Itrazol capsules 100mg, No. 14

• Dermatomycosis;

• fungal keratitis;

• onychomycosis caused by dermatophytes and / or yeasts and molds;

• systemic mycoses: systemic aspergillosis and candidiasis, cryptococcosis (including cryptococcal meningitis), histoplasmosis, sporotrichosis, paracoccidioidomycosis, blastomycosis and other systemic or tropical mycoses;

• candidomycosis with lesions of the skin or mucous membranes (including vulvovaginal candidiasis);

• pityriasis versicolor.

Reception mode is individual

Hard gelatin capsules, No. 0, white; the contents of the capsules are pellets (spherical microgranules) from light yellow to brownish yellow.

1 caps.

itraconazole (in the form of pellets) 100 mg

Excipients: sugar pellets (sucrose - 80-91.5%, corn starch - 8.5-20%) - 207.44 mg, poloxamer 188 (Lutrol) - 25.94 mg, poloxamer 188 (Lutrol) micronized - 0.51 mg, hypromellose - 130.11 mg.

• Simultaneous use with drugs metabolized by the CYP3A4 isoenzyme (terfenadine, astemizole, mizolastine, cisapride, dofetilide, quinidine, pimozide, simvastatin, lovastatin, triazolam, midazolam);

• children under 3 years old;

• pregnancy;

• lactation period (breastfeeding);

• hypersensitivity to the components of the drug.

  The drug should be used with caution in patients with severe heart failure, with liver diseases (including those accompanied by liver failure).

Trade name of the drug : ItrazolЃ

International Non-Proprietary Name (MHH) : Itraconazole

Dosage form : capsules

Composition : itraconazole pellets 464 mg
Active ingredient : itraconazole 100 mg
Excipients : wheat starch, poloxamer (Lutrol), hypromellose, sucrose Hard
gelatin capsules : gelatin, titanium dioxide.

Description : White capsules No. 0. The contents of the capsules are spherical microgranules from light yellow to brownish yellow.

Pharmacotherapeutic group : Antifungal agent
ATX code J02AC02

Pharmacological properties
Pharmacodynamics
Itraconazole is a synthetic broad-spectrum antifungal agent, a triazole derivative. Inhibits the synthesis of ergosterol of the cell membrane of fungi, which causes the antifungal effect of the drug.
Itraconazole is active against infections caused by dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum), yeast-like. fungi and yeasts (Cryptococcus neoformans, Pityrosporum spp., Candida spp., including C. albicans, C. glabrata and C. krusei); Aspergillus spp., Histoplasma spp., Paracoccidioides brasiliensis, Sporpthrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatidis, as well as other yeasts and molds.

Pharmacokinetics
Absorbed from the gastrointestinal tract is quite complete. Taking itraconazole capsules immediately after meals increases bioavailability. The maximum plasma concentration is reached within 3-4 hours after ingestion. Equilibrium concentration when taking 100 mg of the drug. Once a day 0.4 ?g / ml; when taking 200 mg 1 time per day - 1.1 ?g / ml, 200 mg 2 times a day - 2 ?g / ml.
The time of the onset of equilibrium plasma concentration with prolonged use is -1-2 weeks.
The connection with plasma proteins is 99.8%.
It penetrates well into tissues and organs (including the mucous membrane of the vagina), it is contained in the secretion of the sebaceous and sweat glands. The concentration of itraconazole in the lungs, kidneys, liver, bones, stomach, spleen, skeletal muscles is 2-3 times higher than its concentration in plasma; in tissues containing keratin - 4 times.
The therapeutic concentration of itraconazole in the skin remains for 2-4 weeks after the termination of 4 weeks of treatment. The therapeutic concentration in nail keratin is achieved 1 week after the start of treatment and persists for 6 months after the completion of 3 months of the course of treatment. Low concentrations are found in the sebaceous and sweat glands of the skin. It is metabolized in the liver with the formation of active metabolites, incl. hydroxyitraconazole. It is an inhibitor of isoenzymes CYP3A4, CYP3A5 and CYPZA7.
Excretion from plasma is two-phase: by the kidneys within 1 week (35% in the form of metabolites, 0.03% in unchanged form) and through the intestines (3-18% in unchanged form). The half-life is 1-1.5 days. Not removed during dialysis.

Indications for use

• dermatomycosis;

• fungal keratitis;

• onychomycosis caused by dermatophytes and / or yeasts and molds;

• systemic mycoses: systemic aspergillosis and candidiasis, cryptococcosis (including crypto-, coccal meningitis), histoplasmosis, sporotrichosis, paracoccidioidomycosis, blastomycosis and other systemic or tropical mycoses;

• candidomycosis with lesions of the skin or mucous membranes, including vulvovaginal candidiasis;

• pityriasis versicolor.

Contraindications

• individual hypersensitivity to the drug or its constituents;

• simultaneous administration of drugs, metabolized with the participation of the CYP3A4 enzyme: terfenadine, astemizole, mizolastine, cisapride, dofetilide, quinidine, pimozide, MMC reductase inhibitors - CoA, such as simvastatin and lovastatin, triazolam and midazolam (see also the section 'Interaction ');

• children's age up to 3 years;

• pregnancy;

• lactation period.

Mode of application:

The reception mode is individual.

Application during pregnancy and lactation

The drug is contraindicated for use during pregnancy and lactation (breastfeeding).

Women of childbearing age , taking ItrazolЃ, need to use adequate methods of contraception throughout the entire course of treatment until the onset of the first menstruation after its completion.

