Instructions Fluconazole film-coated tablets 150 mg blister No. 2
Composition
Active ingredient: fluconazole.
1 tablet contains 150 mg of fluconazole.
Excipients: lactose monohydrate, potato starch, povidone, colloidal anhydrous silica, croscarmellose sodium, magnesium stearate, hypromellose (hydroxypropylmethylcellulose), titanium dioxide (E 171), talc, polyethylene glycol 6000 (macrogol 6000), polysorbate 80.
Dosage form
Film-coated tablets.
Main physicochemical properties: round, film-coated tablets, white or almost white in color, with convex upper and lower surfaces. When broken, when examined under a magnifying glass, a core surrounded by one continuous layer is visible.
Pharmacotherapeutic group
Antifungal agents for systemic use. Triazole derivatives.
ATX code J02A C01.
Pharmacological properties
Pharmacodynamics
Mechanism of action.
Fluconazole, a triazole antifungal agent, is a potent and selective inhibitor of fungal enzymes required for ergosterol synthesis. Its primary mechanism of action is inhibition of fungal cytochrome P450-mediated 14 alpha-lanosterol demethylation, an essential step in fungal ergosterol biosynthesis. Accumulation of 14 alpha-methyl sterols correlates with subsequent loss of ergosterol from the fungal cell membrane and may be responsible for the antifungal activity of fluconazole. Fluconazole is more selective for fungal cytochrome P450 enzymes than for various mammalian cytochrome P450 systems.
Fluconazole 50 mg daily for 28 days had no effect on plasma testosterone levels in men or on endogenous steroid levels in women of reproductive age. Fluconazole 200-400 mg daily had no clinically significant effect on endogenous steroid levels or the response to ACTH stimulation in healthy male volunteers.
An interaction study with antipyrine demonstrated that single or multiple doses of 50 mg fluconazole did not affect the metabolism of antipyrine.
In vitro sensitivity.
Fluconazole has demonstrated antifungal activity in vitro against the most common Candida species (including C. albicans, C. parapsilosis, C. tropicalis). C. glabrata exhibits a wide range of susceptibility to fluconazole, while C. krusei is resistant to it.
Fluconazole also demonstrates in vitro activity against Cryptococcus neoformans and Cryptococcus gattii, as well as against the endemic molds Blastomices dermatitidis, Coccidioides immitis, Histoplasma capsulatum, and Paracoccidioides brasiliensis.
Mechanism of resistance.
Candida species exhibit multiple mechanisms of resistance to azole antifungal agents. Fluconazole exhibits a high minimum inhibitory concentration against fungal strains that possess one or more mechanisms of resistance, which negatively affects its efficacy in vivo and in clinical practice. Superinfection with Candida spp. other than C. albicans, a commonly encountered species, has been reported. Albicans, a species that is often insensitive to fluconazole (e.g. Candida krusei). Alternative antifungal agents should be used in such cases.
Pharmacokinetics
The pharmacokinetic properties of fluconazole are similar after intravenous and oral administration.
Absorption.
Fluconazole is well absorbed after oral administration, and plasma levels and systemic bioavailability exceed 90% of those achieved after intravenous administration. Concomitant food intake does not affect oral absorption. Peak plasma concentrations are reached 0.5-1.5 hours after administration. Plasma concentrations are dose-proportional. Steady-state concentrations of 90% are reached on the second day of treatment when a loading dose of twice the usual daily dose is administered on the first day.
Distribution.
The volume of distribution is approximately equal to the total body water content. Plasma protein binding is low (11-12%).
Fluconazole penetrates well into all body fluids studied. Fluconazole levels in saliva and sputum are similar to plasma concentrations. In patients with fungal meningitis, fluconazole levels in cerebrospinal fluid reach 80% of plasma concentrations.
