Diflucan - Instructions For Use, Reviews, Price, Analogues, Capsules

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Diflucan

Diflucan: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Diflucan

ATX code: J02AC01

Active ingredient: fluconazole (Fluconazole)

Manufacturer: Pfizer Inc. (Pfizer, Inc.) USA; Fareva Amboise (France)

Description and photo update: 2019-18-09

Prices in pharmacies: from 131 rubles.

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Diflucan is an antifungal drug.

Release form and composition

• capsules 50/100/150 mg: No. 4 / No. 2 / No. 1 hard gelatinous; turquoise lid and white body / white lid and body / turquoise lid and body; black marking in the form of the Pfizer and FLU-50 / FLU-100 / FLU-150 logos; capsules contain powder from slightly yellow to white (capsules 50 and 100 mg: 7 pieces in blisters made of PVC / Al foil, in a cardboard box with instructions for use 1 or 4 blisters; 150 mg capsules: 1 or 4 each pcs in blisters made of PVC / Al foil; in a cardboard box with instructions for use 1 blister 1 or 4 pcs., 2 blisters 1 pc., 3 blisters 4 pcs.);
• powder for preparation of suspension for oral administration: from almost white to white, without visible contamination [50 mg / 5 ml or 200 mg / 5 ml each in plastic (HDPE) vials with a screw cap with child protection system and a plastic ring for control of the first opening; in a cardboard box with instructions for use 1 bottle complete with a measuring spoon made of plastic];
• solution for intravenous (iv) administration: clear colorless liquid (25, 50, 100 or 200 ml of solution in vials of colorless transparent glass of type I, sealed with a rubber stopper and crimped with an aluminum cap equipped with a plastic insert of the "flip off" type and plastic holder; in a cardboard box with instructions for use 1 bottle).

Composition of 1 capsule:

• active substance: fluconazole - 50/100/150 mg;
• auxiliary components: lactose - 49.708 / 99.415 / 149.123 mg; corn starch - 16.5 / 33.0 / 49.5 mg; colloidal silicon dioxide - 0.117 / 0.235 / 0.352 mg; magnesium stearate - 1.058 / 2.115 / 3.173 mg; sodium lauryl sulfate - 0.117 / 0.235 / 0.352 mg;
• capsule shell: gelatin - up to 100%; [titanium dioxide (E171) - 4.47%, patented blue dye (E 131) - 0.03%] / [titanium dioxide (E171) - 3%] / [titanium dioxide (E171) - 1.47%, dye patented blue (E 131) - 0.03%];
• ink for capsule marking: shellac glaze - 63%, black iron oxide (E172) - 25%, N-butyl alcohol - 8.995%, industrial methylated alcohol 74 OP - 2%, soy lecithin - 1%, antifoam component DC 1510 - 0.005 %.

Composition for 1 ml of ready-made suspension prepared from powder, 50 mg / 5 ml or 200 mg / 5 ml:

• active substance: fluconazole - 10 or 40 mg;
• auxiliary components: anhydrous citric acid - 4.20 / 4.21 mg; sodium benzoate - 2.37 / 2.38 mg; xanthan gum - 2.03 / 2.01 mg; titanium dioxide (E 171) - 1.0 / 0.98 mg; sucrose - 576.23 / 546.27 mg; colloidal anhydrous silicon dioxide - 1.0 / 0.98 mg; sodium citrate dihydrate - 3.17 / 3.17 mg; orange flavoring (essential orange oil, maltodextrin, water) - 10/10 mg.

Composition for 1 ml of solution for intravenous administration:

• active substance: fluconazole - 2 mg;
• auxiliary components: sodium chloride - 9 mg, water for injection - up to 1 ml.

Pharmacological properties

Pharmacodynamics

The active ingredient of Diflucan - fluconazole, is a member of the triazole group, has antifungal activity based on a powerful selective inhibition of sterol synthesis in the fungal cell.

Fluconazole has been shown to be active in clinical infections and in vitro against most of the following microorganisms: Candida albicans, Candida parapsilosis, Candida glabrata (many strains exhibit moderate sensitivity), Candida tropicalis and Cryptococcus neoformans.

The in vitro activity of fluconazole has been shown against the following microorganisms (clinical significance unknown): Candida dubliniensis, Candida kefyr, Candida guilliermondii, Candida lusitaniae.

Both when taken orally and parenterally (i.v.), fluconazole was active in various models of fungal infections in animals:

• opportunistic mycoses: caused by Candida spp. (including generalized candidiasis in the studied animals with suppressed immunity), Cryptococcus neoformans (including intracranial infections), Trichophyton spp., Microsporum spp. and etc.;
• endemic mycoses: caused by Blastomyces dermatitidis, Coccidioides immitis (including intracranial infections) and Histoplasma capsulatum in animals with normal / suppressed immunity.

Fluconazole is highly specific for enzymes of fungi dependent on CYP450.

The use of Diflucan in a daily dose of 50 mg for 4 weeks does not affect the plasma testosterone concentration in men or the level of steroids in women of childbearing age. Fluconazole in a daily dose of 200-400 mg on the levels of endogenous steroids, as well as their response to stimulation of ACTH (adrenocorticotropic hormone) in healthy male volunteers has no clinically significant effect.

