Fluconazole Obolenskoe instructions for use. Medicinal reference book geotar

Release form

Compound

Fluconazole 150 mg. Excipients: corn starch, povidone (low molecular weight polyvinylpyrrolidone), calcium stearate. Hard gelatin capsules: titanium dioxide, patent blue dye, gelatin, preservatives - methylhydroxybenzoate, propylhydroxybenzoate.

Pharmacological effect

Fluconazole, a member of the triazole antifungal class, is a potent selective inhibitor of the fungal enzyme 14-α-demethylase. The drug prevents the transition of lanosterol to ergosterol, the main component of fungal cell membranes. The drug is effective against opportunistic mycoses, incl. caused by Candida spp. (Candida albicans, Candida tropicalis), Cryptococcus neoformans, Microsporum spp., Trichophyton spp. Fluconazole has also been shown to be active in models of endemic mycoses, including infections caused by Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum.

Pharmacokinetics

After oral administration, fluconazole is well absorbed, its bioavailability is 90%. The maximum concentration (Cmax) after oral administration, on an empty stomach, 150 mg is 90% of the plasma content when administered intravenously at a dose of 2.5 - 3.5 mg/kg. Concomitant food intake does not affect the absorption of the drug taken orally. Plasma concentrations reach a peak 0.5-1.5 hours (TCmax) after administration. Plasma concentrations are directly proportional to dose. A 90% level of equilibrium concentration is achieved by the 4-5th day of treatment with the drug (when taken 1 time / day). Use on the first day of a dose 2 times higher than the usual daily dose allows you to achieve a level of the drug in plasma equal to 90% of the equilibrium concentration, by the second day. The apparent volume of distribution approximates the total volume of body water. Plasma protein binding is low - 11-12%. Fluconazole penetrates well into all biological fluids of the body, including cerebrospinal fluid. Concentrations of the drug in saliva and sputum are similar to its levels in plasma. In patients with fungal meningitis, the content of fluconazole in the cerebrospinal fluid reaches 80% of its level in plasma. In the stratum corneum, epidermis, dermis and sweat fluid, high concentrations are reached that exceed serum concentrations. Less than 5% of fluconazole is metabolized during the first passage through the liver. The half-life (T1/2) of fluconazole is about 30 hours. Fluconazole is excreted mainly by the kidneys; approximately 80% of the administered dose is excreted unchanged by the kidneys. Fluconazole clearance is proportional to creatinine clearance. No fluconazole metabolites were detected in peripheral blood.

Indications

· Cryptococcosis, including cryptococcal meningitis and other localizations of this infection (including lungs, skin), both in patients with a normal immune response and in patients with various forms of immunosuppression (including in patients with AIDS, during transplantation organs); the drug can be used to prevent cryptococcal infection in patients with AIDS; generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidal infections (infections of the peritoneum, endocardium, eyes, respiratory and urinary tract). Treatment can be carried out in patients with malignant neoplasms, patients in intensive care units, patients undergoing cytostatic or immunosuppressive therapy, 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 (including atrophic candidiasis of the oral cavity associated with wearing dentures), esophagus, non-invasive bronchopulmonary candidiasis, candiduria, skin candidiasis; prevention of relapse of oropharyngeal candidiasis in patients with AIDS; genital candidiasis: vaginal candidiasis (acute and chronic 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 neoplasms who are predisposed to such infections as a result of chemotherapy with cytostatics or radiation therapy; · mycoses of the skin, including mycoses of the feet, body, and groin area; pityriasis versicolor, onychomycosis; skin candidiasis; deep endemic mycoses, including coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis in patients with normal immunity.

Contraindications

Hypersensitivity to fluconazole, other components of the drug or other azole compounds; simultaneous use of terfenadine (while constantly taking fluconazole at a dose of 400 mg/day or more), cisapride or astemizole and other drugs that prolong the QT interval and increase the risk of developing severe arrhythmias; lactation period; children under 3 years of age (for this dosage form). With caution: liver and/or renal failure, the appearance of a rash during the use of fluconazole in patients with superficial fungal infection and invasive/systemic fungal infections, simultaneous use of terfenadine and fluconazole at a dose of less than 400 mg/day, potentially proarrhythmogenic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance, concomitant use of drugs that cause arrhythmias); patients with acetylsalicylic acid intolerance, pregnancy.

Use during pregnancy and breastfeeding

The use of the drug in pregnant women is not advisable, with the exception of severe or life-threatening forms of fungal infections, when the potential benefit from the use of fluconazole for the mother significantly exceeds the risk to the fetus. Since the concentration of fluconazole in breast milk and plasma is the same, use of the drug during lactation is contraindicated.

