Orungamin

Orungamin – the anti-mycotic medicine of a broad spectrum of activity derivative of triazole; shows activity concerning yeast, drozhzhepodobny mushrooms and dermatophytes.

Form of release and structure

Dosage form of drug Orungamin – capsules: No. 0, blue opaque lid and transparent gelatinous case; contents – spherical microgranules (pellets – 0,455 g) from yellowish-beige till light yellow color (on 15 capsules in blister strip packagings, 1 packaging in a cardboard pack; on 5 capsules in blister strip packagings, 1 or 3 packagings in a cardboard pack; on 4, 10, 14, 20, 30 capsules in blister strip packagings, 10 packagings in a cardboard pack; on 50 capsules in containers a polymeric, 1 container in a cardboard pack).

Contains in 1 capsule:

• Active ingredient: итраконазол – 0,1 g;
• Auxiliary components: the gidroksipropilmetiltsellyuloza of E-5 (gipromelloz), eudragit E-100 (copolymer of dimethylaminoethylmethacrylate, butylmethacrylate and methylmethacrylate [2:1:1]), sucrose (sugar);
• Capsule case: gelatin;
• Capsule lid: dye indigo carmine, titanium dioxide, gelatin.

Indications to use

• The inflammation of a cornea of eyes (keratitis) caused by a fungal infection;
• The infectious damage of nails caused by different types of a pathogenic fungi (onychomycosis);
• Dermatomycoses;
• System mycoses: cryptococcosis (including cryptococcal meningitis), system candidiasis and aspergillosis, histoplasmosis, paracoccidioidomycosis, sporotrichosis, zymonematosis, other system and tropical mycoses;
• Deep visceral (system) candidiases;
• Candidiases with defeat mucous or skin, including vulvovaginal candidiasis;
• Chromophytosis.

Contraindications

• The Chronic Heart Failure (CHF), including data in the anamnesis, (an exception – therapy of zhizneugrozhayushchy states);
• Glyukozo-galaktozny malabsorption, deficit of invertase/isomaltase, intolerance of fructose;
• Children's age up to 3 years;
• Hypersensitivity to an itrakonazol, other azoles and/or auxiliary components of Orungamin.

Reception of an itrakonazol along with such drugs / substances is prohibited:

• Astemizol, bepridit, дофетилид, левацетилметадол, цизаприд, мизоластин, Pimozidum, сертиндол, терфенадин, quinidine (as they are metabolized by CYP3A4 isoenzyme, can cause lengthening of an interval of QT);
• Lovastatin, симвастатин (GMG-KOA-reduktazy inhibitors, metaboliziruyemy CYP3A isoenzyme);
• To triazoles and midazolam in a dosage form for oral administration;
• Digidroergotamin, ergotamine, ergometrine, methylergometrine (ergot alkaloids);
• Nisoldipin, элетриптан.

Orungamin take with caution at: a renal/liver failure, peripheral neuropathy, coronary heart disease, damage of heart valves, a serious illness of lungs, including a chronic obstructive pulmonary disease, and the states which are followed by an edematous syndrome – risk factors of chronic heart failure; a hearing disorder, a concomitant use of blockers of "slow" calcium channels, at children's and advanced age.

Drug use by pregnant women is allowed only when the predicted advantage for the woman exceeds potential risks for a fruit.

Hit of an itrakonazol in breast milk therefore if therapy by Orungamin is necessary during a lactation, then breastfeeding for the period of treatment should be interrupted is possible.

Route of administration and dosage

Capsules accept inside, swallowing entirely, right after meal, it promotes optimum absorption of an itrakonazol.

The recommended dosing mode at damages of skin and mucous membranes:

• Vulvovaginal candidiasis: on 0,2 g 2 times a day, a course – 1 day, or on 0,2 g of 1 times a day, a course – 3 days;
• Chromophytosis: on 0,2 g of 1 times a day, a course – 7 days;
• Dermatomycosis of smooth skin: on 0,2 g of 1 times a day, a course – 7 days, or on 0,1 g of 1 times a day, a course – 15 days;
• Fungal keratitis: on 0,2 g of 1 times a day, a course – 21 days; in case of defeat of the high-keratinized sites of skin, such as feet or hands, the additional course of therapy for 15 days on 0,1 g a day is required;
• Oral candidiasis of 0,1 g of 1 times a day, a course – 15 days.

Oral administration of Orungamin at candidiasis of a mucous oral cavity can reduce bioavailability of an itrakonazol at some patients with the broken immunity (for example, at a neutropenia, AIDS or organ transplantation) therefore increase in a dose can be necessary twice.

For treatment of onychomycoses use pulse therapy which one course consists in the following: for 1 week Orungamin accept 2 times a day 0,2 g.

The recommended therapy duration (including intervals between courses – 3 weeks during which it is not necessary to accept drug):

• Fungal infections of nails of fingers of hands: the general duration – 5 weeks (includes 2 courses);
• Fungal infections of nails of fingers of feet with defeat (or without) nails of fingers of brushes: the general duration – 9 weeks (includes 3 courses).

Performing continuous therapy at damage of nails of fingers of feet with defeat (or without) nails of fingers of brushes is also possible: 0,2 g a day within 3 months.

Clinical results will be visible after the end of therapy, in process of growth of nails. As итраконазол it is brought out of nail plates and skin more slowly, than out of plasma, it is necessary to expect optimum clinical and mycologic effects of drug use in 2-4 weeks after the end of therapy of infections of skin, and 6-9 months later upon termination of therapy of nail infections.

