Itrazol
Itrazol: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. In case of impaired renal function
- 11. For violations of liver function
- 12. Drug interactions
- 13. Analogs
- 14. Terms and conditions of storage
- 15. Terms of dispensing from pharmacies
- 16. Reviews
- 17. Price in pharmacies
Latin name: Itrazole
ATX code: J02AC02
Active ingredient: Itraconazole
Manufacturer: VERTEX (Russia)
Description and photo update: 2019-12-08
Prices in pharmacies: from 283 rubles.
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Itrazol is a systemic antifungal drug.
Release form and composition
Dosage form Itrazol - capsules: hard gelatinous, white, size No. 0; contents - pellets from light yellow to brownish-yellow color (6 pcs. in blister packs, 1 pack in a cardboard box; 7 pcs. in blister packs, 2 or 6 packs in a cardboard box).
Active ingredient: itraconazole, in 1 capsule - 100 mg.
Additional substances: sugar pellets (sucrose and corn starch), micronized poloxamer 188 (Lutrol), poloxamer 188 (Lutrol), hypromellose.
Capsule composition: titanium dioxide, gelatin.
Pharmacological properties
Pharmacodynamics
Itraconazole - the active component of Itrazol - is a synthetic broad-spectrum antifungal agent. It belongs to the derivatives of triazole and slows down the biosynthesis of ergosterol - the most important component of fungal cell membranes, which ensures their structural integrity. Disruption of ergosterol production causes changes in membrane permeability and cell lysis. This explains the antifungal effect of itraconazole.
The substance is active against infectious diseases provoked by the following fungi:
- yeast-like fungi: Geotrichum spp., Candida spp. (including crusei, C. albicans, C. parapsilosis, C. tropicalis), Trichosporon spp., Malassezia spp., Cryptococcus neoformans, Penicillium marneffei, Aspergillus spp., Pseudallescheria boydii, Histoplasma spp. (including H. capsulatum), Coccidioides immitis, Paracoccidioides brasiliensis, Blastomyces dermatitidis, Cladosporium spp., Fonsecaea spp., Sporothrix schenckii and others;
- dermatophytes: Epidermophyton floccosum, Microsporum spp., Trichophyton spp.
Varieties of Candida fungi with the least sensitivity to the action of itraconazole: Candida tropicalis, Candida glabrata and Candida crusei.
Some types of fungal microorganisms, on the vital activity and reproduction of which Itrazol does not have a clinically significant effect: Scopulariopsis spp., Zygomycetes (Absidia spp., Rhizopus spp., Mucor spp. And Rhizomucor spp.), Scedosporium spp. and Fusarium spp.
Resistance to azoles in fungi develops gradually and often results from a number of genetic mutations. Insensitivity to itraconazole is due to overexpression of the ERG11 gene, which encodes the 14α-demethylase enzyme. The latter is most susceptible to the action of azoles. ERG11 point mutations are also observed, reducing the degree of binding of azoles to enzymes and / or activating transport systems, which increases the rate of elimination of azoles. There is a cross-resistance of Candida spp. to drugs in the azole group, although resistance to one drug in this category does not necessarily mean lack of sensitivity to other drugs in the azole group. Itrazol-resistant strains of Aspergillus fumigates are also known.
Pharmacokinetics
Since itraconazole has non-linear pharmacokinetics, it accumulates in blood plasma during long-term treatment. Its equilibrium concentration is usually established approximately 15 days after the start of dosing, while the area under the concentration-time curve (AUC) and the maximum concentration of the active substance are about 4-7 times higher with repeated dosing than the corresponding indicators with a single dosing. The maximum equilibrium concentration of the active component of itraconazole in blood plasma is approximately 2 μg / ml when taking Itrazole 200 mg once a day. The final elimination half-life traditionally ranges from 16 to 28 hours with a single dose and from 34 to 42 hours with multiple doses. The content of itraconazole in blood plasma decreases to an almost undetectable value within 7-14 days after discontinuation of treatment, depending on the duration of therapy and the prescribed dose. The clearance of itraconazole decreases at higher doses of the drug due to the saturation of its metabolic pathways in the liver.
After oral administration, itraconazole is absorbed at a high rate. The maximum level of the substance in unchanged form is recorded in the blood plasma 2–5 hours after ingestion. In this case, the absolute bioavailability of the compound in oral administration is approximately 55%. The maximum bioavailability of itraconazole is recorded when the drug is taken immediately after a meal.
