Itracon capsules 100 mg No. 6 (itraconazole)

Composition per capsule:

Active substance:

itraconazole pellets - 464.00 mg, containing itraconazole - 100.00 mg.

Excipients included in
itraconazole pellets:
sugar pellets - 207.44 mg (sucrose - 80.0 - 91.5%, corn starch - 8.5 - 20.0%, water - maximum 1.5%), hypromellose - 130.11 mg, poloxamer 188 (Lutrol F68) - 25.94 mg, micronized poloxamer 188 (Lutrol micro 68) - 0.51 mg.

Hard gelatin capsules:

water – 13-16%, sunset yellow dye (E110) – 1%, titanium dioxide – 1%, gelatin – up to 100%.

Description

Hard gelatin capsules No. 0 are orange in color, containing spherical microgranules (pellets) from light yellow to yellowish-beige.

Pharmacotherapeutic group.

Antifungal agent

ATX code

[J02AC02]

Pharmacological properties

Pharmacodynamics

Itraconazole, a triazole derivative, is active against infections caused by dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum), yeast-like fungi and yeasts (Candida spp., including C.albicans, C.glabrata and C.krusei, Cryptococcus neoformans, Pityrosporum spp., Trichosporon spp., Geotrichum spp.); Aspergillus spp., Histoplasma spp., Paracoccidioides brasiliensis, Sporothrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatitidis, Pseudallescheria boydii, Penicillium marneffei, as well as other yeasts and molds.

Itraconazole disrupts the synthesis of ergosterol, which is an important component of the cell membrane of fungi, which determines the antifungal effect of the drug.

Pharmacokinetics

When administered orally, maximum bioavailability of itraconazole is observed when capsules are taken immediately after meals. Maximum plasma concentrations are achieved within 3-4 hours after oral administration. Elimination from plasma is biphasic with a terminal half-life of 24-36 hours. With long-term use, equilibrium concentration is achieved within 1-2 weeks. The equilibrium concentration of itraconazole in plasma 3-4 hours after taking the drug is 0.4 mcg/ml (100 mg when taken once a day), 1.1 mcg/ml (200 mg when taken once a day) and 2. 0 mcg/ml (200 mg when taken twice daily). Itraconazole is 99.8% bound to plasma proteins. The concentration of itraconazole in the blood is 60% of the concentration in plasma.

The accumulation of the drug in keratin tissues, especially in the skin, is approximately 4 times higher than the accumulation in plasma, and the rate of its elimination depends on the regeneration of the epidermis.

In contrast to plasma concentrations, which are undetectable 7 days after cessation of therapy, therapeutic skin concentrations persist for 2-4 weeks after cessation of a 4-week course of treatment. Itraconazole is detectable in nail keratin as early as one week after initiation of treatment and persists for at least 6 months after completion of 3 months of therapy. Itraconazole is also detected in sebum and, to a lesser extent, in sweat.

Itraconazole is well distributed in tissues that are susceptible to fungal infections. Concentrations in the lungs, kidneys, liver, bones, stomach, spleen and muscles were two to three times higher than the corresponding plasma concentrations. Therapeutic concentrations in vaginal tissues remain for another 2 days after the end of a 3-day course of treatment at a dose of 200 mg per day, and 3 days after the end of a one-day course of treatment at a dose of 200 mg twice a day.

Itraconazole is metabolized by the liver to form a large number of metabolites. One such metabolite is hydroxy-itraconazole, which has antifungal activity comparable to itraconazole in vitro. Antifungal concentrations of the drug determined by microbiological methods were approximately 3 times higher than those measured by HPLC. Excretion in feces ranges from 3 to 18% of the dose. Renal excretion is less than 0.03% of the dose. Approximately 35% of the dose is excreted as metabolites in the urine within 1 week.

Since the total half-life of itraconazole and its plasma concentration are slightly increased in patients with renal failure, dose adjustment may be required (see section "Special Instructions").

Since the total half-life of itraconazole and its plasma concentration are slightly increased in patients with cirrhosis, dose adjustment may be required (see section "Special Instructions").

Pharmacodynamics and pharmacokinetics

The active substance is a triazole . Produced synthetically, it has a wide spectrum of effects.

The antifungal mechanism is based on suppressing the production and synthesis of ergosterol in the fungal cell. Active against molds, dermatophytes, yeasts.

The effectiveness of antifungal therapy is assessed one month after completion of treatment (for mycoses ). For onychomycosis, effectiveness is assessed as the nail plate changes (6-9 months).

Indications for use

• 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 all patients with central nervous system cryptococcosis, Itraconazole capsules should only be prescribed when first-line treatment is not appropriate or effective.
• histoplasmosis,
• sporotrichosis,
• paracoccidioidomycosis,
• blastomycosis
• other rare systemic or tropical mycoses;
• candidomycosis with damage to the skin or mucous membranes, including vulvovaginal candidiasis;
• pityriasis versicolor.