The concentration of fluconazole in nails after 4 months of 150 mg once weekly was 4.05 μg/g in healthy volunteers and 1.8 μg/g in nail diseases; fluconazole was detected in nail samples 6 months after the end of therapy. Biotransformation. Fluconazole is metabolized to a small extent. When a dose labeled with radioactive isotopes is administered, only 11% of fluconazole is excreted unchanged in the urine. Fluconazole is a selective inhibitor of CYP 2C9 and CYP3A4 isoenzymes, as well as an inhibitor of the 2C19 isoenzyme.
Excretion. The plasma half-life of fluconazole is approximately 30 hours. The majority of the drug is excreted by the kidneys, with 80% of the administered dose being excreted unchanged in the urine. Fluconazole clearance is proportional to creatinine clearance. No circulating metabolites have been identified.
The long plasma half-life allows for a single dose for vaginal candidiasis, as well as once-weekly dosing for other indications.
Kidney failure.
In patients with severe renal insufficiency (glomerular filtration rate < 20 ml/min), the half-life increases from 30 hours to 98 hours. Therefore, this category of patients requires a change in the dose of fluconazole. Fluconazole is removed by hemodialysis, to a lesser extent by intraperitoneal dialysis. A 3-hour hemodialysis session reduces the level of fluconazole in the blood plasma by approximately 50%.
Elderly patients.
Changes in pharmacokinetics in elderly patients depend on renal function parameters.
Indication
Acute vaginal candidiasis when topical therapy is inappropriate. Candidal balanitis when topical therapy is inappropriate.
Contraindication
Hypersensitivity to fluconazole, other azole compounds or to any of the excipients of the drug. Concomitant use of fluconazole and terfenadine in patients receiving multiple doses of fluconazole at doses of 400 mg/day and above (according to the results of a multiple-dose interaction study). Concomitant use of fluconazole and other drugs that prolong the QT interval and are metabolized by the CYP3A4 enzyme (e.g. cisapride, astemizole, pimozide, quinidine, amiodarone and erythromycin).
Interaction with other medicinal products and other types of interactions
The concomitant use of fluconazole and the following drugs is contraindicated.
Cisapride: Cardiac adverse reactions, including torsades de pointes, have been reported in patients receiving fluconazole and cisapride concomitantly. Concomitant administration of fluconazole 200 mg once daily and cisapride 20 mg four times daily resulted in significant increases in plasma cisapride levels and prolongation of the QT interval. Concomitant administration of fluconazole and cisapride is contraindicated (see Contraindications).
Terfenadine: Cases of serious cardiac arrhythmias caused by prolongation of the QTc interval have been reported in patients receiving azole antifungals concomitantly with terfenadine. No prolongation of the QTc interval was observed with fluconazole at a dose of 200 mg/day. Fluconazole at doses of 400 mg and 800 mg/day has been shown to significantly increase plasma levels of terfenadine when administered concomitantly with these drugs. Concomitant use of fluconazole at doses of 400 mg or higher with terfenadine is contraindicated (see section 4.3). When fluconazole is administered concomitantly with terfenadine at doses below 400 mg, the patient should be closely monitored.
Astemizole: Concomitant use of fluconazole and astemizole may reduce the clearance of astemizole. The resulting increase in plasma astemizole concentrations may lead to QT prolongation and, in rare cases, torsades de pointes. Concomitant use of fluconazole and astemizole is contraindicated.
Pimozide and quinidine: Concomitant use of fluconazole and pimozide or quinidine may result in inhibition of the metabolism of pimozide or quinidine. Increased plasma concentrations of pimozide or quinidine may cause prolongation of the QT interval and, in rare cases, paroxysmal torsades de pointes. Concomitant use of fluconazole and pimozide or quinidine is contraindicated.
Erythromycin: Concomitant use of erythromycin and fluconazole may potentially lead to an increased risk of cardiotoxicity (QT prolongation, torsades de pointes) and, as a result, sudden cardiac arrest. The combination of these drugs is contraindicated.