In patients with low acidity of gastric juice, the absorption of itraconazole decreases, for example, while taking medications that inhibit the synthesis of hydrochloric acid in the stomach (proton pump inhibitors or antagonists of H 2 -histamine receptors). The same phenomenon is observed in patients with a diagnosis of achlorhydria, accompanied by various diseases. In these patients, itraconazole on an empty stomach is better absorbed when taken with drinks that have an acidic environment (eg, non-diet cola).
The degree of binding of itraconazole to blood plasma proteins, mainly albumin, is 99.8% (for the binding of hydroxyitraconazole to albumin, this figure is 99.6%). Also, the substance has an affinity for lipids. In the blood plasma, the content of itraconazole in unchanged form is not more than 0.2%.
The apparent volume of distribution exceeds 700 liters, which indicates a significant distribution of the active component of Itrazole in the tissues. Its level in muscles, lungs, spleen, stomach, kidneys and bones is 2-3 times higher than the concentration in blood plasma. At the same time, the concentration of itraconazole in tissues, the component of which is keratin, especially in the skin, is 4 times higher than that in blood plasma. Its content in the cerebrospinal fluid is significantly lower than in the blood plasma, however, the effectiveness of itraconazole in relation to the causative agents of infections found in the cerebrospinal fluid is noted.
In vitro studies have shown that the main enzyme responsible for the metabolism of itraconazole is the CYP3A4 isoenzyme. The active substance is actively metabolized in the liver, forming many metabolites. The most important metabolite is hydroxyitraconazole, in vitro with antifungal activity comparable to that of itraconazole. Plasma levels of hydroxyitraconazole are approximately 2 times that of itraconazole.
Itraconazole is excreted mainly through the intestines (54%) and kidneys (35%) as inactive metabolites. The results of a study of the pharmacokinetics of this substance, labeled with a radioactive isotope of carbon 14 C, indicate that after ingestion through the intestine, 3-18% of the dose of itraconazole is excreted unchanged.
Since itraconazole is not significantly redistributed in the tissues containing keratin, its excretion depends on the regeneration of the epidermis. In contrast to blood plasma, the concentration of a substance in the skin is determined within 2-4 weeks after the end of therapy, which lasted 4 weeks. The concentration of itraconazole in the keratin of the nail remains practically unchanged for 6 months after the end of the course of treatment, which lasted 3 months. In this case, the substance is found in the nail plates already 1 week after the start of therapy.
Itraconazole is metabolized mainly in the liver. With a single dose of 100 mg of itraconazole in patients with liver cirrhosis, the maximum concentration of this compound was significantly lower (by 47%) than in healthy volunteers. In patients with liver cirrhosis, a single dose of the drug led to an increase in the mean half-life, which in this case was 37 ± 17 hours. In healthy volunteers, this indicator was 16 ± 5 hours. The average AUC in healthy volunteers and patients with liver cirrhosis was almost the same. There are no data on the long-term use of Itrazol in patients with liver cirrhosis.
There is currently insufficient data on the consequences of oral itraconazole in patients with renal dysfunction. In patients with uremia with an average creatinine clearance of 13 ml / min / 1.73 m 2, the AUC is slightly lower than in other patients. The pharmacokinetic parameters of itraconazole are practically not affected by hemodialysis or peritoneal dialysis performed on an outpatient basis.
Information on the long-term use of itraconazole in patients with renal dysfunction is limited. Dialysis does not affect clearance or elimination half-life of itraconazole or hydroxyitraconazole.
Information on the pharmacokinetics of itraconazole when used in children is insufficient. Clinical studies of pharmacokinetic parameters in children and adolescents (ages from 5 months to 17 years) were carried out using the drug in the form of an intravenous solution, an oral solution and capsules. Individually adjusted doses of itraconazole in the form of oral solution and capsules were 1.5–12.5 mg / kg / day when taken 1–2 times a day. When itraconazole was taken in the same daily dose 2 times a day, compared with taking it once a day, the minimum and maximum plasma concentrations of the substance were comparable to those in adult patients who received the drug once a day. No significant differences in AUC and total clearance of itraconazole depending on the patient's age have been reported. Occasionally, there was an insignificant relationship between the age of patients and the end half-life, maximum concentration and volume of distribution. The volume of distribution and the established clearance of a given substance are determined by the patient's body weight.
Indications for use
- Fungal keratitis;
- Dermatomycosis;
- Pityriasis versicolor;
- Onychomycosis caused by yeasts and molds and / or dermatophytes;
- Candidomycosis with lesions of the skin or mucous membranes (including vulvovaginal candidiasis);
- Systemic mycoses: sporotrichosis, histoplasmosis, paracoccidioidomycosis, cryptococcosis (including cryptococcal meningitis), blastomycosis, systemic aspergillosis and candidiasis, other tropical or systemic mycoses.
