for medical use
active substance: fluconazole;
1 tablet contains fluconazole 150 mg;
excipients: lactose monohydrate, microcrystalline cellulose, povidone K30, talc, magnesium stearate, sodium starch (type A), sodium croscarmellose.
Pharmaceutical form. Tablets.
Basic physico-chemical properties: white, round beveled edge tablets, with a break-line on one side.
Pharmacotherapeutic group. ATC code. Antimycotics for systemic use. Triazole derivatives. ATC code J02A C01.
Mechanism of action.
Fluconazole, antifungal agent of the triazole class, is a potent selective inhibitor of fungal enzymes that are necessary for the synthesis of ergosterol. Its primary mechanism of action is inhibition of fungal lanosterol 14 alpha-demethylation mediated by cytochrome P450, which is an essential step in fungal ergosterol biosynthesis. The accumulation of 14 alpha-methyl sterols correlates with the subsequent loss of ergosterol of fungal cell membrane and may be responsible for the antifungal activity of fluconazole. Fluconazole is more selective to fungal cytochrome P450 enzymes than for various cytochrome P450 enzymes of mammals.
The use of fluconazole at a dose of 50 mg per day for 28 days does not affect testosterone plasma levels in men or the level of endogenous steroids in women of reproductive age. Fluconazole at a dose of 200-400 mg per day shows no clinically significant effect on endogenous steroid levels or on response to ACTH stimulation in healthy male volunteers.
Study of interaction with antipyrine has shown that a single or repeated dose of 50 mg of fluconazole has no effect on the metabolism of antipyrine.
Susceptibility in vitro.
Fluconazole in vitro shows antifungal activity against species Candida that are most common (including C.albicans, C.parapsilosis, C.tropicalis). C.glabrata demonstrates a wide range of susceptibility to fluconazole, while C.krusei is resistant to it.
Also, fluconazole in vitro shows activity against Cryptococcus neoformans and Cryptococcusgattii, and against the endemic molds Blastomices dermatitidis, Coccidioides immitis, Histoplasma capsulatum and Paracoccidioides brasiliensis.
Pharmacodynamics – Pharmacokinetics.
According to the results of animal studies, there is a correlation between the minimum inhibitory concentration and efficacy against experimental models of mycoses, caused by Candida species. According to the clinical trial results, there is a linear dependence between the AUC and the dose of fluconazole (approximately 1:1). Also, there is a direct, but insufficient connection between the dose and AUC or a positive clinical response to an oral candidiasis treatment and to a lesser extent of candidemia. Similarly, the treatment of infections, caused by strains to which fluconazole demonstrates a high minimum inhibitory concentration, is less satisfactory.
Microorganisms of Candida genus demonstrate multiple mechanisms of resistance to azole antifungal agents. Fluconazole demonstrates high minimum inhibitory concentration against strains of fungi, which have one or more mechanisms of resistance, which have negative effect on efficacy in vivo and in clinical practice. It has been reported about cases of Candida spp. superinfection, other than C. Albicans species, that are often unsusceptible to fluconazole (e.g. Candida krusei). To treat such cases, alternative antifungals should be used.
Fluconazole has similar pharmacokinetic properties when used intravenously and orally.
Fluconazole is well absorbed after an oral use, and the drug level in plasma and systemic bioavailability exceed 90% of plasma level of fluconazole in, which is achieved by intravenous administration of the drug. Concomitant food intake has no effect on the absorption of the drug when oral administration. A peak plasma concentration is reached within 0.5-1.5 hours after the drug administration. The drug concentration in plasma is proportional to the dose. Equilibrium concentration of 90% is achieved on the second day of treatment when a loading dose, which is double the usual daily dose, was used on the first day.
The volume of distribution is approximately equal to the total content of body fluids. Binding to plasma proteins is low (11-12%).
Fluconazole penetrates well into all body fluids that are studied. The level of fluconazole in saliva and sputum is similar to the drug plasma concentration. The level of fluconazole in saliva and sputum are similar to the concentration of drug in blood plasma. In patients with fungal meningitis, fluconazole level in the cerebrospinal fluid is 80% of its plasma concentration.
