for medical use
of Flukonazol Torgovoye medicine a name
Mezhdunarodnoye the unlicensed
name Flukonazol Lekarstvennaya a form
of the Capsule of 50 mg and 150 mg
One capsule contains
active agent – flukonazol 50 mg or 150 mg,
excipients: lactoses monohydrate, starch prezhelatinizirovanny, silicon dioxide colloidal (aerosil), magnesium stearate, sodium lauryl sulfate
gelatinous solid capsules:
for a dosage of 50 mg:
the body – the titan E 171 dioxide, gelatin,
a cover – the titan E 171 dioxide, dye an azoruby E 122, dye crimson (ponso 4R) E 124, gelatin,
for a dosage of 150 mg:
the body – the titan E 171 dioxide, gelatin,
a cover – the titan E 171 dioxide, dye a sunset yellow E 110, dye crimson (ponso 4R) E 124, gelatin.
Solid gelatin capsules No. 2 with the body of white color and a lid of pink color. Contents of capsules – powder of color, white or white with a yellowish shade (for a dosage of 50 mg).
Solid gelatin capsules No. 1 with the body of white color and a lid of pinkish-orange color. Contents of capsules – powder of color, white or white with a yellowish shade (for a dosage of 150 mg).
Antifungal drugs for system use. Triazole derivatives. Flukonazol.
The ATX J02AC01 code
Pharmacokinetics Later properties of intake flukonazol is well soaked up, meal does not influence the speed of absorption of a flukonazol, its bioavailability – 90%.
Time of achievement of the maximum concentration in blood plasma after intake, on an empty stomach 150 mg of drug – also is 0.5-1.5 hours 90% of concentration in plasma at intravenous administration in a dose of 2.5 – 3.5 mg/l. Elimination half-life of a flukonazol makes 30 h. Communication with proteins of plasma – 11-12%. Concentration in plasma is in direct dependence on a dose. 90% the level of equilibrium concentration are reached by 4-5 day of drug treatment (at reception of 1 times/days).
Introduction of the ‘a shock dose’ (in the first day) twice exceeding a usual daily dose allows to reach the level of the concentration corresponding to 90% of equilibrium concentration by second day.
Flukonazol well gets into all biological liquids of an organism. Concentration of active agent in breast milk, articulate liquid, saliva, a phlegm and peritoneal liquid it is similar to its level in plasma. Constant values in a vaginal secret are reached in 8 h after intake and keep at this level not less than 24 h Flukonazol well gets into cerebrospinal fluid (SMZh), in fungal meningitis the concentration in SMZh makes about 85% of its level in plasma. In stalemate liquid, epidermis and a corneal layer (selection accumulation) the concentration exceeding serumal are reached. After intake of a dose of 150 mg on 7 put concentration of a flukonazol in a corneal layer of skin – 23.4 mkg/g, and in 1 week after reception of the second dose – 7.1 mkg/g, concentration in nails after 4 months of use in a dose of 150 mg once a week – 4.05 mkg/g in healthy and 1.8 mkg/g in the affected nails. The volume of distribution approaches the general content of water in an organism.
Is CYP2C9 isoenzyme inhibitor in a liver. It is removed mainly by kidneys (80% – in not changed look, 11% – in the form of metabolites). The clearance of a flukonazol is proportional to clearance of creatinine. Metabolites of a flukonazol in peripheral blood are not revealed.
The pharmacokinetics of a flukonazol significantly depends on a functional condition of kidneys, at the same time there is inverse relation between elimination half-life and clearance of creatinine. After a hemodialysis during 3 h the concentration of a flukonazol in plasma decreases by 50%.
Antifungal means, possesses highly specific action, inhibiting activity of enzymes of the mushrooms dependent on P450 cytochrome. Blocks transformation of a lanosterol of cells of mushrooms into a membrane lipid – ergosterol, increases permeability of a cellular membrane, breaks its growth and replication.
Flukonazol, being high-selective for P450 cytochrome of mushrooms, practically does not oppress these enzymes in a human body (in comparison with itrakonazoly, Clotrimazolum, econazoly and ketokonazoly to a lesser extent suppresses oxidizing processes, dependent on P450 cytochrome, in microsomes of a liver of the person). Has no anti-androgenic activity.
It is active in the opportunistic mycoses including caused by Candida spp. (including generalized forms of candidiasis against the background of an immunosuppression), Cryptococcus neoformans and Coccidioides immitis (including intracranial infections), Microsporum spp. and Trichophyton spp, in the endemic mycoses caused by Blastomyces dermatidis, Histoplasma capsulatum (including at an immunosuppression).