There are the following mechanisms for the development of resistance to fluconazole: a qualitative or quantitative modification of the target enzyme for fluconazole - lanosterol 14-α-demethylase, or a decrease in access to it (a combination of two mechanisms is possible).

Point mutations in the ERG11 gene encoding the target enzyme lead to modification of the target with a subsequent decrease in the affinity for azoles. Due to the increase in the expression of the ERG11 gene, the target enzyme is produced in high concentrations, creating the need to increase the level of fluconazole in the intracellular fluid in order to suppress all enzyme molecules in the cell.

Another significant mechanism of resistance consists in the active removal of fluconazole from the intracellular space by activating two types of transporters involved in efflux (active elimination) of substances from the fungal cell. Such transporters are the main mediator, encoded by multidrug resistance (MDR) genes, and the superfamily of ATP-binding cassette transporters, encoded by the genes for resistance of Candida to azoles antimycotics (CDR). Overexpression of the MDR gene develops resistance to fluconazole, while overexpression of the CDR genes may result in the formation of resistance to various azoles.

Resistance to Candida glabrata usually results from overexpression of the CDR gene, which causes resistance to many azoles. For strains with a minimum inhibitory concentration (MIC), defined as intermediate, in the range of 16–32 μg / ml, it is recommended to use fluconazole at maximum doses.

Candida krusei must be considered as resistant to fluconazole. The mechanism of its resistance is based on the reduced sensitivity of the target enzyme to the inhibitory effect of the drug.

Pharmacokinetics

Fluconazole is a selective inhibitor of CYP2C9 and CYP3A4 isoenzymes, and an inhibitor of CYP2C19 isoenzyme.

The pharmacokinetics of fluconazole when administered intravenously and orally are similar and demonstrate the following characteristics:

• absorption: after oral administration, fluconazole is well absorbed, plasma concentration and total bioavailability amount to more than 90% of these indicators for intravenous administration; simultaneous food intake does not affect absorption. The level of the substance in blood plasma is proportional to the dose and reaches maximum values (Cmax) 0.5–1.5 hours after taking Diflucan on an empty stomach, the half-life (T _1/2) is ~ 30 hours. Up to 90% of the equilibrium concentration (Css) is achieved by 4–5 days from the start of treatment (provided that Diflucan is taken once a day). The introduction on the 1st day of a loading dose, 2 times higher than the usual daily, contributes to the achievement of 90% Css by the 2nd day of therapy. The volume of distribution (Vd) approaches the total amount of water in the body. 11-12% of the substance binds to plasma proteins;
• distribution: fluconazole penetrates well into body fluids, its concentration in saliva and sputum is similar to that in blood plasma. In patients with fungal meningitis in the cerebrospinal fluid, the concentration index is about 80% of the level of the substance in the blood plasma. In the epidermis, dermis, and sweat, the concentrations exceed those of serum. Fluconazole accumulates in the superficial (stratum corneum) layer of the epidermis. The application of a dose of 50 mg once a day will provide a fluconazole concentration of 73 μg / g after 12 days; 7 days after completion of treatment, the indicator will be 5.8 μg / g. Application at a dose of 150 mg once a week on the 7th day will provide a concentration in the stratum corneum - 23.4 μg / g, and 7 days after taking the 2nd dose - 7.1 μg / g. The level of the substance in the nail plates after applying a dose of 150 mg once a week for 4 months will be 4,05 μg / g in healthy nails and 1.8 μg / g in affected nails; six months after the end of treatment, fluconazole is still detected in the nails;
• metabolism and excretion: no circulating metabolites of fluconazole have been detected; the drug is excreted mainly by the kidneys, up to 80% of the administered dose is found unchanged in the urine. The rate of clearance of fluconazole is proportional to the value of CC (creatinine clearance).

Prolonged elimination of the substance from the blood plasma makes it possible to take Diflucan once for vaginal candidiasis, for other indications - once a day or once a week.

When comparing the concentrations of fluconazole in blood plasma and saliva after a single dose of 100 mg in the form of a suspension (subject to rinsing, keeping in the mouth for 2 minutes, swallowing) and a capsule, it was found that the Cmax of the substance in saliva after taking the suspension was reached after 5 minutes and in 182 times higher than Cmax after taking the capsule, reached after 4 hours. After about 4 hours, the level of fluconazole in saliva was the same. AUC _0–96 (mean area under the concentration-time curve) for the period from the start of administration to 4 days, in saliva was significantly higher when taking the suspension than capsules. The use of two oral dosage forms did not reveal significant differences in the rate of elimination from saliva and in the parameters of pharmacokinetics in blood plasma.

Pharmacokinetic parameters of fluconazole use in children:

• oral administration (capsules, suspension): age from 9 months to 13 years - a single dose of 2 mg / kg or 8 mg / kg, T _1/2, respectively, 25 or 19.5 h, AUC 94.7 or 362.5 μg × h / ml; average age 7 years - a multiple dose of 3 mg / kg, T _1/2 = 15.5 h, AUC = 41.6 μg × h / ml;
• parenteral (i / v) administration (solution): age from 11 days to 11 months - a single dose of 3 mg / kg, T _1/2 = 23 h, AUC = 110.1 μg × h / ml; age from 5 to 15 years - multiple dose 2/4/8 mg / kg, T _1/2 (noted on the last day of therapy) - 17.4 / 15.2 / 17.6 h, AUC (noted on the last day of therapy) - 67.4 / 139.1 / 196.7 μg × h / ml.

