Выберите категорию:

Candiflu ® Neo – infusion solution

INSTRUCTIONS FOR MEDICAL USE

KANDIFLYU® NEO

Trade name of the drug: Candiflu® Neo

Active substance (INN): Fluconazole

Dosage form: solution for infusion.

Contents:

100 ml of the solution contains:

active substance: fluconazole – 200 mg.

Excipients: sodium chloride – 900 mg, water for injections up to 100 ml.

Description: clear, colorless or light yellow liquid.

Pharmacotherapeutic group: Antifungal agent.

ATX code: J02AC01

Pharmacological properties

Pharmacodynamics

Fluconazole is representative of the class of triazole derivatives, it is a selective inhibitor of sterol synthesis in fungal cells. It blocks conversion of lanosterol of fungal cells to ergosterol; it increases cell membrane permeability. Fluconazole, being highly selective for cytochrome P450 of fungi, does not suppress cytochrome P450 system in humans (compared to itraconazole, clotrimazole, econazole and ketoconazole it suppresses cytochrome P450 dependent oxidation processes in human liver microsomes to a lesser extent). It has no androgenic activity. The drug is active in mycosis caused by Candida spp., Cryptococcus neoformans, Microsporum spp., Trichophyton spp., Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum.

Pharmacokinetics

After intravenous administration fluconazole penetrates well into tissues and body fluids. Drug concentrations in saliva and sputum are similar to its levels in plasma. In patients with fungal meningitis fluconazole content in cerebrospinal fluid reaches 80% of the corresponding levels in plasma. Plasma concentrations are in direct proportional relationship to the dose. 90% of the equilibrium concentration level is reached by day 4-5 after several injections of one dose per day.

Using a dose twice the usual daily dose on the first day allows achieving such plasma levels of the drug that are close to 90% of the equilibrium concentrations by the second day. The apparent volume of distribution is close to the total body fluid volume. A small part of fluconazole (11-12%) is bound to plasma proteins. The elimination half-life is long (30 hours).

Fluconazole is excreted mainly by the kidneys; approximately 80% of the administered dose is excreted unchanged. Fluconazole clearance is in direct proportion to creatinine clearance. No metabolites were detected in peripheral blood.

Indications for use

Cryptococcosis: cryptococcal meningitis, cryptococcal infections of the lungs and skin: prevention of recurrent cryptococcosis in patients with AIDS, in organ transplants or in other cases of immunodeficiency;

generalized candidiasis: candidemia, disseminated candidomycosis and other forms of invasive candidiasis infections (abdominal, endocardial, eye, respiratory and urinary tract infections);

candidiasis of mucous membranes: oral cavity, pharynx, esophagus and non-invasive bronchopulmonary infections, candiduria;

Vaginal candidiasis – acute or chronic recurrent form;

prevention of fungal infections in patients with malignant neoplasms that are predisposed to such infections as a result of cytostatic chemotherapy or radiation therapy;

genital candidiasis, acute or recurrent vaginal candidiasis, prophylaxis to reduce the frequency of recurrent vaginal candidiasis (3 or more episodes per year), candidal balanitis;

Mycoses of the skin, including mycoses of the feet, body, groin area, pityriasis, onychomycosis, and cutaneous candidiasis;

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

Dosage and administration

Fluconazole in the form of infusion solution is administered intravenously by drip at a rate not exceeding 20 mg (10 ml) min. There is no need to change the daily dose when transferring from intravenous administration to capsule administration and vice versa.

The solution for infusion is compatible with the following solvents: 20% glucose solution, Ringer’s solution, Hartmann’s solution, potassium chloride solution in glucose, aminofusin, isotonic sodium chloride solution.

Fluconazole infusions can be given with conventional transfusion kits using one of the fluids listed above.

Use for adults

For cryptococcal infections the usual dose of fluconazole is 400 mg once a day on the first day of treatment and 200-400 mg once a day thereafter. The duration of treatment for cryptococcal infections depends on the clinical efficacy confirmed by mycological examination, usually ranging from 6 to 8 weeks.

