Universal reference book for medicines
Product name: ORUNGAMIN (ORUNGAMIN)

Active substance: itraconazole

Type: Antifungal medication

Manufacturer: OZONE (Russia)
Composition, form of production and packaging
Capsules
№0, with a blue opaque lid and a pink transparent casing;
the contents of the capsules are spherical microgranules from light yellow to yellowish-beige.
1 caps.

itraconazole 100 mg

5 pieces.
- packings of cellular contour (1) - packs cardboard.
5 pieces.
- packings cellular planimetric (3) - packs cardboard.
15 pcs.
- packings of cellular contour (1) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2005.

PHARMACHOLOGIC EFFECT

Antifungal preparation of a wide spectrum of action, a derivative of triazole.
The mechanism of action is associated with the ability of itraconazole to inhibit the synthesis of ergosterol from the fungal cell membrane.
It is active against dermatophytes, yeast-like fungi and yeast Trichophyton spp., Microsporum spp., Epidermophyton floccosum, Cryptococcus neoformans, Pityrosporum spp., Candida spp.
(including Candida albicans, Candida glabrata and Candida krusei), Aspergillus spp., Histoplasma spp., Paracoccidioides brasiliensis, Sporothrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatitidis.
PHARMACOKINETICS

Suction

When administered, the maximum bioavailability of itraconazole is noted when taking capsules immediately after a dense meal.
C max in plasma is achieved within 3-4 hours after ingestion.
Distribution

With long-term admission, C ss is achieved within 1-2 weeks and is 3-4 hours after taking the drug 0.4 μg / ml (when taking 100 mg 1 time / day), 1.1 μg / ml (with the intake of 200 mg 1 time / day ) and 2.0 μg / ml (with the intake of 200 mg 2 times / day).
Binding to plasma proteins - 99.8%. The accumulation of the drug in keratin tissues, especially in the skin, is about 4 times higher than the accumulation in the plasma, and the rate of its removal depends on the regeneration of the epidermis.
Unlike plasma concentrations that can not be detected after 7 days after discontinuation of therapy, therapeutic concentrations in the skin persist for 2-4 weeks after the end of the 4-week course of treatment.
Itraconazole is found in the nail keratin just 1 week after the start of treatment and persists for at least 6 months after the completion of the 3-month course of therapy. Itraconazole is also found 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 2-3 times higher than the corresponding concentrations in the plasma. Therapeutic concentrations in the tissues of the vagina persist for 2 days after the end of the 3-day course of treatment at a dose of 200 mg / day, and 3 days after the end of the one-day course of treatment at a dose of 200 mg 2 times / day.
Metabolism

Itraconazole is biotransformed in the liver with the formation of a large number of metabolites, one of which, hydroxyitraconazole, has an antifungal action comparable to itraconazole in vitro.

Excretion

Excretion from the plasma is biphasic with T 1/2 in the terminal phase from 24 h to 36 h. Through the intestine, from 3 to 18% of the dose is excreted.
Approximately 35% of the dose is excreted in the form of metabolites with urine for 1 week.
INDICATIONS

-dermatomycosis;

- fungal keratitis;

-nichomycosis 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;

-kondidomycosis with skin or mucous membrane damage, incl.
vulvovaginal candidiasis;
- deep visceral candidiasis;

-oarrow fever.

DOSING MODE

For optimal absorption of itraconazole, Orungamine must be taken immediately after a meal.
Capsules should be swallowed whole.
Indication Dose Duration

Vulvovaginal candidiasis 200 mg 2 times / day 1 day

200 mg 1 time / day 3 days

Pityriasis 200 mg 1 time / day 7 days

Dermatomycosis smooth skin 200 mg 1 time / day 7 days

100 mg 1 time / day 15 days

Fungal keratitis 200 mg 1 time / day 21 days

Lesions of highly keratinized areas of the skin, such as hands and feet, require additional treatment for 15 days at 100 mg / day

Oral candidiasis 100 mg 1 time / day 15 days

The 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.
With onychomycosis, pulse therapy is used.
One course of pulse therapy is a daily intake of 2 caps. Orungamine 2 times / day (200 mg 2 times / day) for 1 week.
For treatment of fungal lesions of the nail plates of the brushes, 2 courses are recommended.
For the treatment of fungal lesions of the nail plates of the feet, 3 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 of onychomycosis 1st week.
2 nd, 3 rd, 4 th week. 5 th week. 6th, 7th, 8th week. 9 th week.
Defeat of the nail plates of the feet with or without lesion of the nail plates of the brushes 1st course interval between courses 2nd course interval between courses 3rd course

Defeat of nail plates of brushes 1 st course of courses between courses 2 nd rate - -

With onychomycosis, it is also possible to carry out continuous therapy of 2 caps.
per day (200 mg once a day) for 3 months.
The removal of itraconazole from the skin and nail plates is slower than from the plasma.
Thus, optimal clinical and mycological effects of the drug are achieved in 2-4 weeks after the end of treatment for skin infection and 6-9 months after the end of treatment of nail infections.
With systemic mycoses, the recommended dosages vary depending on the type of infection.