Directions for use and doses

For adults and children over 15 years of age (body weight more than 50 kg) for cryptococcal meningitis and cryptococcal infections of other localizations, 400 mg (8 capsules of 50 mg each) is usually prescribed on the first day, and then treatment is continued at a dose of 200 mg (4 capsules of 50 mg each). ) – 400 mg (8 capsules of 50 mg each) 1 time per day. The duration of treatment for cryptococcal infections depends on clinical effectiveness confirmed by mycological examination; for cryptococcal meningitis, the course of treatment should be at least 6–8 weeks. To prevent relapse of cryptococcal meningitis in patients with AIDS, after completing the full course of primary therapy, fluconazole is prescribed at a dose of 200 mg (4 capsules of 50 mg) per day for a long period of time .For candidemia, disseminated candidiasis and other invasive candidal infections, on the first day the dose is 400 mg (8 capsules of 50 mg each), and then 200 mg (4 capsules of 50 mg each) per day. If clinical effectiveness is insufficient, the dose of the drug can be increased to 400 mg (8 capsules of 50 mg each) per day. The duration of therapy depends on the clinical effectiveness. For oropharyngeal candidiasis, the drug is usually prescribed 150 mg once a day, the duration of treatment is 7–14 days. If necessary, in patients with a pronounced decrease in immunity, treatment can be longer. To prevent relapses of oropharyngeal candidiasis in patients with AIDS after completing the full course of primary therapy - 150 mg 1 time per week. For atrophic oral candidiasis associated with wearing dentures - 50 mg 1 time per day for 14 days in combination with local antiseptic drugs for treatment of the prosthesis. For other localizations of candidiasis (except genital), for example, with esophagitis, non-invasive bronchopulmonary lesions, candiduria, candidiasis of the skin and mucous membranes, etc. , the effective dose is usually 150 mg/day with a treatment duration of 14–30 days. 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 once a 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 orally at a single dose of 150 mg/day. For the prevention of candidiasis, the recommended dose is 50–400 mg 1 time per day, depending on the degree of risk of developing a fungal infection. For the prevention of candidiasis in patients with malignant neoplasms, the recommended dose of fluconazole is 150–400 mg once a 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/day. Fluconazole is prescribed several days before the expected onset of neutropenia; after the number of neutrophils increases to more than 1 thousand/μl, treatment is continued for another 7 days. For mycoses of the skin, including mycoses of the feet, skin of the groin area, and skin candidiasis, the recommended dose is 150 mg once a week or 50 mg once a day, The dosage regimen depends on the clinical and mycological effect. The duration of therapy in normal cases is 2–4 weeks, however, with mycoses of the feet, longer therapy (up to 6 weeks) may be required. For pityriasis versicolor - 300 mg (2 capsules of 150 mg each) once a week for 2 weeks, for some patients a third dose of 300 mg per week is required, while in some cases a single dose of 300–400 mg is sufficient; an alternative treatment regimen is to use 50 mg once a 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). For the re-growth of nails on the fingers and toes, it normally takes 3–6 months and 6–12 months, respectively. For deep endemic mycoses, the drug may need to be used in a dose of 200 mg (4 capsules of 50 mg) – 400 mg (8 capsules of 50 mg each). mg) per day for up to 2 years. The duration of therapy is determined individually; it can be 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 that would exceed that in adults, i.e. no more than 400 mg/day. The drug is used daily, once a day.

Side effects

From the digestive system: decreased appetite, changes in taste, abdominal pain, vomiting, nausea, diarrhea, flatulence, rarely - impaired liver function (jaundice, hepatitis, hepatonecrosis, hyperbilirubinemia, increased activity of alanine aminotransferase, aspartate aminotransferase, increased activity of alkaline phosphatase, hepatocellular necrosis ), incl. severe. From the nervous system: headache, dizziness, excessive fatigue, rarely - convulsions. From the hematopoietic organs: rarely - leukopenia, thrombocytopenia (bleeding, petechiae), neutropenia, agranulocytosis. Allergic reactions: skin rash, rarely - exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), anaphylactoid reactions (including angioedema, facial swelling, urticaria, skin itching). From the cardiovascular system: increased duration of the interval QT, ventricular fibrillation/flutter. Others: rarely - renal dysfunction, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Overdose

Symptoms: hallucinations, paranoid behavior. Treatment: symptomatic - gastric lavage, forced diuresis. Hemodialysis within 3 hours reduces plasma concentrations by approximately 50%.

