Текназол®

General characteristics. Structure:

Active ingredient: 460 mg of an itrakonazol of a micropellet (it is equivalent to an itrakonazol – 100.00).

Excipients: a gidroksipropilmetiltsellyuloz (E5), evdragit E 100, sugar spheres.

Structure of a cover of the capsule. Case: caramel simple (E-150a), gelatin. Lid: azoruby (Е 122), blue patent V (Е 131), titanium dioxide (E171), gelatin.

Pharmacological properties:

Pharmacodynamics. Текназол® is the antifungal drug belonging to group of triazoles, possesses a wide range of antifungal action; influences by means of inhibition of synthesis of ergosterol which is a vital component of a cell wall of fungi. Has fungicidal effect. The researches in vitro showed what итраконазол inhibits cytochrome-P450-dependent synthesis of ergosterol.

It is active concerning dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum), drozhzhepodobny mushrooms of Candida spp. (including C.albicans, C.glabrata, C.krusei), mold mushrooms (Cryptococcus neoformans, Aspergillus spp., Histoplasma spp., Paracoccidioides brasiliensis, Sporothrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatitidis), etc.

Pharmacokinetics. After intake absolute bioavailability of drug of an itrakonazol makes about 55%. The maximum bioavailability is observed at joint reception with food.

At reception of a double dose of drug increase in concentration of an itrakonazol in a blood plasma is observed three times.

Itrakonazol, mainly, is metabolized in a liver, the main metabolite is hydroxy-itrakonazol. Itrakonazol contacts proteins of a blood plasma for 99.8%, and hydroxy-itrakonazol for 99.5%.
Itrakonazol is distributed in different body tissues. Concentration of an itrakonazol in lungs, kidneys, a liver, a bone tissue, a stomach, a spleen, skeletal muscles by 2–3 times exceeds its concentration in a blood plasma. Accumulation it in skin by 4 times exceeds its level in a blood plasma. Therapeutic concentration of an itrakonazol in skin remains for 2–4 weeks after the termination of a 4 weeks course of therapy. Therapeutic concentration of an itrakonazol in a keratin of nails is reached in 1 week from an initiation of treatment and remains for 6 months after end of a 3-month course of treatment. Therapeutic concentration in tissues of a vagina remain for 2 days after the termination of a 3-day course of treatment in a dose of 200 mg/days and 3 days after one-day use in a dose of 200 mg 2 times a day. Allocation also happens to a secret grease and sweat glands of skin. Final half-life of an itrakonazol makes about 17 hours after reception of a single dose, raises till 34-42 o'clock at repeated administration of drug. After the treatment termination concentration of an itrakonazol in plasma decreases to almost indiscernible within 7 days.

Excretion of initial substance with excrements makes 3-18% of the accepted dose. Renal excretion of not changed itrakonazol makes less than 0,03% of the accepted dose. About 40% of the accepted dose are removed as inactive metabolites with urine.

Influence on concentration of an itrakonazol in a blood plasma at a liver failure is not established. In this regard, patients with a liver failure have to be under careful observation in case of use of an itrakonazol.

Indications to use:

Treatment of gynecologic diseases:

- vulvovaginal candidiasis.

Skin diseases / mucous and eye:

- dermatomycosis;

- chromophytosis;

- candidiasis of an oral cavity;

- the onychomycosis caused by dermatophytes and/or yeast;

- system mycoses;

- system aspergillosis and candidiasis;

- a cryptococcosis (including prevention of kriptokkovy meningitis);

- histoplasmosis;

- zymonematosis.

Route of administration and doses:

For optimum absorption of the Teknazol® capsule have to be accepted right after nourishing food. Capsules have to be swallowed entirely.

Indications to use	Dose	Treatment duration
Vulvovaginal candidiasis	On 200 mg (2 capsules) twice a day	1 day
	200 mg of 1 times a day	3 days
High degree of keratinization of integuments, as at a dermatofitiya of feet and palms	On 200 mg twice a day or 200 mg once a day	7 days or 30 days
Chromophytosis	200 mg (2 capsules) once a day	7 days
Orofaringealny candidiasis	100 mg once a day	15 days
At some immunokompromitirovanny persons (for example, with a neutropenia, AIDS or transferred organ transplantation) peroral bioavailability of an itrakonazol from the Teknazol® capsules can be reduced. Therefore, doubling of a dose can be required.