Indicators of some pharmacokinetic characteristics with parenteral (i / v) administration of Diflucan solution to premature infants (about 28 weeks of development) at a dose of 6 mg / kg every 3rd day (maximum 5 doses), while in the intensive care unit:

• average T _1/2 - 74 hours (in the range from 44 to 185 hours) on the 1st day, with a decrease by the 7th day to an average of 53 hours (in the range from 30 to 131 hours), by the 13th day on average up to 47 hours (in the range from 27 to 68 hours);
• AUC - 271 μg × h / ml (in the range from 173 to 385 μg × h / ml) on the 1st day, increasing to 490 μg × h / ml (in the range from 292 to 734 μg × h / ml) to On the 7th day and a decrease on average to 360 μg × h / ml (in the range from 167 to 566 μg × h / ml) on the 13th day;
• Vd - 1183 ml / kg (in the range from 1070 to 1470 ml / kg) on the 1st day, with an increase on average up to 1184 ml / kg (in the range from 510 to 2130 ml / kg) by the 7th day and up to 1328 ml / kg (ranging from 1040 to 1680 ml / kg) by the 13th day.

The pharmacokinetics of fluconazole was studied in elderly patients 65 years of age and older with a single oral administration of Diflucan at a dose of 50 mg (some patients were simultaneously taking diuretics). Cmax = 1.54 μg / ml was reached 1.3 hours after administration; average AUC = 76.4 ± 20.3 μg × h / ml; mean T _1/2 = 46.2 hours. The parameters were slightly higher than in young patients, most likely, this effect is due to the reduced renal function characteristic of the elderly. Reception simultaneously with diuretics did not significantly affect the AUC and Cmax values. Characteristics that are lower in old age than in young patients: CC = 74 ml / min; unchanged excreted by the kidneys over the period from 0 to 24 hours - 22% of fluconazole; renal clearance = 0.124 ml / min / kg.

Indications for use

Capsules

Diflucan capsules are prescribed for the treatment of the following diseases in adult patients:

• coccidioidomycosis;
• cryptococcal meningitis;
• invasive candidiasis;
• mucous candidiasis, including esophageal candidiasis, candiduria, oropharyngeal candidiasis, chronic mucocutaneous candidiasis;
• chronic atrophic candidiasis of the oral cavity associated with wearing dentures, with insufficient adherence to oral hygiene or local therapy;
• acute or recurrent vaginal candidiasis, if local therapy is impossible;
• candidal balanitis, if it is impossible to use local therapy;
• dermatomycosis, including dermatophytosis of the feet and (or) trunk, inguinal dermatophytosis, cutaneous candidiasis, versicolor versicolor, if necessary, systemic therapy;
• onychomycosis (nail dermatophytosis), if therapy with other drugs is unacceptable.

Diflucan capsules are indicated for the prevention of the following diseases in adult patients:

• cryptococcal meningitis, prevention of relapse in patients at high risk of recurrence;
• oropharyngeal candidiasis and esophageal candidiasis in patients with HIV infection at high risk of recurrence;
• vaginal candidiasis in patients with 4 or more episodes per year, to reduce the frequency of relapses;
• prolonged neutropenia in hematopoietic malignancies due to chemotherapy or hematopoietic stem cell transplantation, for the prevention of candidal infections.

For children, Diflucan capsules are prescribed for the treatment of mucous candidiasis (oropharyngeal and digestive organs), cryptococcal meningitis, invasive candidiasis and for the prevention of candidal infections with weakened immunity. At a high risk of recurrence of cryptococcal meningitis in children, fluconazole is recommended for maintenance therapy in order to prevent recurrence of the disease.

Powder for suspension preparation, solution for intravenous administration

• cryptococcosis, including cryptococcal meningitis, infectious lesions of the lungs, skin and other organs in patients with normal immunity, recipients of transplanted organs, in patients with various forms of immunodeficiency and AIDS; maintenance therapy in AIDS patients in order to prevent relapses of cryptococcosis;
• generalized candidiasis, including disseminated candidiasis, candidemia, invasive candidal infections of the eyes, peritoneum, endocardium, urinary and respiratory tract, including in cancer patients undergoing intensive therapy with immunosuppressive and cytotoxic drugs, and in patients with other pathologies that predispose to candidiasis;
• candidal balanitis, genital candidiasis, vaginal candidiasis - treatment of acute or recurrent forms and prevention of reducing the frequency of relapses (3 or more cases per year);
• candidiasis of the mucous membranes of the body, including the oral cavity, pharynx, esophagus, non-invasive bronchopulmonary infections, candiduria, chronic mucocutaneous and atrophic oral candidiasis caused by wearing dentures, in patients with normal and impaired immune function; in AIDS patients - prevention of oropharyngeal candidiasis;
• deep endemic mycoses (coccidioidomycosis, paracoccidioidomycosis, histoplasmosis and sporotrichosis) in patients with normal immunity;
• pityriasis versicolor, mycosis (feet, groin, body skin), onychomycosis and skin candidal infections.

