Orungal capsules 100mg, No. 14

Treatment of mycoses caused by pathogens sensitive to the drug, including:

• dermatomycosis;

• fungal keratitis;

• onychomycosis caused by dermatophytes and / or yeasts and molds;

• systemic mycoses:

• systemic aspergillosis and candidiasis, cryptococcosis (including cryptococcal meningitis; in immunocompromised patients and in all patients with cryptoccosis of the central nervous system, Orungal should be prescribed only if first-line drugs are not applicable in this case or are ineffective),

• histoplasmosis, sporotrichosis, paracoccidioidomycosis, blastomycosis and other systemic and tropical mycoses;

• candidiasis with lesions of the skin and mucous membranes (including vulvovaginal candidiasis); deep visceral candidiasis;

• pityriasis versicolor.

Capsules should be taken immediately after meals, without chewing, swallowing whole and with a little water.

The oral bioavailability of itraconazole may be reduced in some immunocompromised patients, such as neutropenic patients, AIDS patients, or organ transplants.

Therefore, a twofold dose increase may be required.

One course of pulse therapy consists in daily intake of 2 capsules of Orungal 2 times a day (200 mg 2 times a day) for 1 week.

For the treatment of fungal infections of the nail plates of the hands, 2 courses are recommended. For the treatment of fungal infections of the nail plates of the feet, 3 courses are recommended. The interval between courses, during which you do not need to take the drug, is 3 weeks. Clinical results will become apparent after the end of treatment, as the nail grows back. In addition to pulse therapy, it is possible to conduct a continuous course.

The drug is prescribed for 2 capsules per day (200 mg once a day) for 3 months. The excretion of Orungal from the skin and nail tissue is slower than from plasma. Thus, the optimal clinical and mycological effects are achieved 2-4 weeks after the end of treatment for skin infections and 6-9 months after the end of treatment for nail infections.

active substance:

itraconazole 100 mg

excipients: sucrose - 192 mg; hypromellose - 150 mg; macrogol 20,000 - 18 mg capsule shell: gelatin - 93.2 mg; titanium dioxide dye (E171) - 2.8 mg; dye indigo carmine (E132) - qs; dye azorubin (E122) - qs

• simultaneous administration of drugs metabolized with the participation of the CYP3A4 enzyme and capable of increasing the QT interval, incl. terfenadine, astemizole, mizolastine, cisapride, dofetilide, quinidine, pimozide, sertindole, levomethadone;

• concomitant use of oral midazolam and triazolam;

• concomitant use of HMG-CoA reductase inhibitors metabolized with the participation of the CYP3A4 enzyme, such as simvastatin and lovastatin;

• concomitant use of ergot alkaloids such as dihydroergotamine, ergometrine, ergotamine and methylergometrine; hypersensitivity to itraconazole and other components of the drug.

• With caution: the drug should be prescribed for cirrhosis of the liver, chronic renal failure, chronic heart failure, hypersensitivity to other drugs of the azole group, as well as children and elderly patients.

pharmachologic effect

Orungal is a broad-spectrum antifungal drug derived from triazole. Itraconazole disrupts the synthesis of ergosterol in the cell membrane of fungi, which causes the antifungal effect of the drug. Itraconazole is active against infections caused by dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum); yeast and yeast fungi (Candida spp., including Candida albicans, Candida glabrata and Candida krusei, Cryptococcus neoformans, Pityrosporum spp., Trichosporon spp., Geotrichum spp.); Aspergillus spp .; Histoplasma spp .; Paracoccidioides brasiliensis; Sporothrix schenckii; Fonsecaea spp .; Cladosporium spp .; Blastomyces dermatitidis; Pseudoallescheria boydii; Penicillium marneffei and others. Candida glabrata and Candida tropicalis are the least sensitive Candida species to itraconazole.The main types of fungi that are not suppressed by itraconazole are Zygomycetes (Rhizopus spp., Rhizomucor spp., Mucor spp., Absidia spp.), Fusarium spp., Scedosporium spp., Scopulariopsis spp.

Indications

Treatment of mycoses caused by pathogens sensitive to the drug, including: dermatomycosis; fungal keratitis; onychomycosis caused by dermatophytes and / or yeasts and molds; systemic mycoses: systemic aspergillosis and candidiasis, cryptococcosis (including cryptococcal meningitis; in immunocompromised patients and in all patients with cryptoccosis of the central nervous system, Orungal should be prescribed only if first-line drugs are not applicable in this case or are ineffective), histoplasmosis, sporotrichosis, paracoccidioidomycosis, blastomycosis and other systemic and tropical mycoses; candidiasis with lesions of the skin and mucous membranes (including vulvovaginal candidiasis); deep visceral candidiasis; pityriasis versicolor.