 

The onychomycosis caused by dermatophytes and/or yeast

Onychomycosis Pulse therapy

Doses and duration of treatment

Pulse therapy includes reception on two capsules twice a day (on 200 mg twice a day) within one week. In case of fungal infections of nails of hands carrying out two courses, and fungal infections of nails of feet – three courses is recommended. Courses pulse therapy have to be always divided by a 3 weeks break. The clinical answer includes regeneration of nails after the therapy termination.

Place of localization of an onychomycosis

1 week

2 week

3 week

4 week

5 week

6 week

7 week

8 week

9 week

Nails of fingers of feet with/without damage of nails of fingers of hands

Pulse 1

Break between courses of treatment itrakonazoly

Pulse 2

Break between courses of treatment itrakonazoly

Pulse 3

Only nails of fingers of hands

Pulse 1

Break between courses of treatment itrakonazoly

Pulse 2

Onychomycosis Long treatment

Dose

Treatment duration

Nails of fingers of feet with/without damage of nails of fingers of hands

200 mg once a day

3 months

Removal of an itrakonazol from skin and nail plates happens more slowly, in comparison with plasma. Thus, the optimum clinical and mycologic answer is reached in 1-4 weeks after the termination of treatment of fungal infections of skin and in 6-9 months after the termination of treatment of fungal infections of nails.

Duration of treatment of system fungal infections depends on the mycologic and clinical response to therapy, and is defined by the attending physician:

System mycoses
Indications to use	Dose	Notes
Aspergillosis	200 mg (2 capsules) once a day	The dose is raised to 200 mg twice a day in case of the invasive or disseminated disease form, duration of treatment of 2-5 months
Candidiasis	100 - 200 mg (1-2 capsules) once a day	Dose 3 weeks-7 months increase to 200 mg twice a day in case of the invasive or disseminated disease form, treatment duration
Not meningeal cryptococcosis	200 mg (2 capsules) once a day	Duration of treatment is from 2 months till 1 year
Cryptococcal meningitis (prevention and treatment of easy forms)	200 mg (2 capsules) twice a day	Duration of treatment is from 2 months till 1 year
Histoplasmosis	200 mg (2 capsules) once a day 200 mg (2 capsules) twice a day	Duration of treatment is 8 months
Zymonematosis	100 mg once a day – on 200 mg twice a day	Duration of treatment is 6 months

Use for patients with a liver and renal failure: data on use of peroral dosage forms of an itrakonazol for patients with a liver and liver failure are limited. Treatment of the considered group of patients has to be carried out with care.

Children: now there are not enough data on use of an itrakonazol for children.

Features of use:

Complications from heart. In a research in/in a dosage form of the itrakonazol which is carried out with participation of healthy volunteers it was reported about passing asymptomatic decrease in fraction of emission of a left ventricle. This indicator was recovered before the following infusion of drug. Clinical relevance of the given observation for peroral dosage forms of drug is not known. According to available data, итраконазол possesses negative inotropic effect, and against the background of treatment by the drug Teknazol® it was reported about cases of congestive heart failure. Heart failure was more often mentioned in spontaneous messages at treatment by drug in the general daily dose of 400 mg, in comparison with messages on treatment in lower general daily doses that allows to assume increase in risk of heart failure at the raised daily dose of an itrakonazol.

