Itrazol

Itrazol is a triazole derivative; broad-spectrum antifungal drug for systemic use.

Release form and composition

Itrazol is available in the form of capsules with a mass of 560 mg (6 or 7 pieces in blisters; 6 or 14 pieces in polymer cans).

The active ingredient is itraconazole, it contains 100 mg in 1 capsule.

Auxiliary components: poloxamer 188, poloxamer 188 micronized, hypromellose and sugar pellets consisting of corn starch and sucrose.

The composition of the shell of the capsule: gelatin and titanium dioxide.

Indications for use

• Systemic mycoses: sporotrichosis, histoplasmosis, paracoccidioidomycosis, cryptococcosis (including cryptococcal meningitis), systemic candidiasis and aspergillosis, blastomycosis and other mycoses, including tropical ones;
• Fungal keratitis;
• Dermatomycosis;
• Tinea versicolor;
• Onychomycoses caused by mold fungi, yeast, dermatophytes;
• Candidomycosis with lesions of the skin or mucous membranes (including vulvovaginal candidiasis).

Contraindications

Strict contraindications to the use of itrazol:

• Pregnancy;
• Lactation period;
• Children's age up to 3 years;
• Taking drugs metabolized by the CYP3A4 isoenzyme (astemizole, terfenadine, mizolastine, quinidine, dofetilide, pimozide, cisapride, simvastatin, triazolam, lovastatin, midazolam);
• Hypersensitivity to the drug.

Patients with liver disease, severe heart failure, and hypersensitivity to other azoles should be under special observation during the treatment period with Itrazol.

For children under 3 years old, the drug is prescribed in cases of extreme necessity and on condition that the expected benefits outweigh the potential risks.

Dosing and Administration

Capsules are ingested after meals, swallowing whole and squeezed water.

Doses and duration of treatment depend on the indications:

• Vulvovaginal candidiasis: 2 caps. 2 times a day for 1 day or 2 caps. 1 time per day for 3 days;
• Pityriasis versicolor: 2 caps. 1 time per day, course duration - 7 days;
• Fungal keratitis: 2 caps. 1 time per day for 21 days. Depending on how positive the dynamics of the overall clinical picture of the disease is, the duration of therapy may be adjusted;
• Dermatomycosis of smooth skin: 2 caps. Once a day for 7 days or 1 caps. within 15 days;
• Candidiasis of the oral mucosa: 1 caps. within 15 days;
• The defeat of highly keratinized areas of the skin (including hands and feet): 2 caps. 2 times a day, a 7-day course or 1 caps. per day 30-day course.

Treatment of onychomycosis is carried out with courses of pulse therapy; one such course involves daily administration of 2 capsules 2 times a day for 1 week. In the case of damage to the nail plate only on the hands, two courses of pulse therapy are shown at 3-week intervals. With the defeat of the nails of the feet, including with the simultaneous defeat of the nail plates of the hands, 3 pulse-treatments are prescribed with 3-week intervals. In some cases, the doctor may prescribe a continuous regimen of treatment of onychomycosis - 2 caps. Once a day for 3 months.

Dose and duration of treatment for systemic mycoses:

• Candidiasis: 1-2 caps. Once a day, the duration of admission - from 3 weeks to 7 months. In the case of disseminated or invasive disease, it is possible to increase the dose to 2 caps. 2 times a day;
• Aspergillosis: 2 caps. Once a day for 2-5 months. In the case of disseminated or invasive disease, it is possible to increase the dose to 2 caps. 2 times a day;
• Cryptococcal meningitis: 2 caps. 2 times a day Treatment can last from 2 months to 1 year;
• Cryptococcosis: 1 caps. 1 time per day. Depending on the dynamics of therapy, it can last from 2 to 12 months. Maintenance dose - 1 caps. Once a day;
• Sporotrichosis: 1 caps. per day for 3 months;
• Paracoccidioidomycosis: 1 caps. per day for 6 months;
• Chromomycosis: 1-2 caps. per day, the duration of admission - 6 months;
• Histoplasmosis: from 2 caps. 1 time / day to 2 caps. 2 times / day, course - 8 months;
• Blastomycosis: from 1 caps. 1 time / day to 2 caps. 2 times / day for 6 months.