The concomitant use of fluconazole and the following medicinal products is not recommended. Halofantrine: Fluconazole may increase plasma concentrations of halofantrine due to inhibition of CYP3A4. Concomitant use of these medicinal products may potentially increase the risk of cardiotoxicity (QT prolongation, torsades de pointes) and, consequently, sudden cardiac arrest. The combination of these medicinal products should be avoided.
Concomitant use of fluconazole and the following drugs requires caution and dose adjustment.
Effects of other drugs on fluconazole
Concomitant food intake, cimetidine, antacids, or subsequent total body irradiation for bone marrow transplantation has no clinically significant effect on the absorption of fluconazole when administered orally.
Rifampicin: Concomitant use of fluconazole and rifampicin resulted in a 25% decrease in AUC and a 20% decrease in the half-life of fluconazole. Therefore, an increase in the dose of fluconazole should be considered in patients taking rifampicin.
Hydrochlorothiazide: In a pharmacokinetic interaction study, co-administration of multiple hydrochlorothiazide to healthy volunteers receiving fluconazole increased fluconazole plasma concentrations by 40%. These interaction parameters do not require changes in the fluconazole dosing regimen for patients receiving concomitant diuretics.
Effect of fluconazole on other drugs
Fluconazole is a potent inhibitor of the cytochrome P450 (CYP) 2C9 isoenzyme and a moderate inhibitor of CYP3A4. Fluconazole is also an inhibitor of CYP2C19. In addition to the observed/documented interactions described below, there is a risk of increased plasma concentrations of other compounds metabolized by CYP2C9 and CYP3A4 when co-administered with fluconazole. Therefore, such combinations should be used with caution and patients should be closely monitored. The enzyme inhibitory effect of fluconazole persists for 4 to 5 days after administration due to its long half-life.
Alfentanil: Concomitant administration of alfentanil 20 mcg/kg and fluconazole 400 mg resulted in a two-fold increase in AUC10, possibly due to inhibition of CYP3A4. Dose adjustment of alfentanil may be required.
Amitriptyline, nortriptyline: Fluconazole potentiates the effects of amitriptyline and nortriptyline. It is recommended to measure the concentrations of 5-nortriptyline and/or
S-amitriptyline at the beginning of combination therapy and after 1 week. If necessary, the dose of amitriptyline/nortriptyline should be adjusted.
Amphotericin B: Concomitant administration of fluconazole and amphotericin B to immunocompetent and immunocompromised infected mice resulted in the following results: a small additive antifungal effect in systemic C. albicans infection, no interaction in intracranial Cryptococcus neoformans infection, and antagonism of the two drugs in systemic A. fumigatus infection. The clinical significance of the findings in these studies is unknown.
Anticoagulants: As with other azole antifungals, bleeding events (hematomas, epistaxis, gastrointestinal bleeding, haematuria and melena) in association with prolonged prothrombin time have been reported with concomitant use of fluconazole and warfarin. A two-fold increase in prothrombin time has been observed with concomitant use of fluconazole and warfarin, presumably due to inhibition of warfarin metabolism by CYP2C9. Prothrombin time should be closely monitored in patients receiving coumarin anticoagulants or indanedione. Dosage adjustment of the anticoagulant may be necessary.
Short-acting benzodiazepines, e.g. midazolam, triazolam: administration of fluconazole after oral midazolam resulted in a significant increase in midazolam concentrations and increased psychomotor effects. Concomitant administration of fluconazole 200 mg and midazolam 7.5 mg orally resulted in a 3.7- and 2.2-fold increase in AUC and half-life, respectively. Administration of fluconazole 200 mg/day and triazolam 0.25 mg orally resulted in a 4.4- and 2.3-fold increase in AUC and half-life, respectively. Potentiation and prolongation of the effects of triazolam were observed with concomitant administration of fluconazole and triazolam.
If a patient undergoing treatment with fluconazole is to be prescribed concomitant therapy with benzodiazepines, the dose of the latter should be reduced and the patient's condition should be adequately monitored.
Carbamazepine: Fluconazole inhibits the metabolism of carbamazepine and causes a 30% increase in serum carbamazepine levels. There is a risk of carbamazepine toxicity. The dose of carbamazepine may need to be adjusted depending on its concentration and effect.