The drug Teknazol® is not recommended to patients with congestive heart failure or having congestive heart failure in the anamnesis (except for cases when the advantage of such treatment, undoubtedly, exceeds its risk). At ratio assessment advantage/risk for certain patients it is necessary to consider such factors as the indication to use, the dosing mode (for example, the general daily dose) and existence of risk factors of development of congestive heart failure (a heart disease, including coronary heart disease and damages of heart valves, a serious illness of a respiratory organs, including the chronic obstructive pulmonary disease, a renal failure and other diseases which are followed by tendency to hypostases). Such patients have to be warned about symptomatology of congestive heart failure, require special attention at treatment and control of emergence of symptoms of congestive heart failure during its carrying out. At identification of the corresponding symptoms administration of drug of Teknazol® should be stopped. Blockers of calcium channels possess negative inotropic effect that can lead to strengthening of the corresponding action of an itrakonazol at co-administration of these drugs. Besides, итраконазол inhibits metabolism of blockers of calcium channels. Thus, in connection with the increased risk of development of ZSN simultaneous treatment itrakonazoly and blockers of calcium channels has to be carried out with care.

Potential of interactions. The drug Teknazol® can enter clinically significant medicinal interactions. (See the section "Medicinal interactions)

Influence of reduced acidity of a gastric juice. Reduced gastric acidity leads to disturbance of absorption of an itrakonazol from the Teknazol® capsules. Kisloto-neytralizuyushchiye drugs (for example, aluminum hydroxide) have to be accepted at least in 2 hours after reception of the Teknazol® capsules. To patients with an achlorhydria, including to patients with AIDS and to the patients accepting blockers of acid secretion (for example, antagonists of H2 receptors, inhibitors of a proton pomp), Teknazol is recommended to wash down with sweet aerated water capsules.

Complications from a liver. Against the background of treatment the drug Teknazol® very seldom reported about cases of a heavy hepatotoxic, including several cases of a fatal acute liver failure. Most of them developed at patients with the preexisting damage of a liver who received Teknazol® on system indications and at the same time had other significant diseases and/or accepted other medicines with a hepatotoxic action. Some patients had no obvious risk factors of damage of a liver. Several cases developed in the first month of therapy, including in the first week. Against the background of treatment by the drug Teknazol® it is necessary to control function of a liver. Patients have to be warned about what about emergence of the symptoms assuming hepatitis such as anorexia, nausea, vomiting, fatigue, an abdominal pain or darkening of urine, it is necessary to tell the doctor at once. In these cases it is necessary to stop immediately administration of drug of Teknazol® and to carry out assessment of function of a liver. To patients with the increased levels of enzymes of a liver, an active disease of a liver or signs of the hepatotoxic caused by other medicines, it is possible to carry out treatment only in cases when its estimated advantage exceeds risk of damage of a liver. Such patients need regular control of level of enzymes of a liver.

Liver failure. Data on use of peroral dosage forms of an itrakonazol for patients with a liver failure are limited. Treatment of the considered group of patients has to be carried out with care.

Renal failure. Data on use of peroral dosage forms of an itrakonazol for patients with a renal failure are limited. Treatment of the considered group of patients has to be carried out with care.

Immunokompromitirovanny patients. At some immunokompromitirovanny persons (for example, with a neutropenia, AIDS or transferred organ transplantation) peroral bioavailability of an itrakonazol from the Teknazol® capsules can be reduced.

Patients with zhizneugrozhayushchy system mycoses. Due to the pharmacokinetic properties of an itrakonazol (see the section "Pharmacokinetics") the ТекназолÒ capsules are not shown for performing treatment of patients with zhizneugrozhayushchy system mycoses.

Patients with AIDS. Need of a maintenance therapy of patients with AIDS having risk of a recurrence of such system mycoses as a sporotrichosis, a zymonematosis, histoplasmosis or a cryptococcosis (meningeal and not meningeal forms) after performing therapy, is established by the attending physician.

Hypersensitivity cross-reactions. The development of cross-reactions of hypersensitivity given whenever possible between itrakonazoly and other antifungal drugs of an azolovy row is absent. The decision on purpose of the Teknazol® capsules to patients with hypersensitivity to other drugs of an azolovy row has to be made reasonably.

Neuropathy. In case of development of neuropathy (which can be side effect of the Teknazol® capsules) administration of drug has to be stopped.

