After oral application the maximum bioavailability of itraconazole observed when taking the capsules immediately after a heavy meal. Maximum plasma concentration is achieved within 3-4 hours after ingestion. Elimination from the plasma is biphasic with a terminal half-life of 1 to 1.5 days. Chronic sustanon 250 for sale administration of the equilibrium concentration is achieved within 1-2 weeks.
The accumulation of the drug in the keratinous tissues, particularly the skin, approximately 4 times greater than the accumulation in the plasma, and it depends on the rate of excretion of regeneration of the epidermis. In contrast to plasma concentrations that are not detectable after 7 days after stopping therapy, therapeutic concentrations in the skin persist for 2-4 weeks after stopping the 4-week course of treatment. Itraconazole is found in nail keratin already one week after initiation of treatment and stored for at least 6 months after 3 months of therapy. Itraconazole is also determined in sebum and to a lesser extent in sweat.
Itraconazole is well distributed in the tissues that are susceptible to fungal attack. The concentrations in the lungs, kidneys, liver, bone, stomach, spleen and muscle of two to three times higher than corresponding concentrations in plasma. Therapeutic concentrations of the vaginal tissues preserved for a further 2 days after 3 days of treatment at a dose of 200 mg per day, and 3 days after the day course of treatment in a dose of 200 mg twice a day.
Itraconazole is metabolized by the liver to form large amounts of metabolites. One of these metabolites is hydroxy-itraconazole, which has comparable with itraconazole antifungal activity in vitro. Antifungal drug concentration determined by microbiological method, about 3 times higher than the concentrations measured by HPLC. Excretion in the feces is from 3 to 18% of the dose. Removing the kidney is less than 0.03% of the dose. Approximately 35% of the dose is excreted as metabolites in the urine within 1 week.
Orun capsules is sustanon 250 for sale indicated for the treatment of the following diseases:
- fungal keratitis;
- onychomycosis caused by dermatophytes and / or yeasts and molds;
- systemic mycoses: systemic aspergillosis and candidiasis, cryptococcosis (including cryptococcal meningitis), histoplasmosis, sporotrichosis, paracoccidioidomycosis, blastomycosis and other systemic or tropical mycoses;
- candidiasis skin or mucous lesions, including vulvovaginal candidiasis;
- deep visceral candidiasis;
Orun Capsules is contraindicated in patients with individual hypersensitivity to the drug or its components.
- Orun Pregnant women should be given only if the expected benefit to the woman outweighs the potential risk to the fetus. Women of childbearing age receiving Orun, you must use adequate contraception methods during the course of treatment until the onset of the first menstrual period after its completion.
- With care – children’s age, severe heart failure, liver disease (including accompanied by hepatic insufficiency).
- Terfenadine, astemizole, mizolastine, cisapride, dofetilide, quinidine, pimozide, metabolizing enzyme with CYP3A4 inhibitors of HMG-CoA reductase such as simvastatin and lovastatin, triazolam, and midazolam should not be taken simultaneously with Orunitom. (See. Also “Interactions with other medicinal products” section).The most frequently reported adverse reactions in connection with the use of itraconazole were reactions from the gastrointestinal tract, such as dyspepsia, nausea, abdominal pain and constipation. In addition, noted: anorexia headache, fatigue, reversible increased activity of “liver” enzymes, cholestatic jaundice, hepatitis, menstrual disorders, dizziness and allergic reactions (such as pruritus, rash, urticaria, angioedema), peripheral neuropathy, Stevens -Dzhonsona, alopecia, hypokalemia, edema, congestive heart failure and pulmonary edema, staining of urine in a dark color, hypercreatininemia.
in very rare cases, when applying Orunita develop severe hepatotoxicity, including cases of acute liver failure with fatal consequences.
No data. In case sustanon 250 for saleof accidental overdose, supportive measures should be used. As to gastric lavage and, if necessary, to assign the activated carbon within the first hour. Itraconazole not appear in hemodialysis. Any specific antidote does not exist.
As clinical data itraconazole capsules in children insufficient itraconazole recommended only if the potential benefit outweighs the potential risk.
Use during pregnancy and lactation
Based on preclinical studies, and due to the fact that research on the use of itraconazole in pregnant women have not been conducted, itraconazole should be administered to pregnant women only in life-threatening systemic fungal infections, where the potential benefits for the woman justifies the potential risk to the fetus . Since a small amount of itraconazole is excreted in human milk, the potential benefits from receiving itraconazole must be weighed against the risk for the baby during breastfeeding. If in doubt, do not breast-feed.
Interaction with other medicinal products
1. Drugs affecting the metabolism of itraconazole.
It has been studied the interaction of itraconazole with rifampicin, rifabutin and phenytoin. Concomitant use of itraconazole with these drugs, which are potential inducers of hepatic enzymes, it is not recommended. Studies of interaction with other hepatic enzyme inducers, such as carbamazepine, phenobarbital and isoniazid were not conducted, however, similar results can be expected.
Since itraconazole is mainly metabolized by the enzyme CYP3A4, potential inhibitors of this enzyme may increase the bioavailability of itraconazole. Examples include ritonavir, indinavir, clarithromycin and erythromycin.
2. Effect of itraconazole on the metabolism of other drugs.
Itraconazole can inhibit the metabolism of drugs, digestive enzymes of CYP3A4. The result may be increased or prologirovanie their actions, including side effects. After the cessation of treatment plasma levels of itraconazole is gradually reduced depending on the dose and duration of treatment (see. Pharmacokinetics ).
Examples of such drugs are: Drugs that can not be administered concurrently with itraconazole :
- Terfenadine, astemizole, mizolastine, cisapride, midazolam and triazolam, dofetilide, quinidine, pimozide, inhibitors of HMG-CoA reductase inhibitors such as simvastatin and lovastatin.
- Calcium channel blockers can have negative inotropic effect which can amplify the same effect exhibited by itraconazole. At the same time taking itraconazole and calcium channel blockers should be careful, because the metabolism of calcium channel blockers may be reduced.
Formulations in which assignment must monitor their concentrations in plasma, by the action, side effects.
In the case of co-administration with itraconazole dose of these preparations, if necessary, should be reduced.
- Oral anticoagulants;
- HIV protease inhibitors such as ritonavir, indinavir, saquinavir;
- Some anti-cancer drugs such as vinca alkaloids, busulfan, docetaxel, trimetrexate;
- Cleaving enzymes sustanon 250 for sale calcium channel blockers, such as dihydropyridine and verapamil;
- Certain immunosuppressive agents: cyclosporine, tacrolimus, sirolimus;
- Other drugs: digoxin, carbamazepine, buspirone, alfentanil, alprazolam, brotizolam, rifabutin, methylprednisolone, ebastine, reboxetine.