In addition, taking the suspension and intravenous administration of the Diflucan solution is indicated for patients with malignant tumors for the prevention of fungal infection against the background of radiation and cytotoxic therapy.

Contraindications

Absolute:

• simultaneous use with terfenadine with a long course of fluconazole therapy in a daily dose of 400 mg or more;
• simultaneous use with cisapride, astemizole, erythromycin, pimozide, quinidine, amiodarone and other drugs that increase the QT interval and are metabolized by the cytochrome P450 3A4 isoenzyme;
• for capsules and suspensions - lactase deficiency, galactose intolerance, glucose-galactose malabsorption;
• for capsules - children under 3 years old;
• period of breastfeeding (lactation);
• hypersensitivity to azole compounds with a structure similar to fluconazole;
• hypersensitivity to fluconazole and the auxiliary components of Diflucan.

Relative (Diflucan should be used with caution, under medical supervision):

• impaired liver / kidney function (hepatic / renal failure);
• pregnancy;
• the appearance of a rash in patients with superficial fungal infection and invasive (systemic) fungal infections while using fluconazole;
• the simultaneous use of terfenadine with fluconazole in a daily dose of less than 400 mg;
• potentially proarrhythmic conditions in patients with multiple risk factors: organic heart disease, electrolyte imbalance, as well as with concomitant therapy that contributes to the development of such diseases.

Instructions for the use of Diflucan: method and dosage

The use of Diflucan can be started before the results of laboratory bacteriological studies, including bacterial culture, are obtained. But immediately after receiving them, it is required to adjust the antifungal therapy accordingly.

Diflucan is taken orally or parenterally (i / v), the choice of the dosage form of the drug and the method of administration depends on the clinical condition of the patient. When a patient is transferred from intravenous fluconazole to oral administration, or vice versa, no correction of the daily dose is required.

Method of using Diflucan, depending on the form of release:

• capsules: taken orally whole, without chewing, food intake does not have a clinically significant effect on the absorption of fluconazole;
• powder for suspension preparation: add 24 ml of water to the contents of the bottle with the powder and shake thoroughly during dilution and before each use; the suspension is taken orally, regardless of food intake;
• solution: administered by intravenous infusion at a rate of ≤ 10 ml / min.

The solution for intravenous administration of Diflucan contains 0.9% NaCl solution, in 1 bottle 100 ml (200 mg) - 15 mmol of sodium and chlorine ions. In patients with sodium or fluid restriction, the rate of infusion should be considered.

The doctor prescribes the daily dose of Diflucan based on an assessment of the nature and severity of the fungal disease. In case of an infection requiring a second course, therapy is continued until the clinical / laboratory symptoms of an active fungal infection disappear. Patients with AIDS, cryptococcal meningitis, and recurrent oropharyngeal candidiasis usually require supportive treatment to prevent recurrence of the disease after seemingly complete recovery.

Treatment of adult patients

Diflucan capsules:

