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Active ingredients
Itraconazole
Release form
Capsules
Composition
Itraconazole 100 mg; Excipients: hypromellose, poloxamer (lutrol), wheat starch, sucrose.; The composition of hard gelatin capsules: gelatin, titanium dioxide, quinoline yellow, ferric oxide red, ferric oxide black, yellow sunset, azorubine.
Pharmacological effect
Synthetic antifungal drug of broad spectrum, a derivative of triazole. Inhibits the synthesis of ergosterol of the cell membrane of fungi, which causes the antifungal effect of the drug. Itraconazole is active against dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum), yeast-like fungi and yeast (Cryptococcus neoformans, using a fraction of a few months to set up a few months, a day to get a few days ago, I use a yeast-like fungus and yeast (Cryptococcus neoformans, I). ., Candida spp., Including Candida albicans, Candida glabrata, Candida krusei), Aspergillus spp.,. against other yeasts and molds.
Pharmacokinetics
Absorption; When administered orally, the maximum bioavailability of itraconazole is observed when taking capsules immediately after a meal. Cmax in plasma is achieved within 3-4 hours after ingestion.; Distribution; With long-term administration, Css is achieved within 1-2 weeks. Css itraconazole in plasma 3-4 hours after taking the drug is 0.4 μg / ml (100 mg when taken 1 time / day), 1.1 μg / ml (200 mg when taken 1 time / day) and 2 μg / ml (200 mg when taken 2 times / day); Plasma protein binding is 99.8% with plasma proteins. Itraconazole penetrates well and is distributed in tissues and organs. The concentration of the drug in the lungs, kidneys, liver, bones, stomach, spleen, skeletal muscles is 2-3 times its concentration in plasma. The accumulation of itraconazole in keratin tissues, especially in the skin, is 4 times its accumulation in plasma, and the rate of excretion depends on the regeneration of the epidermis. In contrast to plasma concentrations that cannot be detected as early as 7 days after cessation of therapy, therapeutic concentrations skin lasts for 2-4 weeks after cessation of a 4-week course of treatment; in the mucous membrane of the vagina - within 2 days after the end of the 3-day course of treatment with the drug at a dose of 200 mg / day and 3 days after the end of the 1-day course of treatment with the drug at a dose of 200 mg 2 times / day. The therapeutic concentration in the keratin of the nails is determined 1 week after the start of treatment and lasts for 6 months after the completion of the 3-month course of therapy.Itraconazole is also determined in the secretion of the sebaceous and sweat glands. Metabolism; Metabolized in the liver to form active metabolites, one of which, hydroxy-itraconazole, has an antifungal effect comparable to itraconazole in vitro; elimination; from 24-36 h; Removal with feces ranges from 3% to 18% of the dose. Excretion in the urine is less than 0.03%. Approximately 35% of the dose is excreted in the form of metabolites in the urine within 1 week.; Pharmacokinetics in special clinical situations; In patients with renal insufficiency, as well as in some patients with impaired immunity (eg, with AIDS, after organ transplantation or in case of neutropenia) perhaps a decrease in the bioavailability of the drug.; In patients with cirrhosis of the liver, the bioavailability of itraconazole is reduced, the T1 / 2 of itraconazole is increased.
Indications
- dermatomycosis; - fungal keratitis; - onychomycosis caused by dermatophytes and / or yeast and mold fungi; - systemic mycoses: systemic aspergillosis and candidiasis; cryptococcosis, including cryptococcal meningitis (patients with immunodeficiency and patients with central nervous system cryptococcosis Rumycoz; should be prescribed only in cases where first-line drugs are not applicable in this case or are not effective); histoplasmosis; sporotrichosis; paracoccidioidomycosis; blastomycosis; other systemic or tropical mycoses; - Candida with lesions of the skin or mucous membranes (including vulvovaginal candidiasis); - deep visceral candidiasis; - pityriasis versicolor.
