Orungamin, capsules 100mg, 14pcs

Composition

Per 1 capsule:

itraconazole pellets 455 mg (Active ingredient:

itraconazole 100 mg,

Auxiliary substances:

hypromellose (hydroxypropylmethylcellulose E-5),

butylmethacrylate,

dimethylaminoethylmethacrylate and methyl methacrylate copolymer [1: 2: 1] (eudragite E-100),

sucrose (sugar)).

Solid gelatin capsules No. 0.

Capsule composition: body:

gelatin; cap: indigo carmine dye, titanium dioxide, gelatin.

Pharmacological action

Itraconazole is a synthetic broad-spectrum antifungal agent derived from triazole. Inhibits the synthesis of ergosterol of the fungal cell membrane, which causes the antifungal effect of the drug.

Itraconazole is active against:

• dermatophytes (Trichophyton spp, Microsporum spp, Epidermophyton floccosum),
• yeasts Candida spp. (including Candida albicans, Candida parapsilosis),
• fungi (Cryptococcus neoformans, Aspergillus spp., Trichosporon spp. Geotrichum spp. Penicillium mameffei, Pseudallescheria boydii, Histoplasma spp., Coccidioides immitis, Responsible braziliensis, Sporothrix schenckii. Fonsecaea spp., Cladosporium spp., Blastomyces dermatidis), Malassezia spp..

Some strains may be resistant to itraconazole: C. glabrata, C. krusei, C. tropicalis, Absidia spp., Fusarium spp., Mucor spp., Rhizomucor spp.. Rhizopus spp., Scedosporium proliferans, Scopulariopsis spp.. The effectiveness of treatment is evaluated in 2-4 weeks after discontinuation of therapy (for systemic mycoses), in 6-9 months-for onychomycosis (as the nails change).

Pharmacokinetics

When administered orally, the maximum bioavailability of itraconazole is noted when taking capsules immediately after a meal. The maximum plasma concentration is reached within 3-3.5 hours after oral use and is 28.34 ng / ml. With prolonged use, the equilibrium concentration is reached within 1-2 weeks. Itraconazole is 99.8% bound to plasma proteins. The concentration of itraconazole in the blood is 60% of the plasma concentration. The accumulation of the drug in keratin tissues, especially in the skin, is approximately 4 times higher than the accumulation in plasma, and the rate of its elimination depends on the regeneration of the epidermis.

Unlike plasma concentrations, which are undetectable as early as 7 days after discontinuation of therapy, therapeutic skin concentrations persist for 2-4 weeks after discontinuation of the 4-week course of treatment. Itraconazole is detected in nail keratin as early as one week after starting treatment and persists for at least 6 months after completing a 3-month course of therapy. Itraconazole is also detected in sebum and to a lesser extent in sweat.

Itraconazole is well distributed in tissues that are susceptible to fungal lesions. Concentrations in the lungs, kidneys, liver, bones, stomach, spleen, and muscles were 2-3 times higher than the corresponding plasma concentrations. Therapeutic concentrations in the vaginal tissues remain for another 2 days after the end of a 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 to form active metabolites, including hydroxyitraconazole. It is an inhibitor of the isoenzymes CYP3A4, CYP3A5 and CYP3A7.

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

Indications

* damage to 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 mycoses:

• systemic aspergillosis and candidiasis;
• cryptococcosis (including cryptococcal meningitis): in patients with immunodeficiency and in all patients with central nervous system cryptococcosis, itraconazole should be prescribed only if first-line drugs are not applicable in this case or are not effective;
• histoplasmosis;
• sporotrichosis;
• paracoccidioidosis;
• blastomycosis;
• other rare systemic mycoses.

Contraindications

1. Hypersensitivity to itraconazole or excipients.

2. Chronic heart failure, including in the anamnesis (except for the treatment of life-threatening conditions).

3. Simultaneous use of the following medications:

• drugs metaboliziruemami the isoenzyme CYP3A4, which can lengthen the QT interval (astemizole, bepridil, cisapride, dofetilide, levacetylmethadol, mizolastine, pimozide, quinidine, sertindole, terfenadine);
• inhibitors of HMG-COA reductase, metabolized by CYP3A4 (simvastatin, lovastatin);
• oral triazolam, and midazolam;
• preparations of ergot alkaloids (dihydroergotamine, ergometrine, ergotamine and methylergometrine);
• nisoldipine, eletriptan.

4. Children under 3 years of age.

5. Fructose intolerance, sucrose/isomaltase deficiency, glucose-galactose malabsorption.

WITH CAUTION — renal / hepatic insufficiency, peripheral neuropathy, risk factors for chronic heart failure (coronary heart disease, heart valve damage, severe lung diseases, including chronic obstructive pulmonary disease, conditions accompanied by edematous syndrome), hearing impairment, simultaneous use of slow calcium channel blockers, children and the elderly.

Side effects

From the side of hematopoietic organs:  leukopenia, neutropenia, and thrombocytopenia.

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

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

From the side of metabolism:  hypertriglyceridemia, hypokalemia.

Nervous system disorders:  peripheral neuropathy, paresthesia, hypesthesia, dizziness.

From the side of the organs of vision and hearing:  visual impairment, including blurring and diplopia, tinnitus, and temporary or permanent deafness.

