Fluconazole-Sandoz - instructions for use, dose, side effects, contraindications

active substance: fluconazole - 50.0 mg; auxiliary substances: lactose monohydrate - 48.75 mg, corn starch - 16.7 mg, magnesium stearate - 1.05 mg, silicon dioxide colloidal anhydrous - 0.125 mg, sodium lauryl sulfate - 0.125 mg; shell capsule: titanium dioxide - 1.33 mg, indigo carmine dye FD & C blue 2 - 0.0167 mg, gelatin - 36.653 mg. Dosage of 100 mg:

active substance: fluconazole - 100.0 mg; auxiliary substances: lactose monohydrate - 97.5 mg, corn starch - 33.4 mg, magnesium stearate - 2.10 mg, silicon dioxide colloidal anhydrous - 0.25 mg, sodium lauryl sulfate - 0.25 mg; shell capsule: titanium dioxide - 1.83 mg, indigo carmine dye FD & C blue 2 - 0.0813 mg, gelatin - 59.089 mg. Dosage of 150 mg

active substance: fluconazole - 150.0 mg; auxiliary substances: lactose monohydrate - 146.25 mg, corn starch - 50.10 mg, magnesium stearate - 3.15 mg, silicon dioxide colloidal anhydrous - 0.375 mg, sodium lauryl sulfate - 0.375 mg; shell capsule: titanium dioxide - 1.52 mg, gelatin - 74.48 mg.

Dosage 200 mg

active substance: fluconazole - 200.0 mg; auxiliary substances: lactose monohydrate - 195.0 mg, corn starch - 66.8 mg, magnesium stearate - 4.2 mg, silicon dioxide colloidal anhydrous - 0.5 mg, sodium lauryl sulfate - 0.5 mg; shell capsule: titanium dioxide - 2.88 mg, dye indigo carmine FD & C blue 2 - 0.0845 mg, dye crimson [Ponso 4R] - 0.144 mg, gelatin - 92.892 mg.

Composition of ink for the marking of capsules: iron (III) dye oxide E172 black.

Description:

Description: hard gelatin snap capsules.

Dosage 50 mg

The cover is blue, the body is white with the inscription FC 50 black.

Dosage of 100 mg

The cover is blue, the body is white with the inscription FC 100 black.Dosage 150 m

The cover and the body of white color with the inscription FC 150 black.

Dosage 200 mg

The lid is purple, the body is white with the inscription FC 200 black.

The contents of capsules are white powder odorless.

Pharmacotherapeutic group:Antifungal agent.

ATX: & nbsp

J.02.A.C Triazole derivatives

J.02.A.C.01 Fluconazole

Pharmacodynamics:

Fluconazole, a representative of the class of triazole antifungal agents, is a potent selective inhibitor of the 14-a-demethylase fungal enzyme. FIpenapaT inhibits the transition of lanosterol to ergosterol, the main component of cell membranes of fungi, which leads to an increase in the permeability of the cell membrane, disruption of its growth and replication.

Fluconazole, being highly selective for cytochrome P450 fungi, practically does not inhibit these enzymes in the human body (in comparison with itraconazole, clotrimazole, econazole and ketoconazole less inhibits oxidative processes dependent on cytochrome P450 in human liver microsomes). Does not have antiadrogenic activity. The drug is effective in opportunistic fungal infections, incl. caused by Candida spp.(Candida albicans, Candida tropicalis), Cryptococcus neoformans, Microsporum spp., Trichophyton spp. Also shown is the activity of fluconazole on models of endemic mycoses, including infections caused by Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum.

Pharmacokinetics:

After oral administration fluconazole it is well absorbed, its bioavailability is 90%. The maximum concentration (Cmax) after ingestion, fasting 150 mg is 90% of the blood plasma level when administered intravenously at a dose of 2.5 to 3.5 mg / kg. Simultaneous food intake does not affect the absorption of the drug taken internally. The concentration in the blood plasma reaches a peak after 0.5-1.5 h (TCmax) after administration. Concentrations in the blood plasma are in direct proportion to the dose. 90% level of equilibrium concentration is achieved by 4-5 days of treatment with the drug (with the use of 1 time / day).

