Irunin - instructions for use, doses, side effects, contraindications

Itraconazole pellets - 464 mg [itraconazole - 100 mg, hypromellose (hydroxypropylmethylcellulose) - 130.17 mg, methacrylic acid copolymer (eudragit) - 16.26 mg, methylparahydroxybenzoate (nipagin) - 0.08 mg, propyl parahydroxybenzoate (nipazole) - 0, 01 mg, sugar grits - 163.17 mg, sucrose (sugar) - 54.31 mg].

Capsules hard gelatinous №0 yellow color:

Titanium dioxide - 1.3333%, dye quinoline yellow - 0.9197%, dye sunset yellow - 0.0044%, gelatin - up to 100%.

Description:

Capsules of yellow color № 0.The contents of capsules are spherical pellets of white or almost white color.

Pharmacotherapeutic group:Antifungal agent

ATX: & nbsp

J.02.A.C.02 Itraconazole

Pharmacodynamics:

Itraconazole is a synthetic broad-spectrum antifungal agent, a triazole derivative. Inhibits the synthesis of ergosterol cell membrane of fungi, which determines the antifungal effect of the drug.

Itraconazole is active against infections caused by dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum), yeast-like fungi and yeast (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 dermatitidis, as well as other yeast and mold fungi.

Pharmacokinetics:

When administered orally, the maximum bioavailability of itraconazole is noted when taking capsules immediately after a dense meal. The maximum concentration in the plasma is reached within 3-4 hours after ingestion. Excretion from the plasma is biphasic with a terminal elimination half-life of 1 to 1.5 days. At long reception the equilibrium concentration is reached within 1-2 weeks. The equilibrium concentration of itraconazole in the plasma 3-4 hours after taking the drug is 0.4 μg / ml (100 mg on admissiononce a day), 1.1 μg / ml (200 mg once a day) and 2.0 μg / ml (200 mg twice daily). Itraconazole 99.8% binds to plasma proteins.

The accumulation of the drug in keratin tissues, especially in the skin, is about 4 times higher than the accumulation in the blood plasma, and its elimination rate depends on the regeneration of the epidermis.

Unlike plasma concentrations that are not detectable within 7 days after cessation of therapy, therapeutic concentrations in the skin persist for 2-4 weeks after discontinuation of a 4-week course of treatment. Itraconazole is found in the nail keratin within one week after the start of treatment and is maintained for at least 6 months after the completion of the 3-month course of therapy. Itraconazole is also determined in sebum and to a lesser extent in sweat.

Itraconazole is well distributed in tissues that are prone to fungal lesions. Concentrations in the lungs, kidneys, liver, bones, stomach, spleen and muscles were two to three times higher than the corresponding concentrations in the plasma. Therapeutic concentrations in the tissues of the vagina persist for another 2 days after the end of the 3-day course of treatment at a dose of 200 mg per day,and 3 days after the end of a one-day course of treatment at a dose of 200 mg twice a day. Itraconazole metabolized by the liver with the formation of a large number of metabolites. One such metabolite is hydroxy-itraconazole, which has an antifungal action comparable to itraconazole in vitro. Antifungal concentrations of the drug, determined by the microbiological method, were approximately 3 times higher than the concentrations measured by HPLC. It is excreted through the gastrointestinal tract from 3 to 18% of the dose. Kidney excretion is less than 0.03% of the dose. Approximately 35% of the dose is excreted as metabolites in urine for 1 week.

Indications:

- Dermatomycosis;

- fungal keratitis;

- onychomycosis caused by dermatophytes and / or yeast and mold fungi;

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

- Candidomycosis with a lesion of the skin or mucous membranes, including vulvovaginal candidiasis;

- deep visceral candidiasis; pityriasis lichen.

Contraindications:

- Individual hypersensitivity to the drug or its constituents;

- simultaneous reception of drugs metabolized with the participation of an enzyme CYP3A4: terfenadine, astemizole, misolastine, cisapride, dofetilide, quinidine, pimozide, GMK-CoA reductase inhibitors, such as simvastatin and lovastatin, triazolam and midazolam (see also the section "Interactions with other drugs").

Carefully:

Childhood age, severe heart failure, liver disease (including those accompanied by liver failure), chronic renal failure.

