Orungal, capsules 100mg, 14pcs

Composition

Active ingredient:  itraconazole 100 mg. Auxiliary substances: sucrose-192 mg; hypromellose-150 mg; macrogol 20000-18 mg. Capsule shell:  gelatin — 93.2 mg; dye titanium dioxide (E 171) — 2.8 mg; dye indigocarmin (E 132) — q. s; dye azorubin (E 122) — q. s.

Pharmacological action

Orungal is a broad-spectrum antifungal drug derived from triazole. Itraconazole disrupts the synthesis of ergosterol in the fungal cell membrane, which causes the antifungal effect of the drug.

Itraconazole is active against infections caused by dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum); yeasts and yeasts (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 whose development is not suppressed by itraconazole are Zygomycetes (Rhizopus spp., Rhizomucor spp., Mucor spp., Absidia spp. ), Fusarium spp., Scedosporium spp., Scopulariopsis spp.

Indications

Treatment of fungal infections caused by drug-sensitive pathogens, including

• ringworm;
• fungal keratitis;
• the onychomycosis caused by dermatophytes and/or yeast and molds;
• systemic mycoses systemic aspergillosis and candidiasis, cryptococcosis (including cryptococcal meningitis; in immunocompromised patients and in all patients with CNS cryptoccosis Orungal should be used only in cases where drugs are the first line of treatment is not applicable or inefficient), histoplasmosis, sporotrichosis, paracoccidioidomycosis leaflets and other system and a tropical mycosis;
• kandidomikoz with lesions of skin and mucous membranes (including vulvovaginal candidiasis);
• deep visceral candidiasis;
• pityriasis versicolor.

Contraindications

• concomitant use of drugs that metabolisierung with the participation of the enzyme CYP3A4 and can increase the QT interval, including terfenadine, astemizole, mizolastine, cisapride, dofetilide, quinidine, pimozide, sertindole, levomethadone;
• concomitant use of midazolam for oral and triazolam;
• simultaneous reception of metabolisierung with the participation of the enzyme CYP3A4 inhibitors HMG-COA reductase inhibitors such as simvastatin and lovastatin;
• simultaneous 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 for children and elderly patients.

Side effects

From the immune system:  very rarely — anaphylactic, anaphylactoid and allergic reactions.

Metabolic disorders:  very rarely — hypokalemia.

Nervous system disorders:  very rarely — peripheral neuropathy, headache, dizziness.

From the cardiovascular system:  very rarely — congestive heart failure.

Respiratory system disorders:  very rarely — pulmonary edema.

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

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

From the side of the skin and subcutaneous adipose tissue:  very rarely — Stevens-Johnson syndrome, angioedema, urticaria, alopecia, photosensitivity, rash, pruritus.

From the side of the reproductive system:  very rarely — violation of the menstrual cycle.

Common disorders:  very rarely — edematous syndrome.

Interaction

1. Drugs that affect the absorption of itraconazole. Drugs that reduce stomach acidity reduce the absorption of itraconazole, which is associated with the solubility of capsule shells.

2. Drugs that affect the metabolism of itraconazole. Itraconazole is mainly broken down by the enzyme CYP3A4. The interaction of itraconazole with rifampicin, rifabutin, and phenytoin, which are potent 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. Concomitant use of itraconazole with these drugs, which are potential inducers of liver enzymes, is not recommended. Interaction studies with other inducers of liver enzymes, 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, may increase the bioavailability of itraconazole.

3. Effect of itraconazole on the metabolism of other drugs. Itraconazole can inhibit the metabolism of drugs broken down by the CYP3A4 enzyme. The result of this may be an increase or prolongation of their action, including side effects. Before starting to take concomitant medications, you should consult 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 medications. Examples of such medications are: Medications that cannot be administered concomitantly with itraconazole:

• Terfenadine, astemizole, mizolastine, cisapride, dofetilide, quinidine, pimozide, levomethadone, sertindole – combined use of these drugs with Itraconazole may increase the level of these substances in the plasma and increase the risk of QT prolongation and in rare cases, the occurrence of atrial fibrillation of the ventricles (torsade de pointes);
• split by the enzyme CYP3A4 inhibitors reductase HMG-COA, such as simvastatin and lovastatin;
• midazolam for oral and triazolam;
• ergot alkaloids such as dihydroergotamine, ergometrine, ergotamine and methylergometrine;
• calcium channel blockers – in addition to the potential pharmacokinetic interaction associated with a common way of metabolism involving CYP3A4 enzyme, calcium channel blockers can have negative inotropic effect, which is enhanced by the simultaneous use with Itraconazole.

Drugs that need to be monitored for their plasma concentrations, effects, and side effects when prescribed. In the case of concomitant use with itraconazole, the dose of these drugs should be reduced, if necessary.

