Orungal

Orungal – derivative triazole, antifungal means of systemic action.

Form of release and structure

• Capsules: the size No. 0, gelatinous firm, with the transparent pink case and an opaque blue lid; contents – pellets of cream color (on 4 or 6 pieces in the blister, in a cardboard pack 1 blister; on 5 pieces in the blister, in a cardboard pack 3 blisters; on 14 pieces in the blister, in a cardboard pack of 1, 2, 3 or 6 blisters);
• Solution for intake: light orange or yellow color, with cherry aroma (on 150 ml in dark glass bottles, in a pack a cardboard 1 bottle complete with a measured cup of 10 ml).

Active agent – итраконазол, its contents:

• 1 capsule – 100 mg;
• 1 ml of solution – 10 mg.

Additional components of capsules:

• Excipients: gipromelloza, sucrose, macrogoal 20 000;
• Structure of a cover: gelatin, titanium dioxide (E171), dye azoruby (E122), dye indigo carmine (E132).

Auxiliary components of solution: Acidum hydrochloricum concentrated sodium saccharinate, propylene glycol, sodium hydroxide, гидроксипропилбетадекс, sorbitol solution of 70%, the water purified fragrance caramel, fragrances cherry 1 and cherry 2.

Indications to use

For capsules – treatment of the mycoses caused by activators, sensitive to an itrakonazol:

• Chromophytosis;
• Candidiases with damage of skin and/or mucous membranes (including vulvovaginal candidiasis);
• Dermatomycoses;
• The onychomycoses caused by dermatophytes and/or barmy and mold mushrooms;
• Deep visceral candidiases;
• Fungal keratitis;
• System mycoses: sporotrichosis, zymonematosis, system candidiasis, paracoccidioidomycosis, system aspergillosis, histoplasmosis, cryptococcosis (including cryptococcal meningitis), and also other system and tropical mycoses.

For solution:

• Treatment of candidiasis of an oral cavity and/or gullet at patients with an immunodeficiency and HIV-positive patients;
• Prevention of system fungal infections at people with malignant diseases of blood and the patients who transferred bone marrow transplantation with high risk of development of a neutropenia (less than 500 cells / мкл).

Contraindications

Absolute:

• Simultaneous use of alkaloids of an ergot (dihydroergotamine, ergometrine, ergotamine or methylergometrine);
• Midazolam co-administration (orally) or triazolama;
• Simultaneous use of medicines which are metabolized with the participation of CYP3A4 enzyme and are capable to increase a QT interval (for example, a mizolastina, an astemizola, a tsizaprida, Pimozidum, quinidine, a sertindol, a dofetilid, left methadone, a terfenadin);
• Concomitant use of inhibitors of GMG-KOA-reduktazy, metaboliziruyemy with CYP3A4 enzyme participation (for example, a lovastatina or a simvastatina);
• Hypersensitivity to any component ascending in composition of drug.

Relative:

• Children's and advanced age;
• Cirrhosis;
• Chronic renal failure;
• Chronic heart failure;
• Hypersensitivity to other drugs of group of azoles.

Route of administration and dosage

Capsules
In this form Orungal it is necessary to accept inside right after food: to swallow of capsules entirely and to wash down with enough liquid.

The recommended dosing modes depending on indications:

• Dermatomycoses of smooth skin: on 200 mg (2 capsules) of 1 times a day within 7 days or on 100 mg (1 capsule) of 1 times a day for 15 days;
• Vulvovaginal candidiasis: on 200 mg 2 times a day within 1 day or on 200 mg of 1 times a day a 3-day course;
• Chromophytosis: on 200 mg of 1 times a day for 7 days;
• Oral candidiasis: on 100 mg of 1 times a day a 15-day course;
• Defeats of the high-keratinized areas of an integument (feet and hands): on 200 mg 2 times a day a course of 7 days or on 100 mg of 1 times a day within 30 days;
• Fungal keratitis: on 200 mg of 1 times a day for 21 days. Depending on a clinical picture of a disease duration of therapy can be adjusted.

At immunity disturbance (for example, at patients with transplanted organs, acquired immunodeficiency syndrome or a neutropenia) bioavailability of an itrakonazol can decrease. In this case increase in a standard dose is necessary twice.

Treatment of onychomycoses carry out pulse therapy:

• Damage of nails standing, including with defeat of nail plates on hands: on 200 mg 2 times a day within 1 week. The general course of therapy consists of bucketed 3-week cycles 3 weeks between cycles;
• Damage of nails on hands: on 200 mg 2 times a day within 1 week. The general course of therapy consists of 2-week cycles with an interval of 3 weeks between cycles.

Also at an onychomycosis performing continuous therapy – on 200 mg of 1 times a day within 3 months is possible.

As from skin and nail fabric removal of an itrakonazol is carried out more slowly, than from a blood plasma, optimum mycologic and clinical effects are reached 2-4 weeks later after the end of treatment of infections of skin and in 6-9 months after the end of therapy of nail infections.

The recommended dosing modes at system mycoses:

• Chromomycosis: on 100-200 mg of 1 times a day a course of 6 months;
• Histoplasmosis: from 200 mg of 1 times a day to 200 mg 2 times a day for 8 months;
• Cryptococcosis (except for meningitis): on 200 mg of 1 times a day, treatment can last from 2 to 12 months;
• Cryptococcal meningitis: on 200 mg 2 times a day, therapy duration – from 2 to 12 months;
• Sporotrichosis: on 100 mg of 1 times a day within 3 months;
• Aspergillosis: on 200 mg of 1 times a day for 2-5 months. At the invasive and disseminated disease forms the dose is increased to 200 mg by 2 times a day;
• Candidiasis: on 100-200 mg of 1 times a day, therapy can last from 3 weeks to 7 months. At the invasive and disseminated disease forms the dose is increased to 200 mg by 2 times a day;
• Parakoktsidiomikoz: on 100 mg of 1 times a day within 6 months;
• Zymonematosis: from 100 mg of 1 times a day to 200 mg 2 times a day a 6-month course.

