ITRAZOL

Active material: Itraconazole
When ATH: J02AC02
CCF: Antifungal agent
ICD-10 codes (testimony): B35.0, B35.1, B35.2, B35.3, B35.4, B35.6, B36.0, B37.0, B37.1, B37.2, B37.3, B37.4, B37.6, B37.7, B37.8, B39, B40, B41, B42, B44, B45, H19.2
When CSF: 08.01.01
Manufacturer: JSC Vertex (Russia)

Pharmaceutical form, composition and packaging

Capsules hard gelatin, №0, white; contents of capsules – Pellets (spherical microgranules) from light yellow to brownish-yellow.

Excipients: wheat starch, poloxamer (lutrol), gipromelloza, sucrose.

Ingredients of the capsule shell: gelatin, Titanium dioxide.

6 PC. – packings Valium planimetric (1) – packs cardboard.
7 PC. – packings Valium planimetric (2) – packs cardboard.
6 PC. – plastic jars (1) – packs cardboard.
14 PC. – plastic jars (1) – packs cardboard.

Pharmacological action

Antifungal agent. Itraconazole – synthetic antifungal broad spectrum, triazole derivative. It inhibits the synthesis of ergosterol cell membrane of fungi, which makes the antifungal effect of the drug.

Itraconazole active against Infections, caused by dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum), yeast fungi and yeasts (Cryptococcus neoformans, Pityrosporum spp., Candida spp., including Candida albicans, Candida glabrata, Candida krusei), Aspergillus spp., Histoplasma spp., P. brasiliensis, Sporothrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatidis, as well as other yeast and fungi.

Pharmacokinetics

Absorption

It is drawn from the blood adequately. After oral administration, C_max plasma levels reached within 3-4 no. Admission itraconazole immediately after a meal increases the bioavailability.

Distribution

Chronic administration of C_ss It reached within 1-2 weeks. C_ss Itraconazole plasma through 3-4 hours after administration of 0.4 ug / ml (100 upon receipt mg 1 time / day), 1.1 ug / ml (200 upon receipt mg 1 time / day) and 2 ug / ml (200 upon receipt mg 2 times / day).

Plasma protein binding is 99.8%.

Itraconazole penetrates well into tissues and organs (incl. vaginal mucosa), contains sebaceous and sweat glands. Concentrations in Lung, kidney, liver, bones, stomach, spleen and skeletal muscle in 2-3 times higher than corresponding concentrations in plasma; tissue, soderzhashtih keratin, – in 4 times.

Therapeutic concentrations persist in the skin for 2-4 weeks after stopping 4 weeks of treatment. Itraconazole is found in nail keratin after 1 week after initiation of treatment and stored, at least, during 6 months after 3 months of therapy. Low concentrations of itraconazole are also defined in the sebum and sweat glands.

Metabolism

Itraconazole is metabolized in the liver with the formation of active metabolites, incl. gidroksiitrakonazol. It is an inhibitor of CYP3A4 isoenzymes, CYP3A5, CYP3A7.

Deduction

Withdrawal from the plasma is biphasic. Excretion in the feces is from 3% to 18% dose (in unchanged form). It is also excreted by the kidneys within 1 of the week (0.03% – in unchanged form, 35% – as metabolites).T_1/2 – 1-1.5 day.

Not removed by hemodialysis.

Testimony

- Ringworm;

- Fungal keratitis;

- Onychomycosis, caused by dermatophytes and / or yeasts and molds;

- Systemic mycosis: systemic aspergillosis and candidiasis, kryptokokkoz (including cryptococcal meningitis), histoplasmosis, sporotrichosis, Paracoccidioidomycosis, blastomycosis and other systemic or tropical mycoses;

- Candidiasis with skin lesions or mucous (incl. vulvovaginal candidiasis);

- Chromophytosis.

Dosage regimen

Itrazol^® It should be taken into, after meal.

The capsules should be swallowed whole.

Table 1.

Onixomikoz

Pulse therapy (cm. Table 2).

One course of pulse therapy is taken daily Itrazola^® by 2 capsules 2 times / day (by 200 mg 2 times / day) during 1 of the week.

For the treatment of fungal infections of the nail plate brushes recommended 2 exchange rate.

For the treatment of fungal infections of the nail plate is recommended to stop 3 exchange rate. The interval between courses, during which do not need to take the drug, is 3 of the week.

Clinical results become apparent after treatment, as regrowth of the nail.

Table 2.

Continuous therapy

By 2 capsules 1 time / day (by 200 mg 1 time / day) during 3 Months.

Withdrawal of itraconazole from skin and nail tissue is slower, than from plasma. Thus, Optimal clinical and mycological effects are achieved through 2-4 weeks after the end of treatment for skin infections and after 6-9 months after the end of treatment of nail infections.

Systemic fungal infections

Recommended doses vary depending on the type of infection.

Table 3.

Side effect

From the digestive system: dyspepsia, nausea, abdominal pain and constipation, anorexia, reversible increases in liver enzymes, cholestatic jaundice, hepatitis; rarely – severe liver toxicity, incl. Cases of acute hepatic failure with a fatal outcome.

From the central and peripheral nervous system: headache, fatiguability, dizziness, perifericheskaya neuropathy.

Allergic reactions: itch, rash, hives, angioedema, Stevens-Johnson syndrome.

Other: menstrual irregularities, alopecia, kaliopenia, swelling, congestive heart failure and pulmonary edema, staining of urine a dark color, giperkreatininemiя.