The use on the first day of a dose, 2 times higher than the usual daily dose, makes it possible to achieve a drug concentration in the blood plasma equal to 90% of the equilibrium concentration value by the second day. The apparent volume of distribution approximates the total volume of water in the body. Binding to blood plasma proteins is small -11-12%.

Fluconazole well penetrates into all body fluids, including cerebrospinal fluid. Concentrations of the drug in saliva and sputum are similar to those in blood plasma.In patients with fungal meningitis, the fluconazole content in the cerebrospinal fluid reaches 80% of its concentration in the blood plasma.

In the stratum corneum, the epidermis, the dermis and the sweat fluid, high concentrations are reached that exceed the serum levels.

Less than 5% of fluconazole is metabolized by the "first pass" through the liver. The half-life (T1 / 2) of fluconazole is about 30 hours. Prolonged T1 / 2 allows the use of a single dose of the drug for the treatment of vaginal candidiasis and provides the drug once a day for other indications. Fluconazole is excreted mainly by the kidneys; approximately 80% of the administered dose is excreted by the kidneys unchanged. The clearance of fluconazole is proportional to the creatinine clearance. Metabolites of fluconazole in peripheral blood were not detected.

Indications:

cryptococcosis, including cryptococcal meningitis and other localizations of this infection (including lungs, skin), both in patients with normal immune response, and in patients with various forms of immunosuppression (including those with AIDS, during transplantation bodies); the drug can be used to prevent cryptococcal infection in patients with AIDS;
generalized candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidiasis infections (peritoneal, endocardial, eye, respiratory and urinary tract infections). Treatment can be performed in patients with malignant neoplasms, patients in intensive care units, patients undergoing cytostatic or immunosuppressive therapy, and in the presence of other factors predisposing to the development of candidiasis;
Candidiasis of mucous membranes, incl. oral cavity and pharynx (including atrophic candidiasis of the oral cavity, associated with the wearing of dentures), esophagus, non invasive bronchopulmonary candidiasis, candiduria, candidiasis of the skin; prevention of recurrence of oropharyngeal candidiasis in patients with AIDS;
genital candidiasis: vaginal candidiasis (acute and chronic recurrent), preventive use to reduce the frequency of recurrences of vaginal candidiasis (3 or more episodes a year); Candidiasis balanitis;
prevention of fungal infections in patients with malignant neoplasms that are predisposed to such infections as a result of chemotherapy with cytostatics or radiation therapy;
mycosis of the skin, including mycosis of the feet, the body, the groin area; pityriasis lichen, onychomycosis; candidiasis of the skin;
Deep endemic mycoses, including coccidiomycosis and histoplasmosis in patients with normal immunity.

Contraindications:

hypersensitivity to fluconazole, other components of the drug, or other azole compounds;
simultaneous administration of drugs prolonging the QT interval and increasing the risk of severe rhythm disturbances or metabolized by the isoenzyme CYP3A4, such as terfenadine (when combined with fluconazole dosages 400 mg / day and higher), cisapride, astemizole, pimozide, quinidine, erythromycin, voriconazole;
rare hereditary diseases, such as galactose intolerance, lactase deficiency, glucose-galactose malabsorption;
lactation period;
Children under 3 years old (for this dosage form).

Carefully:

hepatic and / or renal failure, the appearance of a rash against the background of fluconazole in patients with superficial fungal infection and invasive / systemic fungal infections, simultaneous use with rifabutin or other drugs metabolized by the cytochrome P450 system,simultaneous reception of terfenadine and fluconazole at a dose of less than 400 mg / day, potentially proaritmogenic conditions in patients with multiple risk factors (organic heart disease, electrolyte balance disorders, simultaneous intake of drugs causing arrhythmias), patients with intolerance to acetylsalicylic acid, pregnancy.

Pregnancy and lactation:

The use of the drug during pregnancy is not advisable, except for severe or life-threatening forms of fungal infections, if the intended benefit to the mother exceeds the possible risk to the fetus.

Fluconazole is found in breast milk in the same concentration as in blood plasma, so its use during breastfeeding is contraindicated.

Dosing and Administration:

Inside. Capsules swallow whole. The daily dose depends on the nature and severity of the fungal infection.