Contraindications Simultaneous administration of drugs metabolized with the participation of the CYP3A4 enzyme and capable of increasing the QT interval, incl. terfenadine, astemizole, mizolastine, cisapride, dofetilide, quinidine, pimozide, sertindole, levomethadone; concomitant use of oral midazolam and triazolam; concomitant use of HMG-CoA reductase inhibitors metabolized with the participation of the CYP3A4 enzyme, such as simvastatin and lovastatin; concomitant use of ergot alkaloids such as dihydroergotamine, ergometrine, ergotamine and methylergometrine; hypersensitivity to itraconazole and other components of the drug. With caution: the drug should be prescribed for liver cirrhosis, chronic renal failure, chronic heart failure, hypersensitivity to other drugs of the azole group, as well as children and elderly patients.

Application during pregnancy and lactation

Pregnancy.

OrungalЃ should not be used during pregnancy, except in life-threatening cases and if the expected positive effect outweighs the possible harm to the fetus. There is not enough data on the use of OrungalЃ solution during pregnancy. During the clinical use of the drug after registration, there were cases of congenital anomalies. Such cases included disorders of the development of vision, skeleton, genitourinary and cardiovascular systems, as well as chromosomal abnormalities and multiple malformations. However, whether the use of OrungalЃ solution is the cause of these disorders has not been reliably established. Epidemiological data regarding the exposure of OrungalЃ in the first trimester of pregnancy, mainly in patients receiving short-term therapy for vulvovaginal candidiasis,did not reveal an increased risk of developing congenital anomalies compared with a control group that was not exposed to any of the known teratogenic factors. Women of childbearing age, taking OrungalЃ solution, need to use adequate methods of contraception throughout the entire course of treatment, until the onset of the first menstruation after its completion.

Lactation.

Since itraconazole can pass into breast milk, if necessary, use during lactation, women using OrungalЃ should stop breastfeeding.

special instructions

Women of childbearing age taking OrungalЃ should use adequate contraceptive methods throughout the course of treatment until the onset of the first menstrual period after its completion. In a study of the dosage form of the drug OrungalЃ for intravenous administration, carried out on healthy volunteers, there was a transient asymptomatic decrease in the left ventricular ejection fraction, which normalized until the next infusion of the drug. The clinical relevance of the data obtained for oral dosage forms is unknown. Found that itraconazole has a negative inotropic effect.

