Producer: JSC VEROPHARM Russia
Code of automatic telephone exchange: J02AC02
Release form: Firm dosage forms. Capsules.
General characteristics. Structure:
Capsules of yellow color No. 10. Contents of capsules — spherical microgranules from light yellow till yellowish-beige color.
Pharmacodynamics. Itrakonazol — the synthetic antifungal broad-spectrum agent derivative of triazole. Inhibits synthesis of ergosterol of a cellular membrane of mushrooms that causes antifungal effect of drug. Itrakonazol is active concerning the infections caused by dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton ftoccosum), drozhzhepodobny mushrooms of t yeast (Cryptococcus neoformans, Pityrosporum spp., Candida spp., including S. of albicans, C.giabrata and C.krusei); Aspergius spp., Histoplasma spp., Paracoccidioides brasiliensis, Sporothrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatitidis, and also other barmy and mold fungi.
Pharmacokinetics. At oral administration the maximum bioavailability of an itrakonazol is noted at reception of capsules at once after dense food. The maximum concentration in plasma is reached within 3–4 hours after intake.
Removal from plasma is two-phase with a final elimination half-life from 1 to 1,5 days. At long reception equilibrium concentration is reached within 1–2 weeks. Equilibrium concentration of an itrakonazol in plasma in 3–4 hours after administration of drug makes 0,4 mkg/ml (100 mg at reception once a day), 1,1 mkg/ml (200 mg at reception once a day) and 2,0 mkg/ml (200 mg at reception two times a day). Itrakonazol for 99,8% contacts proteins of plasma. Accumulation of drug in keratinaceous fabrics, especially in skin, approximately by 4 times exceeds accumulation in a blood plasma, and its speed of removal depends on regeneration of epidermis. Unlike concentration in plasma which do not give in to detection in 7 days after the therapy termination therapeutic concentration in skin remain within 2–4 weeks after the termination of a 4-week course of treatment. Itrakonazol is found in a keratin of nails in one week after an initiation of treatment and remains , at least, within 6 months after end of a 3-month course of therapy. Itrakonazol is defined also in skin fat and to a lesser extent in sweat. Itrakonazol is well distributed in fabrics which are subject to fungal infections. Concentration in lungs, kidneys, a liver, bones, a stomach, a spleen and muscles by two-three times exceeded the corresponding concentration in plasma. Therapeutic concentration in tissues of a vagina remain within 2 days after the termination of a 3-day course of treatment in a dose of 200 mg a day, and 3 days after the termination of a one-day course of treatment in a dose of 200 mg twice a day. Itrakonazol is metabolized by a liver with formation of a large number of metabolites. One of such metabolites is hydroxy-itrakonazol which possesses comparable with itrakonazoly antifungal action of in vitro. The antifungal concentration of drug determined by a microbiological method approximately by 3 times exceeded the concentration measured by means of VEZhH. Removal with a stake makes from 3 to 18% of a dose. Removal by kidneys makes less than 0,03% of a dose. About 35% of a dose are allocated in the form of metabolites with urine within 1 week.
Indications to use:
- fungal keratitis;
- the onychomycoses caused by dermatophytes and/or yeast and mold mushrooms;
- system mycoses: a system aspergillosis and candidiasis, a cryptococcosis (including cryptococcal meningitis), histoplasmosis, a sporotrichosis, a paracoccidioidomycosis, a zymonematosis and other system or tropical mycoses;
- candidiases with damage of skin or mucous, including vulvovaginal candidiasis;
- deep visceral candidiases;
Route of administration and doses:
For optimum absorption of drug it is necessary to accept Irunin in capsules right after food.