Hearing loss. During treatment itrakonozoly it was reported about a temporary or constant hearing loss. The concomitant use of quinidine was mentioned in several messages that is a contraindication to drug use. Hearing is, as a rule, recovered after the treatment termination, however the hearing loss can remain at some patients.

Pregnancy and period of a lactation. In need of use of Teknazola® in the period of a lactation, breastfeeding should be stopped as итраконазол it can be allocated with breast milk.

The women of childbearing age accepting Teknazol® have to use appropriate methods of contraception. Effective contraception has to be continued also in the first menstrual cycle after completion of treatment by the drug Teknazol®.

Features of influence of medicine on ability to manage the vehicle or potentially dangerous mechanisms. Taking into account possible development of such side effects as a sight illegibility, dizziness, it is necessary to be careful at control of vehicles or potentially dangerous mechanisms.

Side effects:

Very seldom (<1/10 000), including single messages:

- leukopenia, neutropenia, thrombocytopenia;

- serum disease, Quincke's disease, anaphylactic, anaphylactoid and allergic reactions;

- gipertriglitseridemiya, hypopotassemia;

- peripheral neuropathy, paresthesia, hypesthesia, headache, dizziness;

- illegibility and ambiguity of sight, diplopia;

- ring/sonitus, passing or constant hearing loss;

- congestive heart failure;

- asthma, fluid lungs;

- pancreatitis, abdominal pain, vomiting, dyspepsia, nausea, diarrhea, lock, loss of appetite, taste disturbance;

- reversible increase in liver enzymes, hepatitis, crushing toxic damage of a liver, including cases of an acute liver failure with a lethal outcome;

- toxic epidermal necrolysis, Stephens-Johnson's syndrome, acute generalized exanthematous пустулез, mnogoformny erythema, exfoliative dermatitis, leykotsitoklastichesky vasculitis, small tortoiseshell, alopecia, photosensitivity, rash, itch;

- mialgiya, arthralgia;

- pollakiuria, urine incontience;

- disturbance of a menstrual cycle, erectile dysfunction;

- hypostasis, fever.

Interaction with other medicines:

The medicines breaking absorption of an itrakonazol. Absorption of an itrakonazol from the Teknazol® capsules is broken by the medicines reducing acidity of a gastric juice (see the section "Special Instructions").

The medicines breaking metabolism of an itrakonazol. Itrakonazol is preferential metabolized by system of CYP3A4 cytochrome. Researches of interactions with rifampicin, rifabutiny and Phenytoinum which are powerful inductors of CYP3A4 enzymes were conducted. The decrease in bioavailability of an itrakonazol and hydroxy-itrakonazola revealed in these researches assumes decrease in efficiency of the studied substance therefore co-administration of an itrakonazol with these fermental inductors is not recommended. Official results of researches of other fermental inductors, such as carbamazepine, phenobarbital and an isoniazid, are not available yet, however it is possible to expect similar observations. Inhibitors of this fermental system, such as ритонавир, индинавир, кларитромицин and erythromycin, can increase bioavailability of an itrakonazol.

Influence of an itrakonazol on metabolism of other medicines. Intrakonazol has an inhibiting effect on metabolism of medicines, metaboliziruyemy family of cytochrome 3A. It leads to strengthening and/or lengthening of their effects including side effects. Before appointing drugs, it is necessary to find out ways of their metabolism in the corresponding instructions. After the treatment termination itrakonazoly its concentration in plasma decreases gradually, depending on a dose and duration of treatment (You watch the section "Pharmacokinetics"). It is necessary to remember it when forecasting an inhibiting effect of an itrakonazol for at the same time appointed medicines.

During treatment itrakonazoly reception of the following drugs is contraindicated:

- астемизол, bepridit, цизаприд, дофетилид, левацетилметадол (levometadit), мизоластин, Pimozidum, quinidine, сертиндол and terfenadit (their co-administration can lead to increase in concentration of these medicinal substances in plasma that can cause lengthening of an interval of QT, and in rare instances - piruetno-ventricular tachycardia);

- GMG-KOA-reduktazy inhibitors, metaboliziruyemy CYP3A4, such, as ловастатин and симвастатин;

- to triazoles and peroral dosage forms of midazolam;

- ergot alkaloids, such as dihydroergotamine, ergometrine (эргоновин), ergotamine and methylergometrine (метилэргоновин);

- нисолдипин.