Caution must be exercised while taking itraconazole and CCB, which may have the same effect. Cases of congestive heart failure associated with the use of OrungalЃ have been reported. OrungalЃ should not be taken by patients with chronic heart failure or with a history of this disease, unless the potential benefit greatly outweighs the potential risk. Factors such as the severity of the indications, the dosage regimen, and individual risk factors for congestive heart failure should be taken into account in an individual assessment of the benefit / risk ratio. Risk factors include the presence of diseases such as coronary artery disease or valvular heart disease; obstructive pulmonary lesions; kidney failure or other diseases accompanied by edema.Such patients should be informed about the signs and symptoms of congestive heart failure. Treatment should be carried out with caution, and the patient should be monitored for symptoms of congestive heart failure. When they appear, OrungalЃ should be discontinued. With low stomach acidity: in this condition, the absorption of itraconazole from OrungalЃ capsules is impaired. Patients taking antacids (for example, aluminum hydroxide) are advised to use them no earlier than 2 hours after taking OrungalЃ capsules. Patients with achlorhydria or using histamine H2 receptor blockers or proton pump inhibitors are advised to take OrungalЃ capsules with cola. In very rare cases, when using OrungalЃ, severe toxic liver damage has developed,including cases of acute liver failure with fatal outcome. In most cases, this was observed in patients who already had liver disease, in patients with other severe diseases who received itraconazole therapy for systemic indications, as well as in patients who received other drugs with hepatotoxic effects. In some patients, there were no obvious risk factors for liver damage. Several of these 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 immediately contact their doctor in case of symptoms suggesting the onset of hepatitis, namely: anorexia, nausea, vomiting, weakness,abdominal pain and darkening of urine. If such symptoms appear, it is necessary to immediately discontinue therapy and conduct a study of liver function. Patients with elevated liver enzymes or liver disease in the active phase, or with previous toxic liver damage while taking other drugs should not be prescribed OrungalЃ treatment unless the expected benefit justifies the risk of liver damage. In these cases, it is necessary to monitor the level of liver enzymes during treatment. Liver dysfunction: Itraconazole is metabolized primarily in the liver. Since in patients with impaired liver function, the total T1 / 2 of itraconazole is slightly increased, it is recommended to monitor plasma concentrations of itraconazole and, if necessary, adjust the dose of the drug.Renal dysfunction: since in patients with renal insufficiency, the total T1 / 2 ofitraconazole is slightly increased, it is recommended to monitor plasma concentrations of itraconazole and, if necessary, adjust the dose of the drug. Immunocompromised patients: The oral bioavailability of itraconazole may be reduced in some immunocompromised patients, such as neutropenic patients, AIDS patients, or organ transplant surgeries. Patients with life-threatening systemic fungal infections: due to the pharmacokinetic characteristics of OrungalЃ in capsule form, it is not recommended to start the treatment of life-threatening systemic mycoses. AIDS patients: The attending physician should assess the need for maintenance therapy for AIDS patients,previously treated for systemic fungal infections such as sporotrichosis, blastomycosis, histoplasmosis, or cryptococcosis (both meningeal and non-meningeal) who are at risk of recurrence. Clinical data on the use of OrungalЃ capsules in pediatric practice are limited. OrungalЃ capsules should not be administered to children, unless the expected benefit outweighs the potential risk. Treatment should be discontinued if peripheral neuropathy occurs, which may be associated with taking OrungalЃ capsules. There is no evidence of cross-hypersensitivity to itraconazole and other azole antifungal drugs.Clinical data on the use of OrungalЃ capsules in pediatric practice are limited. OrungalЃ capsules should not be administered to children, unless the expected benefit outweighs the potential risk. Treatment should be discontinued if peripheral neuropathy occurs, which may be associated with taking OrungalЃ capsules. There is no evidence of cross-hypersensitivity to itraconazole and other azole antifungal drugs.Clinical data on the use of OrungalЃ capsules in pediatric practice are limited. OrungalЃ capsules should not be administered to children, unless the expected benefit outweighs the potential risk. Treatment should be discontinued if peripheral neuropathy occurs, which may be associated with taking OrungalЃ capsules. There is no evidence of cross-hypersensitivity to itraconazole and other azole antifungal drugs.There is no evidence of cross-hypersensitivity to itraconazole and other azole antifungal drugs.There is no evidence of cross-hypersensitivity to itraconazole and other azole antifungal drugs.

Composition

Active ingredient: itraconazole 100 mg.

Excipients: sucrose - 192 mg; hypromellose - 150 mg; macrogol 20,000 - 18 mg.

Capsule shell: gelatin - 93.2 mg; titanium dioxide dye (E171) - 2.8 mg; dye indigo carmine (E132) - qs; dye azorubin (E122) - qs

Method of administration and dosage

Capsules should be taken immediately after meals, without chewing, swallowing whole and with a little water. The oral bioavailability of itraconazole may be reduced in some immunocompromised patients, such as neutropenic patients, AIDS patients, or organ transplants. Therefore, a two-fold dose increase may be required. One course of pulse therapy consists in daily intake of 2 capsules of Orungal 2 times a day (200 mg 2 times a day) for 1 week. For the treatment of fungal infections of the nail plates of the hands, 2 courses are recommended. For the treatment of fungal infections of the nail plates of the feet, 3 courses are recommended. The interval between courses, during which you do not need to take the drug, is 3 weeks. Clinical results will become apparent after the end of treatment,as the nail grows back. In addition to pulse therapy, it is possible to conduct a continuous course. The drug is prescribed for 2 capsules per day (200 mg 1 time per day) for 3 months. The excretion of Orungal from the skin and nail tissue is slower than from plasma.

Thus, the optimal clinical and mycological effects are achieved 2-4 weeks after the end of treatment for skin infections and 6-9 months after the end of treatment for nail infections.

Side effects

From the immune system: very rarely - anaphylactic, anaphylactoid and allergic reactions. Metabolic disorders: very rarely - hypokalemia.

From the nervous system: very rarely - peripheral neuropathy, headache, dizziness.

From the side of the cardiovascular system: very rarely - congestive heart failure.

From the respiratory system: very rarely - pulmonary edema;

From the gastrointestinal tract: very rarely - abdominal pain, vomiting, dyspepsia, nausea, loss of appetite, diarrhea, constipation.