For prophylaxis of recurrence of cryptococcal meningitis in AIDS patients after the completion of the initial complete course of therapy, fluconazole is prescribed in doses not less than 200 mg/day for a long period.

For candidemia, disseminated candidiasis, and other invasive, candida infections, the daily dose is 400 mg in the first day and 200 mg in subsequent days. Depending on the clinical efficacy of the drug, the dose may be increased up to 400 mg/day. Treatment duration depends on clinical efficacy.

For oropharyngeal candidiasis, including patients with immune impairment, the usual dose is 50-100 mg once daily for 7-14 days. If necessary, treatment may be prolonged, especially in severe immune disorders.

For other candidal infections, such as esophagitis, non-invasive bronchopulmonary infections, candiduria, candidiasis of skin and mucous membranes, the usual daily dose is 50-100 mg for 14-30 days.

For prophylaxis of fungal infections in patients with malignant neoplasms, a dose of fluconazole should be 50 mg once a day for as long as the patient is at high risk due to cytostatic therapy or radiotherapy.

Use for children

As with similar infections in adults, the duration of treatment depends on clinical and mycological effects. For children, the daily dose of the drug should not exceed that of adults. Fluconazole is used daily once a day.

In candidiasis of mucous membranes, the recommended dose of fluconazole is 3 mg/kg/day. On the first day, a shock dose of 6 mg/kg may be administered in order to achieve constant equilibrium concentrations more quickly.

For treatment of generalized candidiasis and cryptococcal infection, the recommended dose is 6-12 mg/kg/day depending on the severity of the disease.

For prophylaxis of fungal infections in immunocompromised children at risk of infection due to neutropenia resulting from cytotoxic chemotherapy or radiation therapy, the drug is prescribed 3-12 mg/kg/day depending on the severity and duration of induced neutropenia.

In children with impaired renal function, the daily dose of the drug should be reduced (in the same proportional relationship as in adults) according to the severity of renal failure.

In elderly patients with no renal dysfunction the drug is used according to the usual dosing regimen.

In patients with impaired renal function, if administered once a day, no change in the drug dosage is required. When administering the drug repeatedly at a CKR of more than 50 ml/min, the drug is administered in a medium dose. In CKR of 11 to 50 ml/min, a shock dose of 50 mg to 400 mg should be administered first, followed by a dose equal to 50% of the recommended dose. Patients who are regularly on dialysis are prescribed one dose of the drug after each hemodialysis session.

Side effects

Digestive system: change of taste, vomiting, nausea, diarrhea, flatulence, abdominal pain; rarely – liver dysfunction (jaundice, hepatitis, hepatonecrosis, hyperbilirubinemia, increased alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase activity).

Nervous system disorders: headache, dizziness, rarely convulsions.

Blood organs: rarely – leukopenia, thrombocytopenia, neutropenia, agranulocytosis.

Cardiovascular system: prolongation of Q-T interval; ventricular fibrillation, torsade de pointes.

Allergic reactions: skin rash, rare – malignant erythema exudative (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome), anaphylactoid reactions.

Other: rarely – renal dysfunction, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Contraindications

  • Concomitant use of terfenadine (concomitant use of fluconazole at a dose of 400 mg/day or more) or astemizole and other drugs that prolong Q-T interval.
  • Hypersensitivity to the drug or similar azole compounds.
  • Children under 1 year of age.
  • Pregnancy, lactation.

Caution hepatic or renal failure, concomitant use of potentially hepatotoxic drugs, alcoholism, proarrhythmogenic states in patients with multiple risk factors (organic heart disease, electrolyte imbalance, concomitant use of drugs that cause arrhythmias).

The use of the drug in pregnant women is inappropriate, except for severe or life-threatening forms of fungal infections, if the expected effect exceeds the possible risk to the fetus. Fluconazole is in breast milk in the same concentration as in plasma, therefore its administration during lactation is not recommended.