Adults with cryptococcal meningitis and cryptococcal infections of other locations on the first day usually prescribed 400 mg, and then continue treatment at a dose of 200 to 400 mg once a day. The duration of treatment for cryptococcal infections depends on clinical effectiveness,confirmed by mycological research; in cryptococcal meningitis, it is usually continued for at least 6-8 weeks.

To prevent the recurrence of cryptococcal meningitis in patients with AIDS, after completing the full course of primary care, fluconazole prescribe at a dose of 200 mg / day for a long period of time.

With candidemia, disseminated candidiasis and other invasive candidiasis infections, the dose is usually 400 mg on the first day, and then on 200 mg. With insufficient clinical efficacy, the dose of the drug can be increased to 400 mg / day; at a severe systemic

candidiasis - it is possible to increase the dose to 800 mg per day. The duration of therapy depends on clinical effectiveness. Treatment should continue at least 2 weeks after receiving negative blood cultures or after the disappearance of symptoms of the disease.

With oropharyngeal candidiasis, the drug is usually prescribed 50-100 mg once a day; duration of treatment - 7 - 14 days. If necessary, in patients with a marked decrease in immunity, treatment may be longer (3 weeks).

With atrophic candidiasis of the oral cavity, associated with the wearing of dentures, fluconazole usually prescribed 50 mg 1 time / day for 14 days in combination with local antiseptic agents for prosthesis treatment.

In other cases of candidiasis (with the exception of genital candidiasis), for example, with esophagitis, non invasive bronchopulmonary disease, candiduria, candidiasis of the skin and mucous membranes, etc., the effective dose is usually 50-100 mg / day with a treatment duration of 14-30 days ; with severe mucous candidiasis - 100 - 200 mg / day. To prevent the recurrence of oropharyngeal candidiasis in patients with AIDS after completing a full course of primary therapy, the drug can be prescribed 150 mg once a week.

With vaginal candidiasis fluconazole taken once inside the dose of 150 mg. To reduce the frequency of recurrences of vaginal candidiasis, the drug can be used at a dose of 150 mg once a month. The duration of therapy is determined individually; it varies from 4 to 12 months. Some patients may require more frequent use.

With balanitis caused by Candida, fluconazole appoint a single dose of 150 mg orally.

For the prevention of candidiasis, the recommended dose of fluconazole is 50 - 400 mg 1 time / day, depending on the degree of risk of fungal infection.If there is a high risk of generalized infection, for example, in patients with expected severe or persistent neutropenia, the recommended dose is 400 mg 1 time / day. Fluconazole appoint a few days before the expected appearance of neutropenia; after increasing the number of neutrophils more than 1000 / mm3 treatment is continued for another 7 days.

In skin mycoses, including foot mycoses, inguinal skin, and skin candidiasis, the recommended dose is 150 mg once a week or 50 mg once a day. Duration of therapy in usual cases is 2-4 weeks, however, with foot mycoses, longer therapy (up to 6 weeks) may be required.

With pityriasis 300 mg once a week for 2 weeks, some patients require a third dose of 300 mg per week, while in some cases a single 300-400 mg intake is sufficient; an alternative treatment regimen is to administer 50 mg once a day for 2-4 weeks.

With onychomycosis, the recommended dose is 150 mg once a week. Treatment should continue until the replacement of the infected nail (growth of uninfected nail). For the repeated growth of the nails on the fingers and toes normally it takes 3-6 months and 6 - 12 months, respectively.

With deep endemic mycoses, it may be necessary to use the drug at a dose of 200 to 400 mg / day for up to 2 years. The duration of therapy is determined individually; it can be 11-24 months with coccidiomycosis; 2-17 months with paracoccidiosis; 1-16 months with sporotrichosis and 3 - 17 months with histoplasmosis.

In children, as with similar infections in adults, the duration of treatment depends on the clinical and mycological effect. In children, the drug should not be used in a daily dose that would exceed that of adults. The drug is used daily 1 time / day.

In mucosal candidiasis, the recommended dose of fluconazole is 3 mg / kg / day. On the first day, an initial loading dose of 6 mg / kg can be assigned to achieve a more rapid equilibrium equilibrium concentration.

