole, the drug should be discontinued. If a rash in patients with invasive / systemic fungal infections should be carefully monitored and cancel fluconazole when a bullous lesions or erythema multiforme.

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

Fluconazole at doses less than 400 mg/day and terfenadina should be under close supervision.

Like other azoles, fluconazole may cause an increase in the QT interval on the ECG. When applying fluconazole increase QT interval and shimmer/ventricular fibrillation observed very rarely in patients with multiple risk factors, such as organic heart disease, violations elektrolitnogo balance and contributing to the development of such violations accompanying therapy. Therefore, such patients with potentially proaritmicheskimi conditions apply fluconazole should be cautious.

Patients with liver disease, hearts and kidneys before application of fluconazole is recommended to consult with a physician. In the application of fluconazole 150 mg about vaginal candidiasis, patients should be warned, that improvement in symptoms usually observed through 24 no, but for their complete disappearance sometimes takes a few days. When you save the symptoms within a few days, should see a doctor.

Effects on ability to drive vehicles and management mechanisms

Experience of application of fluconazole demonstrated that, that the deterioration of the ability to drive a car and mechanisms, associated with the use of the drug, unlikely.

Overdose

In one case, an overdose of fluconazole at 42-year-old patient, living with HIV, after administration 8200 mg fluconazole appeared hallucinations and paranoid behavior. The patient was hospitalized, his condition returned to normal within 48 no.

Treatment: adequate effect can give symptomatic therapy (incl. support measures and gastric lavage).

Fluconazole write mainly with urine, therefore forced diuresis, probably, can speed up its excretion. Dialysis session duration 3 h reduces the level of fluconazole in plasma approximately 50%.

Drug Interactions

Antykoahulyantы: like other antifungal agents – derivatives azola, fluconazole if you are applying with warfarin increases prothrombin time (on 12%), in connection with what may develop bleeding (hematoma, nosebleeds and stomach, hematuria, ground). Patients, receiving coumarin anticoagulants, There is a need to constantly monitor prothrombin time.

Azithromycin: While applying inward in a single dose of fluconazole 800 mg in a single dose of azithromycin 1200 mg express pharmacokinetic interaction is not installed.

Benzodiazepines (short-acting): after intake of Midazolam fluconazole significantly increases the concentration of Midazolam and psychomotor effects, and this effect is more pronounced after taking fluconazole inside, than in its application in/at. If necessary, concomitant therapy with benzodiazepines in patients, taking fluconazole, should be monitored for appropriate dose reduction of benzodiazepine.

Cisapride: in concurrent usage of fluconazole and cisapride are possible unwanted reactions on the part of the heart, incl. flicker / ventricular flutter (the type of arrhythmia “pirouette”). Usage of fluconazole at a dose 200 mg 1 times/day and cisapride dose 20 mg 4 times / day leads to a pronounced increase in plasma concentrations of cisapride and an increase in the QT interval on the ECG. Concomitant use of cisapride and fluconazole is contraindicated.

Cyclosporine: in patients after kidney transplantation application of fluconazole at a dose 200 mg/day leads to slow increased concentrations of Cyclosporine. However at repeated admission of fluconazole at a dose 100 mg/day changes in the concentration of Cyclosporine in recipients of bone marrow were observed. In concurrent usage of fluconazole and Cyclosporin recommended monitor the concentration of Cyclosporine in the blood.

Gidroxlorotiazid: repeated use of hydrochlorothiazide simultaneously with fluconazole leads to an increase in the concentration of fluconazole in 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, however, this should be taken into account.

Oral contraceptives: with the simultaneous use of a combined oral contraceptive with fluconazole in a dose 50 mg significant effect on hormone levels has not been established, While daily admission 200 mg fluconazole AUC of ethinyl estradiol and levonorgestrel increased by 40% and 24% respectively, and when receiving 300 mg fluconazole once a week – AUC of ethinyl estradiol and norethindrone is increased by 24% and 13% respectively. Thus, repeated use of fluconazole at the indicated doses is unlikely to affect the effectiveness of the combined oral contraceptive.

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

Rifabutin: fluconazole and rifabutin may increase serum concentrations of the last. With the simultaneous use of fluconazole and rifabutin, cases of uveitis have been described. Patients, while receiving rifabutin and fluconazole, must be carefully observed.

Rifampicin: simultaneous use of fluconazole and rifampicin leads to a decrease in AUC by 25% and duration of T_1/2 of fluconazole 20%. Patients, at the same time taking rifampicin, must be considered feasibility of increasing doses of fluconazole.

Drugs sulfonylureas: fluconazole while admission leads to an increase in T_1/2 oral sulfonylureas (hlorpropamyda, glibenclamide, tolbutamide and glipizide). Patients with diabetes mellitus can be co-administered with fluconazole and oral sulfonylureas, but should take into account the possibility of hypoglycemia.

Tacrolimus: the simultaneous use of fluconazole and tacrolimus leads to an increase in serum concentrations of the latter. Cases of nephrotoxicity have been reported. Patients, taking tacrolimus and fluconazole at the same time, It should be carefully monitored.

Terfenadin: 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 in a dose 200 mg / day increase in the QT interval has not been established, however, the use of fluconazole in doses 400 mg/day and above causes a significant increase in plasma terfenadine concentrations. Simultaneous reception of fluconazole at doses 400 mg/day or more with terfenadine is contraindicated. Treatment flukonazolom in doses of less than 400 mg/day in combination with terfenadine should be under close supervision.

Theophylline: If you are applying with flukonazolom in dose 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 should be monitored for the appearance of symptoms of theophylline overdose and, if necessary, adjust therapy accordingly.

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

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

Concomitant use of fluconazole with astemizole or other drugs, whose metabolism is carried out by isoenzymes of the cytochrome P450 system, can be accompanied by increased serum concentrations of these funds. While appointing fluconazole, in the absence of reliable information, Care must be taken. Patients should be closely monitored..

Interaction studies of oral forms of fluconazole when taken simultaneously with food, cimetidine, antaцidami, as well as after total body irradiation for bone marrow transplants have shown, that these factors do not have a clinically significant effect on induction of fluconazole.

The listed interactions were established with repeated use of fluconazole.; drug interactions resulting from a single dose of fluconazole are unknown.

It should be taken into account, that interactions with other drugs have not been specifically studied, but it is possible.

Pharmaceutical interaction

Diflucan^® – solution for intravenous administration is compatible with the following solutions: 20% glucose, Ringer, solution Hartmann, solution of potassium chloride in glucose, 4.2% solution of sodium bicarbonate, aminofuzin, isotonic saline.

Conditions of supply of pharmacies

The drug is released under the prescription. The preparation is in the form of capsules 150 mg is approved for use as a means of non-prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 30 ° C. Avoid freezing solution and suspension.

Shelf life of capsules and solution for intravenous administration - 5 years. Shelf life of powder for preparation of suspension for oral administration - 3 year. Shelf life of the finished suspension – 14 days.