Contraindications
Absolute:
- Children under 3 years old;
- Pregnancy and lactation;
- Concomitant use of drugs metabolized by the CYP3A4 isoenzyme, such as mizolastine, dofetilide, quinidine, simvastatin, cisapride, astemizole, terfenadine, lovastatin, pimozide, midazolam, triazolam;
- Individual hypersensitivity to the components of Itrazol.
Relative:
- Heart failure, including a history of heart failure;
- Diseases of the liver, including those accompanied by liver failure;
- Hypersensitivity to other azoles.
Instructions for the use of Itrazol: method and dosage
Itrazol is taken orally after meals, swallowing the capsules whole and drinking water.
Recommended therapy regimens, depending on the indications:
- Vulvovaginal candidiasis: 2 capsules 2 times a day for a 1-day course or 2 capsules 1 time a day for 3 days;
- Pityriasis versicolor: 2 capsules 1 time per day for 7 days;
- Dermatomycosis of smooth skin: 2 capsules 1 time per day for a 7-day course or 1 capsule 1 time per day for 15 days;
- Oral mucosa candidiasis: 1 capsule 1 time per day for 15 days;
- Fungal keratitis: 2 capsules 1 time per day for a 21-day course (depending on the dynamics of the clinical picture, the duration of therapy can be adjusted);
- Lesions of highly keratinized areas of the skin (feet and hands): 2 capsules 2 times a day for 7 days or 1 capsule 1 time a day for 30 days.
With onychomycosis, continuous or pulse therapy can be prescribed:
- Continuous treatment means taking Itrazol 2 capsules 1 time per day for 3 months. Since itraconazole is excreted from the tissues of the skin and nails more slowly than from plasma, the optimal mycological and clinical effects are achieved 2-4 weeks after the end of the course of therapy for skin infections and 6-9 months after the end of the treatment for infections of the nail plates;
- Pulse therapy implies a daily intake of 2 capsules of Itrazol 2 times a day for 1 week. The number of such courses depends on the indications: for fungal diseases of the nails on the hands, 2 courses are carried out with a 3-week interval, for fungal diseases of the toenails (including those with damage to the nail plates of the hands) - 3 courses at 3-week intervals.
Recommended dosage regimens of Itrazol for systemic mycoses, depending on the type of infection:
- Aspergillosis: 2 capsules 1 time per day for 2-5 months. For invasive or disseminated diseases, the dose may be increased up to 2 capsules 2 times a day;
- Candidiasis: 1-2 capsules 1 time per day, the course of treatment can last from 3 weeks to 7 months. For invasive or disseminated diseases, the dose may be increased up to 2 capsules 2 times a day;
- Cryptococcosis (with the exception of meningitis): 2 capsules 1 time per day, duration of therapy - from 2 to 12 months;
- Cryptococcal meningitis: 2 capsules 2 times a day, the course of treatment is 2-12 months. Maintenance dose - 2 capsules once a day;
- Sporotrichosis: 1 capsule 1 time per day for 3 months;
- Histoplasmosis: 2 capsules 1 time per day for 8 months. If necessary, the dose can be increased to 2 capsules 2 times a day;
- Blastomycosis: 1 capsule 1 time per day for 6 months. If necessary, the dose can be increased to 2 capsules 2 times a day;
- Chromomycosis: 1-2 capsules 1 time per day for a 6-month course;
- Paracoccidioidomycosis: 1 capsule 1 time per day for 6 months.
Side effects
- From the digestive system: abdominal pain, dyspepsia, constipation, nausea, anorexia, hepatitis, cholestatic jaundice, a reversible increase in the activity of liver enzymes; extremely rarely - severe toxic liver damage, including acute liver failure with a fatal outcome;
- From the side of the central and peripheral nervous system: dizziness, fatigue, headache, peripheral neuropathy;
- Allergic reactions: urticaria, itching, rash, Stevens-Johnson syndrome, angioedema;
- Others: alopecia, edema, hypokalemia, dark urine staining, menstrual irregularities, hypercreatininemia, pulmonary edema, congestive heart failure.
Overdose
Overdose cases of Itrazol are very rare. When it occurs, it is recommended to rinse the stomach within the first hour after taking the drug in a high dose and, if necessary, take activated charcoal. There is no specific antidote. Itraconazole is not excreted by hemodialysis.
special instructions
The bioavailability of oral itraconazole may be reduced in immunocompromised patients, for example, in organ transplant patients with AIDS or neutropenia, so they may need to double the dose.
Itrazole dose adjustment may also be necessary in patients with renal insufficiency (since the bioavailability of itraconazole may decrease).