Contraindications
- simultaneous use of drugs metabolized with CYP3A4 isoenzyme, which can increase the QT interval (terfenadine, astemizol, mizolastine, cisapride, dofetilide, quinidine, pimozide, levometadone, sertindol); inhibitors of HMG-CoA reductase metabolizing with CYP3A4 isoenzyme (simvastatin, lovastatin); midazolam and triazolam (for oral administration); ergot alkaloid preparations (dihydroergotamine, ergometrine, ergotamine and methylergometrine); - Hypersensitivity to the components of the drug. With caution should use the drug in children, in patients with severe heart failure, with liver disease (includingaccompanied by liver failure), with chronic renal failure.
Use during pregnancy and lactation
During pregnancy, the drug should be prescribed only when the potential benefit of therapy for the mother outweighs the potential risk to the fetus. If you need to use the drug during lactation, breastfeeding should be discontinued. the entire course of treatment until the onset of the first menstruation after its completion.
Dosage and administration
The drug is administered orally after a meal.; Table 1.; Vulvovaginal candidiasis 200 mg 2 times / day for 1 day; 200 mg 1 time / day for 3 days; Pityrias psoriasis 200 mg 1 time / day for 7 days; day 7 days; 100 mg 1 time / day 15 days; Lesions of highly keratinized areas of the skin such as hands and feet 200 mg 2 times / day 7 days; 100 mg 1 time / day 30 days; Oral candidiasis 100 mg 1 time / 15 days; Fungal keratitis 200 mg 1 time / day for 21 days; Possible correction of the duration of treatment, taking into account the positive dynamics of the clinical picture; Bioavailability and strain Oral administration can be reduced in some immunocompromised patients, such as patients with neutropenia, AIDS sufferers or organ transplants. In such cases, it may be necessary to double the dose.; Onychomycosis caused by dermatophytes and / or yeast, mold fungi; Pulse therapy; One course of pulse therapy consists of taking 200 mg Rumycoz daily (2 capsules. 2 / day) for 1 week (Table 2); For the treatment of fungal infections of the nail plate brushes, 2 courses are recommended.; For the treatment of fungal infections of the nail plates of the feet 3 courses are recommended.; 3 weeks. Clinical results become apparent after the end of treatment, as nails grow back; Continuous therapy; With damage to the nail plates of the feet with or without damage to the nail plates of the hands, the dose is 200 mg / day, the duration of the treatment is 3 months. tissue is slower than from plasma. Thus, optimal clinical and mycological effects are achieved 2-4 weeks after the end of treatment for skin lesions and 6-9 months after the end of the treatment of nail diseases .;
Side effects
On the part of the digestive system: dyspepsia, nausea, vomiting, loss of appetite, abdominal pain, diarrhea, constipation, reversible increase in liver enzymes, hepatitis; very rarely - severe toxic liver damage, incl. cases of acute liver failure with a lethal outcome.; From the side of the central nervous system and peripheral nervous system: headache, dizziness, peripheral neuropathy.; Allergic reactions: skin rash, pruritus, urticaria, angioedema; rarely - erythema multiforme exudative (Stevens-Johnson syndrome) .; Dermatological reactions: alopecia, photosensitization.; Other: menstrual disorders, hypokalemia, edema syndrome, congestive heart failure and pulmonary edema, dyeing the urine dark, hypercreatininemia.
Overdose
Data on cases of drug overdose Rumycoz; no treatment; in case of an accidental overdose, supportive measures should be taken. During the first hour, carry out a gastric lavage and, if necessary, prescribe activated charcoal. Itraconazole is not excreted by hemodialysis. There is no specific antidote.