Drug interactions

When fluconazole is used with warfarin, an increase in prothrombin time by 12% has been noted. In this regard, it is recommended to monitor prothrombin time in patients receiving this drug in combination with coumarin anticoagulants. Co-administration of fluconazole increases T1/2 of oral hypoglycemic drugs – sulfonylurea derivatives (chlorpropamide, glibenclamide, glipizide and tolbutamide). Concomitant administration of fluconazole and oral hypoglycemic agents is allowed, but the possibility of hypoglycemia should be taken into account.

Concomitant use of fluconazole and phenytoin may be accompanied by an increase in phenytoin concentrations to a clinically significant degree. Therefore, if concomitant use of these drugs is necessary, phenytoin concentrations should be monitored and the dose should be adjusted to ensure therapeutic plasma concentrations.

Concomitant use of fluconazole and rifampicin decreases the area under the curve “concentration – time” (AUC) by 25% and shortens the T1/2 of fluconazole from plasma by 20%. Therefore, it is recommended to increase the dose of fluconazole in patients receiving simultaneously rifampicin. It is recommended to monitor the blood concentration of cyclosporine in patients receiving fluconazole, because when using fluconazole and cyclosporine in patients with kidney transplantation, fluconazole administration at a dose of 200 mg/day leads to a slow increase in plasma concentration of cyclosporine.

Patients receiving theophylline in high doses, or who are likely to develop theophylline intoxication, should be monitored for early detection of symptoms of theophylline overdose, because concomitant administration of fluconazole leads to a decrease in the average rate of clearance of theophylline from plasma.

When concomitant use of fluconazole and terfenadine or cisapride, cases of adverse cardiac reactions, including paroxysms of ventricular tachycardia (arrhythmias of the type “pirouette”) have been described. There have been reports of interaction of fluconazole and rifabutin, accompanied by increased serum levels of the latter. When concomitant use of fluconazole and rifabutin, cases of uveitis have been described. Patients receiving rifabutin and fluconazole concomitantly should be closely monitored.

During concomitant use of fluconazole and zidovudine, an increase in plasma concentrations of zidovudine is noted, which is caused by a decrease in the conversion of the latter to its metabolite.

Concomitant use of fluconazole with midazolam increases the risk of psychomotor effects, with tacrolimus – increased risk of nephrotoxicity.

Special indications

In rare cases fluconazole use was accompanied by toxic liver changes, including fatal, mainly in patients with severe comorbidities. In the case of hepatotoxic effects associated with fluconazole, no clear dependence on the total daily dose, duration of therapy, sex, and age of the patient was noted. Hepatotoxic effects of fluconazole were usually reversible; their signs disappeared after discontinuation of therapy. If clinical signs of liver damage appear, which may be associated with fluconazole, the drug should be discontinued.

AIDS patients are more prone to develop severe skin reactions when using many drugs. In cases where patients with superficial fungal infection develop a rash and it is considered to be definitely related to fluconazole, the drug should be discontinued. If rash appears in patients with invasive/systemic fungal infections, they should be closely monitored and fluconazole should be discontinued if bullous changes or erythema multiforme appear.

For patients with impaired renal function, no dose adjustment is required during a single use of the drug. When repeated use it is guided by CKD. If CKR is more than 50 ml/min, in case of CKR 11 to 20 ml/min the dose adjustment is not required, 33% of usual dose is taken at 72 hours interval. If CK of 21 to 40 ml/min, half the usual dose is taken at 48-hour intervals. For patients who are regularly on dialysis, one dose is taken after each session of hemodialysis.

Caution should be exercised when concomitant administration of fluconazole with cisapride, rifabutin or other drugs metabolized by cytochrome P450 system.

Treatment should be continued until clinical and hematological remission occurs, since premature discontinuation leads to relapses.

Use only clear solution in an intact vial! Failure to observe the storage and transportation conditions can lead to the formation of micro-cracks on the vial, thereby increasing the risk of microbial contamination of the solution.

For single-use sampling only!

Do not freeze or heat!

Overdose

Hallucinations and paranoid behavior have been described. In case of overdose, gastric lavage, forced diuresis and symptomatic treatment should be administered. After a 3-hour session of hemodialysis the drug concentration in plasma is decreased by 50%.