Celecoxib: Concomitant administration of fluconazole (200 mg) and celecoxib (200 mg) increased celecoxib Cmax and AUC by 68% and 134%, respectively. The celecoxib dose may need to be halved when celecoxib and fluconazole are administered concomitantly.
Cyclophosphamide: Concomitant use of cyclophosphamide and fluconazole has been shown to increase serum bilirubin and creatinine levels. These drugs may be used concomitantly, taking into account the risk of increased serum bilirubin and creatinine concentrations.
Fentanyl: One fatal case of fentanyl intoxication has been reported due to a possible interaction between fentanyl and fluconazole. In addition, fluconazole has been shown to significantly slow the elimination of fentanyl. Increased fentanyl concentrations may lead to respiratory depression, so the patient should be closely monitored. Fentanyl dosage adjustment may be necessary.
HMG-CoA reductase inhibitors: Concomitant use of fluconazole and HMG-CoA reductase inhibitors metabolized by CYP3A4 (atorvastatin and simvastatin) or HMG-CoA reductase inhibitors metabolized by CYP2C9 (fluvastatin) increases the risk of myopathy and rhabdomyolysis. If concomitant use of these drugs is necessary, the patient should be closely observed for symptoms of myopathy and rhabdomyolysis and creatine kinase levels should be monitored. In the event of an increase in creatine kinase levels, as well as when myopathy/rhabdomyolysis is diagnosed or suspected, the use of HMG-CoA reductase inhibitors should be discontinued.
Immunosuppressants (e.g. cyclosporine, everolimus, sirolimus and tacrolimus)
Cyclosporine: Fluconazole significantly increases the concentration and AUC of cyclosporine. When fluconazole was administered concomitantly at a dose of 200 mg/day and cyclosporine at a dose of 2.7 mg/kg/day, a 1.8-fold increase in the AUC of cyclosporine was observed. These drugs can be used concomitantly, provided that the dose of cyclosporine is reduced depending on its concentration.
Everolimus: Fluconazole may increase serum concentrations of everolimus by inhibiting CYP3A4.
Sirolimus: Fluconazole increases serum concentrations of sirolimus, possibly by inhibiting sirolimus metabolism by CYP3A4 and P-glycoprotein. These drugs can be co-administered with dose adjustments of sirolimus based on drug concentration and effects.
Tacrolimus: Fluconazole may increase the serum concentrations of tacrolimus by 5-fold when administered orally due to inhibition of tacrolimus metabolism by the CYP3A4 enzyme in the intestine. No significant changes in pharmacokinetics have been observed with intravenous administration of tacrolimus. Elevated tacrolimus levels are associated with nephrotoxicity. The oral dose of tacrolimus should be reduced depending on tacrolimus concentrations.
Losartan: Fluconazole inhibits the metabolism of losartan to its active metabolite (E-31 74), which accounts for most of the angiotensin II receptor antagonism of losartan. It is recommended that patients' blood pressure be monitored closely.
Methadone: Fluconazole may increase the serum concentration of methadone. Methadone dose adjustment may be necessary when methadone and fluconazole are used concomitantly.
Non-steroidal anti-inflammatory drugs: When co-administered with fluconazole, the Cmax and AUC of flurbiprofen increased by 23% and 81%, respectively, compared to flurbiprofen alone. Similarly, when co-administered with racemic ibuprofen (400 mg), the Cmax and AUC of the pharmacologically active isomer S-(+)-ibuprofen increased by 15% and 82%, respectively, compared to racemic ibuprofen alone.
Fluconazole has the potential to increase the systemic exposure of other NSAIDs metabolized by CYP2C9 (e.g. naproxen, lornoxicam, meloxicam, diclofenac). Periodic monitoring for adverse reactions and toxicities associated with NSAIDs is recommended. Dose adjustment of NSAIDs may be necessary.