Interaction with other drugs
Drugs that affect the absorption of itraconazole; Preparations that reduce the acidity of gastric juice, reduce the absorption of itraconazole.; Drugs that affect the metabolism of itraconazole; Itraconazole is mainly metabolized by the isoenzyme CYP3A4. With simultaneous use of rifampicin, rifabutin, phenytoin, carbamazepine, isoniazid, are powerful CYP3A4 isoenzyme inducers, bioavailability of itraconazole and hydroxy-itraconazole is significantly reduced, which leads to a significant decrease in the effectiveness of the drug (use of Rumikoza with these drugs has no benefit of this drug. CYP3A4 enzymes, such as ritonavir, indinavir, clarithromycin and erythromycin, can increase the bioavailability of itraconazole. The effect of itraconazole on the metabolism gp other drugs; Itraconazole can inhibit CYP3A4-mediated metabolism of drugs that can lead to increased or prolongation of their actions, including side effects.After discontinuation of treatment with Rumycoz; plasma concentration of itraconazole decreases gradually, depending on the dose and duration of treatment. This should be considered when you need a combination therapy.; Drugs that can not be prescribed simultaneously with itraconazole; Calcium channel blockers, in addition to the possible pharmacokinetic interaction associated with a common CYP3A4-mediated metabolism, can have a negative inotropic effect, which can enhance the similar effect exerted by itraconazole. ; Drugs, the appointment of which is necessary to monitor their concentration in plasma, action, side effects; - Oral anticoagulants; - HIV protease inhibitors (ritonavir, indinavir, saquinavir); - anticancer drugs (Vinca pink alkaloids, busulfan, docetaxel, trimetrexate); - calcium channel blockers (dihydropyridine, verapamil), metabolized by CYP3A4 isoenzyme; - immunosuppressive agents (cyclosporine, tacrolimus, sirolimus); - HMG-CoA reductase inhibitors, metabolized by CYP3A4 isoenzyme; - some GKS (budesonide, dexamethasone and methylprednisolone); - other drugs: digoxin, carbamazepine, buspirone, alfentanil, alprazolam, brotizolam, midazolam for intravenous administration, rifabutin, ebastine, reboxetine, cilostazol, disopyramide, eletriptan, halofantrine, repaglinid, cidostamol, disopyramide, eleptriptan, halofantrine, repaglinide, cidostamol, disopyramide, eletriptan, halofantrin, reparidine, cilostazol, disopyramide, eletriptan, halofantrin, reparidine of these drugs.; There was no interaction between itraconazole and zidovudine, fluvastatin.; Itraconazole was not observed to affect ethinyl estradiol and norethisterone metabolism. In vitro studies showed no The interactions between itraconazole and propranolol, imipramine, diazepam, cimetidine, indomethacin, tolbutamide, sulfamethazine when bound to plasma proteins.
special instructions
In the study of intravenous dosage form of itraconazole, a transient asymptomatic decrease in the left ventricular ejection fraction was observed, normalized until the next infusion of the drug.; Itraconazole was found to have a negative inotropic effect. Reported cases of heart failure associated with taking Rumikoza.Therefore, the drug is not prescribed to patients with chronic heart failure or with the presence of this disease in history, except in cases where the expected benefit of therapy far exceeds the potential risk.; Calcium channel blockers may have a negative inotropic effect, which may enhance the similar effect of itraconazole; Itraconazole is able to slow down the metabolism of calcium channel blockers. With simultaneous use of itraconazole and calcium channel blockers, caution is required.; In patients with renal insufficiency, bioavailability of itraconazole may be reduced, in such cases dose adjustment may be required. Patients receiving antacid preparations (for example, aluminum hydroxide) are recommended to take them no earlier than 2 hours after taking Rumicose. Patients with achlorhydria, as well as patients taking histamine H2 receptor blockers or proton pump inhibitors, are recommended to take itraconazole with acidic drinks. In very rare cases, when using Rumycoz, severe toxic liver damage developed, sometimes with acute hepatic insufficiency and death. This was observed in patients with already existing liver diseases, as well as in patients who received other drugs with a hepatotoxic effect. 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 Rumycoz;;; Treatment should be stopped if neuropathy occurs, which may be associated with taking Rumycoz.; There is no evidence of cross-hypersensitivity to itraconazole and other azole antifungal drugs. Rumycoz; should be used with caution in patients with hypersensitivity to other azole antifungal agents. In patients with impaired immunity (AIDS, condition after organ transplantation, neutropenia), an increase in the dose of Rumycoz may be required.; Pediatric use; Rumycoz; should not be given to children, except when the expected benefit of therapy exceeds the possible risk.; Impact on ability to drive vehicles and control mechanisms; Influence on ability to drive a car and work with the technique was not observed.