• cryptococcal meningitis and cryptococcal infections of other localization: the initial daily dose is 400 mg, then treatment is continued at a daily dose of 200–400 mg per dose. The duration of the course depends on the clinical and mycological efficacy of Diflucan; therapy for cryptococcal meningitis usually lasts a minimum of 6–8 weeks. For life-threatening infections, the daily dose can be increased to 800 mg. To prevent the recurrence of cryptococcal meningitis in patients with a high risk of recurrence of the disease after the completion of the full course of primary therapy, Diflucan can be continued in a daily dose of 200 mg indefinitely;
• coccidioidomycosis: it may be necessary to take daily doses of 200-400 mg, for more severe infections, especially with lesions of the meninges, an increase in the daily dose to 800 mg is possible. The duration of the course is determined individually, treatment can last up to 24 months, including with coccidioidomycosis - 11-24 months; with paracoccidioidomycosis - 2-17 months; with sporotrichosis - 1–16 months; with histoplasmosis - 3–17 months;
• candidemia, disseminated candidiasis, other invasive candidal infections: saturating daily dose on the first day - 800 mg, subsequent daily doses - 400 mg. The duration of the course depends on the clinical effectiveness, it is recommended to continue treatment for two weeks after the first negative blood culture result and the disappearance of symptoms and signs of candidemia;
• oropharyngeal candidiasis: saturating daily dose on the first day - 200-400 mg, subsequent daily doses - 100-200 mg, course duration from 7 to 21 days. If necessary, with a pronounced suppression of the immune function, therapy can be extended. For the prevention of recurrence of oropharyngeal candidiasis in patients with HIV infection with a high risk of recurrence of the disease, Diflucan is used in a daily dose of 100-200 mg daily or 200 mg daily 3 times a week for the treatment of patients with chronically lowered immunity for an indefinite period of time;
• candiduria: effective daily dose - 200-400 mg, course duration from 7 to 21 days. Patients with severely compromised immune system function may require longer treatment;
• chronic mucocutaneous candidiasis: daily dose - 50-100 mg, course duration up to 28 days; longer treatment may be prescribed depending on the severity of the disease, concomitant infection and disorders of the immune system;
• esophageal candidiasis: saturating daily dose on the first day - 200-400 mg, subsequent daily doses - 100-200 mg. The course of therapy is 14-30 days (until remission is achieved). Patients with severely compromised immune system function may require longer treatment. For the prevention of recurrence of esophageal candidiasis in patients with HIV infection and a high risk of recurrence of the disease, Diflucan is used in a daily dose of 100-200 mg daily or 200 mg daily 3 times a week when treating patients with chronically lowered immunity for an indefinite period of time;
• chronic atrophic candidiasis of the oral cavity associated with wearing dentures: a daily dose of 50 mg at a time in a course of 14 days in combination with the treatment of the denture with local antiseptics;
• acute vaginal candidiasis, candidal balanitis: Diflucan is used once in a dose of 150 mg. In order to reduce the frequency of relapses of vaginal candidiasis, capsules of 150 mg are taken 1 time in three days, only 3 pcs. (on the 1st, 4th and 7th day), after which they switch to prophylactic administration in a maintenance dose - 150 mg once every 7 days, the duration of the prophylactic course can be up to 6 months;
• dermatomycosis of the skin, including dermatophytosis of the feet, dermatophytosis of the trunk, inguinal dermatophytosis, candidal infections: the effective dose is 150 mg once a week or 50 mg once a day. The duration of the course is usually from 2 to 4 weeks, with mycoses of the feet, a longer treatment may be needed - up to 6 weeks;
• versicolor versicolor: effective dose - 300-400 mg once a week. The course usually lasts 1 to 3 weeks. According to another scheme, Diflucan is taken at 50 mg 1 time per day for 2-4 weeks;
• onychomycosis: effective dose - 150 mg once a week; the therapy is continued until the infected nail plate is replaced with a healthy one. Re-growth of nails on the fingers takes 3-6 months, on the toes - 6-12 months. At the same time, the growth rate in different people can vary widely and also depend on the patient's age. As a result of successful treatment of chronic infections that persist for a long time, it is sometimes possible to change the shape of the nails;
• prevention of candidiasis in patients with malignant tumors: daily dose - 200-400 mg (depending on the degree of risk of developing fungal infection). With a high likelihood of developing a generalized infection, for example, with severe or long-term neutropenia, it is recommended to take 400 mg 1 time per day. Diflucan begin to take a few days before the predicted development of neutropenia, then, after an increase in the number of neutrophils more than 1000 mm ³, therapy is continued for another 7 days.

Powder for suspension preparation, solution for intravenous administration:

• cryptococcal meningitis and cryptococcal infections of other localization: saturating daily dose on the first day - 400 mg, subsequent daily doses - 200-400 mg. The duration of the course depends on the clinical and mycological efficacy of Diflucan; therapy for cryptococcal meningitis usually lasts a minimum of 6–8 weeks. To prevent the recurrence of cryptococcal meningitis in AIDS patients, upon completion of the full course of primary therapy, Diflucan can be continued indefinitely at a daily dose of 200 mg;
• candidemia, disseminated candidiasis, other invasive candidal infections: saturating daily dose on the first day - 400 mg, subsequent daily doses - 200 mg. An increase in the daily daily dose of up to 400 mg is allowed, depending on the severity of the clinical effect of Diflucan. The duration of the course depends on the clinical effectiveness of therapy;
• oropharyngeal candidiasis: the standard daily dose is 50–100 mg, the duration of the course is 7–14 days. Patients with severe suppression of immune function, if necessary, can be extended treatment. In patients with AIDS, in order to prevent recurrence of oropharyngeal candidiasis, after completion of the full course of primary therapy, Diflucan can be prescribed 1 time per week, 150 mg;
• chronic atrophic candidiasis of the oral cavity associated with wearing dentures: daily dose - 50 mg at a time in a course of 14 days with simultaneous treatment of the prosthesis with local antiseptics;
• esophagitis, non-invasive bronchopulmonary infections, candiduria, candidiasis of the skin / mucous membranes, other candidal infections of the mucous membranes (except for genital candidiasis): an effective daily dose of 50 mg per dose for 14–30 days;
• vaginal candidiasis, balanitis caused by Candida spp.: single dose, only for oral dosage forms, by mouth at a dose of 150 mg. In order to reduce the frequency of relapses of vaginal candidiasis, Diflucan can be used once a week at a dose of 150 mg. The duration of preventive treatment is determined individually and, as a rule, can be up to 6 months. Children under 18 years old and patients over 60 years old should not use a single dose without a doctor's prescription;
• prevention of candidiasis in patients with malignant tumors: daily dose - 50-400 mg (depending on the degree of risk of developing fungal infection). With a high likelihood of developing a generalized infection, for example, with severe or long-term neutropenia, it is recommended to take 400 mg 1 time per day. Diflucan begins to take a few days before the predicted development of neutropenia, then, after an increase in the number of neutrophils more than 1000 mm ³, therapy is continued for another 7 days;
• mycoses of feet, smooth skin, groin area, other skin infections, including candidiasis: an effective dose is 150 mg once a week or 50 mg once a day. The duration of the course is usually from 2 to 4 weeks, with mycoses of the feet, a longer treatment may be needed - up to 6 weeks;
• pityriasis versicolor: effective dose - 300 mg 1 time per week course - 2 weeks; some patients may need a third dose of 300 mg per week, while others may need a single dose of 300-400 mg Diflucan. According to another scheme, the drug is taken at 50 mg 1 time per day for 2-4 weeks;
• onychomycosis: effective dose - 150 mg once a week; the therapy is continued until the infected nail plate is replaced with a healthy one. Re-growth of nails on the fingers takes 3-6 months, on the toes - 6-12 months. At the same time, the growth rate in different people can vary widely and also depend on the patient's age. As a result of successful treatment of chronic infections that persist for a long time, it is sometimes possible to change the shape of the nails;
• deep endemic mycoses: it may be necessary to use Diflucan in a daily dose of 200-400 mg. The duration of the course is determined individually, the treatment can last up to 24 months; with coccidioidomycosis - 11-24 months.