Application for violations of liver function

Patients with increased activity of liver enzymes or liver disease in the active phase or with previous toxic liver damage while taking other drugs should not be prescribed treatment with Itrazol unless the expected benefit justifies the risk of liver damage. In these cases, it is necessary during treatment to monitor the activity of liver enzymes.

Application for impaired renal function

Patients with renal insufficiency may require dose adjustment of the drug.

Application in children

Contraindicated in children under 3 years of age.

special instructions

In a study of the intravenous dosage form of itraconazole, conducted on healthy volunteers, there was a transient asymptomatic decrease in the left ventricular ejection fraction, which normalized until the next infusion of the drug. The clinical relevance of the data obtained for oral dosage forms is unknown.

Found that itraconazole has a negative inotropic effect. Cases of heart failure associated with taking itraconazole have been reported. The drug should not be prescribed to patients with heart failure or with a history of this disease, unless the potential benefit significantly outweighs the potential risk.

Calcium channel blockers can have a negative inotropic effect, which can enhance the similar effect of itraconazole; itraconazole may reduce the metabolism of calcium channel blockers. Caution should be exercised when taking itraconazole and calcium channel blockers at the same time.

With a decreased acidity of the stomach, the absorption of itraconazole is impaired. Patients receiving antacids (for example, aluminum hydroxide) are advised to use them no earlier than 2 hours after taking Itrazol capsules. Patients with achlorhydria or using histamine H2 receptor blockers or proton pump inhibitors are advised to take Itrazol capsules with acidic drinks.

With prolonged use of itraconazole (more than 1 month), with the use of itraconazole in patients receiving other drugs with hepatotoxic effects, as well as in patients with liver disease, it is recommended to regularly monitor liver function. Patients should be warned to contact their physician immediately if they develop symptoms suggestive of hepatitis, such as anorexia, nausea, vomiting, weakness, abdominal pain and dark urine. If such symptoms appear, it is necessary to immediately stop therapy and conduct a study of liver function.

In patients with renal insufficiency, in case of a decrease in the bioavailability of itraconazole, a dose adjustment of the drug may be required.

Treatment should be discontinued if neuropathy occurs, which may be associated with taking Itrazol capsules.

There is no evidence of cross-hypersensitivity to itraconazole and other azole antifungal drugs. ItrazolЃ should be used with caution in patients with hypersensitivity to other azoles.

In patients with impaired immunity (AIDS, after organ transplantation, with neutropenia), an increase in the dose may be required.

Use in pediatrics

The use of the drug in children over 3 years of age is recommended only if the potential benefit of therapy outweighs the potential risk.

Influence on the ability to drive vehicles and mechanisms

There was no effect on the ability to drive and work with equipment.

Overdose

No data available.

Treatment: during the first hour, gastric lavage should be performed, and if necessary, activated charcoal should be prescribed. Itraconazole is not excreted during hemodialysis. There is no specific antidote.

Drug interactions

Medicines affecting the metabolism of itraconazole

The interaction of itraconazole with rifampicin, rifabutin and phenytoin was studied. The simultaneous use of itraconazole with these drugs, which are potential inducers of hepatic enzymes, is not recommended. Interaction studies with other inducers of hepatic enzymes, such as carbamazepine, phenobarbital and isoniazid, have not been conducted, however, similar results can be assumed.

Because Itraconazole is mainly metabolized by the CYP3A4 isoenzyme, and potent inhibitors of this enzyme can increase the bioavailability of itraconazole. Examples include ritonavir, indinavir, clarithromycin, and erythromycin.

Effect of itraconazole on the metabolism of other drugs

Itraconazole can inhibit the metabolism of drugs cleaved by the CYP3A4 isoenzyme. The result of this may be an increase or prolongation of their action, incl. and side effects.

Drugs that should not be administered concomitantly with itraconazole:

• terfenadine, astemizole, mizolastine, cisapride, triazolam, midazolam, dofetilide, quinidine, pimozide, HMG-CoA reductase inhibitors such as simvastatin and lovastatin;

• calcium channel blockers can have a negative inotropic effect, which can enhance the same effect exhibited by itraconazole. Caution should be exercised while taking itraconazole and calcium channel blockers. the metabolism of calcium channel blockers may be reduced.

Drugs, in the appointment of which it is necessary to monitor their plasma concentration, action, side effects (in the case of simultaneous administration with itraconazole, the dose of these drugs, if necessary, should be reduced):

• oral anticoagulants;

• inhibitors of HIV protease such as ritonavir, indinavir, saquinavir;

• some anticancer drugs such as vinca alkaloids, busulfan, docetaxel, trimetrexate;

• CYP3A4 isoenzyme cleavable calcium channel blockers such as dihydropyridine and verapamil;

• some immunosuppressive drugs: cyclosporine, tacrolimus, sirolimus;

• other drugs: digoxin, carbamazepine, buspirone, alfentanil, alprazolam, brotizolam, rifabutin, methylprednisolone, ebastine, reboxetine.

No interactions have been found between itraconazole and zidovudine and fluvastatin.

There was no effect of itraconazole on the metabolism of ethinylestradiol and norethisetron.

Effect on plasma protein binding

In vitro studies have demonstrated that there is no competition for plasma protein binding between itraconazole and drugs such as imipramine, propranolol, diazepam, cimetidine, indomethacin, tolbutamide and sulfamethazine.

Storage conditions of the drug ItrazolЃ

The drug should be stored out of the reach of children, protected from light at a temperature not exceeding 25 ? C.

Shelf life of the drug ItrazolЃ

The shelf life is 2.5 years.

Terms of sale

The drug is available with a prescription.