Indication Dose Mean duration Notes

Aspergillosis 200 mg 1 time / day 2-5 months to increase the dose to 200 mg 2 times / day in case of invasive or disseminated disease

Candidiasis 100-200 mg 1 time / day from 3 weeks to 7 months

Cryptococcosis (except for meningitis) 200 mg 1 time / day from 2 months to 1 year -

Cryptococcal meningitis 200 mg 2 times / day from 2 months to 1 year maintenance therapy (cases of meningitis) 200 mg 1 time / day

Histoplasmosis from 200 mg 1 time / day to 200 mg 2 times / day 8 months -

Sporotrichosis 100 mg 1 time / day 3 months -

Paracoccidioidomycosis 100 mg 1 time / day 6 months -

Chromomycosis 100-200 mg 1 time / day 6 months -

Blastomycosis from 100 mg 1 time / day to 200 mg 2 times / day 6 months -

SIDE EFFECT

On the part of the digestive system: dyspepsia, nausea, abdominal pain, constipation, reversible increase in hepatic enzyme activity, cholestatic jaundice, hepatitis;very rarely - severe toxic liver damage (including cases of acute hepatic insufficiency with a lethal outcome).

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

On the part of the reproductive system: violations of the menstrual cycle.

From the side of the urinary system: hypercreatininaemia, staining the urine in a dark color.

From the metabolism: edema, hypokalemia.

From the cardiovascular system: possible congestive heart failure, edema, pulmonary edema.

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

Other: alopecia.

CONTRAINDICATIONS

- simultaneous administration of terfenadine, astemizole, misolastine, cisapride, dofetilide, quinidine, pimozide, triazolam, midazolam (metabolized with the enzyme CYP3A4);

- simultaneous administration of HMG-CoA reductase inhibitors (simvastatin, lovastatin);

-increased sensitivity to the components of the drug.

In pregnancy, Orungamine is prescribed only in cases where the expected benefit of therapy for the mother exceeds the potential risk to the fetus.

Caution is prescribed in childhood, with severe heart failure, liver diseases (including those accompanied by liver failure).

PREGNANCY AND LACTATION

Based on the results of preclinical studies and the fact that studies on the use of itraconazole in pregnant women have not been performed, itraconazole should be given to pregnant women only in life-threatening systemic fungal infections, when the potential benefit for a woman justifies the possible risk to the fetus.

Women of childbearing age who take Orungamine should use adequate contraceptive methods throughout the course of treatment until the onset of the first menstrual period after completion.

Since a small amount of itraconazole is excreted in the mother's milk, the expected benefit of taking itraconazole must be compared with the risk for the baby during breastfeeding.
In case of doubt, breastfeeding should be discarded.
APPLICATION FOR FUNCTIONS OF THE LIVER

In patients with renal insufficiency, the bioavailability of itraconazole for oral administration may be reduced (dose adjustment may be required).

APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Caution is prescribed for liver diseases (including those accompanied by liver failure).

APPLICATION FOR CHILDREN

The drug is administered with caution in childhood.

SPECIAL INSTRUCTIONS

When examining iv in the dosage form of itraconazole, conducted on healthy volunteers, there was a transient asymptomatic decrease in the left ventricular ejection fraction normalized until the next infusion of the drug.
The clinical significance of the data obtained for oral dosage forms is unknown.
Itraconazole has a negative inotropic effect.
There have been reports of heart failure associated with Orungamine administration, and therefore the drug should not be given to patients with chronic heart failure (or indicating a previous history of the disease), unless the potential benefit of such therapy is significantly greater than the potential risk. When evaluating the benefit-risk ratio individually, factors such as the severity of the indications, the dosing regimen, and individual risk factors for heart failure (including heart disease / IHD or valve lesions /, severe lung disease / obstructive pulmonary disease /, renal failure, or other) should be taken into account. diseases accompanied by edema). Patients should be informed about the signs and symptoms of heart failure. Treatment should be carried out with care, thus it is necessary to observe the patient for the purpose of revealing the symptoms of congestive heart failure. When they appear, Orungamine should be discontinued.
Calcium channel blockers (verapamil) may have a negative inotropic effect, which may enhance a 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.
With a decreased acidity of the gastric contents, the absorption of itraconazole is impaired.
Patients taking antacid preparations (for example, aluminum hydroxide), it is recommended to use them not earlier than 2 hours after taking Orungamine capsules. Patients with achlorhydria or with the use of blockers of histamine H 2 -receptors or proton pump inhibitors are advised to take Orungamine capsules with acidic drinks.
In very rare cases, using Orungamin, severe toxic liver damage developed (including cases of acute hepatic insufficiency with a fatal outcome), in most cases in patients with existing liver diseases or who received therapy for systemic indications, or other serious medical conditions, and also with combined therapy with drugs with hepatotoxic properties.
In some patients, there were no obvious risk factors for liver damage. 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. Patients should be warned about the need to consult a doctor immediately if symptoms arise that suggest hepatitis, namely: anorexia, nausea, vomiting, weakness, abdominal pain and darkening of the urine. In the case of such symptoms it is necessary to immediately stop therapy and conduct a study of liver function. Patients with increased hepatic enzyme activity or liver disease in the active phase, or with transferred toxic liver damage with other medications should not be prescribed by Orungamine, unless the expected benefit justifies the risk of liver damage. In these cases it is necessary during the treatment to monitor the activity of liver enzymes.
When the duration of Orungamine intake is more than 1 month, liver function control is necessary.

