Description
Latin name
ORUNGAL
Release form
Solution for oral administration
Packaging
Bottle 150 ml.
Pharmacological action of
Orthanol – inhibiting H +, K + -ATPase.
Pharmacodynamics
Omeprazole inhibits the H + / K + -ATPase enzyme ( proton pump ) in the parietal cells of the stomach and thereby blocks the final stage of hydrochloric acid secretion. This leads to a decrease in the level of basal and stimulated secretion, regardless of the nature of the stimulus. )
Aspergillus spp. Histoplasma spp. Paracoccidioides brasiliensis Sporothrix schenckii Fonsecaea spp. Cladosporium spp. Candida glabrata and Candida tropicalis Blastomyces dermatitidis Pseudallescheria boydii Penicillium marneffei et al.
are the least sensitive species of Candida to itraconazole.
The main types of fungi whose development is not inhibited by itraconazole are Zygomycetes (Rhizopus spp., Rhizomucor spp., Mucor sp p. and Absidia spp.), Fusarium spp., Scedosporium spp. and Scopulariopsis spp.
Pharmacokinetics
In general, itraconazole is well absorbed. C max in plasma is achieved 2.5 hours after taking the drug. Itraconazole is metabolized in the liver to form a large number of metabolites. The main metabolite is hydroxyitraconazole, the concentration of which in plasma is almost 2 times higher than the corresponding concentration of itraconazole. The final T1 / 2 of itraconazole is 40 hours after repeated administration. In patients with renal and hepatic insufficiency, T1 / 2 of itraconazole is slightly increased.
The pharmacokinetics of itraconazole is characterized by non-linearity, as a result of which accumulation in plasma is achieved with prolonged use. Equilibrium plasma concentrations of itraconazole are reached after 15 days with a Cmax value of about 2 μg / ml (with the appointment of 200 mg of itraconazole 1 time per day). The clearance of itraconazole decreases at higher doses due to saturation of hepatic metabolism.
Itraconazole is rapidly absorbed after application of the solution. The absolute bioavailability of itraconazole when taking the drug with food is about 55%, which in vitro has an antifungal effect comparable to that of itraconazole.
Plasma concentrations of hydroxylated metabolite are almost 2 times higher than corresponding concentrations of itraconazole.
As shown in in vitro studies, itraconazole is metabolized mainly with the participation of the enzyme CYP3A4.
About 35% of itraconazole in the form of inactive metabolites is excreted in the urine during the week and about 54% with feces. From 3 to 18% of the dose of the starting substance is excreted in the feces. Renal excretion of the starting material is less than 0.03% of the dose.
Indications
Treatment of candidiasis of the oral cavity and / or esophagus in HIV-positive patients and patients with immunodeficiency prevention of systemic fungal infections in patients with malignant blood diseases or in patients with bone marrow transplantation with a high probability of neutropenia (
Use during pregnancy and lactation
Pregnancy. Orungal ® should not be used during pregnancy unless life-threatening and if the expected beneficial effect exceeds the potential harm to the fetus.
There is insufficient data on the use of Orungal ® solution during pregnancy. During the clinical use of the drug after registration, cases of congenital anomalies were noted. Such cases included impaired vision, skeleton, urogenital and cardiovascular systems, as well as chromosomal abnormalities and multiple malformations. However, whether the use of Orungal ® solution is the cause of these violations has not been reliably established.
Epidemiological data on the effects of Orungal ® in the first trimester of pregnancy, mainly in patients receiving short-term therapy for vulvovaginal candidiasis, did not reveal an increased risk of congenital malformations compared with the control group not exposed to any of the known teratogenic factors.
Women of childbearing age, taking Orungal ® solution, must use adequate methods of contraception throughout the 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 Orungal ® should stop breastfeeding.
Composition
1 ml. the solution contains:
Active ingredient: itraconazole 10 mg
Excipients: hydroxypropyl -? – cyclodextrin sorbitol 70% non-crystallizing sodium solution saccharin propylene glycol acid hydrochloric concentrated sodium hydroxide flavorings (cherry, caramel) purified water.
Dosage and administration
Inside, on an empty stomach. The solution needs to rinse your mouth and then swallow it. After this, do not rinse your mouth with water.
Treatment of candidiasis of the oral cavity and / or esophagus: 200 mg (2 measuring cups) per day in one or two doses for 1 week. In the absence of a positive effect after 1 week, treatment should be continued for another week.
Treatment of candidiasis of the oral cavity and / or esophagus, with resistance to fluconazole: 200-400 mg (2-4 measured cups) per day in 1-2 doses for 2 weeks. In the absence of a positive effect after 2 weeks, treatment should be continued for another 2 weeks.
Prevention of fungal infections: 5 mg / kg / day in 2 divided doses. Taking the drug begins one week before the start of treatment with cytostatics or a week after bone marrow transplantation. Reception of Orungal ® is continued until the number of neutrophils is restored (at least 1000 cells / μl).