High concentrations of fluconazole in the skin, which exceed serum concentrations, are achieved in the stratum corneum, epidermis, dermis and sweat. Fluconazole accumulates in the stratum corneum.
Fluconazole is slightly metabolized. When radiolabeled dose administration, only 11% of fluconazole are excreted with the urine in a modified form. Fluconazole is a selective inhibitor of CYP2C9 and CYP3A4 isoenzymes and isoenzyme CYP2C19 inhibitor.
Half-life of fluconazole from plasma is about 30 hours. The major part of the drug is excreted by the kidneys, with 80% of the administered dose detected in the urine in unchanged form. Fluconazole clearance is proportional to creatinine clearance. Circulating metabolites were not detected.
The long plasma half-life of the drug makes possible its single administration for vaginal candidiasis, as well administration 1 time per week for other indications
In patients with severe renal insufficiency (glomerular filtration rate is
Changes in pharmacokinetics in elderly patients depend on the parameters of renal function.
Acute vaginal candidiasis when local therapy is not appropriate.
Candidal balanitis when local therapy is not appropriate.
Hypersensitivity to fluconazole, other azole compounds or to any of the drug excipients.
– Concomitant use of fluconazole and terfenadine in patients who use multiple doses of fluconazole 400 mg/day and more.
– Concomitant use of fluconazole and other drugs that prolong QT interval and are metabolized by the enzyme CYP3A4 (e.g. cisapride, astemizole, pimozide, quinidine and erythromycin).
Interaction with other medicinal products and other forms of interaction.
Coadministration of fluconazole and the following drugs is contraindicated.
Cisapride: there have been reports on cardiac adverse effects, including torsade de pointes recurrent ventricular tachycardia in patients using fluconazole and cipraside concomitantly. Concomitant use of fluconazole 200 mg 1 time day and cipraside 20 mg 4 times per day resulted in a significant elevation of cipraside level in blood plasma and in QT interval prolongation. Concomitant use of fluconazole and cipraside is contraindicated (see section “Contraindications”).
Terfenadine: because of the cases of severe cardiac arrhythmias caused by QTc interval prolongation, in patients using azole antifungal agents concomitantly with terfenadine, studies of these drugs have been conducted. When using fluconazole 200 mg per day, no QTc interval prolongation has been observed. The use of fluconazole 400 mg per day or more results in a significant increase in plasma level of terfenadine when using these drugs concomitantly. Concomitant use of fluconazole 400 mg or more with terfenadine is contraindicated (see section “Contraindications”). When using fluconazole at a dose less than 400 mg per day concomitantly with terfenadine, the patient’s condition should be closely monitored.
Astemizole: concomitant use of fluconazole and astemizole may decrease clearance of astemizole. The resulting increased plasma concentrations of astemizole can lead to QT interval prolongation and in rare cases to torsade de pointes recurrent ventricular tachycardia. Concomitant use of fluconazole and astemizole is contraindicated.
Pimozide and quinidine: concomitant use of fluconazole and pimozide or quinidine may result in inhibition of metabolism of pimozide or quinidine. Increases plasma concentrations of pimozide or quinidine may cause QT interval prolongation, and in rare cases it may lead to torsade de pointes recurrent ventricular tachycardia. Concomitant use of fluconazole and pimozide or quinidine is contraindicated.
Erythromycin:concomitant use of fluconazole and erythromycin potentially may lead to the increased risk of cardiotoxicity (prolonged QT interval, torsade de pointes recurrent ventricular tachycardia), and consequently to a sudden heart death. The use of combination of these two drugs is contraindicated.
Concomitant use of fluconazole with the following other medicinal products is not recommended.
Halofantrine: fluconazole can cause increased plasma concentrations of halofarine through inhibition of CYP3A4. Concomitant use of these medicinal agents may potentially lead to the increased risk of cardiotoxicity (QT interval prolongation, torsade de pointes recurrent ventricular tachycardia), and consequently to a sudden heart death. The use of combination of these two drugs should be avoided.