Form of production

Infusion solution 200 mg/100 ml or 400 mg/200 ml in 100 ml or 200 ml vials.

Storage conditions

Store in a dry, dark place at a temperature not exceeding 25°C. Keep out of the reach of children!

Shelf life

2 years. Do not use after the expiration date.

Conditions of dispensing from pharmacies

Released by a doctor’s prescription.

Candiflu ® Neo – capsules

INSTRUCTIONS FOR MEDICAL USE

CANDIFLU NEO

Trade name of the drug: Candiflu® Neo

Active substance (INN): Fluconazole

Package name: 150 mg capsules

Contents:

1 capsule contains:

active substance: Fluconazole – 150 mg;

Excipients: sugar, lactose, aerosil, potato or corn starch, calcium stearate or magnesium stearate

Description: Solid white gelatin capsules with white or almost white color powder, odorless.

Pharmacotherapeutic group: Antifungal agent.

ATX code: J02AC01

Pharmacological properties

Fluconazole, a representative of a new class of triazole antifungal agents. It has a highly specific action by inhibiting the activity of cytochrome P450-dependent fungal enzymes. It blocks the conversion of fungal cell lanosterol into ergosterol; it increases cell membrane permeability, disrupts cell growth and replication. Fluconazole, being highly selective for cytochrome P450 of fungi, practically does not inhibit these enzymes in humans (in comparison with itraconazole, clotrimazole, econazole and ketoconazole it inhibits cytochrome P450 dependent oxidative processes in human liver microsomes to a lesser extent). It does not have antiadrogenic activity.

It is active in opportunistic mycoses, including those caused by Candida spp. (including generalized candidiasis against immunosuppression), Cryptococcus neoformans and Coccidioides immitis (including intracranial infections), Microsporum spp. and Trichophyton spp.; in endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulatum (including immunosuppression).

Pharmacokinetics

Absorption

After oral administration, fluconazole is well absorbed. Simultaneous intake of food has no effect on the absorption rate (absorption) of the drug when taken orally. Time of maximum concentration achievement ( ТСmax) after oral use on an empty stomach of fluconazole 150 mg – 0.5-1.5 hours, and makes 90% of concentration in plasma in intravenous division of 2.5-3.5 mg/l.

Distribution

Plasma concentration is in direct relation to the dose. Equilibrium plasma concentration (Css) of the drug is reached by day 4-5 of administration (when taken once daily). Administration of “shock” dose (on the first day), 2 times higher than the usual daily dose, allows achieving a concentration corresponding to 90% of Css by the second day.

Good penetration into all body fluids. Active substance concentrations in breast milk, joint fluid, saliva, sputum and peritoneal fluid are similar to those in plasma. Constant values in vaginal secretion are reached 8 hours after oral administration and are maintained at this level for at least 24 hours. It penetrates well into the cerebrospinal fluid (CSF); in fungal meningitis, the concentration in the CSF is about 85% of that in plasma. In sweat fluid, dermis and stratum corneum (selective accumulation) high concentrations exceeding serum concentrations are achieved. When administered at a dose of 50 mg once daily, fluconazole concentrations were 73 µg/g after 12 days and 5.8 µg/L after 7 days of discontinuation of treatment. After oral administration of 150 mg once a week. – on day 7, the concentration of fluconazole in the stratum corneum of the skin was 23.4 µg/g, and 7 days after the second dose was 7.1 µg/g.

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

The apparent volume of distribution (Vd) approached the total extracellular fluid content in the body. The binding to plasma proteins is low – 11-12%.

Metabolism and excretion

The elimination half-life (T1/2) is 30 hours. It is an inhibitor of CYP2C9 isoenzyme in the liver. It is eliminated mainly by the kidneys (80% – unchanged, 11% – as metabolites). Clearance of fluconazole is proportional to creatinine clearance.

Fluconazole pharmacokinetics depends significantly on the functional state of the kidneys, and there is an inverse relationship between T1/2 and creatinine clearance ( Cc). After hemodialysis, within 3 hours, plasma concentration of fluconazole decreases by 50%.