Interaction with other drugs

When fluconazole is used with warfarin, the PT increases (by an average of 12%). In this regard, it is recommended to carefully monitor PT parameters in patients receiving the drug in combination with coumarin anticoagulants. Fluconazole increases the plasma half-life of oral hypoglycemic agents - sulfonylurea derivatives (chlorpropamide, glibenclamide, glipizide, tolbutamide) in healthy people. The combined use of Fluconazole and oral hypoglycemic agents in patients with diabetes is allowed, but the doctor must keep in mind the possibility of developing hypoglycemia. The simultaneous use of Fluconazole and phenytoin may lead to an increase in the concentration of phenytoin in plasma to a clinically significant extent. Therefore, if it is necessary to use these drugs together, it is necessary to monitor the concentration of phenytoin with adjustment of its dose in order to maintain the level of the drug within the therapeutic interval. The combination with rifampicin leads to a decrease in AUC by 25% and a shortening of the half-life of fluconazole from plasma by 20%. Therefore, for patients receiving rifampicin at the same time, it is advisable to increase the dose of Fluconazole. It is recommended to monitor the concentration of cyclosporine in the blood in patients receiving Fluconazole, because the use of fluconazole and cyclosporine in patients with a kidney transplant (taking Fluconazole at a dose of 200 mg / day) leads to a slow increase in the concentration of cyclosporine in plasma. Patients who receive high doses of theophylline or who are likely to develop theophylline intoxication should be monitored for early detection of symptoms of a theophylline overdose, because taking fluconazole leads to a decrease in the average rate of clearance of theophylline from plasma. With the simultaneous use of fluconazole with terfenadine and cisapride, cases of adverse reactions from the heart, including paroxysms of ventricular tachycardia (torsades de points), are described. The simultaneous use of fluconazole and hydrochlorothiazide can lead to an increase in the concentration of fluconazole in plasma by 40%. There are reports of interaction between fluconazole and rifabutin, accompanied by an increase in serum levels of the latter. Cases of uveitis have been described with the simultaneous use of Fluconazole and rifabutin. It is necessary to carefully monitor patients simultaneously receiving rifabutin and fluconazole. In patients receiving a combination of fluconazole and zidovudine, an increase in the concentration of zidovudine is observed, which is caused by a decrease in the conversion of the latter to its main metabolite, so an increase in the side effects of zidovudine should be expected. Increases the concentration of midazolam, which increases the risk of developing psychomotor effects (most pronounced when using fluconazole orally rather than intravenously). Increases the concentration of tacrolimus, which increases the risk of nephrotoxicity.

special instructions

Treatment must be continued until clinical and hematological remission occurs. Premature cessation of treatment leads to relapses. During treatment, it is necessary to monitor blood counts, kidney and liver function. If renal and liver dysfunction occurs, you should stop taking the drug. 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. In the case of hepatotoxic effects associated with fluconazole, there was no obvious dependence 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. If clinical signs of liver damage that may be associated with fluconazole appear, the drug should be discontinued. AIDS patients are more likely to develop severe skin reactions when using many drugs. In cases where a rash develops in patients with a superficial fungal infection and is assessed as definitely related to fluconazole, the drug should be discontinued. If a rash appears in patients with invasive/systemic fungal infections, they should be carefully monitored and fluconazole should be discontinued if bullous changes or erythema multiforme appear. Caution must be exercised when taking fluconazole simultaneously with cisapride, rifabutin or other drugs metabolized by the cytochrome P 450 system. Effect on ability to drive a car and machinery Impaired ability to drive a car and machinery associated with the use of the drug is unlikely.

Obolenskoe farm. enterprise, Russian Federation, Systemic lesions caused by Cryptococcus fungi, including meningitis, sepsis, lung and skin infections, both in patients with a normal immune response and in patients with various forms of immunosuppression

Antifungal agent, triazole derivative. It is a selective inhibitor of sterol synthesis in fungal cells. Fluconazole has high specificity for fungal enzymes dependent on cytochrome P450. When administered orally and administered intravenously, fluconazole showed activity in various models of fungal infections in animals. Fluconazole is active against opportunistic mycoses, incl. caused by Candida spp., including generalized candidiasis in animals with reduced immunity; Cryptococcus neoformans, including intracranial infections; Microsporum spp. and Trychoptyton spp. Active in animal models of endemic mycoses, including infections caused by Blastomyces dermatitidis, Coccidioides immitis, including intracranial infections, and Histoplasma capsulatum in animals with normal and reduced immunity.

Cryptococcosis, including cryptococcal meningitis and infections of other sites (for example, lungs, skin), incl. in patients with a normal immune response and in patients with AIDS, organ transplant recipients and patients with other forms of immunodeficiency; maintenance therapy to prevent relapses of cryptococcosis in patients with AIDS. Generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidiasis, such as infections of the peritoneum, endocardium, eyes, respiratory and urinary tract, incl. in patients with malignant tumors who are in the ICU and receiving cytotoxic or immunosuppressive drugs, as well as in patients with other factors predisposing to the development of candidiasis. Candidiasis of the mucous membranes, including the mucous membranes of the oral cavity and pharynx, esophagus, non-invasive bronchopulmonary infections, candiduria, mucocutaneous and chronic atrophic 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; prevention to reduce the frequency of relapses of vaginal candidiasis (3 or more episodes per year); candidal balanitis. Mycoses of the skin, including mycoses of the feet, body, groin area, pityriasis versicolor, onychomycosis and cutaneous candidal infections. Deep endemic mycoses in patients with normal immunity, coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis. Prevention of fungal infections in patients with malignant tumors who are predisposed to the development of such infections as a result of cytotoxic chemotherapy or radiation therapy.