Side effects

Possible side effects of itrazol:

• Digestive system: abdominal pain and constipation, dyspepsia, nausea, cholestatic jaundice, reversible increase in liver enzymes, anorexia hepatitis; extremely rare - severe toxic liver damage (there are cases of acute liver failure with a fatal outcome);
• Central and peripheral nervous system: dizziness, fatigue, headache, peripheral neuropathy;
• Allergic reactions: rash and / or itching, urticaria, angioedema, Stevens-Johnson syndrome;
• Others: alopecia, edema, hypokalemia, menstrual disorders, hypercreatininemia, dark urine staining, pulmonary edema, congestive heart failure.

There are no official reports of cases of overdose of Itrazol. When taking too much of a dose, standard gastro-intestinal cleansing measures are recommended - gastric lavage, taking a sorbent (eg, activated carbon). There is no specific antidote for itraconazole. Hemodialysis is ineffective. Further treatment is symptomatic.

special instructions

The bioavailability of itraconazole may be reduced if immunity is impaired, for example, in patients with AIDS, patients with neutropenia or transplanted organs. They may need to increase the dose by 2 times.

Dose adjustment of Itrazol may also be necessary for patients with renal insufficiency, which is caused by a decrease in the bioavailability of itraconazole.

Regular monitoring of liver function is necessary in patients with diseases of this organ, with prolonged use of the drug (more than 1 month) and in the case of a combination of Itrazol with other drugs that have a hepatotoxic effect. Patients should be informed of the need to immediately consult a doctor if they develop symptoms that suggest the development of hepatitis, namely, weakness, nausea and / or vomiting, abdominal pain, anorexia, dark urine.

Itraconazole has been found to have a negative inotropic effect. There is also evidence that this substance can lead to the development of heart failure. For this reason, patients with heart failure, including a history, Itrazol may be prescribed only in exceptional cases where the intended benefit outweighs the possible risks.

It should also be borne in mind that calcium channel blockers can also have a negative inotropic effect, and when used simultaneously with Itrazole, it can be enhanced. If necessary, such a combination should be especially careful.

Absorption of itraconazole is impaired with low acidity of the stomach, so antacids are taken no earlier than 2 hours after administration of Itrazol. For the same reason, people who have been diagnosed with achlorhydria, as well as patients using proton pump inhibitors or histamine H ₂ -receptor blockers, should be taken with Itrazol with acidic beverages.

In case of neuropathy, treatment should be discontinued immediately.

Negative effects of the drug on the rate of psychophysical reactions and the ability to concentrate were not noted.

Drug interaction

The simultaneous administration of Itrazol with drugs that are potential inducers of hepatic enzymes - rifampicin, phenytoin and rifabutin, is not recommended. they significantly reduce the bioavailability and, consequently, the effectiveness of itraconazole. Studies about its interaction with other inducers of liver enzymes (phenobarbital, carbamazepine, isoniazid) have not been conducted, but there is every reason to assume similar results.

Itrazol should not be used simultaneously with calcium channel blockers, HMG-CoA reductase inhibitors, mizolastine, astemizole, cisapride, terfenadine, triazolam, quinidine, dofetilide, pimozide, midazolam.

Potent inhibitors of the isoenzyme CYP3A4 (for example, erythromycin, clarithromycin, ritonavir, and indinavir) increase the bioavailability of itraconazole.

Itraconazole can slow down the metabolism of drugs that biotransform with the participation of the CYP3A4 isoenzyme, because of which prolongation or enhancement of their actions and side effects is possible.

When prescribing the following drugs simultaneously with Itrazol, it is necessary to monitor their concentration in the blood, the effects and side effects, in some cases it may be necessary to reduce their dose:

• Some antitumor agents, including docetaxel, busulfan, trimetrexate, and Vinca roseal alkaloids;
• HIV protease inhibitors, incl. indinavir, ritonavir, and saquinavir;
• Oral anticoagulants;
• Calcium channel blockers that are cleaved by the CYP3A4 isoenzyme, including dihydropyridine and verapamil;
• Some immunosuppressive drugs: sirolimus, tacrolimus and cyclosporine;
• Other drugs: brotizolam, alprazolam, rifabutin, alfentanil, methylprednisolone, buspirone, ebastine, carbamazepine, reboxetine, digoxin.

Terms and conditions of storage

Store at temperatures up to 25 ºС in a dark place, out of reach of children.

Shelf life is 2.5 years.