Concomitant use of fluconazole with the following other medicinal products requires caution and dosage adjustment.
Effect of other medicinal products on fluconazole.
Simultaneous food intake, cimetidine, antacids, as well as radiotherapy of the whole body part (for bone marrow transplantation) have no clinically significant effect on absorption of oral fluconazole.
Rifampicin: concomitant use of fluconazole and rifampicin resulted in AUC decrease by 25% and reduced half-life of fluconazole by 20%. Therefore, for patients using rifampicin, appropriateness of increasing the dose of fluconazole should be considered.
Effect of fluconazole on other medicinal products.
Fluconazole is a potent inhibitor of isozyme 2C9 cytochrome P450 (CYP) and a moderate inhibitor of CYP3A4. Fluconazole is also an inhibitor of isozyme CYP2S19. In addition to fixed and described interactions given below, there is a risk of an increase in plasma concentrations of other compounds metabolized by CYP2C9 and CYP3A4, when using them with fluconazole. Therefore, such a combination of drugs should be used with caution; along with this, it is necessary to carefully monitor the condition of patients. Due to the long half-life of fluconazole its inhibitory effect on enzymes persists for 4-5 days.
Alfentanil: concomitant use of fluconazole 400 mg and altenafil 20 µg/kg is accompanied by a two-fold increase in AUC10 (probably through inhibition of CYP3A). This makes necessary altenafil dose adjustment.
Amitriptyline, nortriptiline: fluconazole increases the effect of amitriptyline and nortriptiline. It is recommended to measure the concentrations of 5-nortriptyline and/or S-amitnptiline at initiation of the combination therapy and 1 week after its start. If necessary, the dosage of amitriptyline and nortriptiline may be adjusted.
AmphotericinВ: concomitant use of fluconazole and amphotericin B in infected mice with normal immunity and infected mice with compromised immunity has shown the following results: a mild additive antifungal effect when systemic infection C. albicans, absence of interaction in intracranial infection Cryptococcus neoformans and antagonism of two drugs in systemic infection A. fumigatus. Clinical significance of these results is unknown.
Anticoagulants: as with other azole antifungal agents, when using concomitantly fluconazole and warfarin, there have been reports on cases of bleeding (hematoma, nasal bleeding, gastrointestinal bleeding, hematuria and melena) at the background of prolonged prothrombin time. When using concomitantly fluconazole and warfarin, a two-fold increase in prothrombin time was observed, probably due to inhibition of metabolism of warfarin via CYP2C9. It is necessary to carefully monitor the prothrombin time in patients simultaneously using coumarin anticoagulants. Warfarin dosage adjustment might be necessary.
Short-acting benzodiazepines, such as midazolam, triazolam: administration of fluconazole after oral midazolam resulted in a significant increase in midazolam concentrations and enhanced psychomotor effects. Concomitant use of fluconazole 200 mg and midazolam 7,5 mg oral led to an increase in AUC and half-life 3.7 and 2.2 times respectively. The use of fluconazole 200 mg / day and oral triazolam 0.25 mg led to an increase in AUC and half-life 4.4 and 2.3 times respectively. When concomitant administration of fluconazole and triazolam potentiation and prolongation of triazolam effects have been observed.
If a patient receiving treatment course with fluconazole should be concomitantly administered benzodiazepine therapy, the dose of the latter should be reduced and the patient should be under careful medical supervision.
Carbamazepine: fluconazole inhibits metabolism of carbamazepine and causes increase in serum levels of carbamazepine by 30%. There is a risk of carbamazepine toxicity. Dosage adjustment may be necessary for carbamazepine depending on its concentration and effect.
Calcium channel blockers: some calcium antagonists (nifedipine, isradipine, amlodipine and felodipine) re metabolized by the enzyme CYP3A4. Fluconazole has the potential to increase the systemic exposure of calcium channel blockers. Careful monitoring of adverse reactions is recommended.
