Orungamin - instructions for use, dose, side effects, contraindications

Itraconazole pellets 455 mg: active substance: itraconazole 100 mg; Excipients: hypromellose (hydroxypropylmethylcellulose E-5), butyl methacrylate, dimethylaminoethyl methacrylate and methyl methacrylate copolymer [1: 2: 1] (eudragit E-100), sucrose (sugar).

Capsules hard gelatinous № 0.

Capsule composition: body: gelatin; cap: indigo carmine dye, titanium dioxide, gelatin.

Description:

Capsules № 0, lid - opaque blue, body - transparent natural gelatin. The contents of the capsules are spherical microgranules from almost white to cream colored.

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:

dermatophytes (Trichophyton spp, Microsporum spp, Epidermophyton floccosum);
yeast fungi Candida spp. (including Candida albicans, Candida parapsilosis);
molds fungi (Cryptococcus neoformans, Aspergillus spp., Trichosporon spp., Geotrichum spp., Penicillium marneffei, Pseudallescheria boydii, Histoplasma spp., Coccidioides immitis, Paracoccidioides brasiliensis, Sporothrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatidis), Malassezia spp.

Some strains may be are stable to action itraconazole: FROM. glabrato, FROM. Krusei, FROM. tropicalis, Absidia spp., Fusorium spp., Mucor spp., Rhizomucor spp., Rhizopus spp., Scedosporiumpraliferam. Scopulariopsis spp.

The effectiveness of treatment is estimated after 2-4 weeks after discontinuation of therapy (with systemic fungal infections), after 6-9 months - with onychomycosis (as the nails change).

Pharmacokinetics:

When administered orally, the maximum bioavailability of itraconazole is noted when taking capsules immediately after meals. The maximum concentration in the plasma is reached within 3-3,5 hours after ingestion and is 28.34 ng / ml.At long reception the equilibrium concentration is reached within 1-2 weeks. Itraconazole on 99.8% binds to plasma proteins. The concentration of itraconazole in the blood is 60% of the concentration in the plasma.

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 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 2-3 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 is metabolized in the liver with the formation of active metabolites, incl. hydroxyitraconazole. Is an inhibitor of isoenzymes CYP3A4, CYP3A5 and CYP3A7.

Excretion from plasma - biphasic: kidneys for 1 week. (35% in the form of metabolites, 0.03% in unchanged form) and through the intestine (3-18% unchanged). The half-life is 1-1.5 days. It is not removed during dialysis.

Indications:

- Lesion of the skin and mucous membranes:

dermatomycosis;
vulvovaginal candidiasis;
multicolored lichen,
Candidiasis of the oral mucosa;
keratomycosis;
deep visceral candidiasis.

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

- Systemic fungal infections:

systemic aspergillosis and candidiasis,
cryptococcosis (including cryptococcal meningitis): in patients with immunodeficiency and in all patients with cryptococcosis of the central nervous system itraconazole should be prescribed only in cases where the first-line drugs are not applicable in this case or are ineffective,
histoplasmosis,
sporotrichosis,
paracoccidioidomycosis,
blastomycosis,
other seldom occurring systemic or tropical mycoses.

Contraindications:

Hypersensitivity to itraconazole or excipients.

Chronic heart failure, incl. in the anamnesis (except for therapy of life-threatening conditions).

Simultaneous reception of the following medicines:

drugs metabolized by isoenzyme CYP3A4, which can lengthen QT interval (astemizole, bepridil, cisapride, dofetilide, levacetylmetadol, misolastine, pimozide, quinidine, sertindole, terfenadine);
inhibitors of HMG-CoA reductase metabolized by isoenzyme CYP3A4 (simvastatin, lovastatin);
oral triazolam and midazolam;
preparations of ergot alkaloids (dihydroergotamine, ergometrine, ergotamine and methylergomethrin);
nisoldipine, eletriptan.

Children up to 3 years.

Intolerance to fructose, a deficiency of sugar / isomaltase, glucose-galactose malabsorption.

Carefully:

Renal / hepatic insufficiency, peripheral neuropathy, risk factors for chronic heart failure (coronary heart disease, heart valve damage, severe lung disease, incl.chronic obstructive pulmonary disease, conditions accompanied by edematous syndrome), hearing impairment, simultaneous reception of blockers of "slow" calcium channels, children and the elderly.

Pregnancy and lactation:

The use of the drug during pregnancy is possible only in cases where the intended benefit to the mother exceeds the potential risk to the fetus.

Because the itraconazole can penetrate into breast milk, if it is necessary to apply during lactation to women using itraconazole, you should stop breastfeeding.

