Itrazol

Itrazol – antifungal drug of systemic action.

Form of release and structure

Dosage form – capsules: firm gelatinous, white color, size No. 0; contents – pellets from light yellow till brownish-yellow color (on 6 pieces in packagings planimetric cell, 1 packaging in a cardboard pack; on 7 pieces in packagings of planimetric cell, 2 or 6 packagings in a cardboard pack).

Active ingredient: итраконазол, in 1 capsule – 100 mg.

Additional substances: sugar pellets (sucrose and starch corn), half-oxameasures 188 (Lutrol) micronized, half-oxameasures 188 (Lutrol), a gipromelloza.

Structure of the capsule: titanium dioxide, gelatin.

Indications to use

• Fungal keratitis;
• Dermatomycoses;
• Chromophytosis;
• The onychomycoses caused by yeast and mold mushrooms and/or dermatophytes;
• Candidiases with damage of skin or mucous (including vulvovaginal candidiasis);
• System mycoses: a sporotrichosis, histoplasmosis, a paracoccidioidomycosis, a cryptococcosis (including cryptococcal meningitis), a zymonematosis, a system aspergillosis and candidiasis, other tropical or system mycoses.

Contraindications

Absolute:

• Children's age up to 3 years;
• Pregnancy and lactation;
• Simultaneous use of the drugs which are metabolized an isoenzyme of CYP3A4 such, as мизоластин, дофетилид, quinidine, симвастатин, цизаприд, астемизол, терфенадин, ловастатин, Pimozidum, midazolam, to triazoles;
• Individual hypersensitivity to drug components.

Relative:

• Heart failure, including in the anamnesis;
• The liver diseases including which are followed by a liver failure;
• Hypersensitivity to other azoles.

Route of administration and dosage

Itrazol accept inside after meal, swallowing capsules entirely and washing down with water.

The recommended schemes of therapy depending on indications:

• Vulvovaginal candidiasis: on 2 capsules 2 times a day a 1-day course or on 2 capsules of 1 times a day within 3 days;
• Chromophytosis: on 2 capsules of 1 times a day for 7 days;
• Dermatomycoses of smooth skin: on 2 capsules of 1 times a day a 7-day course or on 1 capsule of 1 times a day within 15 days;
• Candidiasis of a mucous membrane of an oral cavity: on 1 capsule of 1 times a day for 15 days;
• Fungal keratitis: on 2 capsules of 1 times a day a 21-day course (depending on dynamics of a clinical picture duration of therapy can be adjusted);
• Defeats of the high-keratinized areas of an integument (feet and hands): on 2 capsules 2 times a day for 7 days or on 1 capsule of 1 times a day within 30 days.

At an onychomycosis it can be appointed continuous or pulse therapy:

• Continuous treatment means Itrazol's reception on 2 capsules of 1 times a day within 3 months. As out of tissues of skin and nails итраконазол it is brought more slowly, than out of plasma, optimum mycologic and clinical effects are reached in 2-4 weeks after the termination of a course of therapy at infections of skin and 6-9 months later after the end of treatment of infections of nail plates;
• Pulse therapy means daily reception on 2 capsules of Itrazol 2 times a day within 1 week. The quantity of such courses depends on indications: at fungus diseases of nails on hands conduct 2 courses with a 3 weeks interval, at fungus diseases of nails standing (including with defeat of nail plates of brushes) – 3 courses with 3 weeks intervals.

The recommended dosing modes at system mycoses depending on a type of an infection:

• Aspergillosis: on 2 capsules of 1 times a day within 2-5 months. At the invasive or disseminated diseases increase in a dose up to 2 capsules 2 times a day is possible;
• Candidiasis: on 1-2 capsules of 1 times a day, the course of treatment can last from 3 weeks to 7 months. At the invasive or disseminated diseases increase in a dose up to 2 capsules 2 times a day is possible;
• Cryptococcosis (except for meningitis): on 2 capsules of 1 times a day, therapy duration – from 2 to 12 months;
• Cryptococcal meningitis: on 2 capsules 2 times a day, a course of treatment – 2-12 months. A maintenance dose – 2 capsules of 1 times a day;
• Sporotrichosis: on 1 capsule of 1 times a day within 3 months;
• Histoplasmosis: on 2 capsules of 1 times a day for 8 months. If necessary the dose can be increased to 2 capsules 2 times a day;
• Zymonematosis: on 1 capsule of 1 times a day within 6 months. If necessary the dose can be increased to 2 capsules 2 times a day;
• Chromomycosis: on 1-2 capsules of 1 times a day a 6-month course;
• Paracoccidioidomycosis: on 1 capsule of 1 times a day for 6 months.