Women of childbearing age should use reliable methods of contraception during the entire course of treatment with Itrazol, up to the onset of the first menstruation after discontinuation of the drug.
Absorption of itraconazole is impaired with low stomach acidity. With the simultaneous use of antacid drugs, at least 2-hour intervals should be observed between medications. In patients with achlorhydria or receiving proton pump inhibitors or histamine H 2 -receptors Itrazol advised to take from acidic beverages.
Periodically during treatment, liver function should be monitored in patients with liver diseases, with prolonged therapy, as well as with the simultaneous use of other drugs with hepatotoxic effects. Patients should be warned about the need to immediately stop taking Itrazol and contact their doctor if they develop symptoms that suggest the development of hepatitis, such as weakness, nausea, vomiting, anorexia, abdominal pain, dark urine.
Treatment should also be discontinued if neuropathy develops.
Cases of a negative effect of Itrazol on the speed of reactions and the ability to concentrate were not recorded.
Application during pregnancy and lactation
Itrazol is prohibited during pregnancy and breastfeeding. Women with preserved reproductive function who are undergoing treatment with the drug should use reliable methods of contraception throughout the course of therapy, until the onset of the first menstruation after its completion.
With impaired renal function
Patients with renal impairment may require dose adjustment of Itrazol.
For violations of liver function
Patients diagnosed with toxic liver damage while taking other drugs, liver disease in the active stage or increased activity of liver enzymes are not recommended to undergo treatment with Itrazol, unless the potential benefit significantly outweighs the risk of liver dysfunction. In this case, the activity of liver enzymes should be constantly monitored during therapy.
Drug interactions
According to the instructions, Itrazol can inhibit the metabolism of drugs that are cleaved by the CYP3A4 isoenzyme, as a result of which it is possible to increase or prolong their action, including side effects.
Potent inhibitors of the CYP3A4 isoenzyme (clarithromycin, erythromycin, indinavir, ritonavir) can increase the bioavailability of itraconazole.
Itraconazole interacts with drugs that are potential inducers of hepatic enzymes (rifabutin, rifampicin, phenytoin), so they are not recommended to be prescribed simultaneously. Studies on the interaction with other inducers of hepatic enzymes, such as isoniazid, phenobarbital and carbamazepine, have not been conducted, however, combined use is also not recommended.
Other drugs that are not recommended for use with itraconazole: calcium channel blockers, HMG-CoA reductase inhibitors (simvastatin and lovastatin), mizolastine, astemizole, midazolam, cisapride, quinidine, terfenadine, dofetilide, triazolam, pimozide.
With the simultaneous appointment of the following drugs with Itrazol, it is necessary to monitor their concentration in the blood plasma, action and side effects (their dose may need to be reduced):
- Some immunosuppressive agents: tacrolimus, cyclosporine, sirolimus;
- HIV protease inhibitors: ritonavir, saquinavir, indinavir;
- Oral anticoagulants;
- Some anticancer drugs: pink vinca alkaloids, docetaxel, busulfan, trimetrexate;
- Calcium channel blockers, cleaved by the CYP3A4 isoenzyme: verapamil, dihydropyridine;
- Other drugs: alfentanil, buspirone, alprazolam, carbamazepine, brotizolam, methylprednisolone, rifabutin, ebastine, digoxin, reboxetine.
Analogs
Analogues of Itrazol are: Isol, Iconazol, Itracon, Itraconazole, Itral, Itrasin, Itrungar, Irunin, Metrix, Mikokur, Mikostop, Orungal, Orungamin, Orunzol, Sporagal, Sporaxol, Trioxal, Funit, Eszol.
Terms and conditions of storage
Store at a temperature not exceeding 25 ° C in a place protected from light and out of reach of children.
The shelf life is 2.5 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Itrazol
According to reviews, Itrazol is an effective drug for the treatment of diseases associated with fungal infections. Most of the patients who took it had a positive opinion of it. They claim that this drug is good for gynecological diseases (dysbiosis and vaginal candidiasis) and nail fungus.
Price for Itrazol in pharmacies
The price of Itrazol in pharmacy chains is approximately 377–388 rubles (for a pack of 6 capsules), 675–718 rubles (for a pack of 14 pcs.) And 984–1038 rubles (for a pack of 42 pcs.).
Itrazol: prices in online pharmacies
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Drug name Price Pharmacy |
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Itrazole 100 mg capsules 6 pcs. 283 r Buy |
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Itrazol capsules 100mg 6 pcs. 437 r Buy |
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Itrazol 100 mg capsules 14 pcs. 559 r Buy |
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Itrazol capsules 100mg 14 pcs. 864 RUB Buy |
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Itrazol 100 mg capsules 42 pcs. 1093 RUB Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