It is necessary to swallow of capsules entirely.
|Vulvovaginal candidiasis||200 mg 2 times a day||1 day|
|or 200 mg of 1 times a day||3 days|
|Chromophytosis||200 mg of 1 times a day||7 days|
|Dermatomycoses of smooth skin||200 mg of 1 times a day||7 days|
|100 mg of 1 times a day||15 days|
|Fungal keratitis||200 mg of 1 times a day||21 days|
|Defeats of the high-keratinized areas of an integument, such as hands and stop, demand additional treatment within 15 days on 100 mg a day.|
|Oral candidiasis||100 mg of 1 times a day||15 days|
|Bioavailability of an itrakonazol at oral administration can be reduced at some patients with the broken immunity, for example, at patients with a neutropenia, patients with AIDS or with transplanted organs. Therefore, double increase in a dose can be required.|
Pulse therapy (see the table).
One course pulse therapy consists in daily reception on 2 capsules of Irunin two times a day (on 200 mg two times a day) within one week.
For treatment of fungal infections of nail plates of brushes two courses are recommended. For treatment of fungal infections of nail plates of feet three courses are recommended (see the table). The interval between courses during which it is not necessary to accept drug makes 3 weeks.
Clinical results will become obvious after the end of treatment, in process of growth of nails.
|Localization of onychomycoses||1st week.||2 weeks.||3 weeks.||4 weeks.||5th week.||6th week.||7th week.||8th week.||9th week.|
|Defeat of nail plates of feet with defeat or without defeat of nail plates of brushes||1st course||Weeks, free from Irunin's reception||2nd course|
|Defeat of nail plates of brushes||1st course||Weeks, free from Irunin's reception||2nd course|
On two capsules a day (on 200 mg once a day) within 3 months.
Irunin's removal from skin and nail fabric is carried out more slowly, than from plasma. Thus, optimum clinical and mycologic effects are reached in 2–4 weeks after the end of treatment at infections of skin and in 6–9 months after the end of treatment of nail infections.
System mycoses (the recommended dosages vary depending on a type of an infection)
|Aspergillosis||200 mg of 1 times a day||2–5 months||To increase a dose to 200 mg 2 times a day in case of the invasive or disseminated disease|
|Candidiasis||100–200 mg of 1 times a day||from 3 weeks to 7 months|
|Cryptococcosis (except meningitis)||200 mg of 1 times a day||from 2 months to 1 year||Maintenance therapy (meningitis cases) of 200 mg of 1 times a day|
|Cryptococcal meningitis||200 mg two times a day|
|Histoplasmosis||from 200 mg of 1 times a day to 200 mg two times a day||8 months|
|100 mg of 1 times a day|
|Sporotrichosis||100 mg of 1 times a day||3 months|
|Paracoccidioidomycosis||100–200 mg of 1 times a day||6 months|
|Chromomycosis||from 100 mg of 1 times a day to 200 mg two times a day||6 months|
|Zymonematosis||from 100 mg of 1 times a day to 200 mg two times a day||6 months|
Features of use:
At a research of an intravenous dosage form of drug итраконазол, conducted on healthy volunteers, the passing bessimtomny reduction of fraction of emission of a left ventricle normalized before the following infusion of drug was noted. The clinical importance of the obtained data for peroral dosage forms is unknown. It is revealed what итраконазол possesses a negative inotropic effect. It was reported about the cases of development of heart failure connected with Irunin's reception. Irunin patients should not accept with chronic heart failure or with existence of this disease in the anamnesis except for cases when the possible advantage considerably surpasses potential risk. At individual assessment of a ratio of advantage and risk it is necessary to take such factors as gravity of indications, the mode of dosing and individual risk factors of developing of heart failure into account. Risk factors include existence of heart diseases, such as coronary heart disease or defeats of valves; serious diseases of lungs, such as obstructive damages of lungs; the renal failure or other diseases which are followed by hypostases. Such patients need to be informed on signs and symptoms of heart failure. Treatment has to be carried out with care, at the same time it is necessary to watch the patient regarding identification of symptoms of congestive heart failure. At their emergence Irunin's reception needs to be stopped. Blockers of calcium channels can render a negative inotropic effect which can strengthen similar effect of an itrakonazol; итраконазол can reduce metabolism of blockers of calcium channels. At a concomitant use of an itrakonazol and blockers of calcium channels it is necessary to be careful. At the lowered acidity