Fluconazole pharmacokinetics is similar when administered intravenously and when taken orally, which allows to easily switch from one type of administration to another.

Indications for use

Mucosal candidiasis: oral cavity, pharynx, esophagus, non-invasive bronchopulmonary candidiasis, candiduria, cutaneous-mucosal and chronic oral atrophic candidiasis (associated with wearing dentures).

Genital candidiasis: vaginal (acute and recurrent). Candida balanitis. Prophylactic use to reduce the frequency of recurrent vaginal candidiasis (three or more episodes per year).

Prophylaxis of fungal infections in patients with malignant tumors against the background of chemo- or radiation therapy; prevention of relapse of oropharyngeal candidiasis in AIDS patients.

Mycosis of the skin: feet, body, inguinal area, onychomycosis, pityriasis, cutaneous candida infections.

Dosage and administration

Inside

In cases of oropharyngeal andidosis, usually 50-100 mg once daily, treatment should be continued for 7-14 days. If necessary, in patients with severe immune impairment, treatment may be longer. For prophylaxis of oropharyngeal candidiasis relapses in AIDS patients after full course of primary therapy, the drug may be prescribed 150 mg once a week.

For vaginal candidiasis, fluconazole is taken once orally in a dose of 150 mg. To reduce the recurrence rate of vaginal candidiasis, the drug may be used in a dose of 150 mg. 1 time per 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 spp., fluconazole is prescribed once in a dose of 150 mg orally. For prophylaxis of candidiasis, the recommended dose of fluconazole is 50-400 mg once daily, depending on the risk of fungal infection. If there is a high risk of generalized infection, such as in patients with expected severe or prolonged neutropenia, the recommended dose is 400 mg once daily. Fluconazole is administered several days before the expected appearance of neutropenia; after an increase in neutrophil count over 1000/mm for another 7 days.

For mycoses of the skin, including mycoses of the feet, skin of the groin, and candidiasis of the rut, the recommended dose is 150 mg once a week or 50 mg once a day. Duration of therapy in common cases is 2-4 weeks, but in case of mycoses of feet a longer therapy (up to 6 weeks) may be required.

For pityriasis – 300 mg once a week for 2 weeks, some patients need a third dose of 300 mg per week, while in some cases a single dose of 300 mg to 400 mg is sufficient; an alternative treatment regimen is 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 (uninfected nail grows back). It takes 3-6 months and 6-12 months, respectively, for the nails on the fingers and toes to re-grow. However, the rate of growth can vary widely from person to person and also depending on age.

For esophageal candidiasis in children, fluconazole is prescribed once in a daily dose of 3 mg/kg, in the following average doses: ages 3-6 years (body weight 15-20 kg) – 50 mg; ages 7-9 years (body weight 21-29 kg) – 50-100 mg; ages 10-12 years (body weight 30-40 kg) – 100-150 mg; ages 12-15 years (body weight 40-50 kg) – 100-150 mg. Duration of therapy – at least 3 weeks and for 2 more weeks after symptoms have regressed.

Forchildren with mucous membrane candidiasis, fluconazole is prescribed once in a daily dose of 3 mg/kg, in the following average doses: 3-6 years old (body weight 15-20 kg) – 100-150 mg on the 1st day, then – 50 mg; 7-9 years old (body weight 21-29 kg) – 100-200 mg on the 1st day, then – 100 mg: at the age of 10-12 years (body weight 30-40 kg) – on the 1st day 100-150 mg, then – by 50-100 mg; at the age of 12-15 years (body weight 40-50 kg) – on the 1st day 250-300 mg, then – by 100-150 mg. The therapy duration is at least 3 weeks.

For generalized candidiasis and cryptococcal infection (including meningitis) in children, fluconazole is indicated in a single daily dose of 6-12 mg/kg, with the following average doses: 3-6 years old (body weight 15-20 kg) – 100-250 mg; 7-9 years old (body weight 21-29 kg) – 100-300 mg; 10-12 years old (body weight 30-40 kg) – 200-350 mg; 12-15 years old (body weight 40-50 kg) – 250-400 mg. Duration of therapy – for 10-12 weeks (until laboratory confirmation of the absence of pathogens in the cerebrospinal fluid).