– a cryptococcosis (including pulmonary, skin, cryptococcal meningitis and other types of a cryptococcosis)
– the disease caused by the human immunodeficiency virus (HIV) with manifestations of candidiasis and other mycoses
– candidiasis (including candidosis stomatitis, pulmonary candidiasis, candidiasis of skin and nails, candidiasis of a vulva and vagina, candidiasis of other urogenital localizations, candidosis meningitis, a candidosis endocarditis, a candidosis septicaemia and candidiasis of other localizations)
– mycosis of nails, brushes, feet, trunks, an inguinal epidermophitia and other dermatofitiya, multi-colored deprive both other specified and not specified superficial mycoses, including a coccidioidomycosis, histoplasmosis, a paracoccidioidomycosis, a sporotrichosis
– prevention of fungal infections at the patients with malignant new growths taking the antineoplastic drugs, undergoing radiological procedures and radiation therapy and also at the persons having a transplanted organ and fabric
the Route of administration and doses
In cryptococcal meningitis and cryptococcal infections of other localizations in the first day usually appoint 400 mg, and then continue treatment in a dose of 200 mg – 400 mg (4-8 capsules on 50 mg) 1 time a day. Treatment duration in cryptococcal infections depends on the clinical performance confirmed with a mycologic research, in cryptococcal meningitis the course of treatment has to be not less than 6-8 weeks.
For prevention of a recurrence of cryptococcal meningitis in the disease caused by HIV with manifestations of mycoses after end of a full course of primary therapy flukonazol appoint in a dose 200 mg a day during the long span.
At a candidosis septicaemia, disseminate candidiasis and other invasive candidosis infections in the first day the dose makes 400 mg, and then – on 200 mg a day. At insufficient clinical performance the dose of drug can be increased up to 400 mg (8 capsules on 50 mg) in day. Duration of therapy depends on clinical performance.
In candidiasis of an oral cavity drug is usually appointed on 150 mg of 1 times/days, treatment duration – 7-14 days. If necessary at patients with the significant decrease in immunity the treatment can be longer.
For prevention of a recurrence of candidiasis of an oral cavity in a disease of primary therapy caused by HIV with manifestation of mycoses after end of a full course – on 150 mg once a week.
In the candidiasis of an oral cavity connected with carrying dentures – 50 mg of 1 times a day within 14 days in combination with local antiseptic medicines for processing of a prosthesis.
In skin candidiases the recommended dose makes 150 mg once a week or 50 mg of 1 times a day, the mode of dosing depends on clinical and mycologic effect.
At other localizations of candidiasis (except for genital candidiasis), for example in an esophagitis, noninvasive bronchopulmonary damage, a kandiduriya, candidiasis of skin and mucous membranes, etc., the effective dose usually makes 150 mg/days lasting treatment of 14-30 days.
In vaginal candidiasis flukonazol accept once inside in a dose 150 mg. For decrease in frequency of a recurrence of vaginal candidiasis drug can be used in a dose of 150 mg within 4-12 months once a month. More frequent use can be required by some patients.
In a candidosis balanitis, flukonazol appoint inside once in a dose 150 mg a day.
For prevention of candidiasis the recommended dose – 50-400 mg of 1 times a day depending on degree of risk of developing a fungal infection. For prevention of candidiasis at patients with malignant new growths the recommended dose of a flukonazol makes 150-400 mg of 1 times/days depending on degree of risk of developing a fungal infection. With high risk of a generalized infection, for example at patients from the expected expressed or it is long the remaining neutropenia, the recommended dose – 400 mg/days Flukonazol are appointed some days before the expected emergence of a neutropenia, after increase in number of neutrophils more than 1 thousand / mkl treatment is continued during 7 days.
In skin mycoses, including mycoses of feet and skin of inguinal area the recommended dose makes 150 mg once a week or 50 mg of 1 times a day, the mode of dosing depends on clinical and mycologic effect. Therapy duration in everyday occurences is 2-4 weeks, however in mycoses of feet longer therapy can be required (up to 6 weeks).
In multi-colored (scaly) herpes – 300 mg once a week during 2 weeks, some patients need the third dose of 300 mg a week while regarding cases it is sufficient single dose of 300-400 mg, the alternative scheme of treatment is use on 50 mg during 2-4 weeks once a day.
In an onychomycosis the recommended dose makes 150 mg once a week. Treatment should be continued before substitution of the infected nail (growth of not infected nail). Repeated growth of nails on fingers of hands and feet normal requires 3-6 months and 6-12 months according to.
In deep endemic mycoses the use of drug in a dose of 200 mg – 400 mg a day during up to 2 years can be required. Duration of therapy is determined individually, it can make 11-24 months in a coccidioidomycosis, 2-17 months in a paracoccidioidomycosis, 1-16 months in a sporotrichosis and 3-17 months in histoplasmosis.
At patients of advanced age in the absence of renal failures it is necessary to adhere to the usual mode of drug dosing. Patients with a renal failure (clearance of creatinine less than 50 ml/min.) should correct the mode of dosing, as shown below.