The recommended dosing mode at system mycoses, depending on a type of an infection:

• Candidiasis: on 0,1-0,2 g of 1 times a day, a course – from 3 to 30 weeks;
• Aspergillosis: on 0,2 g of 1 times a day, a course – 2-5 months (increase in a dose up to 0,2 g 2 times a day is allowed at the invasive or disseminated disease);
• Cryptococcosis (except for meningitis): on 0,2 g of 1 times a day, a course – 2-12 months;
• Cryptococcal meningitis: on 0,2 g 2 times a day, a course – 2-12 months (a maintenance therapy – on 0,2 g of 1 times a day);
• Zymonematosis: from 0,1 g of 1 times a day to 0,2 g 2 times a day, a course – 6 months;
• Histoplasmosis: from 0,2 g of 1 times a day to 0,2 g 2 times a day, a course – 8 months;
• Paracoccidioidomycosis: on 0,1 g of 1 times a day, a course – 6 months;
• Sporotrichosis: on 0,1 g of 1 times a day, a course – 3 months;
• Chromomycosis: 0,1-0,2 g of 1 times a day, a course – 6 months.

Side effects

• Respiratory system: fluid lungs;
• Integuments: Stephens-Johnson's syndrome, toxic epidermal necrolysis, mnogoformny erythema, leykoklastichesky vasculitis, exfoliative dermatitis, photosensitization, alopecia, rash, small tortoiseshell, itch;
• Urinogenital system: urine incontience, pollakiuria, erectile dysfunction, disturbance of a menstrual cycle;
• Nervous system: peripheral neuropathy, hypesthesia, paresthesia, dizziness;
• Metabolism: hypopotassemia, gipertriglitseridemiya;
• Musculoskeletal system: arthralgia, mialgiya;
• Bodies of a hemopoiesis: neutropenia, thrombocytopenia, leukopenia;
• Acoustic organs and sight: a vision disorder, including a diplopia and a vagueness, a sonitus, deafness (passing or constant);
• Alimentary system: disturbance of flavoring perception, vomiting, nausea, abdominal pain, lock, diarrhea, increase in activity of hepatic transaminases, dyspepsia, hyperbilirubinemia, hepatotoxic, hepatitis, acute liver failure;
• Cardiovascular system: congestive heart failure;
• Hypersensitivity reactions: Quincke's disease, serum disease, anaphylactoid and anaphylactic reactions;
• Another: hypostases.

Special instructions

Women of fertile age at therapy itrakonazoly need to use adequate methods of protection from pregnancy during all course of treatment and to the first periods which came after its end.

For the purpose of prevention of a reinfitsirovaniye treatment of both sexual partners at the same time (at the same time it is necessary to refrain from sexual contacts) and observance of rules of personal hygiene is recommended. In case of preservation of symptoms of an infection upon completion of therapy for confirmation of the diagnosis it is necessary to conduct a repeated microbiological research.

Orungamin's efficiency for therapy of fungal infections at a heavy neutropenia is unknown, in this case drug is used if 1 line of therapy is insufficiently efficient.

If in the course of therapy itrakonazoly emergence of coronary heart disease, damage of heart valves, a serious illness of lungs, including a chronic obstructive pulmonary disease, and the states which are followed by an edematous syndrome – risk factors of chronic heart failure is noted, the course should be interrupted immediately.

Owing to Orungamin's reception at some patients passing and constant deafness was noted.

The maintenance of grain units in 1 capsule of drug – 4 XE.

Medicinal interaction

• Rifampicin, рифабутин and Phenytoinum (strong inductors of microsomal enzymes of a liver) – is not recommended simultaneous use with itrakonazoly as these drugs can reduce its concentration in a blood plasma;
• Carbamazepine, phenobarbital and isoniazid (other inductors of liver enzymes) – researches of interaction were not conducted, but by analogy it is possible to allow development of effect of decrease in concentration of an itrakonazol in a blood plasma;
• Ritonavir, индинавир, кларитромицин, erythromycin and other strong inhibitors of CYP3A4 enzyme of system _{of P450 cytochrome} – can increase bioavailability of an itrakonazol as it is generally metabolized with the participation of this isoenzyme;
• Terfenadin, мизоластин, астемизол, цизаприд, midazolam, to triazoles, дофетилид, Pimozidum, quinidine; ловастатин and симвастатин – GMG-KOA-reduktazy inhibitors (drugs which are metabolized by CYP3A4 isoenzyme) – cannot be applied together with Orungamin as итраконазол can inhibit their metabolism therefore strengthening or prolongation of their action, including side effects is probable;
• Blockers of calcium channels – in a combination with Orungamin apply with care because of their negative inotropic effect capable to strengthen similar reaction of an itrakonazol who, in turn, can reduce metabolism of blockers of calcium channels;
• Indinavir, ритонавир, саквинавир (HIV protease inhibitors), бусульфан, alkaloids of a periwinkle pink, dotsetakset, триметрексат (some antineoplastic drugs), the verapamil and dihydropyridine (which are biotransformed with the participation of CYP3A4 isoenzyme blockers of calcium channels), такролимус, cyclosporine, сиролимус (some immunodepressants), peroral anticoagulants, alfentanit, to alprazola, carbamazepine, digoxin, brotiozolam, буспирон, рифабутин, эбастин, Methylprednisolonum, ребоксетин – in case of simultaneous use with itrakonazoly it is necessary to control their concentration in a blood plasma, and if necessary to adjust a dose on decrease;
• Zidovudine and флувастатин – interaction with itrakonazoly is not revealed;
• Ethinylestradiol and Norethisteronum – influence of an itrakonazol on their metabolism was not noted;
• Propranolol, Imipraminum, diazepam, indometacin, Tolbutamidum, Cimetidinum, Sulfamethazinum – is absent the competition with itrakonazoly for linkng with proteins of plasma (by results of the research in vitro).

Terms and storage conditions

To store at a temperature up to 25 °C, in unavailable to children, the dry and dark place.

Period of validity – 3 years.