The use of Diflucan in children

As in the treatment of similar infections in adults, the duration of therapy is determined by the attending physician, depending on the clinical and mycological effectiveness. The daily dose of fluconazole for children should not exceed that for adult patients. The maximum daily dose of Diflucan for children is 400 mg.

Diflucan should be used daily, once a day, in accordance with the recommendations:

• therapy for candidiasis of the mucous membranes: 3 mg / kg / day; on the first day, for a faster achievement of Css, a saturating daily dose of 6 mg / kg can be applied;
• therapy of generalized candidiasis and cryptococcal infections: from 6 to 12 mg / kg / day, depending on the complexity of the infection;
• prevention of recurrence of cryptococcal meningitis in children with AIDS: 6 mg / kg;
• prevention of fungal infections in immunosuppressed children whose risk of infection is associated with neutropenia developing against the background of cytotoxic chemotherapy or radiation therapy: from 3 to 12 mg / kg / day, depending on the severity and duration of the persistence of induced neutropenia.

Since fluconazole is excreted slowly in newborns, at 1 and 2 weeks of life, Diflucan is used in the same dose of mg / kg as in the treatment of older children, but with an interval of 1 every 3 days. For newborns 3 and 4 weeks of life, the same dose is used 1 time in 2 days.

If it is difficult to take Diflucan capsules by children over 3 years old, it is recommended to consider replacing them with other dosage forms of the drug (powder for preparation of suspension for oral administration or solution for intravenous administration) in equivalent doses.

Side effects

The tolerance of all dosage forms of Diflucan when used in compliance with the recommended dosage regimen is usually very good.

According to the results of clinical and post-marketing studies, the following adverse reactions were noted:

• nervous system: dizziness *, headache, seizures *, paresthesia, change in taste *, insomnia / drowsiness, tremors;
• digestive system: abdominal pain, flatulence, diarrhea, nausea, vomiting *, dyspepsia *, dryness of the oral mucosa, constipation;
• hepatobiliary system: hepatotoxicity (in some cases up to death), increased bilirubin levels, increased serum activity of liver enzymes [alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP)], liver dysfunction *, jaundice *, hepatitis *, cholestasis, hepatocellular necrosis *, hepatocellular lesion;
• skin: alopecia *, rash, exfoliative skin lesions * (including Stevens-Johnson syndrome and Lyell's syndrome), acute generalized exanthematous pustulosis; additionally, when taking capsules and suspensions - increased sweating, drug rash; additionally, when taking the suspension - itching, urticaria, swelling of the face;
• hematopoietic organs and lymphatic system *: anemia, thrombocytopenia, leukopenia (including neutropenia and agranulocytosis);
• immune system *: anaphylaxis (including angioedema; additionally, when taking solution and suspension - urticaria, itching, swelling of the face);
• cardiovascular system *: an increase in the QT interval on the electrocardiogram (ECG), torsade de pointes (ventricular tachysystolic arrhythmia of the "pirouette" type), in addition, when taking a suspension - arrhythmia;
• metabolism *: increased plasma cholesterol and triglyceride levels, hypokalemia;
• musculoskeletal system: myalgia;
• other reactions: asthenia, weakness, fever, fatigue, vertigo; additionally when taking the solution - hyperhidrosis.

* - based on the results of post-marketing research.

With the use of Diflucan, as well as drugs with a similar mechanism of action, in some patients, especially with such serious diseases as AIDS or malignant neoplasms, changes in renal and liver function, blood parameters were observed, but the clinical significance of such changes and their relationship with the use of fluconazole is not installed.

Overdose

Overdose of Diflucan was reported, but only in one episode in a 42-year-old patient infected with HIV, hallucinations and paranoid behavior were noted due to the intake of fluconazole at a dose of 8.2 g. The patient was immediately hospitalized and within 2 days his condition returned to normal.

In case of an overdose, symptomatic treatment is carried out (including supportive measures and gastric lavage).