• Oral anticoagulants;
• HIV protease inhibitors, such as ritonavir, indinavir, saquinavir;
• Some antitumor drugs, such as pink periwinkle alkaloids, busulfan, docetaxel, trimetrexate;
• CYP3A4-degradable calcium channel blockers, such as verapamil and dihydropyridine derivatives;
• Some immunosuppressive agents: cyclosporine, tacrolimus, sirolimus (also known as rapamycin);
• Some CYP3A4-degradable HMG-CoA reductase inhibitors, such as atorvastatin;
• Some glucocorticosteroids, such as budesonide, dexamethasone, and methylprednisolone
• Other drugs: digoxin, carbamazepine, buspirone, alfentanil, alprazolam, brotisolam, midazolam for intravenous use, rifabutin, Ebastine, reboxetin, cilostazol, disopyramide, eletriptan, halofantrin, repaglinide;

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

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

How to take it, course of use and dosage

Capsules should be taken immediately after meals, without chewing, swallowed whole and washed down with a small amount of water.

The oral bioavailability of itraconazole may be reduced in some immunocompromised patients, such as patients with neutropenia, AIDS patients, or organ transplants. Therefore, a doubling of the dose may be necessary.

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

For the treatment of fungal lesions of the nail plates of the hands,2 courses are recommended. For the treatment of fungal lesions 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 2 capsules per day (200 mg once a day) for 3 months.

Removal of Orungal from the skin and nail tissue is slower than from plasma. Thus, 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.

Overdose

No overdose cases of Orungal have been reported.

Treatment: in case of accidental overdose, gastric lavage should be performed within the first hour after taking the drug and, if necessary, activated charcoal should be prescribed.

Itraconazole is not eliminated by hemodialysis. There is no specific antidote.

Special instructions

Women of childbearing age taking Orungal® should use adequate methods of contraception throughout the course of treatment up to the onset of the first menstrual period after its completion.

In a study of the IV dosage form of Orungal® conducted on healthy volunteers, a transient, asymptomatic decrease in the left ventricular ejection fraction was noted, which normalized until the next infusion of the drug.

The clinical significance of the data obtained for oral dosage forms is unknown.

Itraconazole was found to have a negative inotropic effect. Caution should be exercised when taking itraconazole and BCC at the same time, which may have the same effect. Cases of congestive heart failure associated with Orungal®have been reported. Orungal® It should not be taken in patients with chronic heart failure or with a history of this disease, unless the possible benefit significantly outweighs the potential risk. Individual assessment of the benefit-risk ratio should take into account factors such as the severity of indications, dosage regimen, and individual risk factors for congestive heart failure.

Risk factors include the presence of diseases such as coronary heart disease or heart valve damage; obstructive pulmonary disease; kidney failure or other diseases accompanied by edema. These 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. If they occur, Orungal® should be discontinued.

With low stomach acidity: in this condition, absorption of itraconazole from Orungal®capsules violated. Patients taking antacid medications (such as aluminum hydroxide) are recommended to use them no earlier than 2 hours after taking Orungal ® capsules.

Patients with achlorhydria or using_H2-histamine receptor blockers or proton pump inhibitors are recommended to take Orungal ® capsules with cola.

In very rare cases, when using Orungal® severe toxic liver damage developed, including cases of acute liver failure with a fatal outcome. In most cases, this was observed in patients who already had liver diseases, in patients with other serious diseases who received itraconazole therapy for systemic indications, as well as in patients who received other drugs that have a hepatotoxic effect. In some patients, no obvious risk factors for liver damage were identified. Some 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 to contact their doctor immediately if they experience symptoms that suggest hepatitis, such as anorexia, nausea, vomiting, weakness, abdominal pain, and dark urine. If such symptoms occur, therapy should be stopped immediately and liver function tests should be performed.

Patients with elevated liver enzyme levels or active liver disease, or who have experienced toxic liver damage while taking other medications, should not be treated with Orungal® 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 function disorders: itraconazole is primarily metabolized in the liver. Since the total T_1/2 of itraconazole is slightly increased in patients with impaired liver function, it is recommended to monitor the plasma concentrations of itraconazole and, if necessary, adjust the dose of the drug.

Impaired renal function: Since the total T_1/2of itraconazole is slightly increased in patients with renal insufficiency, it is recommended to monitor the plasma concentrations of itraconazole and, if necessary, adjust the dose of the drug.

Patients with immunodeficiency: The oral bioavailability of itraconazole may be reduced in some immunocompromised patients, such as those with neutropenia, AIDS patients, or those undergoing organ transplantation.

Patients with life-threatening systemic fungal infections: Due to its pharmacokinetic characteristics, Orungal® capsules are not recommended for starting treatment of life-threatening systemic mycoses.

AIDS patients: The attending physician should evaluate the need for maintenance therapy in AIDS patients who have previously received treatment for systemic fungal infections, such as sporotrichosis, blastomycosis, histoplasmosis, or cryptococcosis (both meningeal and non-meningeal), and who are at risk of relapse.

Clinical data on the use of Orungal®capsules in pediatric practice, they are limited. Orungal®Capsules do not use in children unless the expected benefit outweighs the possible risk.

Treatment should be discontinued if peripheral neuropathy occurs, which may be associated with taking Orungal capsules.

There are no data on cross-hypersensitivity to itraconazole and other azole antifungal drugs.

Storage conditions

At a temperature of 15-30 °C.

Keep out of reach of children.

Shelf life

3 years

Active ingredient

Itraconazole

Conditions of release from pharmacies

By prescription

Dosage form

Capsules

Purpose

For adults as prescribed by a doctor, Pregnant women as prescribed by a doctor, Children as prescribed by a doctor

Indications

Skin Fungus, Nail Fungus, Thrush, Scalp Fungus