Due to the increased risk of development of ZSN, co-administration of an itrakonazol and blockers of calcium channels has to be carried out with care. In addition to the possible pharmacokinetic interactions mediated by enzyme of medicinal metabolism CYP3A4, blockers of calcium channels possess negative inotropic effect which can strengthen the corresponding action of an itrakonazol.

The following medicines have to be appointed with care that means control of their concentration in plasma, effects or side effects. There can be a need for a dose decline:

- peroral anticoagulants;

- HIV protease inhibitors, such, as индинавир, ритонавир and саквинавир;

- some antineoplastic drugs, such as бусульфан, dotsetakset, триметрексат and periwinkle alkaloids;

- blockers of calcium channels, metaboliziruyemy CYP3A4, such as dihydropyridines and verapamil;

- some immunodepressants: cyclosporine, рапамицин (сиролимус) and такролимус;

- some inhibitors of GMG-KOA-reduktazy, metaboliziruyemy CYP3A4, such, as аторвастатин;

- some glucocorticosteroids, such, as будесонид, dexamethasone, флутиказон and Methylprednisolonum;

- digoxin (interacts through R-glycoprotein inhibition);

- other drugs: alfentanil, to alprazola, brotiozolam, буспирон, carbamazepine, цилостазол, Disopyramidum, эбастин, элетриптан, fentanyl, галофантрин, V/V midazolam, ребоксетин, репаглинид, рифабутин.

Interaction of an itrakonazol with a zidovudine (AZT) and fluvastatiny was not defined. The inducing action of an itrakonazol on metabolism of ethinylestradiol and Norethisteronum was not observed.

Influence on linkng with proteins. In the researches in vitro interaction between itrakonazoly and Imipraminum, propranolol, diazepam, Cimetidinum, indometacin, Tolbutamidum and Sulfamethazinum which would influence the level of linkng of an itrakonazol with proteins of plasma was not defined.

Contraindications:

- hypersensitivity to an itrakonazol or other excipients of drug.

During treatment by the drug Teknazol® reception is contraindicated:

- inhibitors of GMG-KOA-reduktazy, metaboliziruyemy CYP3A4, such, as ловастатин and симвастатин;

- triazolam and peroral dosage forms of midazolam;

- alkaloids of an ergot, such as dihydroergotamine, ergometrine (эргоновин), ergotamine and methylergometrine (метилэргоновин);

- nisoldipina;

- drugs, metaboliziruyemy CYP3A4 which can extend QT interval, for example, of an astemizol a bepridila, a tsizaprida, a dofetilida, a levatsetilmetadol (levometadil), a mizolastin, Pimozidum, quinidine, a sertindol and a terfenadin (because of increase in concentration of these medicinal substances in plasma that can cause lengthening of an interval of QT, and in rare instances - piruetno-ventricular tachycardia);

- existence of symptoms of ventricular dysfunction of heart (for example, the congestive heart failure (CHF) now or the anamnesis), except for cases of treatment of zhizneugrozhayushchy or other serious infections;

- pregnancy and period of a lactation;

- children's and teenage age up to 18 years.

Overdose:

Data are absent.

Treatment: symptomatic treatment. A gastric lavage, the prima of a sorbent if necessary (as a sorbent it is possible to give absorbent carbon). Itrakonazol is not brought at a hemodialysis.

The special antidote is not established.

Storage conditions:

To store in the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children! Period of storage 3 years. Not to apply after a period of storage.

Issue conditions:

According to the recipe

Packaging:

On 4 or 5 capsules place in a blister strip packaging from a film of polyvinyl chloride and printing aluminum foil.

On 1 (with 4 capsules), 3 or 6 (with 5 capsules) planimetric packagings together with the instruction on a medical use in the state and Russian languages place in a pack cardboard with the hologram of manufacturing firm.