Itrazol, capsules 100mg, 14pcs

Composition

1 capsule contains:

Active ingredient:

itraconazole 100 mg;

Auxiliary substances:

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

Pharmacological action

Intrazole is an antifungal agent.

Pharmacodynamics

Itraconazole is a synthetic broad-spectrum antifungal agent derived from triazole. Inhibits the synthesis of ergosterol of the fungal cell membrane, 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, Sporothrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatidis, as well as other yeast and mold fungi.

Pharmacokinetics

It is absorbed from the gastrointestinal tract quite fully. Taking itraconazole capsules immediately after a meal increases bioavailability. Cmax in plasma is reached within 3-4 hours after oral use. Css when taking 100 mg of the drug 1 time a day — 0.4 mcg / ml; when taking 200 mg 1 time a day-1.1 mcg/ml,200 mg 2 times a day-2 mcg/ml.

The time of onset of Css in plasma with prolonged use is 1-2 weeks. Binding to plasma proteins is 99.8%.

It penetrates well into tissues and organs (including the mucous membrane of the vagina), is contained in the secret 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 is maintained for 2-4 weeks after discontinuation of the 4-week course of treatment. The therapeutic concentration in nail keratin is reached 1 week after the start of treatment and persists for 6 months after the completion of a 3-month course of treatment. Low concentrations are detected in the sebaceous and sweat glands of the skin.

It is metabolized in the liver to form active metabolites, including hydroxyitraconazole. It is an inhibitor of the isoenzymes CYP3A4, CYP3A5 and CYP3A7.

Elimination from plasma is two — phase: by the kidneys for 1 week (35% – in the form of metabolites,0.03% – unchanged) and through the intestine (3-18% – unchanged). T1 / 2 — 1-1.5 days. It is not removed during dialysis.

Indications

• ringworm;
• fungal keratitis;
• the 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 system or tropical mycoses;
• kandidomikoz with a lesion of the skin or mucous membranes, including vulvovaginal candidiasis;
• pityriasis versicolor.

Contraindications

• individual hypersensitivity to the drug or its component parts;
• concomitant use of drugs metabolized with the participation of the enzyme CYP3A4: terfenadine, astemizole, mizolastine, cisapride, dofetilide, quinidine, pimozide, inhibitors of HMG-COA reductase such as lovastatin and simvastatin, triazolam and midazolam (see “Interaction”);
• pregnancy;
• lactation;
• children’s age (up to 3 years).

With caution:  severe heart failure; liver diseases (including those accompanied by liver failure). Itrazol® is recommended for use in children over 3 years of age only if the potential benefit outweighs the potential risk.

Side effects

From the gastrointestinal tract:  dyspepsia, nausea, abdominal pain and constipation, reversible increase in liver enzyme activity, cholestatic jaundice, hepatitis, anorexia. In very rare cases, when using the drug Itrazol® severe toxic liver damage developed, including a case of acute liver failure with a fatal outcome.

From the central nervous system:  headache, fatigue, dizziness, peripheral neuropathy.

From the CCC side:  congestive heart failure and pulmonary edema.

From other organs and systems:  menstrual disorders, allergic reactions (such as pruritus, rash, urticaria, and angioedema), Stevens-Johnson syndrome, alopecia, hypokalemia, edema, dark urine staining, and hypercreatininemia.

Interaction

DRUGS that affect the metabolism of itraconazole

The interaction of itraconazole with rifampicin, rifabutin, and phenytoin was studied. Concomitant use of itraconazole with these drugs, which are potential inducers of liver enzymes, is not recommended. Interaction studies with other inducers of hepatic enzymes, such as carbamazepine, phenobarbital and isoniazid, have not been conducted, but similar results can be assumed due to the fact that itraconazole is mainly metabolized by the CYP3A4 enzyme, powerful 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 broken down by the CYP3A4 enzyme. The result of this may be an increase or prolongation of their action, including side effects.

Drugs that should not be administered concomitantly with itraconazole

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

– BCC may have a negative inotropic effect, which may enhance the same effect shown by itraconazole. Caution should be exercised when taking itraconazole and BCC at the same time, as the metabolism of BCC may be reduced.

Drugs that need to be monitored for their plasma concentrations and effects, side effects, etc.