Bioavailability of the drug for oral administration is somewhat reduced in patients with cirrhosis (a dose adjustment may be required).

In patients with renal insufficiency, the bioavailability of itraconazole for oral administration may be reduced (dose adjustment may be required).

Treatment should be discontinued if neuropathy occurs, which may be associated with Orungamine administration.

There is no evidence of cross-sensitivity to itraconazole and other azole antifungal agents.
Orungamine 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 Orungamine dose may be necessary.

Use in Pediatrics

Clinical data on the use of itraconazole in children is not enough, and therefore Orungamine should be prescribed only if the possible benefit exceeds the potential risk.

OVERDOSE

To date, cases of an overdose of Orungamine have not been described.

Treatment: with an accidental overdose within the first hour after taking the drug, you should do a gastric lavage, if necessary - assign activated charcoal.Symptomatic and maintenance therapy is indicated.
Itraconazole is not removed from the body by hemodialysis. The specific antidote is not known.
DRUG INTERACTION

It is not recommended simultaneous use with rifampicin, rifabutin and phenytoin (strong inducers of microsomal liver enzymes),
these drugs can reduce the concentration of itraconazole in the blood plasma. Studies on the interaction of itraconazole with other inducers of hepatic enzymes, such as carbamazepine, phenobarbital and isoniazid, have not been carried out, but a similar effect can be expected.
Because
itraconazole is mainly metabolized with the participation of the cytochrome P 450 isoenzyme CYP3A4, strong inhibitors of this enzyme (including ritonavir, indinavir, clarithromycin and erythromycin) can increase the bioavailability of itraconazole.
Itraconazole can inhibit the metabolism of drugs that are biotransformed with the participation of the CYP3A4 isoenzyme.
The result of this can be an increase or prolongation of their action (including side effects). In the course of treatment with itraconazole, drugs metabolized by the isoenzyme CYP3A4 (terfenadine, astemizole, misolastine, cisapride, triazolam, midazolam, dofetilide, quinidine, pimozide), HMG-CoA reductase inhibitors (simvastatin and lovastatin) should not be used.
Calcium channel blockers have a negative inotropic effect, which can enhance the similar effect of itraconazole;
Itraconazole may reduce the metabolism of calcium channel blockers (use of this combination requires caution).
Preparations, when used simultaneously with itraconazole, require monitoring of their concentrations in the blood plasma and, if necessary, dose reduction: oral anticoagulants;
HIV protease inhibitors (ritonavir, indinavir, saquinavir); some anticancer drugs (vinca alkaloids pink, busulfan, docetaxel, trimetrexate); calcium channel blockers metabolized with the participation of the CYP3A4 isoenzyme (dihydropyridine and verapamil); Some immunosuppressants (cyclosporine, tacrolimus, sirolimus); other drugs - digoxin, carbamazepine, buspirone, alfentanil, alprazolam, brothisolam, rifabutin, methylprednisolone, ebastin, reboxetine. With simultaneous use with itraconazole, if necessary, the dose of these drugs should be reduced.
Interactions between itraconazole and zidovudine and fluvastatin were not detected.
There was no effect of itraconazole on the metabolism of ethinylestradiol and norethisterone.
In vitro studies have demonstrated a lack of competition between itraconazole and such drugs as imipramine, propranolol, diazepam, cimetidine, indomethacin, tolbutamide and sulfamethazine for binding to plasma proteins.

TERMS AND CONDITIONS OF STORAGE

List B. The drug should be stored in a dry, protected from light, out of reach of children at a temperature of no higher than 25 ° C.
Shelf life - 3 years.
Conditions of leave from pharmacies

The drug is released by prescription.

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