Individual. Intended for oral and intravenous administration. For adults, depending on the indications, treatment regimen and clinical situation, the daily dose is 50-400 mg, the frequency of use is 1 time / day. For children, the dose is 3-12 mg/kg/day, the frequency of use is 1 time/day. In patients with impaired renal function, the dose of fluconazole is reduced depending on QC. The duration of treatment depends on the clinical and mycological effect.

From the nervous system: headache, dizziness, convulsions, change in taste. From the digestive system: abdominal pain, diarrhea, flatulence, nausea, dyspepsia, vomiting, hepatotoxicity (including rare cases with fatal outcome), increased levels of alkaline phosphatase, bilirubin, serum levels of aminotransferases (ALT and AST), impaired liver function, hepatitis, hepatocellular necrosis, jaundice. From the cardiovascular system: increased QT interval on ECG, ventricular fibrillation/flutter. Dermatological reactions: rash, alopecia, exfoliative skin diseases including Stevens-Johnson syndrome and toxic epidermal necrolysis. 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 (including angioedema, facial swelling, urticaria, itching).

Concomitant use of terfenadine during repeated use of fluconazole at a dose of 400 mg/day or more; simultaneous use of cisapride; hypersensitivity to fluconazole; increased sensitivity to azole derivatives with a structure similar to fluconazole.

Use with caution in case of abnormal liver function tests during the use of fluconazole, when a rash appears during the use of fluconazole in patients with superficial fungal infection and invasive/systemic fungal infections, with simultaneous use of terfenadine and fluconazole at a dose of less than 400 mg/day, with potentially proarrhythmic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance and concomitant therapy that contributes to the development of such disorders). 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 or symptoms of liver damage that may be associated with fluconazole occur, it should be discontinued. 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 the use of fluconazole, it should be discontinued. If rash occurs in patients with invasive/systemic fungal infections, they should be monitored closely and fluconazole should be discontinued if bullous lesions or erythema multiforme develop. Concomitant use of fluconazole in doses less than 400 mg/day and terfenadine should be carried out under close supervision. When using fluconazole, an increase in the QT interval and ventricular fibrillation/flutter were observed very rarely in patients with multiple risk factors, such as organic heart disease, electrolyte imbalances and concomitant therapy that contributes to the development of such disorders. Therapy can be started pending results of cultures and other laboratory tests. However, anti-infective therapy needs to be adjusted accordingly when the results of these studies become known. 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.

When used simultaneously with warfarin, fluconazole increases prothrombin time (by 12%), and therefore bleeding may develop (hematomas, bleeding from the nose and gastrointestinal tract, hematuria, melena). In patients receiving coumarin anticoagulants, prothrombin time must be constantly monitored. After oral administration of midazolam, fluconazole significantly increases midazolam concentrations and psychomotor effects, and this effect is more pronounced after fluconazole is administered orally than when administered intravenously. If concomitant benzodiazepine therapy is necessary, patients taking fluconazole should be monitored for an appropriate benzodiazepine dose reduction. With the simultaneous use of fluconazole and cisapride, adverse reactions from the heart are possible, incl. ventricular fibrillation/flutter (pirouette arrhythmia). 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. In patients after kidney transplantation, 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 concomitantly, it is recommended to monitor the concentration of cyclosporine in the blood. Repeated use of hydrochlorothiazide simultaneously with fluconazole leads to an increase in plasma concentrations of fluconazole by 40%. An effect of this magnitude does not require a change in the fluconazole dosage regimen in patients receiving concomitant diuretics, but this should be taken into account. With the 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 intake of 200 mg of fluconazole, the AUC of ethinyl estradiol and levonorgestrel increases by 40% and 24%, respectively, and when taking 300 mg of fluconazole 1 time per day week - AUC of ethinyl estradiol and norethindrone increase 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. Concomitant use of fluconazole and phenytoin may be accompanied by a clinically significant increase in phenytoin concentrations. With this combination, phenytoin concentrations should be monitored and the dose adjusted accordingly to ensure therapeutic serum concentrations. Concomitant use of fluconazole and rifabutin may lead to increased serum concentrations of the latter. Cases of uveitis have been described with the simultaneous use of fluconazole and rifabutin. Patients receiving rifabutin and fluconazole concomitantly should be monitored closely. The simultaneous use of fluconazole and rifampicin leads to a decrease in AUC by 25% and the duration of T1/2 of fluconazole by 20%. In patients concomitantly taking rifampicin, the advisability of increasing the dose of fluconazole must be considered. Fluconazole, when taken simultaneously, leads to an increase in T1/2 of oral sulfonylurea drugs (chlorpropamide, glibenclamide, glipizide and tolbutamide). In patients with diabetes mellitus, fluconazole and oral sulfonylureas can be prescribed together, but the possibility of hypoglycemia should be taken into account. The simultaneous use of fluconazole and tacrolimus leads to an increase in plasma concentrations of the latter. Cases of nephrotoxicity have been described. Patients with this combination should be carefully monitored. With the simultaneous use of azole antifungals and terfenadine, serious arrhythmias may occur as a result of an increase in the QT interval. When taking fluconazole at a dose of 200 mg/day, an increase in the QT interval 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 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. 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. When used simultaneously with fluconazole, an increase in zidovudine concentrations is observed, which is likely 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. When zidovudine 200 mg every 8 hours for 7 days was used in HIV-infected patients with or without fluconazole 400 mg/day with an interval of 21 days between the two regimens, a significant increase in zidovudine AUC was found (74%) when used simultaneously with fluconazole. Patients receiving this combination should be monitored for side effects of zidovudine. The 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. Patients with such combinations should be carefully monitored.