In the case of concomitant use with itraconazole, the dose of the following drugs should be reduced, if necessary:

– oral anticoagulants;

– the HIV protease inhibitors such as ritonavir, indinavir, saquinavir;

– some anticancer drugs such as the Vinca alkaloids, busulfan, docetaxel, trimetrexate;

– splitting enzyme BPC CYP3A4, such as verapamil;

– some immunosuppressive tools: cyclosporine, tacrolimus, sirolimus;

– other medications: digoxin, carbamazepine, buspirone, was Alfentanil alprazolam, brotizolam, rifabutin, methylprednisolone, Ebastinee, reboxetine.

Interactions between itraconazole and zidovudine and fluvastatin were not detected.

There was no effect of itraconazole on the metabolism of ethinyl estradiol and norethisterone.

Effect on protein binding

In vitro studies have shown no competition between itraconazole and drugs such as imipramine, propranolol, diazepam, cimetidine, Indometacin, tolbutamide, and sulfadimidine when binding to plasma proteins.

How to take, course of use and dosage

Capsules Itrazole is taken orally after a meal.

Onychomycosis-200 mg 1 time a day for 3 months or 200 mg 2 times a day for 1 week, followed by a break of 3 weeks; for onychomycosis of the feet,3 courses of treatment are recommended, for hands-2 courses;

Vulvovaginal candidiasis – 200 mg 2 times for 1 day or 200 mg 1 time a day for 3 days; Pityriasis versicolor-200 mg 1 time a day for 7 days;

Dermatomycosis and candidiasis of the oral cavity-100-200 mg 1 time a day for 7-15 days (if necessary, repeat the course);

Fungal keratitis-200 mg once a day for 21 days; systemic mycoses-100-200 mg 1-2 times a day for 2-12 months (depending on the pathogen).

Overdose

No data available.

Treatment:  during the first hour, perform gastric lavage and, if necessary, prescribe activated charcoal, symptomatic treatment. Itraconazole is not eliminated by hemodialysis. There is no specific antidote to the drug.

Special instructions

Women of childbearing age taking Itrazol® should use adequate contraceptive measures throughout the course of treatment until the first menstrual period occurs after its completion.

When studying the IV dosage form of itraconazole, a transient, asymptomatic decrease in the left ventricular ejection fraction was noted, which normalized until the next infusion of the drug.

Itraconazole has a negative inotropic effect. Cases of itraconazole-related heart failure have been reported. Itraconazole should not be used in patients with CHF or a history of this disease, unless the possible benefit significantly outweighs the potential risk.

BCAAs may have a negative inotropic effect, which may increase the similar effect of itraconazole; itraconazole may reduce the metabolism of BCAAs. Caution should be exercised when taking itraconazole and BCC at the same time.

With low stomach acidity, the absorption of itraconazole is disrupted. Patients taking antacid medications (such as aluminum hydroxide) are advised to use them no earlier than 2 hours after taking Itrazol ® capsules. Patients with achlorhydria or using H2-histamine receptor blockers or proton pump inhibitors are recommended to take Itrazole ® capsules with acidic drinks.

With prolonged use of itraconazole (more than 1 month), when using itraconazole in patients receiving other drugs with hepatotoxic effects, as well as patients with liver diseases, it is recommended to regularly monitor liver function. Patients should be warned to contact their doctor immediately if they experience symptoms that suggest hepatitis, such as anorexia, nausea, vomiting, weakness, abdominal pain, and dark urine. If such symptoms occur, therapy should be stopped immediately and liver function tests should be performed.

In patients with renal insufficiency, the bioavailability of itraconazole may be reduced, and therefore dose adjustment is necessary.

Treatment should be discontinued if neuropathy occurs, which may be associated with taking Itrazole capsules. There are no data on cross-hypersensitivity to itraconazole and other azole antifungal drugs. Itrazol ® capsules should be used with caution in patients with hypersensitivity to other azoles.

In patients with compromised immunity (AIDS, post-organ transplant, neutropenia), an increase in the dose of Itrazole®may be required.

Form of production

Capsules

Storage conditions

In a dark place, at a temperature not exceeding 25 °C

Shelf

life 2.5 years

Active ingredient

Itraconazole

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

Adults as prescribed by a doctor, Children as prescribed by a doctor, Pregnant women as prescribed by a doctor

Indications

Thrush