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

For the prevention of fungal infections in children with reduced immunity, at which the risk of infection is associated with neutropenia, resulting from cytotoxic chemotherapy or radiation therapy,the drug is prescribed at 3-12 mg / kg / day, depending on the severity and duration of preservation of induced neutropenia.

The maximum daily dose for children is 12 mg / kg.

Due to the fact that it is not always possible to provide the required dosage regimen in mg / kg, it is recommended for children to use the drug in the form of other dosage forms.

Dosing for patients with renal insufficiency

Fluconazole is excreted mainly by the kidneys in unchanged form. With a single admission, a dose change is not required. In patients (including children) with renal dysfunction in repeated use of the drug, an initial dose of 50 to 400 mg should be initially administered, after which the daily dose (depending on the indications) is set according to the following table:

Creatinine clearance (ml / mol)	Percent recommended dose
>50	100%
<50 (without dialysis)	50%
regular dialysis	100% after each dialysis

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 degree of renal insufficiency.

In elderly patients in the absence of violations of kidney function should follow the usual dosage regimen.

Side effects:

According to the World Health Organization (WHO), adverse reactions are classified according to their frequency of development as follows: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, < 1/100), rarely (> 1/10000, <1/1000) and very rarely (<1/10000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

From the side of the immune system: rarely: anaphylactic reactions.

From the hemopoietic system: infrequently: anemia;

rarely: agranulocytosis, leukopenia, thrombocytopenia, neutropenia.

From the nervous system: often: headache;

infrequently: dizziness, impaired taste, cramps, insomnia,

paresthesia, drowsiness; rarely: a tremor.

From the senses: infrequently: vertigo.

From the cardiovascular system:

often: prolongation of the QT interval, polymorphic ventricular tachycardia of the "pirouette" type.

From the gastrointestinal tract:

often: pain in the abdominal cavity, diarrhea, nausea, vomiting;

infrequently: indigestion, constipation, flatulence, dry mouth.

From the liver and bile ducts:

often: increased activity of "liver" transaminases, increased activity of alkaline phosphatase;

infrequently: increased bilirubin concentration, congestion of the biliary tract, jaundice;

rarely: hepatic insufficiency, hepatocellular necrosis, hepatitis, hepatotoxicity, in some cases with a fatal outcome, impaired liver function, hepatocellular damage.

From the side of metabolism:

rarely: increased concentration of cholesterol and triglycerides in blood plasma, hypokalemia.

From the skin: often: rash;

infrequently: skin itching, urticaria, edema, drug-induced rash,

increased sweating;

rarely: toxic epidermal necrolysis, Stevens-Johnson syndrome, angioedema, facial edema, alopecia, dermatitis, acute generalized exanthematous pustulosis.

From the musculoskeletal and connective tissue: infrequently: myalgia;

Other:

infrequently: fatigue, asthenia, anxiety, weakness, fever.

Overdose:

Symptoms: nausea, vomiting, diarrhea, in severe cases, convulsions, hallucinations, paranoid behavior may occur.

Treatment: symptomatic, gastric lavage; since fluconazole

excreted by the kidneys it is recommended forced diuresis. Hemodialysis within 3 hours reduces the concentration of fluconazole in blood plasma by 2 times.

Interaction:

The following interactions are established with repeated application of fluconazole; interactions with drugs as a result of a single administration of fluconazole are not known. When fluconazole is used concomitantly with other drugs, the following drug interactions are possible:

the interaction of fluconazole with terfenadine (when combined with doses of fluconazole 400 mg / day and above), cisapride and astemizole may lead to an increase in the concentration of these drugs in the blood plasma, which in turn may cause prolongation of the QT interval and lead to serious heart rhythm disturbances. Fluconazole inhibits the enzymes of the P450 system in the liver, thereby reducing the metabolism of terfenadine, cisapride and astemizole. The combined use of fluconazole with terfenadine (when combined with doses of fluconazole 400 mg / day and above), cisapride and astemizole is contraindicated. When using terfenadine and fluconazole at doses below 400 mg / day, patients should be closely monitored.

with the combined use of warfarin and fluconazole prolonged prothrombin time. In this regard, it is necessary to monitor prothrombin time in patients simultaneously receiving fluconazole and anticoagulants of the coumarin series.