Phenytoin: Fluconazole inhibits the metabolism of phenytoin in the liver. Simultaneous multiple administration of 200 mg of fluconazole and 250 mg of phenytoin intravenously leads to an increase in phenytoin AUC24 by 75% and Cmin by 128%. When these drugs are used simultaneously, phenytoin serum concentrations should be monitored to exclude the development of phenytoin toxicity.
Prednisone: A case report has been made of a liver transplant patient receiving prednisone who developed acute adrenal insufficiency after discontinuation of a three-month course of fluconazole. Discontinuation of fluconazole is likely to have resulted in increased CYP3A4 activity, leading to increased metabolism of prednisone. Patients receiving long-term concomitant treatment with fluconazole and prednisone should be carefully monitored for the development of adrenal insufficiency after discontinuation of fluconazole.
Saquinavir: Fluconazole increases the AUC and Cmax of saquinavir by approximately 50% and 55%, respectively, due to inhibition of the hepatic metabolism of saquinavir by CYP3A4 and inhibition of P-glycoprotein. Interactions between fluconazole and saquinavir/ritonavir have not been studied and may therefore be more severe. Saquinavir dose adjustment may be necessary.
Sulfonylureas: Fluconazole prolongs the half-life of oral sulfonylureas (chlorpropamide, glibenclamide, glipizide and tolbutamide) when used concomitantly. Regular monitoring of blood sugar levels and appropriate dose reduction of sulfonylureas are recommended when used concomitantly with fluconazole.
Theophylline: Fluconazole 200 mg for 14 days decreased the mean plasma clearance of theophylline by 18%. Patients receiving high doses of theophylline or who are otherwise at increased risk of theophylline toxicity should be monitored for signs of theophylline toxicity. Therapy should be changed if signs of toxicity occur.
Vinca alkaloids: Fluconazole, probably through inhibition of CYP3A4, may cause an increase in plasma concentrations of vinca alkaloids (e.g. vincristine and vinblastine), leading to the development of neurotoxic effects.
Vitamin A: A patient receiving all-trans retinoic acid (the acid form of vitamin A) and fluconazole was reported to have experienced a CNS adverse reaction in the form of pseudotumor cerebri, which resolved after discontinuation of fluconazole. These drugs can be used concomitantly, but the risk of CNS adverse reactions should be considered.
Voriconazole (CYP2C9 and CYP3A4 inhibitor): Co-administration of oral voriconazole (400 mg every 12 hours for 1 day, then 200 mg every 12 hours for 2.5 days) and oral fluconazole (400 mg on day 1, then 200 mg every 24 hours for 4 days) to male volunteers resulted in an increase in voriconazole Cmax and AUCτ by an average of 57% (90% CI: 20%, 107%) and 79% (90% CI: 40%, 128%), respectively. It is unknown whether reducing the dose and/or frequency of voriconazole or fluconazole would eliminate this effect. When voriconazole is administered after fluconazole, monitoring for adverse events associated with voriconazole should be performed.
Zidovudine: Fluconazole increases the Cmax and AUC of zidovudine by 84% and 74%, respectively, due to a decrease in zidovudine clearance of approximately 45% when administered orally. The half-life of zidovudine was also prolonged by approximately 128% after the combination of fluconazole and zidovudine. Patients receiving this combination should be monitored for adverse reactions associated with zidovudine. A reduction in the dose of zidovudine may be considered.
Azithromycin: No significant pharmacokinetic interactions were identified.
Oral contraceptives: Fluconazole 50 mg had no effect on hormone levels, while fluconazole 200 mg daily increased the AUC of ethinylestradiol by 40% and levonorgestrel by 24%. This suggests that multiple doses of fluconazole are unlikely to affect the efficacy of a combined oral contraceptive.
Ivacaftor: Co-administration with ivacaftor, a cystic fibrosis transmembrane conductance regulator enhancer, increases ivacaftor exposure 3-fold and hydroxymethylivacaftor (M1) exposure 1.9-fold. For patients concomitantly taking moderate CYP3A inhibitors such as fluconazole and erythromycin, a dose reduction of ivacaftor to 150 mg once daily is recommended.