of a stomach absorption of an itrakonazol is broken. To the patients accepting antiacid drugs (for example, aluminum hydroxide), it is recommended to use them not earlier than in 2 hours after reception of capsules of Irunin. To patients with an achlorhydria or the applying H2 histamine blockers or inhibitors of a protonew pomp, it is recommended to accept Irunin's capsules with acid drinks. Seldom or never at Irunin's use crushing toxic damage of a liver, including cases of an acute liver failure with a lethal outcome developed. In most cases it happened to patients who already had liver diseases, for the patients who were receiving therapy according to system indications, having other serious medical states and also for the patients receiving other medicines possessing a hepatotoxic action. At some patients obvious risk factors concerning damage of a liver did not come to light. Several such cases arose in the first month of therapy, and some — in the first week of treatment. In this regard it is regularly recommended to control function of a liver at the patients receiving therapy itrakonazoly. Patients should be warned about need to contact immediately the doctor in case of the symptoms assuming developing of hepatitis namely: anorexias, nausea, vomitings, weaknesses, abdominal pains and darkenings of urine, in case of such symptoms it is necessary immediately to stop terapiyu to conduct a research of function of a liver. Patients with a superactivity of "hepatic" enzymes or a disease of a liver in an active phase, or at the postponed toxic damage of a liver at reception of other drugs, should not appoint treatment Iruniny unless the expected advantage justifies risk of damage of a liver. In these cases it is necessary to control activity of "hepatic" enzymes during treatment. Abnormal liver functions: Itrakonazol is metabolized preferential in a liver. The elimination half-life of an itrakonazol at patients with cirrhosis is a little increased. Bioavailability of drug at oral administration is a little reduced at patients with cirrhosis. In this case, perhaps, dose adjustment will be necessary. Lasting reception more than one month control of function of a liver is necessary. Renal failures: At patients with a renal failure bioavailability of an itrakonazol can be reduced. In this case, perhaps, dose adjustment will be necessary. Treatment should be stopped when developing neuropathy which can be connected with reception of capsules of Irunin. There are no data on cross hypersensitivity to an itrakonazol and other azolovy antifungal drugs. Irunin in capsules patients should appoint with care with hypersensitivity to other azoles. At patients with the broken immunity (AIDS, after organ transplantation, a neutropenia) increase in a dose can be required. Impact on ability to drive the car and to work with the equipment was not observed. Use in pediatrics As is not enough clinical data on use of an itrakonazol in capsules at children, it is recommended to use итраконазол only if the possible advantage surpasses potential risk. Use during pregnancy and a lactation on the basis of results of preclinical trials and because researches on use of an itrakonazol for pregnant women were not conducted, итраконазол pregnant women should appoint only at life-threatening system mycoses when the potential advantage for women justifies possible risk for a fruit. As a small amount of an itrakonazol is allocated with maternal milk, the expected advantage of reception of an itrakonazol needs to be compared with risk for the child when breastfeeding. In case of doubts it is not necessary to nurse
Reactions from digestive tract, such as dyspepsia, nausea, abdominal pain and lock were the most often noted side reactions in connection with use of an itrakonazol. Besides, were noted: anorexia, a headache, fatigue, reversible increase in activity of pechenochnrment, cholestatic jaundice hepatitis, disturbances of a menstrual cycle, dizziness and allergic reactions (such as itch, rash, urticaria and Quincke's disease), peripheral neuropathy, Stephens-Johnson's syndrome, an alopecia, a hypopotassemia, hypostases, congestive heart failure and a fluid lungs, coloring of urine in dark color, a giperkretininemiya. Seldom or never at Irunin's use crushing toxic damage of a liver, including a case of an acute liver failure with a lethal outcome developed.
Interaction with other medicines:
The medicines exerting impact on metabolism of an itrakonazol. Interaction of an itrakonazol with rifampicin, rifabutiny and Phenytoinum was studied. Simultaneous use of an itrakonazol with these drugs which are potential inductors of liver enzymes is not recommended.