Fluconazole prolongs Ti / 2 oral hypoglycemic drugs (sulfonylurea derivatives). Patients with diabetes mellitus can simultaneously be prescribed fluconazole and derivatives of sulfonylureas, however, it is necessary to take into account the possible risk of developing hypoglycemia.

it is necessary to take into account that with the repeated simultaneous use of hydrochlorothiazide and fluconazole, the concentration of fluconazole in the blood plasma increases.

rifampicin accelerates the metabolism of fluconazole. It is necessary to increase the dose of fluconazole accordingly during their simultaneous use.

in patients who underwent renal transplantation, fluconazole can increase the concentration of cyclosporine in the blood plasma. In this regard, it is recommended to monitor the concentration of cyclosporine in patients simultaneously receiving ciclosporin and fluconazole.

fluconazole increases the concentration of theophylline in the blood plasma. In this regard, it is recommended to monitor the concentration of theophylline in patients simultaneously receiving theophylline and fluconazole.

fluconazole can increase the concentration in the blood plasma of indinavir and midazolam. With the simultaneous use of these drugs with fluconazole, their doses should be appropriately reduced.

Clinical studies have shown that as a result of slowing the metabolism of zidovudine, its concentration in blood plasma can be increased with simultaneous application with fluconazole. It is necessary to monitor patients who are simultaneously receiving both of these drugs, since in this case, the incidence of side effects of zidovudine may increase.

fluconazole increases serum concentrations of phenytoin. With simultaneous use, it is necessary to monitor the doses of phenytoin and adjust them accordingly.

rifabutin: simultaneous application of fluconazole and rifabutin can lead to an increase in serum concentrations of the latter up to 80%. With the simultaneous use of fluconazole and rifabutin, cases of uveitis are described. Patients simultaneously receiving rifabutin and fluconazole, should be under close medical supervision.

increases the concentration of tacrolimus - the risk of nephrotoxicity.

fluconazole can increase concentration amitriptyline, nortriptyline. When combined, it is recommended that

monitor plasma concentrations of amitriptyline, nortriptyline, and adjust its dose.

benzodiazepines (short-acting): after ingestion of midazolam, fluconazole significantly increases the concentration of midazolam and psychomotor effects, and this effect is more pronounced after taking fluconazole orally than with its use intravenously. If concomitant therapy with benzodiazepines is required in patients taking fluconazole, should be monitored to assess the appropriateness of an appropriate dose reduction for benzodiazepine. while concurrent administration of a single dose of triazolam, fluconazole increases the AUC of triazolam by approximately 50%, Cmax by 25-50% and half-life by 25-50% due to inhibition of triazolam metabolism. You may need to adjust the dose of triazolam. fluconazole when combined with celecoxib leads to an increase in its concentration in the blood plasma,in connection with which the dose of celecoxib should be reduced by half.

inhibitors of HMG-CoA reductase: with simultaneous application

fluconazole with HMG-CoA reductase inhibitors metabolized by the CYP3A4 isoenzyme (such as, atorvastatin and simvastatin) or the isoenzyme CYP2D6 (such as, fluvastatin), the risk of developing myopathy and rhabdomyolysis increases. If it is necessary to simultaneously treat these drugs, patients should be observed to identify the symptoms of myopathy and rhabdomyolysis. It is necessary to monitor the concentration of creatinine kinase. In the case of a significant increase in the concentration of creatinine kinase, or if there is a diagnosis or suspected development of myopathy or rhabdomyolysis, therapy with HMG-CoA reductase inhibitors should be discontinued.

simultaneous application of fluconazole and losartan may lead to an increase in losartan concentration and a decrease in its concentration

active metabolite in the blood plasma. It is recommended that the blood pressure be monitored regularly in patients receiving this combination.

fluconazole may slow the metabolism of trimetrexate, leading to an increase in its concentration.In this regard, it is necessary to monitor the concentration of trimetrexate in the serum.

the simultaneous use of erythromycin and fluconazole is contraindicated, as the risk of cardiotoxicity (prolongation of the QT interval) increases, which can lead to sudden cardiac death.

because the fluconazole and non-steroidal anti-inflammatory drugs are metabolized by the cytochrome CYP2C29 system, when combined they may increase the risk of developing side effects of the latter, which may require adjusting their dose.