Celecoxib: when using concomitantly fluconazole (200 mg daily) and celecoxib (200 mg) Cmax and AUC of celecoxib increased by 68% and 134%, respectively. In concomitant administration of fluconazole and celecoxib, a two-fold reduction of celecoxib dose might be necessary.
Cyclophosphamide: concomitant use of cyclophosphamide and fluconazole leads to increased serum levels of bilirubin and creatinine. These drugs may be used concomitantly, taking into account the possible risk of increase in serum concentrations of bilirubin and creatinine.
Fentanyl: one lethal outcome of fentanyl intoxication due to the possible interaction between fentanyl and fluconazole has been reported. Fluconazole significantly shows down elimination of fentanyl. Increased fentanyl concentrations may lead to respiratory depression; therefore, the patient’s condition should be closely monitored. Fentanyl dosage correction may be necessary.
HMG-CoA reductase inhibitors: concomitant use of fluconazole and HMG-CoA reductase inhibitors that are metabolized by CYP3A4 (atorvastatin and simvastatin) or HMG-CoA reductase inhibitors that are metabolized by CYP2C9 (fluvastatin) increases the risk of myopathy and rhabdomyolysis. If the concomitant use of these drugs is necessary, the patient should be closely monitored for the symptoms of myopathy and rhabdomyolysis, creatinkinase levels should also be monitored. In case of significant increase in creatinkinase, as well as when myopathy/rhabdomyolysis is suspected or detected, the use of HMG-CoA reductase inhibitors should be stopped.
Immunosuppressive agents (e.g., cyclosporine, everolimus, tacrolimus and sirolimus).
Cyclosporine: fluconazole significantly increases concentration and AUC of cyclosporine. When using concomitantly fluconazole 200 mg/day and cyclosporine 2.7 mg/kg/day, a 1.8-fold increase in AUC of cyclosporine has been observed. These drugs may be used concomitantly on condition if the dose of cyclosporine is reduced taking into account its concentration.
Everolimus: fluconazole may increase the serum concentration of everolimus through CYP3А4inhibition.
Sirolimus: fluconazole increases the serum concentration of sirolimus probably by inhibiting metabolism of sirolimus by the enzyme CYP3A4 and P-glycoprotein. These drugs may be used concomitantly on condition of sirolimus dosage adjustment depending on the drug’s concentration and effect.
Tacrolimus: fluconazole may increase serum concentrations of tacrolimus up to 5-fold when it is used orally through inhibition of tacrolimus metabolism in the intestine by CYP3A4. When using tacrolimus intravenously, no changes in pharmacokinetics have been observed. Increased levels of tacrolimus are associated with nephrotoxicity. Oral doses of tacrolimus should be decreased depending on the concentration of tacrolimus.
Losartan: fluconazole inhibits conversion of losartan to its active metabolite (E-31 74). Constant monitoring of blood pressure in patients is recommended.
Methadone: fluconazole may increase serum methadone concentrations. When using concomitantly methadone and fluconazole, methadone dosage adjustment might be necessary.
Nonsteroidal anti-inflammatory drugs: in concomitant administration with fluconazole, Cmax and AUC of flurbiprofen increased by 23% and 81% respectively compared to the corresponding indices when using only flurbiprofen. Similarly, when using concomitantly fluconazole and racemic ibuprofen (400 mg), Cmax and AUC of the pharmacologically active isomer S-(+)-ibuprofen increased by 15% and 82% respectively, compared to the corresponding indices when using only racemic ibuprofen.
Fluconazole has the potential to increase the systemic exposition of other NSAIDs, which are metabolized by CYP2C9 (e.g., naproxen, lornoxicam, meloxicam, diclofenac). Periodical monitoring of adverse reactions and toxicity manifestations associated with NSAIDs is recommended. NSAIDs dosage adjustment may be necessary.