Fluconazole is excreted mainly through the kidneys, so there is a high probability that forced diuresis can accelerate the excretion of the drug. After a 3-hour hemodialysis session, the concentration of fluconazole in the blood plasma is reduced by about 50%.

special instructions

There have been reports of superinfection with strains of Candida other than Candida albicans (eg Candida krusei), which are often naturally resistant to fluconazole. In such cases, alternative antimycotic therapy may be needed.

In rare cases, during the use of fluconazole, toxic changes in the liver, including fatal ones, were recorded, mainly in patients with serious concomitant diseases. Hepatotoxic reactions associated with the use of fluconazole did not reveal an obvious dependence on the daily dose of Diflucan, the duration of the course of therapy, gender and age of the patients. Usually, this effect was reversible and after stopping therapy, its signs disappeared. Patients with impaired liver function are recommended to be closely monitored for signs of more serious hepatic abnormalities. If clinical signs or symptoms of impaired hepatic function correlate with the use of fluconazole, Diflucan should be canceled.

Like other azoles, fluconazole can rarely cause anaphylaxis.

In rare cases, during therapy with Diflucan, exfoliative skin lesions such as Stevens-Johnson syndrome (malignant exudative erythema) and Lyell's syndrome (toxic epidermal necrolysis) developed. With the use of many drugs, including fluconazole, AIDS patients are more likely to develop such severe skin reactions. The appearance of a rash in a patient during treatment of a superficial fungal infection, which can be associated with fluconazole, requires discontinuation of the drug. Rashes in patients with invasive / systemic fungal lesions should be carefully monitored, and in the event of the appearance of bullous lesions or exudative erythema multiforme, immediately cancel Diflucan.

Fluconazole, like other azoles, can cause an increase in the QT interval on the ECG. An increase in the QT interval, as well as ventricular fibrillation / flutter due to the use of fluconazole, was extremely rare in patients with severe illnesses aggravated by multiple risk factors. For example, with organic lesions of the heart, electrolyte imbalance, as well as concomitant therapy that contributes to the development of such deviations. In this connection, fluconazole should be used with caution in patients with potentially proarrhythmic conditions.

If you have diagnosed liver, kidney and heart diseases, you should consult your doctor before using Diflucan.

Oral fluconazole 150 mg for vaginal candidiasis usually improves symptoms after 24 hours, and sometimes it may take several days to completely heal. If the symptoms of the disease persist for a long time, you should consult a doctor.

Cases of specific incompatibility of fluconazole with other medicinal solutions have not been described, nevertheless, it is not recommended to mix Diflucan solution in the infusion system with any drugs other than those listed in the “Drug Interactions” chapter before administration.

Due to the limited evidence base for the effectiveness of fluconazole in the treatment of other types of endemic mycoses, for example, paracoccidioidomycosis, sporotrichosis, histoplasmosis, it is not possible to determine specific recommendations for the dosage regimen.

Fluconazole is a potent inhibitor of the CYP2C9 isoenzyme, a moderate inhibitor of the CYP3A4 isoenzyme, in addition, it inhibits the CYP2C19 isoenzyme. The use of Diflucan simultaneously with drugs of a narrow therapeutic profile, metabolized by these isoenzymes, must be carried out with caution.

Influence on the ability to drive vehicles and complex mechanisms

Patients using Diflucan, if it is necessary to perform types of work that require an increased concentration of attention and a high reaction rate, should take into account the possibility of developing side effects such as dizziness and convulsions.

Application during pregnancy and lactation

There have been no adequate and well-controlled studies on the use of fluconazole during pregnancy.

There have been reports of cases of spontaneous abortion, the development of congenital abnormalities in newborns whose mothers in the first trimester of pregnancy received fluconazole once at a dose of 150 mg or repeatedly. Also described are episodes of multiple congenital anomalies in infants whose mothers received therapy with fluconazole at a high dose of 400 to 800 mg / day for most or throughout the first trimester. The following pathologies were recorded: brachycephaly, impaired formation of the cranial vault, impaired development of the facial part of the skull, cleft palate, thinning / lengthening of the ribs, curvature of the femurs, arthrogryposis, congenital heart defects.

In connection with the above, during pregnancy, the use of fluconazole should be avoided, except for the need for treatment of severe (life-threatening) fungal infections, when the expected benefits of treatment for the mother significantly outweigh the potential risks to the fetus.

Fluconazole is found in breast milk in an amount comparable to plasma concentration, therefore it is not recommended for women during lactation.

Women of childbearing age, if it is necessary to use Diflucan, need to consider effective methods of contraception for the entire period of treatment, as well as for approximately 1 week (5-6 half-lives) after completion of the course.

Pediatric use

Diflucan capsules are contraindicated for children under 3 years of age.

A suspension prepared from a powder and a solution for intravenous administration is allowed to be used in newborns from the first days of life according to indications, according to the dosage regimen prescribed by the doctor.

With impaired renal function

If you need a single use of Diflucan in patients with impaired renal function, dose adjustment is not required.

Patients with renal insufficiency, including children, with repeated use of Diflucan are initially administered a loading dose of 50-400 mg (depending on the indication), after which the daily dose is adjusted as follows:

• CC> 50 - standard dose;
• QC ≤ 50 (without dialysis) - ¹ / ₂ standard dose;
• regular dialysis is a standard dose after each session.