Flukonazol is brought generally with urine in not changed look. In chronic kidney disease the ‘shock’ dose of 50-400 mg is originally entered. If the clearance of creatinine (CC) is more than 50 ml/min., the usual dose of drug (100% of the recommended dose) is applied. At KK from 11 to 50 ml/min. 50% of the recommended dose or a usual dose of 1 times in 2 days are applied.
The patient who is regularly on dialysis, one dose of drug is applied after each session of a hemodialysis.
Often (from ≥1/100 to & lt, 1/10)
– a headache
– nausea, vomiting, an abdominal pain, diarrhea
– increase in level of alkaline phosphatase, serumal level of aminotransferases (ALT and ACT)
Infrequently (from ≥1/1.000 to ≤1/100)
– insomnia, drowsiness
– spasms, dizziness, paresthesia, change of taste
– dyspepsia, a meteorism, dryness in a mouth
– a cholestasia, jaundice, increase in level of bilirubin
– an itching, urticaria, the increased sweating
– fatigue, an indisposition, weakness, fever
Seldom (from ≥1/10.000 to ≤1/1.000)
– an agranulocytosis, a leukopenia, a neutropenia, thrombocytopenia
– an anaphylaxis, a Quincke’s disease
– a gipertriglitseridemiya, a hypercholesterolemia, a hypopotassemia
– a tremor
– tachycardia, blinking/trembling of ventricles, increase in an interval of QT
– dyspepsia, a meteorism, dryness in a mouth
– hepatotoxicity, including exceptional cases with a lethal outcome, a liver failure, hepatocellular necrosis, hepatitis, hepatocellular damages
– a toxic epidermal necrolysis, Stephens-Johnson’s syndrome, sharp generalized exanthematous pustulez, exfoliative dermatitis, a face edema, an alopecia
At patients about AIDS or cancer, at treatment by Flukonazol and similar drugs were observed changes of indicators of blood, function of kidneys and a liver, however the clinical value of these changes and their communication with treatment are not established
– hypersensitivity to a flukonazol, other components of drug or azolny substances from similar to a flukonazol by structure
– a concomitant use of a terfenadin during repeated use of Flukonazol in a dose of 400 mg / cyт and more
– a concomitant use of the medicines extending an interval of QT and which are metabolized by means of CYP3A4 enzyme, such as tsizaprid, astemizol, erythromycin, Pimozidum and quinidine
– patients with rare hereditary problems of intolerance of a galactose, a lactose intolerance or glyukozo-galaktozny malabsorption, t. to the capsule of a flukonazol contain lactose
– pregnancy and the period of a lactation
– the children’s age up to 18 years
At use of a flukonazol with warfarin increases a prothrombin time (on average by 12%). In this regard it is recommended to watch carefully indicators of a prothrombin time at the patients receiving drug in combination with coumarinic anticoagulants.
Flukonazol increases plasma elimination half-life of oral hypoglycemic means – sulphonylurea derivatives (chlorpropamide, glibenclamide, glipizid, tolbutamide) at healthy people. Combined use of a flukonazol and oral hypoglycemic means at patients with diabetes is allowed, however the doctor has to mean a possibility of development of a hypoglycemia.
Simultaneous use of a flukonazol and Phenytoinum can lead to increase of concentration of Phenytoinum in plasma to clinically significant degree. Therefore in need of combined use of these drugs it is necessary to monitorirovat concentration of Phenytoinum with correction of its dose for the purpose of maintenance of level of drug within a therapeutic interval.
The combination with rifampicin leads to decrease in bioavailability (AUC) by 25% and shortening of elimination half-life of a flukonazol from plasma for 20%. Therefore the patient receiving at the same time rifampicin, it is reasonable to increase a dose of a flukonazol.
It is recommended to exercise control of concentration of cyclosporine in blood at the patients receiving flukonazol as at the patients with the replaced kidney receiving cyclosporine, reception of a flukonazol in a dose of 200 mg/days led to slow increase in concentration of cyclosporine in plasma.
Patients who receive high doses of theophylline or who have a likelihood of developing teofillinovy intoxication have to be under observation of the doctor for the purpose of early identification of symptoms of overdose of theophylline as reception of a flukonazol leads to decrease in average speed of clearance of theophylline from plasma.
At simultaneous use of a flukonazol and terfenadin, tsizaprid, cases of undesirable reactions from heart, including paroxysms of ventricular tachycardia (torsades de points) are described.
Simultaneous use of a flukonazol and hydrochlorothiazide can lead to increase of concentration of a flukonazol in plasma for 40%.
There are messages about interaction of the flukonazol and a rifabutin which was followed by increase in serumal levels of the last. At simultaneous use of a flukonazol and rifabutin, uveitis cases are described. It is necessary to observe carefully the patients who are at the same time receiving rifabutin and flukonazol.