From the cardiovascular system:  congestive heart failure.

Respiratory system disorders:  pulmonary edema.

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

From the musculoskeletal system:  myalgia, arthralgia.

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

Other services:  edema.

Interaction

Drugs that affect the absorption of itraconazole.

Drugs that reduce the acidity of gastric juice disrupt the absorption of itraconazole, which is associated with the solubility of capsule shells.

Drugs that affect the metabolism of itraconazole.

Itraconazole is mainly metabolized by the CYP3A4 isoenzyme. When used concomitantly with rifampicin, rifabutin, and phenytoin, which are powerful inducers of the CYP3A4 isoenzyme, the bioavailability of itraconazole and hydroxyitraconazole is significantly reduced, which leads to a significant decrease in the effectiveness of the drug. Concomitant use of itraconazole with these drugs, which are potential inducers of microsomal liver enzymes, is not recommended.

Potent inhibitors of the CYP3A4 isoenzyme, such as ritonavir, indinavir, clarithromycin, and erythromycin, may 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 CYP3A isoenzymes. This may result in an increase or prolongation of their action, including side effects. When using concomitant medications, it is necessary to study information related to their metabolism. After discontinuation of treatment, plasma concentrations of itraconazole decrease gradually depending on the dose and duration of treatment (see section “Pharmacokinetics”). This should be taken into account when evaluating the inhibitory effect of itraconazole on the metabolism of concomitantly administered drugs.

Medications that are not recommended to be administered concomitantly with itraconazole:

* Terfenadine, astemizole, bepridil, mizolastine, cisapride, dofetilide, quinidine, pimozide, sertindol, levacetylmethadol, HMG-CoA reductase inhibitors such as simvastatin and lovastatin.

* Midazolam for oral use and triazolam.

* Ergot alkaloid preparations such as dihydroergotamine, ergometrine, ergotamine, and methylergometrine.

* Nisoldipine

* Slow calcium channel blockers may have a negative inotropic effect, which is enhanced when taken concomitantly with itraconazole. Caution should be exercised when taking itraconazole and slow calcium channel blockers at the same time, as the metabolism of slow calcium channel blockers may be reduced.

Drugs that are recommended for simultaneous use to monitor their plasma concentrations, effects, and side effects.

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

• indirect anticoagulants;

• the HIV protease inhibitors (ritonavir, indinavir, saquinavir);

• some anticancer drugs (the Vinca alkaloids, including vincristine and vinblastine; busulfan, docetaxel, trimetrexate);

• metaboliziruemami a CYP3A4 blockers “slow” calcium channels (verapamil and dihydropyridine derivatives);

• some immunosuppressive agents (cyclosporine, tacrolimus, sirolimus);

• some metaboliziruemami by CYP3A4, inhibitors of HMG – COA reductase inhibitor (atorvastatin);

• some corticosteroids (budesonide, dexamethasone, fluticasone and methylprednisolone);•. digoxin (due to inhibition of P-glycoprotein);

* other drugs: carbamazepine, buspirone, alfentanil, alprazolam, brotisolam, midazolam for intravenous use, rifabutin, Ebastine, reboxetin, cilostazol, disopyramide, halofantrin, repaglinide, fentanyl.

There was no interaction between itraconazole, zidovudine, and fluvastatin. There was no effect of itraconazole on the metabolism of ethinyl estradiol and norethisterone. Effect on protein binding.

In vitro studies have shown no interaction between itraconazole and drugs such as imipramine, propranolol, diazepam, cimetidine, Indometacin, tolbutamide, and sulfamerazine when binding to plasma proteins.

How to take, course of use and dosage

Inside, after eating. Onychomycosis — 200 mg once a day for 3 months or 200 mg twice a day for 1 week, followed by a break of 3 weeks; for onychomycosis of the feet,3 courses of treatment are recommended, for hands-2 courses; vulvovaginal candidiasis-200 mg 2 times for 1 day or 200 mg 1 time a day for 3 days; Pityriasis versicolor-200 mg once a day for 7 days; dermatomycosis and candidiasis of the oral cavity-100-200 mg once a day for 7-15 days (if necessary, repeat the course); fungal keratitis-200 mg once a day for 21 days; systemic mycoses-100-200 mg 1-2 times a day for 2-12 months (depending on the pathogen).

Overdose

No data available. In case of accidental overdose, within the first hour after taking the drug, gastric lavage should be performed, and activated charcoal should be taken.

Symptomatic treatment. Hemodialysis is not effective. There is no specific antidote.

Special instructions

• To prevent reinfection, simultaneous treatment of sexual partners and personal hygiene is necessary. During the treatment period, it is recommended to refrain from sexual contact. If signs of infection persist after treatment is completed, a second microbiological examination should be performed to confirm the diagnosis.

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

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

• Some patients experienced transient and permanent deafness when taking itraconazole.

* 1 capsule of orungamin contains 4 bread units (XE).

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 25°C. Keep out of reach of children.

Shelf

life is 3 years. Do not use after the expiration date

Active ingredient

Itraconazole

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

Children as prescribed by a doctor, Adults as prescribed by a doctor

Indications

Scalp Fungus, Skin Fungus, Thrush, Fungus, Nail Fungus