Side effects

• From the alimentary system: abdominal pain, dyspepsia, lock, nausea, anorexia, hepatitis, cholestatic jaundice, reversible increase in activity of liver enzymes; extremely seldom – crushing toxic damage of a liver, including an acute liver failure with a lethal outcome;
• From the central and peripheral nervous system: dizziness, fatigue, headache, peripheral neuropathy;
• Allergic reactions: urticaria, itch, rash, Stephens-Johnson's syndrome, Quincke's disease;
• Others: an alopecia, hypostases, a hypopotassemia, coloring of urine in dark color, disturbances of a menstrual cycle, a giperkreatininemiya, a fluid lungs, congestive heart failure.

Special instructions

Bioavailability of the itrakonazol accepted inside can be reduced at the broken immunity, for example, at patients with transplanted organs, patients with AIDS or a neutropenia therefore double increase in a dose can be required by them.

Dose adjustment can be also necessary for patients with a renal failure (since decrease in bioavailability of an itrakonazol is possible).

Women of childbearing age should apply reliable methods of contraception during all course of treatment by Itrazol, up to approach of the first periods after drug withdrawal.

Absorption of an itrakonazol is broken at the lowered acidity of a stomach. At simultaneous use of antiacid drugs it is necessary to observe at least 2-hour intervals between receptions of medicines. To patients with an achlorhydria or _{H2 receptors} receiving inhibitors of the protonew pump or blockers histamine Itrazol is recommended to accept with acid drinks.

Periodically during treatment patients should control function of a liver with liver diseases, at long therapy, and also at simultaneous use of other medicines with a hepatotoxic action. Patients have to be warned about need to immediately stop Itrazol's reception and to see the attending physician in case of emergence at them of symptoms on the basis of which it is possible to assume development of hepatitis, such as weakness, nausea, vomiting, anorexia, an abdominal pain, urine darkening.

Treatment also should be stopped at development of a neuropathy.

Cases of a negative impact of Itrazol on the speed of reactions and ability to concentration of attention were not registered.

Medicinal interaction

Itrakonazol can inhibit metabolism of the drugs split by CYP3A4 isoenzyme owing to what strengthening or prolongation of their action, including side effects is possible.

Powerful inhibitors of an isoenzyme CYP3A4 (кларитромицин, erythromycin, индинавир, ритонавир) can increase bioavailability of an itrakonazol.

Itrakonazol interacts with the drugs which are potential inductors of liver enzymes (rifabutiny, rifampicin, Phenytoinum) therefore it is not recommended to appoint them at the same time. Researches on an interaction occasion with other inductors of liver enzymes, such as isoniazid, phenobarbital and carbamazepine, were not conducted, however the combined use is also not recommended.

Other drugs which are not recommended to be applied along with itrakonazoly: blockers of calcium channels, GMG-KOA-reduktazy inhibitors (симвастатин and ловастатин), мизоластин, астемизол, midazolam, цизаприд, quinidine, терфенадин, дофетилид, to triazoles, Pimozidum.

At co-administration of the following drugs it is necessary to watch their concentration in a blood plasma, action and side effects (decrease in their dose can be required):

• Some immunosuppressive means: такролимус, cyclosporine, сиролимус;
• HIV protease inhibitors: ритонавир, саквинавир, индинавир;
• Peroral anticoagulants;
• Some antineoplastic drugs: alkaloids of a periwinkle pink, dotsetakset, бусульфан, триметрексат;
• The blockers of calcium channels split by CYP3A4 isoenzyme: verapamil, dihydropyridine;
• Other drugs: alfentanit, буспирон, to alprazola, carbamazepine, brotiozolam, Methylprednisolonum, рифабутин, эбастин, digoxin, ребоксетин.

Terms and storage conditions

To store at a temperature not above 25 °C in the place protected from light and unavailable to children.

Period of validity – 2,5 years.