Dosing and Administration:

Accept itraconazole inside, right after eating. Capsules should be swallowed whole.

Indication	Dose	Duration
Vulvovaginal candidiasis	200 mg twice daily or 200 mg once a day	1 day or 3 days
Multicolored lichen	200 mg once a day	7 days
Dermatomycosis of smooth skin	200 mg once a day or 100 mg once a day	7 days or 15 days


Defeats high-keratinized areas of the skin, such as the hands of the foot	200 mg twice daily or 100 mg once a day	7 days or 30 days
Candidiasis of the oral mucosa	100 mg once a day	15 days
Fungal keratitis	200 mg once a day	21 day It is possible to correct the duration of treatment taking into account the positive dynamics of the clinical picture

In candidiasis, the oral bioavailability of the drug may be reduced in some patients with impaired immunity, for example, in patients with neutropenia, AIDS patients or patients with grafted organs. In these cases, a double dose increase may be required.

Onychomycosis caused by dermatophytes and / or yeast, mold fungi
		Doses and duration of treatment
Pulse therapy		One course: daily intake of 200 mg 2 times (2 capsules 2 times a day) for one week. For treatment fungal infection of the nail plates of the fingers two courses are recommended. For treatment fungal lesions of the nail plates of the toes three courses are recommended. The interval 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	1st week	2nd week	3rd week		4th week	5th week	6th week	7th week	8th week	9th week
Lesion of the nail plates of the toes with or without defeat of the nail plates of the fingers	1st course	Weeks without reception Orungama				2 nd course	Weeks without reception Orungama			3rd course
Lesion of the nail plates of the fingers	1st kupc	Weeks without reception Orungama				2 nd course
Continuous treatment				Doses			Duration treatment
Lesion of the nail plates of the toes with or without defeat of the nail plates of the fingers				200 mg per day			3 months

The removal of itraconazole from the skin and nail tissue is slower than from the plasma. Thus, the optimal clinical and mycological effect is 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.

Other infrequent systemic mycoses
Indication	Dose	Average Duration treatment	Remarks
Aspergillosis	200 mg once a day	2-5 months	In the case of an invasive or disseminated disease, the dose should be increased to 200 mg twice a day
Candidiasis	100-200 mg once a day	from 3 weeks up to 7 months	In the case of an invasive or disseminated disease, the dose should be increased to 200 mg twice a day
Cryptococcosis (except for meningitis)	200 mg once a day	from 2 months up to 1 year
Cryptococcal meningitis	200 mg twice daily	from 2 months up to 1 year	Supportive therapy 200 mg once a day
Histoplasmosis	from 200 mg once a day to 200 mg twice a day	8 months
Blastomycosis	from 100 m g once a day to 200 mg twice a day	6 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

Side effects:

From the hematopoiesis: leukopenia, neutropenia, thrombocytopenia.

Allergic reactions: serum sickness, angioedema, anaphylactic and anaphylactoid reactions, hypersensitivity.

From the skin: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis, leukoclastic vasculitis, alopecia, photosensitivity, urticaria, rash, itching.

From the side of metabolism: hypertriglyceridemia, hypokalemia.

From the nervous system: peripheral neuropathy, paresthesia, hypoesthesia, dizziness.

On the part of the organs of sight and hearing: impaired vision, including vagueness and diplopia, tinnitus, transient or permanent deafness.

From the cardiovascular system: congestive heart failure.

From the respiratory system: pulmonary edema.

From the digestive system: abdominal pain, vomiting, nausea, diarrhea, impaired taste, increased activity of "liver" enzymes, dyspepsia, constipation, hepatitis, hyperbilirubinemia, hepatotoxicity, acute liver failure.

From the side of the musculoskeletal system: myalgia, arthralgia.

From the genitourinary system: pollakiuria, urinary incontinence, menstrual irregularity, erectile dysfunction.

Other: edema.

Overdose:

No data available. If an accidental overdose occurs within the first hour after taking the drug, you should wash the stomach, take Activated carbon. Symptomatic treatment. Hemodialysis is ineffective. There is no specific antidote.

Interaction:

Medicines that affect the absorption of itraconazole

Drugs that reduce the acidity of gastric juice, violate the absorption of itraconazole, which is due to the solubility of capsule shells.

Medicines that affect the metabolism of itraconazole

Itraconazole is mainly metabolized with the participation of isoenzyme CYP3A4. When used simultaneously with rifampicin, rifabutin, phenytoin, which are potent inducers of isoenzyme CYP3A4, bioavailability of itraconazole and hydroxyitraconazole is significantly reduced, which leads to a significant decrease in the effectiveness of the drug. Simultaneous application of itraconazole with these drugs, which are potential inducers of microsomal hepatic enzymes, is not recommended.