fluconazole may increase the concentration of drugs containing the alkaloid Barvinca (vinblastine, vincristine, vindesine), which can lead to an increased risk of neurotoxicity.

concomitant use with fentanyl may lead to lethal depressing of the respiratory center, since fluconazole reduces the elimination of fentanyl.

reduces the effectiveness of oral contraceptives.

pimozide: Despite the fact that no relevant

studies in vitro or in vivo, the simultaneous use of fluconazole and pimozide can lead to inhibition of the metabolism of pimozide.In turn, an increase in plasma concentrations of pimozide can lead to an extension of the QT interval and, in some cases, the development of a torsade de pointes ventricular tachysystolic type arrhythmia. Simultaneous use of pimozide and fluconazole is contraindicated.

quinidine: Despite the fact that no relevant

in vitro or in vivo studies, simultaneous use of fluconazole and quinidine may also lead to inhibition of quinidine metabolism. The use of quinidine is associated with prolongation of the QT interval and, in some cases, with the development of torsade de pointes, a ventricular tachysystolic type arrhythmia. Simultaneous use of quinidine and fluconazole is contraindicated. alfentanil: a decrease in clearance and volume of distribution, an increase in the half-life of alfentanil. Perhaps this is due to the inhibition of the isoenzyme CYP3A4 by fluconazole. Alfventanyl dosage adjustment may be required.

amphotericin B: in studies on mice (including

immunosuppression), the following results were noted: a slight additive antifungal effect in systemic infection caused by C.albicans, lack of interaction with intracranial infection caused by Cryptococcus neoformans and antagonism in systemic infection caused by A. fumigatus. The clinical significance of these results is not clear.

azithromycin: with the simultaneous administration of fluconazole in a single dose of 800 mg with azithromycin in a single dose of 1200 mg, no pronounced pharmacokinetic interaction between the two drugs has been established.

carbamazepine: fluconazole inhibits the metabolism of carbamazepine and

increases the serum concentration of carbamazepine by 30%. It is necessary to consider the risk of development of toxicity of carbamazepine. it is necessary to evaluate the need for correcting the dose of carbamazepine as a function of concentration / effect.

calcium channel blockers: some calcium channel antagonists (nifedipine, isradipine, amlodipine, verapamil and felodipine) are metabolized by the isoenzyme CYP3A4. Fluconazole increases the systemic exposure of calcium channel antagonists. It is recommended to control the development of side effects.

cyclophosphamide: with the simultaneous use of cyclophosphamide and

fluconazole increased serum concentrations

bilirubin and creatinine.This combination is risk-tolerant

increased concentrations of bilirubin and creatinine.

halofantrine: fluconazole may increase concentration

halofantrine in blood plasma in connection with inhibition of the isoenzyme

CYP3A4.

methadone: fluconazole can increase the plasma concentration of methadone. Methadone dose adjustment may be necessary. prednisone: there is a report on the development of acute adrenal insufficiency in the patient after liver transplantation with a fluconazole withdrawal after a three-month course of therapy. Presumably, discontinuation of fluconazole therapy caused an increase in the activity of the isoenzyme CYP3A4, which led to an increased metabolism of prednisone. Patients receiving combination therapy with prednisone and fluconazole should be under close medical supervision with the withdrawal of fluconazole in order to assess the state of the adrenal cortex.

saquinavir: the area under the concentration-time curve (AUC) rises by approximately 50%, Cmax by 55%, saquinavir clearance decreases by approximately 50% due to inhibition of hepatic metabolism of the CYP3A4 isoenzyme and inhibition of the P-glycoprotein.You may need to adjust the dose of saquinavir. sirolimus: an increase in the concentration of sirolimus in the blood plasma, presumably due to the inhibition of the metabolism of sirolimus through inhibition of the isoenzyme CYP3A4 and P-glycoprotein. This combination can be applied with appropriate correction of the dose of sirolimus depending on the effect / concentration.

vitamin A: there is a report of one case of development of undesirable reactions from the central nervous system (CNS) in the form of a pseudotumor of the brain with simultaneous application of all transretinic acid and fluconazole, which disappeared after the withdrawal of fluconazole. The use of this combination is possible, but one should remember about the possibility of undesirable reactions from the CNS.