At all system mycoses duration of treatment can be adjusted depending on clinical performance of drug.

Solution for intake
In this dosage form Orungal it is necessary to accept inside on an empty stomach. Regulations of Admission of drug: to gather solution, to rinse a mouth and only then to swallow it. It is not necessary to rinse clear water an oral cavity after that.

The recommended dosing modes:

• Treatment of candidiasis of an oral cavity and/or gullet: on 200 mg (2 measured cups) a day in 1-2 receptions. The course of treatment makes 1 week. In case of lack of positive effect therapy is prolonged for 1 week;
• Treatment of candidiasis of an oral cavity and/or gullet at patients with resistance to a flukonazol: on 200-400 mg a day in 1-2 receptions. The course of treatment makes 2 weeks. In case of lack of positive effect therapy is prolonged for 2 weeks;
• Prevention of system fungal infections: on 5 mg/kg/days in 2 receptions. It is necessary to begin drug use in 1 week prior to cytostatic therapy or in 1 week after bone marrow transplantation and to continue reception before recovery of quantity of neutrophils (not less than 1000 cells / мкл).

Side effects

Orungal is had generally well. The following side effects are in rare instances possible:

• From the alimentary system: tranzitorny increase in level of liver enzymes in a blood plasma, an abdominal pain, a diarrhea/lock, nausea, dyspepsia, vomiting, hepatitis; in isolated cases – toxic damage of a liver (cases of an acute liver failure with a lethal outcome are known);
• From the central and peripheral nervous system: headache, peripheral neuropathy, вертиго;
• From reproductive system: disturbances of a menstrual cycle;
• From cardiovascular system: fluid lungs, congestive heart failure;
• Dermatological and allergic reactions: skin itch, rash, small tortoiseshell, alopecia, photosensitivity, Stephens-Johnson's syndrome, Quincke's disease, anaphylactic and anaphylactoid reactions;
• Others: edematous syndrome, hypopotassemia.

Special instructions

The patient with an immunodeficiency and to patients with a cryptococcosis of the central nervous system Orungal appoint only if there are contraindications to use of drugs of the first line of therapy or they were inefficient.

At patients with renal failures and a liver during treatment it is necessary to control concentration of an itrakonazol in plasma and if necessary to adjust a drug dose.

The women of childbearing age receiving итраконазол need to use reliable methods of contraception during all course of therapy and until approach of the first periods after its end.

Orungal it is necessary to cancel in case of development of a neuropathy.

Data on clinical safety of use of drug for children are not enough therefore in pediatric practice it is applied only if the expected advantage surpasses potential risks. According to separate messages, итраконазол it is applied to prevention of fungal infections at children with a neutropenia (on 5 mg/kg 2 times a day).

Orungal does not exert a negative impact on the speed of reactions and ability to the increased concentration of attention.

Medicinal interaction

Absorption of an itrakonazol is broken at the lowered acidity of a gastric juice therefore at co-administration of antacids (for example, aluminum hydroxide) them is recommended to be accepted not earlier than in 2 hours after Orungal.

Patients with an achlorhydria or _{H2 receptors} receiving inhibitors of a protonew pomp or blockers histamine are recommended to wash down after reception capsules with Coca.

Potential inhibitors of an isoenzyme CYP3A4 (for example, кларитромицин, индинавир, erythromycin, ритонавир) increase bioavailability of an itrakonazol.

Itrakonazol can suppress metabolism of medicines which are metabolized by CYP3A4 isoenzyme owing to what strengthening or prolongation of their effects, including collateral is possible.

At simultaneous use of the following medicines it is necessary to watch their concentration in a blood plasma, expressiveness of action and side effects, if necessary to adjust a dose: the peroral anticoagulants which are metabolized CYP3A4 isoenzyme blockers of calcium channels (for example, verapamil, dihydropyridine), HIV protease inhibitors (for example, индинавир, ритонавир, саквинавир), some glucocorticosteroids (including будесонид, Methylprednisolonum, dexamethasone), some immunosuppressive means (including такролимус, cyclosporine, сиролимус), some metaboliziruyemy CYP3A4 enzyme GMG-KOA-reduktazy inhibitors (аторвастатин), some antineoplastic drugs (for example, alkaloids of a periwinkle pink, dotsetakset, бусульфан, триметрексат), midazolam (intravenously), эбастин, Disopyramidum, элетриптан, alfentanit, carbamazepine, brotiozolam, цилостазол, рифабутин, галофантрин, to alprazola, буспирон, ребоксетин, репаглинид, Methylprednisolonum, digoxin.

When performing treatment by Orungal surely it is necessary to consider drugs which cannot be applied at the same time (are described in the section "Contraindications").

It is not recommended to apply at the same time blockers of calcium channels as they render a negative inotropic effect which can strengthen similar effect of an itrakonazol.

Orungal's use in a combination with the drugs which are potential inductors of liver enzymes is not recommended (including rifampicin, Phenytoinum, rifabutiny, phenobarbital, an isoniazid, carbamazepine).

Terms and storage conditions

To store in the place, unavailable to children, at a temperature: capsules – 15-30 ºС, solution – no more than 25 ºС.

Period of validity of capsules – 3 years, a thaw for intake – 2 years (after the first opening of a bottle – 1 month).