Patients on regular dialysis need to apply 100% of the recommended dose after each session. On days when the procedure is not performed, the dose is reduced in accordance with the QC indicator.

For violations of liver function

Due to the limited experience of using fluconazole in case of impaired liver function (liver failure) in this category of patients, Diflucan should be prescribed with caution.

Use in the elderly

According to the instructions, Diflucan is prescribed for elderly patients in the absence of signs of renal failure in the usual dose according to the indications. Elderly patients with renal impairment (CC <50 ml / min) require dose adjustment.

Drug interactions

The simultaneous use of cisapride, terfenadine (with a dose of 400 mg of fluconazole per day or more) and Diflucan is contraindicated due to the high likelihood of undesirable cardiac effects. Combined treatment with terfenadine at a fluconazole dose of less than 400 mg per day is possible with careful monitoring of the plasma concentration of terfenadine.

When taken simultaneously with coumarin anticoagulants, prothrombin time increases, this can lead to the development of nasal and gastrointestinal bleeding, hematomas, melena, hematuria.

Diflucan increases the concentration and psychotropic effects of short-acting benzodiazepines, this effect is more pronounced after taking capsules and suspensions.

With multiple simultaneous administration of thiazide diuretics, an increase in the concentration of fluconazole in the blood plasma occurs. This effect should be taken into account, although it does not require a revision of the dose of fluconazole in patients.

Simultaneous intake of Diflucan with food, antacids, cimetidine has no clinically significant effect on the absorption of fluconazole.

Long-term use of fluconazole in doses of 200-300 mg does not affect the effectiveness of combined oral contraceptives.

Fluconazole promotes a clinically significant increase in the serum concentration of phenytoin, rifabutin, tacrolimus, astemizole and other drugs, the metabolism of which is realized by isoenzymes of the cytochrome P450 system. If necessary, these combinations, patients should be carefully monitored.

Concomitant use with rifampicin leads to a decrease in the pharmacokinetic parameters (AUC) and the half-life (T _1/2) of fluconazole.

Diflucan increases the T _{1/2 of} oral sulfonylureas (glipizide, glibenclamide, chlorpropamide and tolbutamide). With the joint appointment of these funds to patients with diabetes mellitus, it is necessary to take into account the possibility of developing hypoglycemia.

Diflucan reduces the mean plasma clearance rate of theophylline.

The effect of fluconazole leads to a significant increase in the AUC of zidovudine, therefore, with the simultaneous use of these funds, it is necessary to carefully monitor the development of side effects of zidovudine.

When used simultaneously with cyclosporine, the level of its concentration in the blood should be monitored.

Diflucan in the form of a solution can be introduced into the infusion system together with isotonic saline, 20% glucose solution, Ringer's solution, aminofusine, Hartman's solution, potassium chloride solution in glucose, sodium bicarbonate solution 4.2%.

Analogs

Diflucan's analogs are Difluzol, Mikosist, Medoflucon, Flucostat, Fluconazole, Fluconazole-Teva, Fluconazole-LEKSVM, Flucorus, Flucomabol, Fluzamed, Fluconaz, Flucoric, Econozol, etc.

Terms and conditions of storage

Keep out of reach of children at temperatures up to 30 ° C. Do not freeze the finished suspension, store at temperatures up to 30 ° C for no more than 14 days.

Shelf life: capsules and solution for intravenous administration - 5 years; powder for suspension preparation - 3 years.

Terms of dispensing from pharmacies

Powder for suspension preparation, solution for intravenous administration, capsules 50 and 100 mg are available by prescription.

150 mg capsules (for the treatment of vaginal candidiasis) are available without a prescription.

Reviews of Diflucan

Most of the reviews about Diflucan are left by women, since the problem of thrush can sooner or later affect everyone. It can be caused by a course of strong antibiotics, hormonal drugs, decreased immunity. With varying success, exacerbation is replaced by remission, turning into a chronic disease. In such cases, capsules at a dosage of 150 mg help very well, especially if they are taken strictly, following the scheme to reduce the frequency of relapses and prevent vaginal candidiasis, even when there is no external manifestation of the disease.

Parents often purchase a suspension powder for the treatment of children, noting that it is effective, easy to use, has a pleasant taste, and children take such a medicine without problems.

All forms of Diflucan release are characterized by patients as expensive, but very effective antifungal agents.

Price for Diflucan in pharmacies

Estimated price of Diflucan:

• solution for intravenous administration 2 mg / ml per 1 bottle: 50 ml - 215–246 rubles; 100 ml - 339-370 rubles; 200 ml - 695-861 rubles;
• powder for preparation of a suspension for oral administration 50 mg / 5 ml: for 1 bottle complete with a dosage spoon - 500-570 rubles;
• capsules: 50 mg 7 pcs. in the package - 789-948 rubles; 150 mg 1 Pcs. in the package - 402–424 rubles; 150 mg 4 Pcs. in the package - 870–958 rubles; 150 mg 12 Pcs. in the package - 2143–2275 rubles.

Diflucan: prices in online pharmacies

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Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!