voriconazole (inhibitor of isoenzymes CYP2C9, CYP2C19 and CYP3A4): simultaneous application of voriconazole (400 mg twice a day on the first day, then 200 mg twice daily for 2.5 days) and fluconazole (400 mg on the first day, then 200 mg per day for 4 days) leads to an increase in the concentration and AUC of voriconazole by 57% and 79%, respectively. It was shown that this effect persists with a reduction in the dose and / or a decrease in the frequency of administration of any of the drugs. Simultaneous use of voriconazole and fluconazole is not recommended.

studies of the interaction of oral forms of fluconazole with its simultaneous intake with food, cimetidine, antacids, and after total body irradiation for preparation for bone marrow transplantation showed that these factors do not have a clinically significant effect on the absorption of fluconazole.

Special instructions:

Treatment can be started in the absence of seeding results or other laboratory tests, but if appropriate, a correction of fungicidal therapy is recommended.

In rare cases, the use of fluconazole was accompanied by toxic changes in the liver, including fatalities, mainly in patients with serious concomitant diseases. In the case of hepatotoxic effects associated with the use of fluconazole, their apparent dependence on the total daily dose of the drug, the duration of therapy, the sex and age of the patient was not noted.

Hepatotoxic effect of the drug was usually reversible, signs of it disappeared after discontinuation of therapy. Patients who are in violation of liver function during therapy should be monitored in order to identify signs of more serious liver damage.

If there are clinical signs and symptoms of liver damage that may be associated with the use of fluconazoa, the drug should be discontinued.

Because the fluconazole is excreted mainly by the kidneys, caution should be exercised in patients with renal insufficiency. In the treatment of multiple doses of fluconazole, dosing should be carried out taking into account the clearance of creatinine.

As with the use of other azoles, fluconazole in rare cases can cause anaphylactic reactions.

During treatment with fluconazole, exfoliative skin lesions rarely developed in patients, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

Patients with AIDS are more likely to develop severe skin reactions with many drugs. In those cases where the rash develops in patients with superficial fungal infection and it is regarded as definitely associated with fluconazole, the drug should be discontinued. When rashes appear in patients with invasive / systemic fungal infections, they should be carefully monitored and canceled fluconazole when there are bullous changes or erythema multiforme.

It is necessary to monitor prothrombin time in patients simultaneously receiving fluconazole and anticoagulants of the coumarin series.

Treatment should continue until the appearance of clinical-hematologic remission. Premature termination of treatment leads to relapse.

There have been reports of superinfection caused by Candida strains other than Candida albicans, which often have a natural resistance to fluconazole (eg, Candida krusei). In such cases, alternative antifungal therapy may be required.

Like other azoles, fluconazole can cause an increase in the QT interval on the ECG. With fluconazole, an increase in the QT interval and fibrillation or flutter of the ventricles were very rare in patients with severe diseases with multiple risk factors, such as organic heart disease, electrolyte imbalance, and concomitant therapy contributing to the development of such disorders. Therefore, in such patients with potentially proarrhythmic conditions, fluconazole with caution. Patients with diseases of the liver, heart and kidneys are advised to consult a doctor before using the drug.When fluconazole 150 mg is used for vaginal candidiasis, patients should be warned that symptom improvement usually occurs after 24 hours, but it often takes several days to completely disappear. If symptoms persist for several days, you should consult a doctor

Effect on the ability to drive transp. cf. and fur:

When using the drug should take into account the possibility of developing dizziness and seizures. If these side effects occur, do not drive vehicles, mechanisms.

Form release / dosage:

Capsules of 50 mg, 100 mg, 150 mg and 200 mg.

Packaging:

1, 7 or 10 capsules per blister. For 1, 2 or 5 blisters in a cardboard box together with instructions for use.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Special precautions when destroying an unused preparation

There is no need for special precautions when destroying an unused preparation.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:Without recipe

Registration number:LSR-010614/09

Date of registration:25.12.2009

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

SANDOZ, d.d. Slovenia

SALUTAS PHARMA, GmbH Germany

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp14.10.2015

Illustrated instructions

Instructions

Fluconazole-Sandoz® (Fluconazole-Sabdoz)