Application features
Ringworm. Fluconazole is not superior to griseofulvin in the treatment of ringworm in children, and the overall efficacy is less than 20%. Therefore, the drug should not be used to treat ringworm.
Cryptococcosis. There is insufficient evidence of fluconazole efficacy in the treatment of cryptococcosis of other sites (e.g., pulmonary cryptococcosis and cutaneous cryptococcosis), and therefore no dosage recommendations can be made for these conditions.
Deep endemic mycoses. Evidence of the effectiveness of fluconazole for the treatment of other forms of endemic mycoses, such as paracoccidioidomycosis, histoplasmosis and cutaneous-lymphatic sporotrichosis, is insufficient, therefore there are no recommendations for a dosage regimen for the treatment of such diseases.
Renal system: The drug should be used with caution in patients with impaired renal function (see section "Method of administration and dosage").
Hepatobiliary system. The drug should be used with caution in patients with impaired liver function. The use of fluconazole has been associated with rare cases of severe hepatotoxicity, including fatalities, mainly in patients with severe underlying diseases. In cases where hepatotoxicity has been associated with the use of fluconazole, there has been no clear relationship between the total daily dose, duration of therapy, gender or age of the patient. Usually, hepatotoxicity caused by fluconazole is reversible and its manifestations disappear after discontinuation of therapy.
Patients who develop abnormal liver function tests while taking fluconazole should be closely monitored for the development of more severe liver damage.
Patients should be informed of symptoms that may indicate serious liver effects (severe asthenia, anorexia, persistent nausea, vomiting and jaundice). In such cases, fluconazole should be discontinued immediately and a doctor should be consulted.
Cardiovascular system. Some azoles, including fluconazole, are associated with prolongation of the QT interval on the electrocardiogram. Very rare cases of QT prolongation and paroxysmal torsades de pointes have been reported with the use of the drug. These reports have involved patients with severe disease and multiple risk factors, such as structural heart disease, electrolyte disturbances, and concomitant use of other drugs that affect the QT interval.
The drug should be used with caution in patients at risk of developing arrhythmias. Concomitant use with drugs that prolong the QTc interval and are metabolized by the cytochrome P450 enzyme CYP3A4 is contraindicated.
Halofantrine: Halofantrine is a substrate of the CYP3A4 enzyme and prolongs the QTc interval at recommended therapeutic doses. Concomitant use of halofantrine and fluconazole is not recommended.
Dermatological reactions. Exfoliative skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported rarely with fluconazole. Patients with AIDS are more prone to developing severe skin reactions with many drugs. If a patient with a superficial fungal infection develops a rash that can be attributed to the use of fluconazole, further use of the drug should be discontinued. If a patient with an invasive/systemic fungal infection develops a skin rash, his condition should be closely monitored, and in the event of the development of bullous rashes or erythema multiforme, fluconazole should be discontinued.
Hypersensitivity: Anaphylactic reactions have been reported in rare cases.
Cytochrome P450. Fluconazole is a potent inhibitor of the CYP2C9 enzyme and a moderate inhibitor of the CYP3A4 enzyme. Fluconazole is also an inhibitor of the CYP2C19 enzyme. Patients should be monitored when concomitantly taking fluconazole and drugs with a narrow therapeutic window that are metabolized by CYP2C9, CYP2C19, and CYP3A4.
Terfenadine: The patient should be carefully monitored when terfenadine and fluconazole are used concomitantly at doses less than 400 mg/day.
Excipients: This medicine contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
The ability to influence the reaction speed when driving or working with mechanisms
Studies on the effect of fluconazole on the ability to drive or use machines have not been conducted. Patients should be informed of the possibility of dizziness or convulsions when using the drug. If such symptoms develop, it is not recommended to drive or use machines.