Interaction researches with other inductors of liver enzymes, such as carbamazepine, phenobarbital and isoniazid, were not conducted, however similar results can be assumed. As итраконазол it is generally metabolized by CYP3A4 enzyme, potential inhibitors of this enzyme can increase bioavailability of an itrakonazol. Can be examples ритонавир, индинавир, кларитромицин and erythromycin.
Influence of an itrakonazol on metabolism of other medicines. Itrakonazol can inhibit metabolism of the drugs split by CYP3A4 enzyme. Strengthening or prolongation of their action including side effects can be result of it.
After the treatment termination levels of an itrakonazol in plasma decrease gradually depending on a dose and duration of treatment (see the section Pharmacokinetics).
Examples of such drugs are: Drugs which it is impossible to appoint along with itrakonazoly:
Terfenadin, астемизол, мизоластин, цисаприд, to triazoles and peroral midazolam, дофетилид, quinidine, Pimozidum, inhibitors of GMG-KOA reductase, such, as симвастатин and ловастатин.
Blockers of calcium channels can render a negative inotropic effect which can strengthen the same effect shown itrakonazoly. At a concomitant use of an itrakornazol and blockers of calcium channels it is necessary to be careful as metabolism of blockers of calcium channels can be reduced.
Drugs at which purpose it is necessary to watch their concentration in plasma and, action by side effects.
In case of co-administration with itrakonazoly a dose of these drugs if it is necessary, it is necessary to reduce.
HIV protease inhibitors, such, as ритонавир, индинавир, саквинавир;
Some antineoplastic drugs, such as alkaloids of the Periwinkle pink, бусульфан, dotsetakset, триметрексат;
The blockers of calcium channels split by CYP3A4 enzyme, such as dihydropyridine and verapamil;
Some immunosuppressive means: cyclosporine, такролимус, сиролимус;
Other drugs: digoxin, carbamazepine, буспирон, alfentanil, to alprazola, brotiozolam, рифабутин, Methylprednisolonum, эбастин, ребоксетин.
Interaction between itrakonazoly and a zidovudine and fluvastatiny is not revealed.
Influence of an itrakonazol on metabolism of ethinylestradiol and Norethisteronum was not noted.
Influence on binding of proteins. The researches in vitro showed lack of the competition between itrakonazoly and such drugs as Imipraminum, propranolol, diazepam, Cimetidinum, indometacin, Tolbutamidum and Sulfamethazinum at linkng with proteins of plasma.
Irunin in capsules is contraindicated to patients with individual hypersensitivity to drug or its components.
Pregnant women Irunin should appoint only if the expected advantage for the woman exceeds potential risk for a fruit. The women of childbearing age accepting Irunin need to use adequate methods a target="_blank" href="">of contraception throughout all course of treatment up to approach of the first periods after its end.
With care — children's age, heavy heart failure, liver diseases (including followed by a liver failure).
Terfenadin, астемизол, мизоластин, цизаприд, дофетилид, the quinidine, Pimozidum metabolizing inhibitors of reductase of MMC with CYP3A4 enzyme participation — KOA such as симвастатин and ловастатин, triazoles and midazolam cannot accept along with Irunin (see also section "Interactions with Other Medicines").
Data are absent. At accidental overdose it is necessary to apply the supporting measures. Within the first hour to carry out a gastric lavage, and if it is necessary, to appoint absorbent carbon. Itrakonazol is not brought at a hemodialysis. Any specific antidote does not exist.
List B. In dry, protected from light and the place, unavailable to children, at a temperature not above 25 °C. Validity term - 2 years. Not to use after a period of validity.
According to the recipe
On 5, 6, 7, 10, 14 or 15 capsules in a blister strip packaging. On 5, 6, 7, 10, 14 or 15 capsules in banks of dark glass. Each can, 1, 2, 3 strip packagings together with the application instruction are placed in a pack.