Pregnancy and lactation:

Pregnant women Irunin® should be prescribed only if the expected benefit for a woman exceeds the potential risk to the fetus.

Since a small amount of itraconazole is excreted in the mother's milk, during the period of treatment it is necessary to refuse breastfeeding.

Dosing and Administration:

Inside, after eating.

Indication	Dose	Duration
Vulvovaginal candidiasis	200 mg twice a day or 200 mg once a day	1 day 3 days
Peregrine lichen	200 mg once a day	7 days
Dermatomycosis smooth skin	200 mg once a day 100 mg once a day	7 days 15 days
Fungal keratitis	200 mg once a day	21 day
Lesions of highly keratinized areas of the skin, such as hands and feet, require additional treatment for 15 days at 100 mg per day.
Oral candidiasis	100 mg once a day	15 days
Bioavailability of itraconazole for oral administration may be reduced in some patients with impaired immunity, for example, in patients with neutropenia, AIDS patients or organ transplants. Therefore, a double dose increase may be required.

Onychomycosis

Pulse therapy (see the table)

One course of pulse therapy is the daily intake of 2 capsules of Irunin® twice a day (200 mg twice a day) for one week.

Two courses are recommended for the treatment of fungal lesions of the nail plates of the brushes. For treatment of fungal lesions of the nail plates of the feet, three courses are recommended (see table). The gap between the courses, during which you do not need to take the drug, is 3 weeks.

Clinical results will become evident after the end of treatment, as the nails grow.

Localization

onychomycosis

1 st

ned.

2nd

ned.

3rd

ned.

4th

ned.

5th

ned.

6th

ned.

7th

ned.

8th

ned.

9th

ned.

Lesions of the nail plates of the feet with or without defeat of the nail plates of the brushes

1st

course

Weeks are free from taking Irunin®

2 nd

course

Weeks are free from taking Irunin®

3rd

course

Lesion of the nail plates of brushes

1st

course

Weeks are free from taking Irunin®

2 nd

course

Continuous treatment:

Two capsules per day (200 mg once a day) for 3 months.

Irunin® excretion from the skin and nail tissue is slower than from the plasma. Thus, optimal clinical and mycological effects are achieved in 2-4 weeks after the end of treatment for skin diseases and 6-9 months after the end of treatment of nail diseases.

Systemic mycoses (the recommended dosages vary depending on the type of infection)

Indication	Dose	Average Duration	Remarks
Aspergillosis	200 mg once a day	2-5 months	Increase the dose to 200 mg twice a day in case of invasive or disseminated disease
Candidiasis	100-200 mg once a day	from 3 weeks to 7 months
Cryptococcosis (except meningitis)	200 mg once a day	from 2 months to 1 year	Supportive therapy (cases of meningitis) 200 mg once a day
Cryptococcal meningitis	200 mg twice daily	from 2 months to 1 year
Histoplasmosis	from 200 mg once a day to 200 mg twice daily	8 months
Sporotrichosis	100 mg once a day	3 months
Paracoccidioidomycosis	100 mg once a day	6 months
Chromomycosis	100-200 mg once a day	6 months
Blastomycosis	from 100 mg once a day to 200 mg twice daily	6 months

Side effects:

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

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

From the side of the cardio-cardiovascular system: congestive heart failure and pulmonary edema.

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

Overdose:

No data available.During the first hour, wash the stomach and, if necessary, assign Activated carbon, symptomatic treatment.

Itraconazole is not excreted by hemodialysis. There is no specific antidote.

Interaction:

1. Medicines that affect the metabolism of itraconazole.

The interaction of itraconazole with rifampicin, rifabutin and phenytoin was studied. Simultaneous use of itraconazole with these drugs, which are powerful inducers of liver enzymes, is not recommended. Studies of interaction with other inducers of hepatic enzymes, such as carbamazepine, phenobarbital and isoniazid, were not conducted, however, similar results can be assumed.

As itraconazole mainly metabolized by enzyme CYP3A4, powerful inhibitors of this enzyme can increase the bioavailability of itraconazole. Examples are ritonavir, indinavir, clarithromycin and erythromycin.

2. The effect of itraconazole on the metabolism of other drugs.

Itraconazole can inhibit the metabolism of enzyme-cleavable drugs CYP3A4. The result of this may be an increase or prolongation of their action, including side effects.