Release form, composition and packaging

1 PC. - contour cellular packaging - cardboard packs.

Clinical and pharmacological group:

Antifungal drug

Pharmacotherapeutic group:

Antifungal agent

Indications

Generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidiasis, such as infections of the peritoneum, endocardium, eyes, respiratory and urinary tract, incl. in patients with malignant tumors who are in the ICU and receiving cytotoxic or immunosuppressive drugs, as well as in patients with other factors predisposing to the development of candidiasis.

Candidiasis of the mucous membranes, including the mucous membranes of the oral cavity and pharynx, esophagus, non-invasive bronchopulmonary infections, candiduria, mucocutaneous and chronic atrophic 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; prevention to reduce the frequency of relapses of vaginal candidiasis (3 or more episodes per year); candidal balanitis.

Mycoses of the skin, including mycoses of the feet, body, groin area, pityriasis versicolor, onychomycosis and cutaneous candidal infections.
Deep endemic mycoses in patients with normal immunity, coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis.

Prevention of fungal infections in patients with malignant tumors who are predisposed to the development of such infections as a result of cytotoxic chemotherapy or radiation therapy.

Dosage regimen

Individual. Intended for oral and intravenous administration.
For adults, depending on the indications, treatment regimen and clinical situation, the daily dose is 50-400 mg, the frequency of use is 1 time / day.
For children, the dose is 3-12 mg/kg/day, the frequency of use is 1 time/day.
In patients with impaired renal function, the dose of fluconazole is reduced depending on QC.
The duration of treatment depends on the clinical and mycological effect.

Side effect

From the nervous system: headache, dizziness, convulsions, change in taste.
From the digestive system: abdominal pain, diarrhea, flatulence, nausea, dyspepsia, vomiting, hepatotoxicity (including rare cases with fatal outcome), increased levels of alkaline phosphatase, bilirubin, serum levels of aminotransferases (ALT and AST), impaired liver function, hepatitis, hepatocellular necrosis, jaundice.
From the cardiovascular system: increased QT interval on the ECG, ventricular fibrillation/flutter.
Dermatological reactions: rash, alopecia, exfoliative skin diseases, including Stevens-Johnson syndrome and toxic epidermal necrolysis.
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 (including angioedema, facial swelling, urticaria, itching).

Contraindications for use

Use during pregnancy and breastfeeding

Adequate and controlled studies of the safety of fluconazole in pregnant women have not been conducted. 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.

Women of childbearing age should use reliable contraception during treatment.
Fluconazole is detected in breast milk in concentrations close to plasma concentrations, so use during lactation (breastfeeding) is not recommended.

Use for liver dysfunction

Fluconazole should be used with caution in patients with severe liver dysfunction.

Use for renal impairment

Fluconazole should be used with caution in patients with severe renal impairment. If renal function is impaired, the dose of fluconazole should be reduced.

Use in children

Contraindicated in children under 1 year of age.

special instructions

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 or symptoms of liver damage that may be associated with fluconazole occur, it should be discontinued.

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 the use of fluconazole, it should be discontinued. If rash occurs in patients with invasive/systemic fungal infections, they should be monitored closely and fluconazole should be discontinued if bullous lesions or erythema multiforme develop.

Concomitant use of fluconazole in doses less than 400 mg/day and terfenadine should be carried out under close supervision.
When using fluconazole, an increase in the QT interval and ventricular fibrillation/flutter were observed very rarely in patients with multiple risk factors, such as organic heart disease, electrolyte imbalances and concomitant therapy that contributes to the development of such disorders.

Therapy can be started pending results of cultures and other laboratory tests. However, anti-infective therapy needs to be adjusted accordingly when the results of these studies become known.
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.

Drug interactions

After oral administration of midazolam, fluconazole significantly increases midazolam concentrations and psychomotor effects, and this effect is more pronounced after fluconazole is administered orally than when administered intravenously. If concomitant benzodiazepine therapy is necessary, patients taking fluconazole should be monitored for an appropriate benzodiazepine dose reduction.
With the simultaneous use of fluconazole and cisapride, adverse reactions from the heart are possible, incl. ventricular fibrillation/flutter (pirouette arrhythmia). 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.

In patients after kidney transplantation, 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 concomitantly, it is recommended to monitor the concentration of cyclosporine in the blood.