For prevention of fungal infections in immunocompromised children, in whom the risk of infection is associated with neutropenia, developed as a result of cytotoxic chemotherapy or radiotherapy, fluconazole is administered by 3-12 mg/kg/day, depending on the severity and duration of induced neutropenia, in the following average doses ages 3-6 years (body weight 15-20 kg) – 50-250 mg; ages 7-9 years (body weight 21-29 kg) – 50-300 mg; ages 10-12 years (body weight 30-40 kg) – 100-350 mg; ages 12-15 years (body weight 40-50 kg) – 100-400 mg. Duration of therapy – until elimination of induced neutropenia.

For children with impaired renal function, the daily dose of the drug should be reduced (in the same proportional relationship as in adults), according to the degree of renal failure.

For elderly patients with no renal impairment, the usual dosing regimen of the drug should be followed. In patients with renal failure (creatinine clearance less than 50 ml/min) the dosage regimen should be adjusted as described below.

Administration of the drug for patients with impaired renal function. Fluconazole is mainly excreted unchanged in the urine. It is not necessary to change the dose if it is administered once. In re-administration of the drug in patients with impaired renal function a “shock” dose of 50 mg to 400 mg should be given first. If creatinine clearance (CK) is 50 ml/min, the usual dose of the drug (100% of the recommended dose) is used once daily. If CK is 11 to 50 ml/min, a dose equal to 50% of the recommended dose is used. If patients are regularly on dialysis, one dose of the drug is administered after each session of hemodialysis.

Side effects

Digestive system disorders: change of taste, vomiting, nausea, diarrhea, flatulence, abdominal pain, liver disorders (jaundice, hyperbilirubinemia, increased alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase activity, hepatitis, hepatocellular necrosis), including with lethal outcome.

Nervous system disorders: headache, dizziness, seizures.

Cardiovascular system: prolongation of the QT interval, ventricular fibrillation/rattling.

Blood organs: leukopenia, thrombocytopenia, neutropenia, agranulocytosis.

Allergic reactions: skin rash, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome), anaphylactoid reactions (including angioedema, facial edema, urticaria, skin itching).

Other: impaired renal function, alopecia, hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Contraindications

Concomitant use of terfenadine (concomitantly with fluconazole at a dose of 400 mg/day or more), astemizole and other drugs that prolong the Q-T interval.

Concomitant use of cisapride.

Hypersensitivity to the drug or similar azole compounds.

Lactose intolerance, lactase deficiency or glucose-galactase malabsorption.

Children under 3 years of age (for this dosage form).

With caution: hepatic and/or renal insufficiency, the appearance of rash against the background of fluconazole administration in patients with superficial fungal infection and invasive/systemic fungal infections, potentially proarrhythmogenic conditions in patients with multiple risk factors (organic heart disease, electrolyte balance disorders, simultaneous use of drugs that cause arrhythmias), simultaneous use of potentially hepatotoxic agents, alcoholism. Simultaneous use of terfenadine and fluconazole in dose less than 400 mg/day.

Drug interactions

Anticoagulants. Fluconazole increases prothrombin time of coumarin anticoagulants (e.g., warfarin) by 12% on average, therefore it is necessary to monitor prothrombin time of patients receiving fluconazole and coumarin anticoagulants carefully.

Sulfonylureas. When concomitant administration of fluconazole and oral sulfonylurea drugs (chlorpropamide, glibenclamide, glipizide and tolbutamide) the elimination half-life of the latter is prolonged, which may lead to hypoglycemia. Blood glucose concentration should be periodically monitored and, if necessary, the dose of hypoglycemic drugs should be adjusted.

Hydrochlorothiazide increases fluconazole plasma concentration by 40%, but it does not require changing the dosing regimen of fluconazole in patients receiving concomitant diuretics.