Drugs that can not be administered simultaneously with itraconazole:

telfenadine, astemizole, misolastine, cisapride, triazolam and oral midazolam, dofetilide, quinidine, pimozide, HMG-CoA reductase inhibitors, such as simvastatin and lovastatin;
bcalcium channel locators can have a negative inotropic effect, which can enhance the same effect as itraconazole. With the simultaneous administration of itraconazole and calcium channel blockers, care must be taken, as the metabolism of calcium channel blockers can be reduced.

Preparations, in the appointment of which it is necessary to monitor their concentration in the plasma and, by the action of side effects

In the case of simultaneous administration with itraconazole dose of these drugs, if necessary, should be reduced:

Poral anticoagulants;
andHIV protease inhibitors, such as ritonavir, indinavir, saquinavir;
Mr.Some anticancer drugs, such as alkaloids Barvinka pink, busulfan, docetaxel, trimetrexate;
Renzyme-cleaved CYP3A4 calcium channel blockers, such as verapamil;
Mr.Some immunosuppressive agents: ciclosporin, tacrolimus, sirolimus;
dOther drugs: digoxin, carbamazepine, buspirone, alfentanil, alprazolam, brotisolam, rifabutin, methylprednisolone, ebastine, 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.

3. Effect on protein binding.

Research in vitro demonstrated a lack of competition between itraconazole and such drugs as imipramine, propranolol, diazepam, cimetidine, indomethacin, tolbutamide and sulfadimidine when binding to plasma proteins.

Special instructions:

- Women of childbearing age who take Irunin® need to use adequate contraceptive measures throughout the course of treatment until the onset of the first menstrual period after completion.

- When studying the intravenous drug form of the drug Itraconazole there was a transient asymptomatic decrease in the left ventricular ejection fraction,normalized to the next infusion of the drug.

- It was found that itraconazole has a negative inotropic effect. There have been reports of cases of heart failure associated with taking Irunin®. Irunin ® should not be taken in patients with chronic heart failure or with a history of the disease, unless the potential benefit far exceeds the potential risk.

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

- In patients with renal insufficiency, the bioavailability of itraconazole can be reduced, which may require dose adjustment.

- With a reduced acidity of the stomach, the absorption of itraconazole is disrupted. Patients taking antacid preparations (for example, aluminum hydroxide), it is recommended that they be used no earlier than 2 hours after taking Irunin® capsules. Patients with achlorhydria or using H₂-gystamine blockers or proton pump inhibitors, it is recommended to take Irunin® capsules with acidic drinks.

- In very rare cases, Irunin® developed severe toxic liver damage, including cases of acute hepatic insufficiency with a fatal outcome. This happened with patients who already had liver diseases, as well as patients who received other drugs that have a hepatotoxic effect. Several such cases occurred in the first month of therapy, and some in the first week of treatment. In this regard, it is recommended to regularly monitor liver function in patients receiving itraconazole therapy.

- Treatment should be discontinued if neuropathy occurs, which may be associated with the use of Irunin®.

- There is no evidence of cross-sensitivity to itraconazole and other azole antifungal agents. Irunin® in capsules should be administered with caution to patients with hypersensitivity to other azoles.

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

Effect on the ability to drive transp. cf. and fur:Not observed.

Form release / dosage:Capsules, 100 mg.

Packaging:

By 5, 6, 7, 10, 14 or 15 capsules in a contour mesh box made of a polyvinylchloride light-protective film and aluminum foil printed lacquer.

By 5, 6, 7, 10, 14 or 15 capsules in a can of light-protective glass with a triangular corolla type BTS, ukuporennuyu cover lid with a sealing element.

Each jar or 1, 2 or 3 contour squares, together with instructions for use, are placed in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N001638 / 01

Date of registration:30.05.2008 / 29.01.2016

Expiration Date:Unlimited

The owner of the registration certificate:VEROPHARM SA VEROPHARM SA Russia

Manufacturer: & nbsp

VEROPHARM SA Russia

Representation: & nbspVEROPHARM, AO VEROPHARM, AO Russia

Information update date: & nbsp28.11.2017

Illustrated instructions

Instructions

Irunin® (Irunin®)