Repeated use of hydrochlorothiazide simultaneously with fluconazole leads to an increase in plasma concentrations of fluconazole by 40%. An effect of this magnitude does not require a change in the fluconazole dosage regimen in patients receiving concomitant diuretics, but this should be taken into account.

With the 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 intake of 200 mg of fluconazole, the AUC of ethinyl estradiol and levonorgestrel increases by 40% and 24%, respectively, and when taking 300 mg of fluconazole 1 time per day week - AUC of ethinyl estradiol and norethindrone increase 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.

Concomitant use of fluconazole and phenytoin may be accompanied by a clinically significant increase in phenytoin concentrations. With this combination, phenytoin concentrations should be monitored and the dose adjusted accordingly to ensure therapeutic serum concentrations.

Concomitant use of fluconazole and rifabutin may lead to increased serum concentrations of the latter. Cases of uveitis have been described with the simultaneous use of fluconazole and rifabutin. Patients receiving rifabutin and fluconazole concomitantly should be monitored closely.

The simultaneous use of fluconazole and rifampicin leads to a decrease in AUC by 25% and the duration of T 1/2 of fluconazole by 20%. In patients concomitantly taking rifampicin, the advisability of increasing the dose of fluconazole must be considered.
Fluconazole, when taken simultaneously, leads to an increase in half-life of oral sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide). In patients with diabetes mellitus, fluconazole and oral sulfonylureas can be prescribed together, but the possibility of hypoglycemia should be taken into account.

The simultaneous use of fluconazole and tacrolimus leads to an increase in plasma concentrations of the latter. Cases of nephrotoxicity have been described. Patients with this combination should be carefully monitored.

With the simultaneous use of azole antifungals and terfenadine, serious arrhythmias may occur as a result of an increase in the QT interval. When taking fluconazole at a dose of 200 mg/day, an increase in the QT interval 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 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.

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.

When used simultaneously with fluconazole, an increase in zidovudine concentrations is observed, which is likely 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.

When zidovudine 200 mg every 8 hours for 7 days was used in HIV-infected patients with or without fluconazole 400 mg/day with an interval of 21 days between the two regimens, a significant increase in zidovudine AUC was found (74%) when used simultaneously with fluconazole. Patients receiving this combination should be monitored for side effects of zidovudine.

The 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. Patients with such combinations should be carefully monitored.

Is a medicine. A doctor's consultation is required.

pharmachologic effect

Antifungal agent, triazole derivative. It is a selective inhibitor of sterol synthesis in fungal cells. Fluconazole has high specificity for fungal enzymes dependent on cytochrome P450.

When administered orally and administered intravenously, fluconazole showed activity in various models of fungal infections in animals.

Fluconazole is active against opportunistic mycoses, incl. caused by Candida spp., including generalized candidiasis in animals with reduced immunity; Cryptococcus neoformans, including intracranial infections; Microsporum spp. and Trychoptyton spp. Active in animal models of endemic mycoses, including infections caused by Blastomyces dermatitidis, Coccidioides immitis, including intracranial infections, and Histoplasma capsulatum in animals with normal and reduced immunity.

Pharmacokinetics

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

After oral administration, fluconazole is well absorbed, its plasma levels (and total bioavailability) exceed 90% of fluconazole plasma levels when administered intravenously. Concomitant food intake does not affect oral absorption. Cmax is achieved 0.5-1.5 hours after taking fluconazole on an empty stomach. The concentration in blood plasma is proportional to the dose.

90% C ss is achieved by the 4-5th day after the start of therapy (with repeated doses 1 time per day).

Administration of a loading dose (on the 1st day), 2 times higher than the average daily dose, allows you to achieve a C ss of 90% by the 2nd day. The apparent V d approaches the total water content in the body. Plasma protein binding is low (11-12%).

Fluconazole penetrates well into all body fluids. Levels of fluconazole in saliva and sputum are similar to its concentrations in plasma. In patients with fungal meningitis, fluconazole levels in the cerebrospinal fluid are approximately 80% of plasma levels.

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

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

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

Long T1/2 from blood plasma allows you to take fluconazole once for vaginal candidiasis and 1 time / day or 1 time / week. for other indications.

Indications

Genital candidiasis; acute or recurrent vaginal candidiasis; prevention to reduce the frequency of relapses of vaginal candidiasis (3 or more episodes per year); candidal balanitis.

Mycoses of the skin, including mycoses of the feet, body, groin area, pityriasis versicolor, onychomycosis and cutaneous candidal infections.

Deep endemic mycoses in patients with normal immunity, coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis.

Prevention of fungal infections in patients with malignant tumors who are predisposed to the development of such infections as a result of cytotoxic chemotherapy or radiation therapy.

Dosage regimen

Individual. Intended for oral and intravenous administration.

For adults, depending on the indications, treatment regimen and clinical situation, the daily dose is 50-400 mg, the frequency of use is 1 time / day.

For children, the dose is 3-12 mg/kg/day, the frequency of use is 1 time/day.

In patients with impaired renal function, the dose of fluconazole is reduced depending on QC.