Phenytoin: fluconazole suppresses metabolism of phenytoin in the liver. Concomitant repeated administration of fluconazole 200 mg and phenytoin 250 mg intravenously results in the increased AUC24 of phenytoin by 75% and Сmin by 128%. When using concomitantly these two drugs, phenytoin serum concentrations should be monitored to avoid the toxic effect of phenytoin.
Prednisone: there is a report of a case where patient after liver transplantation during treatment with prednisone developed acute failure of the adrenal cortex, which occurred three months after cessation of therapy with fluconazole. Withdrawal of fluconazole probably resulted in the increased activity of CYP3A4 which lead to accelerated metabolism of prednisone. Careful monitoring is recommended for patients who use fluconazole and prednisone for a long time, to prevent the development of failure of the adrenal cortex after withdrawal of fluconazole.
Rifabutin: fluconazole increases serum concentration of rifabutin resulting in the increase of rifabutin AUC by up to 80%. When using concomitantly fluconazole and rifabutin, cases of uveitis have been reported. When using such a combination of drugs, the symptoms of toxic effect of rifabutin should be taken into account.
Saquinavir: fluconazole increases AUC and Cmax of saquinavir approximately by 50% and 55%, respectively, through inhibition of saquinavir metabolism in the liver by the enzyme CYP3A4 and through inhibition of P-glycoprotein. Interaction between fluconazole and saquinavir/ritonavir has not been studied, therefore they may be more pronounced. Saquinavir dosage adjustment may be necessary.
Sulfonylurea derivatives: concomitant use of fluconazole with oral sulfonylurea derivatives (chlorpropamide, glibenclamide, glipizide and tolbutamide) resulted in their half-life prolongation. It is recommended to control blood sugar frequently and accordingly recuse the dose of sulfonylurea derivatives when used concomitantly with fluconazole.
Theophylline: the use of fluconazole 200 mg for 14 days resulted in decreased mean plasma clearance of theophylline by 18%. Patients using theophylline at high doses or having increased risk of toxic manifestations of theophylline for other reasons should be monitored for the signs toxic effect of theophylline. The therapy should be changed if the signs of toxicity occur.
Vinca alkaloids: fluconazole, probably through CYP3A4 inhibition, may cause increased plasma concentrations of vinca alkaloids (e.g., vincristine and vinblastine), which lead to the development of neurotoxic effects.
Vitamin A: it has been reported that a patient who used concomitantly transretinic acid (acid form of vitamin A) and fluconazole had CNS adverse reactions in the form of pseudotumour cerebri, which disappeared after discontinuation of fluconazole treatment. This combination may be used but the incidence of CNS related undesirable effects should be kept in mind
Voriconazole (CYP2C9 and CYP3A4 inhibitor): concomitant use of oral voriconazole (400 mg every 12 hours during 1 day, then 200 mg every 12 hours during 2.5 days) and oral fluconazole (400 mg in the first day, then 200 mg every 24 hours during 4 days) resulted in increased Сmax and AUCτ of voriconazole on average by 57% (90% CI: 20%, 107%) and 79% (90% CI: 40%, 128%), respectively. It is unknown whether reduction of the dose and/or frequency of the use of voriconazole or fluconazole to disappearance of such effect. When using voriconazole after fluconazole, the development of voriconazole- associated adverse effects should be monitored.
Zidovudine: fluconazole increases Сmax and AUC of zidovudine by 84 % and 74 % respectively, which is due to the reduced clearance of zidovudine by approximately 45%, when used orally. The half-life of zidovudine was prolonged approximately by 128% after the use of the combination of fluconazole and zidovudine. The patients using such drug combination should be monitored for the development of zidovudine-associated adverse reactions. Appropriateness of zidovudine dose reduction may be considered.
Azithromycin: when using concomitantly a single dose of azithromycin and fluconazole of 1200 mg and 800 mg, respectively, no significant pharmacokinetic interactions have been detected.