At the patients receiving a combination of a flukonazol and a zidovudine the increase in concentration of a zidovudine which is caused by decrease in transformation of the last into its main metabolite therefore it is necessary to expect increase in side effects of a zidovudine is observed.
Increases concentration of midazolam in this connection risk of development of psychomotor effects increases.
Increases serumal concentration of a takrolimus in this connection the risk of nephrotoxic action increases.
Combined use of a flukonazal and the combined oral contraceptives containing ethinylestradiol and levonorgestrel has no significant effect on the level of hormones, but at some patients the decrease in ethinylestradiol by 40% and levonorgestrel for 33% was noted.
Simultaneous use of a flukonazol with astemizoly or other drugs which are metabolized the system of P450 cytochrome can be followed by increase in concentration of these drugs in blood serum. It is necessary to watch such patients carefully.
instructions Treatment need to be continued before emergence of kliniko-hematologic remission. The premature termination of treatment leads to a recurrence.
In rare instances use of a flukonazol was followed by toxic changes of a liver, including with a lethal outcome, mainly at patients with serious associated diseases. In case of the hepatotoxic effects connected with flukonazoly the obvious dependence them from the general daily dose, duration of therapy, a sex, and age of the patient is noted. Hepatotoxic action of a flukonazol usually was reversible, its signs disappeared after the therapy termination. At emergence of clinical signs of damage of a liver which can be connected with flukonazoly, drug should be cancelled.
Persons in the disease caused by HIV with manifestation of mycoses are more inclined to development of heavy skin reactions at use of many drugs. When at patients with a superficial fungal infection the rash develops, and it is regarded as definitely connected with flukonazoly, drug should be cancelled. At appearance of rash in patients with invasive/system fungal infections, they should be observed and cancelled carefully flukonazol at emergence of bullous changes or a mnogoformny erythema.
Flukonazol is CYP2C9 inhibitor of strong action and CYP3A4 inhibitor of average action. The patients undergoing treatment flukonazoly who accept the accompanying therapy by the drugs with a narrow therapeutic window which are metabolized through CYP2C9 and CYF3A4 have to be examined.
It is necessary to be careful at a concomitant use of a flukonazol with tsizapridy, rifabutiny or other drugs which are metabolized the system of P 450 cytochrome.
At Flukonazol’s use (once 150 mg) concerning vaginal candidiasis the patients have to be warned that improvement of symptoms is usually observed in 24 hours, but their total disappearance sometimes requires several days. At preservation of symptoms within several days, it is necessary to see a doctor.
With care it is necessary to take the drug at patients with a liver failure, with renal dysfunction, at appearance of rash against the background of use of a flukonazol for patients with a superficial fungal infection and invasive/system fungal infections, at a concomitant use of a terfenadin and a flukonazol in a dose less than 400 mg/days, at a concomitant use of potentially gepatotoksichny medicines, alcoholism, potentially proaritmogenny states at patients with multiple factors of risk (organic heart diseases, disturbances of electrolytic balance, a concomitant use of the medicines causing arrhythmias).
At Flukonazol’s use the increase in an interval of QT and blinking/trembling of ventricles at patients with multiple factors of risk, such as organic heart diseases, disturbances of electrolytic balance and the accompanying therapy contributing to the development of similar disturbances is very seldom observed. Therefore such patients with potentially pro-arrhythmic states should apply Flukonazol with care.
Features of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms.
Due to possible side effects (dizziness, spasms) it is necessary to be careful at control of vehicles or potentially dangerous mechanisms.
Symptoms: hallucinations, paranoid behavior.
Treatment: symptomatic: gastric lavage, artificial diuresis. The hemodialysis during 3 h reduces concentration in plasma approximately by 50%.
Form of release and packing
of the Capsule of 50 mg and 150 mg.
On 1 (for a dosage of 150 mg) or 7 (for a dosage of 50 mg) capsules in blister strip packaging from a film of the polyvinylchloride and printing aluminum foil varnished.
1 blister strip packaging together with the instruction for medical use in the state and Russian languages is placed in a pack from cardboard.
not to use a period of storage after expiry date.
To Store storage conditions in the place protected from light at a temperature not over 25 ºС.
To store out of children’s reach!
According to the prescription
Valenta Pharmatsevtika Open Joint Stock Company Russian Federation Producer 141101, Shchyolkovo, Moscow Region, Fabrichnaya St., 2
the Owner of the registration certificate
Valenta Pharmatsevtika Open joint stock company
Russian Federation 141101, Shchyolkovo, Moscow Region, Fabrichnaya St., 2
the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products (goods) of Valenta Aziya LLP the Republic of Kazakhstan, 050009, Almaty, the ave. of Abay, ug. Radostovts St., 151/115, business center “Ala Tau”, office No. 1102telefon/fax 8 (727) 334-15-51Электронный address:
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