From the hepatobiliary system: very rarely - severe toxic liver damage (including several cases of acute liver failure with a fatal outcome), hepatitis, a reversible increase in liver enzymes.

On the part of the skin and subcutaneous fat: very rarely - Stevens-Johnson syndrome, angioedema, urticaria, alopecia, photosensitivity, rash, itching.

On the part of the reproductive system: very rarely - menstrual irregularities.

General disorders: very rarely - edema syndrome.

Drug interactions

1. Medicines affecting the absorption of itraconazole. Medicines that reduce gastric acidity reduce the absorption of itraconazole, which is associated with the solubility of the capsule shells.

2. Medicines affecting the metabolism of itraconazole. Itraconazole is mainly cleaved by the CYP3A4 enzyme. The interaction of itraconazole with rifampicin, rifabutin and phenytoin, which are powerful inducers of the CYP3A4 enzyme, was studied. The study found that in these cases, the bioavailability of itraconazole and hydroxy-itraconazole is significantly reduced, which leads to a significant decrease in the effectiveness of the drug.

The simultaneous use of itraconazole with these drugs, which are potential inducers of hepatic enzymes, is not recommended. Interaction studies with other hepatic enzyme inducers such as carbamazepine, phenobarbital and isoniazid have not been conducted, however, similar results can be assumed. Strong inhibitors of the CYP3A4 enzyme, such as ritonavir, indinavir, clarithromycin, and erythromycin, can increase the bioavailability of itraconazole.

3. The effect of itraconazole on the metabolism of other drugs. Itraconazole can inhibit the metabolism of drugs cleaved by the CYP3A4 enzyme. The result of this can be an increase or prolongation of their action, including side effects. Before you start taking concomitant medications, you should consult with your doctor about the metabolic pathways of this drug indicated in the instructions for medical use. 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 discussing the inhibitory effect of itraconazole on concomitant drugs. Examples of such drugs are: Drugs that should not be administered concomitantly with itraconazole:Terfenadine, astemizole, mizolastine, cisapride, dofetilide, quinidine, pimozide, levomethadone, sertindole - the combined use of these drugs with itraconazole can cause an increase in plasma levels of these substances and increase the risk of prolongation of the QT interval and, in rare cases, the occurrence of atrial fibrillation (torsade de pointes); CYP3A4 degraded HMG-CoA reductase inhibitors such as simvastatin and lovastatin; oral midazolam and triazolam; ergot alkaloids such as dihydroergotamine, ergometrine, ergotamine, and methylergometrine; calcium channel blockers - in addition to a possible pharmacokinetic interaction associated with a common metabolic pathway involving the CYP3A4 enzyme, calcium channel blockers may have a negative inotropic effect,which is enhanced when taken simultaneously with itraconazole. Drugs, in the appointment of which it is necessary to monitor their plasma concentrations, action, side effects. In the case of simultaneous administration with itraconazole, the dose of these drugs should be reduced, if necessary. Oral anticoagulants; HIV protease inhibitors such as ritonavir, indinavir, saquinavir; Certain anticancer drugs such as vinca alkaloids, busulfan, docetaxel, trimetrexate; CYP3A4 cleavable calcium channel blockers such as verapamil and dihydropyridine derivatives; Some immunosuppressive drugs: cyclosporine, tacrolimus, sirolimus (also known as rapamycin); Certain CYP3A4-degraded HMG-CoA reductase inhibitors such as atorvastatin; Some glucocorticosteroidssuch as budesonide, dexamethasone, and methylprednisolone Other drugs: digoxin, carbamazepine, buspirone, alfentanil, alprazolam, brotizolam, intravenous midazolam, rifabutin, ebastine, reboxetine, cilostazol, disopyramide, repetnium No interactions have been found between itraconazole and zidovudine and fluvastatin. There was no effect of itraconazole on the metabolism of ethinyl estradiol and norethisterone.

4. Influence on protein binding. In vitro studies have demonstrated that there is no interaction between itraconazole and drugs such as imipramine, propranolol, diazepam, cimetidine, indomethacin, tolbutamide and sulfamethazine when binding to plasma proteins.

Overdose

Orungal overdose cases have not been reported. Treatment: in case of accidental overdose within the first hour after taking the drug, gastric lavage should be performed and, if necessary, activated charcoal should be prescribed. Itraconazole is not excreted during hemodialysis. There is no specific antidote.

Storage conditions

Keep out of the reach of children at a temperature not exceeding 25 ? C.

Shelf life is 3 years.

Active substance

Itraconazole

Conditions of dispensing from pharmacies

On prescription