Oral contraceptives: when using fluconazole 50 mg, there was no effect on the level of hormones, while when using fluconazole 200 mg per day, increase in AUC of ethinyl estradiol by 40% and of levonorgestrel by 24% was observed. This indicated that repeated use of fluconazole at the indicated doses is unlikely to affect the efficacy of the combined oral contraceptive.
Dermatomycosis. It is known that when using fluconazole for treatment of dermatomycosis in children, efficacy of the latter does not exceed that of griseofulvin, and the overall efficacy index is less than 20%. Therefore, fluconazole should not be used for treatment of dermatomycosis.
Cryptococcosis. The evidence of efficacy of fluconazole for treatment of cryptococcosis of other locations (e.g., pulmonary cryptococcosis and skin cryptococcosis) is insufficient; therefore, there are no recommendations on the dosage regimen for treatment in such situations.
Deep endemic mycosis. The evidence of efficacy of fluconazole for treatment of other forms of endemic mycoses, such as paracoccidioidomycosis, histoplasmosis and cutaneous lymphatic sporotrichosis, is insufficient, therefore, there are no recommendations on the dosage regimen for treatment of such diseases.
Rena system. Patients with impaired renal functions should take the drug with caution (see section “Dosage and administration”).
Hepatobiliary system. Patients with impaired hepatic function should use the drug with caution. The use of fluconazole was associated with rare cases of severe hepatotoxicity, including lethal cases, mainly in patients with severe underlying diseases. In cases when development of hepatotoxicity was associated with the use of fluconazole, no obvious dependence on the total daily dose of the drug, treatment duration, age or sex of the patient has been marked. Usually fluconazole-induced hepatotoxicity is reversible, and its manifestations disappear after discontinuation of therapy.
The patients having deviations in liver function tests when using fluconazole should be under careful observation for the development of a more severe liver lesion.
The patients should be informed about the symptoms that may indicate a serious impact on the liver (pronounced asthenia, anorexia, constant nausea, vomiting and jaundice). In such case, the use of fluconazole should be stopped immediately and medical attention should be sought.
Cardiovascular system. Some azoles, including fluconazole, are associated with QT interval prolongation on electrocardiogram. Very rare cases of QT interval prolongation and torsade de pointes recurrent ventricular tachycardia have been reported when using fluconazole. These reports referred to the patients with severe diseases and several risk factors, such as structural heart diseases, electrolyte exchange violations and concomitant use of other medicinal agents that effect QT interval.
Fluconazole should be used with caution in patients at risk of arrhythmia. Concomitant use with other medicinal agents that prolong QTc interval and are metabolized with cytochrome P450enzyme CYP3А4 is contraindicated.
Halofantrine. Halofantrine is a substrate of the enzyme CYP3А4 and prolongs QTc interval when used in recommended therapeutic doses. Concomitant use of halofantrine and fluconazole is not recommended.
Dermatological reactions. When using fluconazole, there have been seldom reports on development of such exfoliative skin reactions as Stevens-Johnson’s syndrome and toxic epidermal necrolysis. Patients with AIDS are more likely to develop serious skin reactions when using many medicinal agents. If a patient with superficial fungal infection has rash, which can be associated with the use of fluconazole, further use of the drug should be discontinued. If a patients with invasive/systemic fungal infection has skin rash, his condition should be carefully observed, and in case of bullous rash or erythema multiforme, the use of fluconazole should be stopped.
Hypersensitivity. In rare cases there have been reports of anaphylactic reactions.
Cytochrome P450. Fluconazole is a potent inhibitor of CYP2C9 enzyme and moderate inhibitor of CYP3А4 enzyme. Fluconazole is also an inhibitor of CYP2C19 enzyme. Patients taking concomitantly fluconazole and the drugs with narrow therapeutic windows that are metabolized with CYP2C9, CYP2C19 and CYP3A4 should be closely monitored.
Terfenadine. The patient’s condition should be closely monitored when using concomitantly terfenadine and fluconazole at a dose less than 400 mg per day.
The drug contains lactose. The patients with rare hereditary diseases, such as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not use this drug.
Use during pregnancy or breastfeeding.