Phenytoin. Concomitant administration of fluconazole and phenytoin is accompanied by an increase in concentrations of the latter to a clinically significant degree. Therefore, it is necessary to monitor phenytoin levels and dose selection to ensure therapeutic concentration in serum.

Oral contraceptives. Repeated use of fluconazole (in doses of 50-200 mg) has no effect on the effectiveness of the combined contraceptive.

Rifampicin. Concomitant use of fluconazole and rifampicin decreased the area under the curve “concentration – time” by 25% and the half-life of fluconazole by 20%. It is necessary to increase fluconazole dose if they are concomitantly administered.

Cyclosporine. When treating with fluconazole at a dose of 200 mg/day, cyclosporine blood concentrations are increased.

Theophylline. Fluconazole prolongs the half-life of theophylline and increases the risk of intoxication (its dose should be corrected).

Terfenadine. Concomitant administration 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 performed under close medical supervision.

Cisapride. When concomitant administration of fluconazole and cisapride, adverse cardiac reactions, including paroxysms of ventricular tachycardia (torsades depointes).

Nifabutin. Cases of uveitis have been described.

Tacrolimus. Increases the concentration of tacrolimus, therefore increasing the risk of nephrotoxic effects.

Zidovudine. In patients receiving a combination of fluconazole and zidovudine, an increase in zidovudine concentration is observed, which is caused by a decrease in conversion of the latter to its main metabolite, so an increase in side effects of zidovudine should be expected.

Midazolam. Increases the concentration of midazolam, and therefore, the risk of psychomotor effects increases (most pronounced when fluconazole is administered orally than intravenously).

Special indications

Treatment should be continued until clinical and hematological remission occurs. Premature discontinuation of treatment leads to relapses.

Treatment can be started in the absence of results of culture or other laboratory tests, but if they are available, appropriate correction of fungicidal therapy is recommended.

Blood counts, kidney and liver function should be monitored during treatment. If renal and liver function abnormalities occur, the drug should be discontinued. In rare cases, the use of fluconazole was accompanied by toxic liver changes. In the case of hepatotoxic effects associated with fluconazole, no clear dependence on the total daily dose, duration of therapy, sex, and age of the patient was noted. Hepatotoxic effects of fluconazole are usually reversible; their signs disappeared after discontinuation of therapy. If clinical signs of liver damage appear, which may be associated with fluconazole, the drug should be discontinued.

AIDS patients are more prone to develop severe skin reactions when using many drugs. In cases where patients with superficial fungal infection develop a rash and it is considered to be definitely related to fluconazole, the drug should be discontinued. If rash appears in patients with invasive/systemic fungal infections, they should be closely monitored and fluconazole should be discontinued if bullous changes or erythema multiforme appear.

Use in pregnancy and during breastfeeding

It is not advisable to use the drug in pregnant women, with the exception of severe or life-threatening forms of fungal infections, if the anticipated benefits to the mother exceed the possible risks to the fetus.

Fluconazole is in breast milk at the same concentration as in plasma, therefore its administration during lactation is not recommended.

Influence on the ability to drive motor transport and operate machinery

In case of adverse reactions on the nervous system side, patients are recommended to refrain from driving a vehicle and other mechanisms as well as to be cautious while carrying out activities requiring high concentration and quick psychomotor reactions.

Overdose

There was described a case of hallucinations and paranoid behavior after 8.2 g of drug administration. The patient was hospitalized and his condition normalized within 48 hours. In case of overdose, gastric lavage, forced diuresis and symptomatic treatment should be administered. After 3-hour session of hemodialysis the drug concentration in plasma is decreased by 50%.

Form of production

Capsules of 150 mg in a contour cellular pack.

Storage conditions

Store in a dry, dark place at a temperature not exceeding 25°C.

Keep out of the reach of children!

Shelf life

3 years. Do not use after the expiration date.

Conditions of dispensing from pharmacies.

Capsules 150 mg #1 – without prescription

Capsules 150 mg #3 – by doctor’s prescription

    ×