The duration of treatment depends on the clinical and mycological effect.

Side effect

From the nervous system: headache, dizziness, convulsions, change in taste.

From the digestive system: abdominal pain, diarrhea, flatulence, nausea, dyspepsia, vomiting, hepatotoxicity (including rare cases with fatal outcome), increased levels of alkaline phosphatase, bilirubin, serum levels of aminotransferases (ALT and AST), impaired liver function, hepatitis, hepatocellular necrosis, jaundice.

From the cardiovascular system: increased QT interval on ECG, ventricular fibrillation/flutter.

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

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 (including angioedema, facial swelling, urticaria, itching).

Contraindications for use

Use during pregnancy and breastfeeding

Women of childbearing age should use reliable contraception during treatment.

Fluconazole is detected in breast milk in concentrations close to plasma concentrations, so use during lactation (breastfeeding) is not recommended.

Use in children

Contraindicated in children under 1 year of age.

Drug interactions

With the simultaneous use of fluconazole and cisapride, adverse reactions from the heart are possible, incl. ventricular fibrillation/flutter (pirouette arrhythmia). 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.

Fluconazole, when taken simultaneously, leads to an increase in half-life of oral sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide). In patients with diabetes mellitus, fluconazole and oral sulfonylureas can be prescribed together, but the possibility of hypoglycemia should be taken into account.

Use for liver dysfunction

Fluconazole should be used with caution in patients with severe liver dysfunction.

Use for renal impairment

Fluconazole should be used with caution in patients with severe renal impairment. If renal function is impaired, the dose of fluconazole should be reduced.

special instructions

Concomitant use of fluconazole in doses less than 400 mg/day and terfenadine should be carried out under close supervision.

When using fluconazole, an increase in the QT interval and ventricular fibrillation/flutter were observed very rarely in patients with multiple risk factors, such as organic heart disease, electrolyte imbalances and concomitant therapy that contributes to the development of such disorders.

Therapy can be started pending results of cultures and other laboratory tests. However, anti-infective therapy needs to be adjusted accordingly when the results of these studies become known.

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.

1 capsule contains: fluconazole 150 mg.

Excipients: corn starch, magnesium stearate, microcrystalline cellulose, colloidal silicon dioxide.
Turquoise capsules, size No. 1. The contents of the capsules are white or almost white powder.

pharmachologic effect

Antifungal agent, triazole derivative. It is a selective inhibitor of sterol synthesis in fungal cells. Fluconazole has high specificity for fungal enzymes dependent on cytochrome P450.
When administered orally and administered intravenously, fluconazole showed activity in various models of fungal infections in animals.
Fluconazole is active against opportunistic mycoses, incl. caused by Candida spp., including generalized candidiasis in animals with reduced immunity, Cryptococcus neoformans, including intracranial infections, Microsporum spp. and Trychoptyton spp. Active in animal models of endemic mycoses, including infections caused by Blastomyces dermatitidis, Coccidioides immitis, including intracranial infections, and Histoplasma capsulatum in animals with normal and reduced immunity.

Indications for use

Cryptococcosis, including cryptococcal meningitis and infections of other sites (for example, lungs, skin), incl. in patients with a normal immune response and in patients with AIDS, organ transplant recipients and patients with other forms of immunodeficiency; maintenance therapy to prevent relapses of cryptococcosis in patients with AIDS.
Generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidiasis, such as infections of the peritoneum, endocardium, eyes, respiratory and urinary tract, incl. in patients with malignant tumors who are in the ICU and receiving cytotoxic or immunosuppressive drugs, as well as in patients with other factors predisposing to the development of candidiasis.
Candidiasis of the mucous membranes, including the mucous membranes of the oral cavity and pharynx, esophagus, non-invasive bronchopulmonary infections, candiduria, mucocutaneous and chronic atrophic 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;
- prevention to reduce the frequency of relapses of vaginal candidiasis (3 or more episodes per year);
- candidal balanitis.
Mycoses of the skin, including mycoses of the feet, body, groin area, pityriasis versicolor, onychomycosis and cutaneous candidal infections.
Deep endemic mycoses in patients with normal immunity, coccidioidomycosis, paracoccidioidomycosis, sporotrichosis and histoplasmosis.
Prevention of fungal infections in patients with malignant tumors who are predisposed to the development of such infections as a result of cytotoxic chemotherapy or radiation therapy.

Mode of application

Individual. Intended for oral and intravenous administration.
For adults, depending on the indications, treatment regimen and clinical situation, the daily dose is 50-400 mg, the frequency of use is 1 time / day.
For children, the dose is 3-12 mg/kg/day, the frequency of use is 1 time/day.
In patients with impaired renal function, the dose of fluconazole is reduced depending on QC.
The duration of treatment depends on the clinical and mycological effect.