The data received when single and repeated use of fluconazole at usual doses (< 200 mg/day) in several hundreds of pregnant women during the I trimester of pregnancy, did not reveal any adverse effects on the fetus. Numerous congenital defects have been in newborns (including bradyphrenia, dysplasia of the ear, bulging anterior fontanelle, deformation of the hip, humeroulnar synostosis) whose mother used high dosed of fluconazole (400-800 mg/day) during at least three or more months for treatment of coccidioidomycosis. The connection between the use of fluconazole and these cases has not been determined.
Animal studies have shown reproductive toxicity.
Do not use usual doses of fluconazole and short-term treatment courses with fluconazole during pregnancy, unless it is absolutely necessary.
Do not use high doses of fluconazole and/or long-term treatment courses with fluconazole during pregnancy, except for treatment of infections that are potentially life-threatening.
Fluconazole penetrates into the breast milk and reaches a concentration, lower than that in blood plasma. Breast feeding may be continued after a single use of a usual dose of fluconazole, which is 200 mg or less.
Breast feeding is not recommended during repeated use of fluconazole or when using high doses of fluconazole.
Effects on ability to drive and use machines.
There have been no studies conducted on the effect of fluconazole on the ability to drive motor transport or work with other mechanisms.
The patients should be informed about the possibility of dizziness or seizures during the use of the drug. If such symptoms develop, it is not recommended to drive motor transport or work with other mechanisms.
Dosage and administration.
The drug is for oral use. Drug administration does not depend on meals.
Use a single 150 mg dose of the drug.
In the absence of signs of renal dysfunction, the usual adult dose should be used for treatment of this category of patients.
Fluconazole is excreted mainly in the urine, unchanged. When using a single dose of fluconazole, dosage adjustment is not required for this category of patients.
Fluconazole should be used with caution in patients with hepatic dysfunction, since information on the use of fluconazole in this category of patients is insufficient.
Efficacy and safety of use of the drug for treatment of genital candidiasis in children have not been established, despite of extensive data on use of fluconazole in children. If there is absolute necessity of using the drug in adolescents (aged from 12 to 17 years), usual adult doses should be used.
Symptoms: hallucinations and paranoid behavior.
Treatment: symptomatic (including gastric lavage and maintenance therapy). Fluconazole is mainly excreted in the urine; therefore forced diuresis can accelerate excretion the drug. Hemodialysis session lasting 3 hours decreases the level of fluconazole approximately by 50%.
Blood and lymphatic system: anemia, agranulocytosis, leukopenia, neutropenia, thrombocytopenia.
Immune system: anaphylaxis.
Metabolic and nutritional disorders: loss of appetite, hypertriglyceridemia, hypercholesterolemia, hypokalemia.
Mental disorders: insomnia, drowsiness.
Nervous system: headache, convulsions, dizziness, paresthesia, taste disorder, tremor.
Organs of hearing and vestibular apparatus: vertigo.
Heart: including torsade de pointes recurrent ventricular tachycardia, QT interval prolongation.
Gastrointestinal tract: abdominal pain, diarrhea, nausea, vomiting, constipation, dyspepsia, flatulence, dry mouth.
Hepatobiliary disorders: increased level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, cholestasis, jaundice, increased bilirubin, liver failure, hepatocellular necrosis, hepatitis, hepatocellular lesions.
Skin and subcutaneous tissue: rash, itching, drug-induced dermatitis, urticaria, increased sweating, toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, exfoliative dermatitis, angioedema, face edema, alopecia.
Musculoskeletal system and connective tissue: myalgia.
General disorders and reactions at the site of administration: increased fatigability, malaise, asthenia, fever.
The frequency and nature of adverse events and deviations from the norm in the laboratory test results are comparable to those of adults.
Shelf life. 3 years.
Store at temperatures not more than 25°С
Keep out of reach of children.
1 tablet is in a blister in a carton package.
Conditions of supply.
KUSUM HEALTHCARE PVT LTD.
SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.