Powerful inhibitors of isoenzyme CYP3A4, such as ritonavir, indinavir, clarithromycin and erythromycin, can increase the bioavailability of itraconazole.

Effect of itraconazole on the metabolism of other drugs

Itraconazole can inhibit the metabolism of drugs that are substrates of isoenzymes CYP3A. The result of this may be an increase or prolongation of their action, including side effects.When using concomitant drugs, it is necessary to study the information concerning their metabolism. After discontinuation of treatment, the concentrations of itraconazole in the plasma are reduced gradually depending on the dose and duration of treatment (see section "Pharmacokinetics"). This should be taken into account when assessing the inhibitory effect of itraconazole on the metabolism of concomitantly prescribed drugs.

Medicines prescribed simultaneously with itraconazole are not recommended:

terfenadine, astemizole, bepridil, misolastine, cisapride, dofetilide, quinidine, pimozide, sertindole, levacetylmetadol, HMG-CoA reductase inhibitors, such as simvastatin and lovastatin;
midazolam for oral administration and triazolam;
preparations of ergot alkaloids, such as dihydroergotamine, ergometrine, ergotamine and methylergomethrin;
nisoldipine;
blockers of "slow" calcium channels may have a negative inotropic effect, which is enhanced by simultaneous administration with itraconazole. With the simultaneous administration of itraconazole and blockers of "slow" calcium channels, care must be taken, since the metabolism of "slow" calcium channel blockers can be reduced.

Drugs, with the simultaneous appointment of which is recommended to monitor their concentration in the plasma, the effect, side effects

If necessary, the dose of these drugs should be reduced:

indirect anticoagulants;
HIV protease inhibitors (ritonavir, indinavir, saquinavir);
Some anticancer drugs (vinca alkaloids pink, including vincristine and vinblastine; busulfan, docetaxel, trimetrexate);
metabolized by the isoenzyme CYP3A4 blockers of "slow" calcium channels (verapamil and dihydropyridine derivatives);
some immunosuppressive agents (ciclosporin, tacrolimus, sirolimus);
some metabolized by the isoenzyme CYP3A4 inhibitors of HMG-CoA reductase (atorvastatin);
some glucocorticosteroids (budesonide, dexamethasone, fluticasone and methylprednisolone);
digoxin (due to inhibition of P-glycoprotein);
other drugs: carbamazepine, buspirone, alfentanil, alprazolam, brotisolam, midazolam for intravenous administration, rifabutin, ebastine, reboxetine, cilostazol, disopyramide, halofantrine, repaglinide, fentanyl.

Interactions between itraconazole, zidovudine and fluvastatin were not detected.

There was no effect of itraconazole on the metabolism of ethinylestradiol and norethisterone.

Effect on protein binding

Research in vitro demonstrated the lack of interaction between itraconazole and such drugs as imipramine, propranolol, diazepam, cimetidine, indomethacin, tolbutamide and sulfamerazine when bound to plasma proteins.

Special instructions:

- Simultaneous treatment of sexual partners and personal hygiene are necessary to prevent reinfection. During treatment it is recommended to abstain from sexual intercourse. If signs of infection persist after treatment is complete, a second microbiological study should be conducted to confirm the diagnosis.

- The effectiveness of itraconazole for the treatment of fungal infections in severe neutropenia is unknown, so in such cases the drug should be used only if the first line of therapy is ineffective.

- If there are risk factors for chronic heart failure (ischemic heart disease, heart valve damage, severe lung disease, incl.chronic obstructive pulmonary disease, conditions accompanied by edematous syndrome) during treatment with itraconazole therapy should be discontinued.

- When taking itraconazole, some patients experienced transient and permanent deafness.

- 1 Orungamine capsule contains 4 bread units (XE).

Effect on the ability to drive transp. cf. and fur:

Impacts on the ability to drive a car and work with technology does not have.

Form release / dosage:Capsules, 100 mg.

Packaging:

5 capsules per circuit cell packaging made of polyvinylchloride film and aluminum foil printed lacquered.

By 5, 10, 15, 20, 30 or 50 capsules into a polymer container. Free space in the container is filled with cotton absorbent cotton.

One container or 1, 2, 3, 4, 5, 6, 8 or 10 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:P N002656 / 01

Date of registration:10.04.2008

The owner of the registration certificate:OZONE, LLC OZONE, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp06.11.2015

Illustrated instructions

Instructions

Orungamine (Orungamin)