Interaction

When used simultaneously with warfarin, fluconazole increases prothrombin time (by 12%), and therefore bleeding may develop (hematomas, bleeding from the nose and gastrointestinal tract, hematuria, melena). In patients receiving coumarin anticoagulants, prothrombin time must be constantly monitored.
After oral administration of midazolam, fluconazole significantly increases midazolam concentrations and psychomotor effects, and this effect is more pronounced after fluconazole is administered orally than when administered intravenously. If concomitant benzodiazepine therapy is necessary, patients taking fluconazole should be monitored for an appropriate benzodiazepine dose reduction.
With the simultaneous use of fluconazole and cisapride, adverse reactions from the heart are possible, incl. ventricular fibrillation/flutter (pirouette arrhythmia). 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.
In patients after kidney transplantation, 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 concomitantly, it is recommended to monitor the concentration of cyclosporine in the blood.
Repeated use of hydrochlorothiazide simultaneously with fluconazole leads to an increase in plasma concentrations of fluconazole by 40%. An effect of this magnitude does not require a change in the fluconazole dosage regimen in patients receiving concomitant diuretics, but this should be taken into account.
With the 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 intake of 200 mg of fluconazole, the AUC of ethinyl estradiol and levonorgestrel increases by 40% and 24%, respectively, and when taking 300 mg of fluconazole 1 time per day week - AUC of ethinyl estradiol and norethindrone increase 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.
Concomitant use of fluconazole and phenytoin may be accompanied by a clinically significant increase in phenytoin concentrations. With this combination, phenytoin concentrations should be monitored and the dose adjusted accordingly to ensure therapeutic serum concentrations.
Concomitant use of fluconazole and rifabutin may lead to increased serum concentrations of the latter. Cases of uveitis have been described with the simultaneous use of fluconazole and rifabutin. Patients receiving rifabutin and fluconazole concomitantly should be monitored closely.
The simultaneous use of fluconazole and rifampicin leads to a decrease in AUC by 25% and the duration of T1/2 of fluconazole by 20%. In patients concomitantly taking rifampicin, the advisability of increasing the dose of fluconazole must be considered.
Fluconazole, when taken simultaneously, leads to an increase in T1/2 of oral sulfonylurea drugs (chlorpropamide, glibenclamide, glipizide and tolbutamide). In patients with diabetes mellitus, fluconazole and oral sulfonylureas can be prescribed together, but the possibility of hypoglycemia should be taken into account.
The simultaneous use of fluconazole and tacrolimus leads to an increase in plasma concentrations of the latter. Cases of nephrotoxicity have been described. Patients with this combination should be carefully monitored.
With the simultaneous use of azole antifungals and terfenadine, serious arrhythmias may occur as a result of an increase in the QT interval. When taking fluconazole at a dose of 200 mg/day, an increase in the QT interval 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 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.
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.
When used simultaneously with fluconazole, an increase in zidovudine concentrations is observed, which is likely 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.
When zidovudine 200 mg every 8 hours for 7 days was used in HIV-infected patients with or without fluconazole 400 mg/day with an interval of 21 days between the two regimens, a significant increase in zidovudine AUC was found (74%) when used simultaneously with fluconazole. Patients receiving this combination should be monitored for side effects of zidovudine.
The 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. Patients with such combinations should be carefully monitored.

Side effect

Contraindications

Concomitant use of terfenadine during repeated use of fluconazole at a dose of 400 mg/day or more;
- simultaneous use of cisapride;
- hypersensitivity to fluconazole;
- increased sensitivity to azole derivatives with a structure similar to fluconazole.

Use during pregnancy and breastfeeding
Adequate and controlled studies of the safety of fluconazole in pregnant women have not been conducted. 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.
Women of childbearing age should use reliable contraception during treatment.
Fluconazole is detected in breast milk in concentrations close to plasma concentrations, so use during lactation (breastfeeding) is not recommended.

Use in children
Contraindicated in children under 1 year of age.

special instructions

Use with caution in case of abnormal liver function tests during the use of fluconazole, when a rash appears during the use of fluconazole in patients with superficial fungal infection and invasive/systemic fungal infections, with simultaneous use of terfenadine and fluconazole at a dose of less than 400 mg/day, with potentially proarrhythmic conditions in patients with multiple risk factors (organic heart disease, electrolyte imbalance and concomitant therapy that contributes to the development of such disorders).
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 or symptoms of liver damage that may be associated with fluconazole occur, it should be discontinued.
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 the use of fluconazole, it should be discontinued. If rash occurs in patients with invasive/systemic fungal infections, they should be monitored closely and fluconazole should be discontinued if bullous lesions or erythema multiforme develop.
Concomitant use of fluconazole in doses less than 400 mg/day and terfenadine should be carried out under close supervision.
When using fluconazole, an increase in the QT interval and ventricular fibrillation/flutter were observed very rarely in patients with multiple risk factors, such as organic heart disease, electrolyte imbalances and concomitant therapy that contributes to the development of such disorders.
Therapy can be started pending results of cultures and other laboratory tests. However, anti-infective therapy needs to be adjusted accordingly when the results of these studies become known.
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.