Use during pregnancy or breastfeeding
Data obtained from single or repeated administration of fluconazole at usual doses (< 200 mg/day) to several hundred pregnant women during the first trimester of pregnancy have not demonstrated an increased risk of adverse reactions in the fetus.
Numerous congenital anomalies (including brachycephaly, auricular dysplasia, excessive anterior fontanelle enlargement, hip dysplasia, brachioradial synostosis) have been reported in newborns whose mothers received high doses of fluconazole (400-800 mg/day) for at least three or more months for the treatment of coccidioidomycosis. The relationship between fluconazole use and these cases has not been established.
Animal studies of fluconazole have demonstrated reproductive toxicity.
Normal doses of fluconazole and short-term courses of fluconazole should not be used during pregnancy unless clearly necessary.
High doses of fluconazole and/or long courses of fluconazole treatment should not be used during pregnancy, except for the treatment of potentially life-threatening infections.
Breastfeeding is not recommended during repeated use of fluconazole or when using high doses of fluconazole.
Method of administration and doses
The tablets should be swallowed whole. Taking the drug does not depend on food intake.
Adults.
The drug should be administered orally at a dose of 150 mg once.
Elderly patients.
In the absence of signs of renal dysfunction, the usual adult dose should be used to treat this category of patients.
Kidney dysfunction.
Fluconazole is excreted mainly in the urine unchanged. With a single dose of the drug, dose adjustment is not required for this category of patients.
Liver dysfunction.
Fluconazole should be used with caution in patients with impaired liver function, as there is insufficient information on the use of fluconazole in this category of patients.
Children
The efficacy and safety of fluconazole for the treatment of genital candidiasis in children have not been established, despite comprehensive data on the use of the drug. If there is an urgent need for the drug in adolescents (aged 12 to 17 years), the usual adult doses should be used.
Overdose
There have been reports of overdose with fluconazole; hallucinations and paranoid behavior have also been reported.
In case of overdose, symptomatic supportive therapy should be carried out and, if necessary, gastric lavage should be performed.
Fluconazole is largely excreted in the urine; forced diuresis may accelerate drug elimination. A 3-hour hemodialysis session reduces plasma fluconazole levels by approximately 50%.
Adverse reactions
From the blood and lymphatic system: anemia, agranulocytosis, leukopenia, neutropenia, thrombocytopenia.
Immune system disorders: anaphylaxis.
Metabolic and nutritional disorders: decreased appetite, hypertriglyceridemia, hypercholesterolemia, hypokalemia.
From the psyche: insomnia, drowsiness.
From the nervous system: headache, convulsions, dizziness, paresthesia, taste disturbance, tremor.
From the side of the organs of hearing and vestibular apparatus: vertigo.
Cardiac: paroxysmal ventricular tachycardia of the "pirouette" type, prolongation of the QT interval.
Gastrointestinal: abdominal pain, diarrhea, nausea, vomiting, constipation, dyspepsia, flatulence, dry mouth.
From the hepatobiliary system: increased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, cholestasis, jaundice, increased bilirubin levels, liver failure, hepatocellular necrosis, hepatitis, hepatocellular damage.
Skin and subcutaneous tissue disorders: rash, pruritus, drug dermatitis (including fixed drug dermatitis), urticaria, increased sweating, toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, exfoliative dermatitis, angioedema, facial edema, alopecia.
Musculoskeletal and connective tissue disorders: myalgia.
General disorders and administration site conditions: fatigue, malaise, asthenia, fever.
Children.
The frequency and nature of adverse reactions and laboratory abnormalities in clinical trials in children are comparable to those in adults.
Expiration date
3 years.
Storage conditions
In the original packaging at a temperature not exceeding 30 ° C. Keep out of the reach of children.
Packaging
2 tablets with a dosage of 150 mg in a blister; 1 blister in a cardboard pack.
Vacation category
Without a prescription.
Producer
PrJSC "Technolog".
Location of the manufacturer and its business address
Ukraine, 20300, Cherkasy region, Uman city, Stara Prorizna Street, building 8.