Contraindications

- Simultaneous application of drugs, metabolized by CYP3A4 isoenzyme (terfenadine, astemizolom, mizolastinom, cizapridom, dofetilidom, xinidinom, pimozidom, simvastatin, lovastatin, triazolamom, midazolamom);

- Children up to age 3 years;

- Pregnancy;

- Lactation (breast-feeding);

- Hypersensitivity to the drug.

FROM caution the drug should be used in patients with severe heart failure, liver diseases (incl. accompanied by hepatic insufficiency).

Pregnancy and lactation

The drug is contraindicated during pregnancy and lactation (breast-feeding).

Women of childbearing age, receiving Itrazol^®, you must use adequate contraception methods during the course of treatment until the onset of the first menstrual period after its completion.

Cautions

In the study of / in the dosage form of the drug Itrazol^®, conducted in healthy volunteers, It noted a transient asymptomatic decrease in left ventricular ejection fraction, normalize until the next infusion. The clinical relevance of the data obtained for oral dosage forms unknown.

Detected, itraconazole has a negative inotropic effect. Cases of heart failure, associated with taking Itrazola^®. The drug should not be used in patients with heart failure or with the presence of this disease in history except in cases, when the potential benefit significantly outweighs the potential risk.

Calcium channel blockers can have negative inotropic effect, which may exacerbate this effect itraconazole; itraconazole can reduce the metabolism of calcium channel blockers. At the same time taking itraconazole and calcium channel blockers should be careful.

At low acidity of gastric absorption of itraconazole is broken. Patients, receiving antacids (eg, aluminum hydroxide), it is recommended to use no earlier than 2 hours after taking the capsules Itrazola^®. Patients with achlorhydria or applied histamine H₂-receptors or proton pump inhibitors is recommended to take the capsule Itrazola^® with acidic beverages.

With prolonged use of itraconazole (more 1 Months), when used in patients itraconazole, receiving other medications, possessing hepatotoxic, and in patients with liver disease are advised to regularly monitor liver function. Patients should be warned about the need to immediately contact your doctor in case of symptoms, suggesting the occurrence of hepatitis, namely: anoreksii, nausea, vomiting, weakness, abdominal pain and dark urine. In the event of such symptoms should immediately discontinue therapy and to conduct a study of liver function.

Patients with kidney failure by decreasing the bioavailability of itraconazole may be necessary to adjust the dose.

Treatment should be discontinued in case of neuropathy, which may be associated with taking capsules Itrazola^®.

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

In patients with impaired immunity (AIDS, after organ transplantation, neutropenic) You may need to increase the dose.

Use in Pediatrics

Use of the drug in older children 3 years It recommended only, if the potential benefit of therapy outweighs the potential risk.

Effects on ability to drive vehicles and management mechanisms

Effects on ability to drive the car and work with the technique was not observed.

Overdose

Data not available.

Treatment: within the first hour should be carried out gastric lavage, and if necessary, assign activated carbon. Itraconazole not appear in hemodialysis. There is no specific antidote.

Drug Interactions

Drugs, affecting the metabolism of itraconazole

It was studied the interaction of itraconazole with rifampicin, rifabutin, and phenytoin. Concomitant use of itraconazole with these drugs, are potential inducers of liver enzymes, not recommended. Interaction studies with other hepatic enzyme inducers, such as carbamazepine, phenobarbital and isoniazid, not carried out, However, similar results can be assumed.

Unnecessarily. itraconazole osnovnom metaboliziruetsya izofermentom CYP3A4, potential inhibitors of this enzyme may increase the bioavailability of itraconazole. Examples include ritonavir, indinavir, clarithromycin and эritromitsin.

Effect of itraconazole on the metabolism of other drugs

Itraconazole can inhibit the metabolism of drugs, cleaved by the CYP3A4 isoenzyme. The result can be increased or prolongation of their actions, incl. and side effects.

Preparations, which can not be administered concurrently with itraconazole:

- Terfenadine, astemizol, mizolastin, cisapride, triazolam, midazolam, dofetilid, quinidine, pimozid, HMG-CoA reductase, Taki how simvastatin and lovastatin.

- Calcium channel blockers can have negative inotropic effect, which can amplify the same effect, shown by itraconazole. At the same time taking itraconazole and calcium channel blockers should be careful, tk. metabolism of calcium channel blockers may be reduced.

Preparations, in which the assignment must monitor their concentrations in plasma, action, side effects (in the case of co-administration with itraconazole doses of these drugs, if necessary, be reduced):

- Oral anticoagulants;

- HIV protease inhibitors, such as ritonavir, indinavir, saquinavir;

- Certain cancer drugs, such as vinca alkaloids, busulfan, docetaxel, trimetrexate;

- Cleavable CYP3A4 isoenzyme calcium channel blockers, such as dihydropyridine and verapamil;

- Some immunosuppressive agents: cyclosporine, tacrolimus, sirolimus;

- Other preparations: Digoxin, Carbamazepine, buspirone, alfentanil, alprazolam, ʙrotizolam, rifabutin, methylprednisolone, eʙastin, reboxetine.

The interactions between itraconazole and zidovudine and fluvastatin is not found.

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

Effect on plasma protein binding

In vitro studies have demonstrated a lack of competition for binding to plasma proteins between itraconazole and these medications, as imipramine, propranolol, diazepam, cimetidine, Indomethacin, tolbutamide and sulfamethazine.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children, dry, dark place at a temperature no higher than 25 ° C. Shelf life – 2.5 year.