Side effects of
From the side of 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 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, decreased appetite, diarrhea, constipation.
From the hepatobiliary system: very rarely – severe toxic damage to the liver (including several cases of acute liver failure with a fatal outcome), hepatitis, reversible increase in liver enzymes.
From the skin and subcutaneous fat: very rarely – Stevens-Johnson syndrome, angioedema, urticaria, alopecia, photosensitivity, rash, itching.
From the reproductive system: very rarely – menstrual irregularities.
General disorders: very rarely – edematous syndrome.
Drug Interaction
Drugs that affect the absorption of itraconazole
Drugs that reduce the acidity of gastric contents reduce the absorption of itraconazole, which is related to the solubility of the capsules.
Medicines, affecting the metabolism of itraconazole
Studies have shown that the interaction of Orungal with rifampicin, rifabutin and phenytoin bioavailability of itraconazole and hydroxy-itraconazole is significantly reduced, which leads to a significant decrease in the effectiveness of the drug. The concomitant use of itraconazole with these drugs, which are potential inducers of hepatic enzymes, is not recommended. No interaction studies have been performed with other inducers of hepatic enzymes, such as carbamazepine, phenobarbital and isoniazid, but similar results can be assumed.
Since itraconazole is mainly metabolised by the CYP3A4 isoenzyme, potential inhibitors of this enzyme (ritonavir, indinavir, clarithromycin and erythromycin) may increase the bioavailability of itraconazole.
Effect of itraconazole on the metabolism of other drugs
Itraconazole may inhibit the metabolism of drugs metabolised by the CYP3A4 isoenzyme. The result can be an increase or prolongation of their action (including side effects). Before you start taking concomitant medicines, you should consult your healthcare provider about the metabolic pathways of this drug, as specified in the instructions for medical use. After discontinuation of treatment, itraconazole plasma concentrations decrease gradually depending on the dose and duration of treatment. This should be taken into account when assessing the inhibitory effect of itraconazole on the metabolism of concomitantly administered drugs.
During the course of treatment with Orungal it is impossible to appoint: – terfenadine, astemizole, mizolastin, cisapride, dofetilide, quinidine, pimozide, sertindol, levomethadone, the use of which together with Orungal may lead to an increase in the concentration of these substances in plasma, which in turn can cause an increase in the QT interval and in rare cases – paroxysmal ventricular tachycardia such as torsade de pointes – torsade de pointes for intake and triazoles
– metabolized by CYP3A4 enzyme HMG-CoA reductase inhibitors such as simvastatin and lovastatin
– preparations of ergot alkaloids such as dihydroergotamine, ergometrin, ergometine
– calcium channel blockers – in addition to the possible pharmacokinetic interaction associated with a common metabolism pathway involving the CYP3A4 enzyme, calcium channel blockers have a negative inotropic effect, which may enhance the similar effect of itraconazole.
When co-administered with Orungal, plasma levels, effects, side effects of oral anticoagulants of HIV protease inhibitors (such as ritonavir, indinavir, saquinavir) of certain antineoplastic drugs (such as alkaloxithelium, barvitase, trivalitase, barvitase, trivalitase, barcinol, etc.) should be monitored. CYP3A4 calcium channel blockers (dihydropyridine and verapamil) of certain immunosuppressive agents (such as cyclosporine, tacrolimus, sirolimus) of some metabolized phe CYP3A4 inhibitors of HMG-CoA reductase inhibitors, such as atorvastatin of certain HCCs, such as budesonide, dexamethasone, and methylprednisolone, and digoxin, carbamazepine, buspirone, alfentanil, alprazolam, brotizolam, brotizolam, brotizolam methylprednisolone, ebastine, reboxetine, repaglinide, disopyramide, cilostazol, eletriptan, halofantrine. When co-administered with Orungal, the dose of the above drugs should be reduced if necessary.
No interaction was found between itraconazole and zidovudine and fluvastatin.
No effect of itraconazole on the metabolism of ethinyl estradiol and norethisetron was noted.
Effects on Protein Binding
In vitro studies have demonstrated a lack of competition for plasma protein binding between itraconazole and drugs such as imipramine, propranolol, diazepam, cimetidine, indomethacin, tolomethacin.
Overdose
No cases of overdose with the drug Orungal have been reported.
Treatment: if you accidentally overdose within the first hour after taking the drug, gastric lavage should be performed and if necessary activated charcoal should be given. Itraconazole is not excreted in hemodialysis. There is no specific antidote.
Storage conditions
At a temperature not exceeding 25 ° C.
Expiration
2 years.
Active ingredient
Itraconazole
Pharmacy terms
Prescription
Dosage
Dosage form
solution for oral administration
Janssen Pharmaceutical N.V., Belgium