Special instructions for the use of the drug Itraconazole

During pregnancy, itraconazole is prescribed only for systemic mycoses, when the expected effect of therapy outweighs the risk of undesirable effects on the fetus. Women of childbearing age are advised to use effective contraception during treatment with itraconazole. During breastfeeding, itraconazole is prescribed only in cases where the expected effect of treatment outweighs the risk of possible negative effects on the child. For patients with elevated levels of transaminases in the blood, itraconazole is prescribed only in cases where the expected effect of therapy outweighs the possible risk of hepatotoxicity; its use is permissible if the value of the AlAT and AST indicators exceeds the upper limit of the norm by no more than 2 times. In case of liver cirrhosis and/or impaired renal function, itraconazole is used under the control of its concentration in the blood plasma and, if necessary, the dose is adjusted. It is necessary to monitor the functional state of the liver during therapy for more than 1 month, as well as if a patient taking itraconazole develops anorexia, nausea, vomiting, increased fatigue, abdominal pain, or dark urine. If liver dysfunction is detected, itraconazole is discontinued. In case of peripheral neuropathy caused by taking itraconazole, it should also be discontinued. Clinical data are not yet sufficient to recommend itraconazole for widespread use in pediatric practice. Children are prescribed only in cases where the expected effect of therapy outweighs the possible risk of side effects.

Contraindications

• hypersensitivity to itraconazole and any of the components of the drug.
• Concomitant use of the following drugs with Itraconazole capsules:
• simultaneous use of CYP3A4 isoenzyme substrates that prolong the QT interval (astemizole, bepridil, cisapride, dofetilide, levacetylmethadol, mizolastine, pimozide, quinidine, sertindole, terfenadine)
• HMG-Coa reductase inhibitors metabolized by the CYP3A4 isoenzyme (lovastatin, simvastatin);
• simultaneous oral administration of triazolam and midazolam, nisoldipine, eletriptan;
• ergot alkaloid preparations such as dihydroergotamine, ergometrine,
• ergotamine and methylergometrine;
• fructose intolerance, sucrase/isomaltase deficiency, glucose-galactose malabsorption;
• children under 3 years of age;
• pregnancy and lactation

Carefully

– with cirrhosis of the liver, chronic renal failure, chronic heart failure, hypersensitivity to other azoles, in children and elderly patients (see also section “Special instructions”).

Drug interactions Itraconazole

During treatment with itraconazole, oral administration of terfenadine, astemizole, cisapride, midazolam, and triazolam is contraindicated. Caution must be exercised when simultaneously prescribing indirect anticoagulants, cyclosporine A, digoxin, calcium channel blockers of the dihydropyridine group, as well as quinidine and vincristine, the metabolism of which is carried out with the participation of enzymes such as cytochrome 3, since it is possible to enhance the effects and/or increase the duration of action of these drugs . Concomitant use of drugs that induce liver enzyme systems (rifampicin, phenytoin, etc.) significantly reduces the bioavailability of itraconazole. Patients with reduced gastric acidity (for example, those taking H2-receptor blockers) are recommended to prescribe itraconazole along with cola. Antacids should be taken no earlier than 2 hours after taking itraconazole. No significant interactions were observed when itraconazole was taken concomitantly with zidovudine, ethinyl estradiol or norethisterone.

Treatment regimens and possible dosages

Itraconazole tablets are taken orally, swallowing them whole with a small amount of water. The optimal time to take is after a meal.

A detailed regimen for taking Itraconazole should be found in the instructions for use; it is also possible to prescribe a personal regimen and select dosages at the discretion of the doctor.

Itraconazole is usually taken according to the following instructions:

• vulvovaginal candidiasis - 200 mg twice a day, duration of administration is 1 day, or 200 mg once a day for three days;
• dermatomycosis – 200 mg once a day for seven days, or 100 mg per day for 15 days;
• skin lesions on the feet and hands due to dermatophytosis - 200 mg twice a day for seven days, or 100 mg once a day for a month;
• pityriasis versicolor – 200 mg per day for at least seven days;
• candidiasis of the oral mucosa - 100 mg of the drug once a day for 15 days (in some situations the dosage can be increased to 200 mg);
• keratomycosis - 200 mg once a day for three weeks (the time of taking Itraconazole can be increased at the discretion of the doctor);
• onychomycosis - 200 mg once a day for three months, or 200 mg twice a day for a week (if the toenails are affected, then three courses of treatment are necessary, if the lesion affects the fingernails, then the course of treatment is repeated twice, in in both cases, the interval between taking the drug is at least three weeks);
• systemic candidiasis - 100 or 200 mg once a day for three weeks to seven months;
• systemic cryptococcal infection - 200 mg once a day for two months to a year, if cryptococcal meningitis is suspected - 200 mg twice a day for two months to a year;
• histoplasmosis - 200 mg once a day for treatment and 200 mg twice a day for eight months for maintenance therapy.

For children under 12 years of age, Itraconazole tablets are prescribed only if the importance of treatment outweighs all the risks possible when taking this drug.

To reduce the risk of adverse reactions, it is recommended to take plenty of fluids during treatment with Itraconazole, and, if necessary, use additional medications as prescribed by your doctor.

If you miss taking the drug, you cannot increase its dosage next time or start the treatment regimen again.

Use of the drug Itraconazole

Inside immediately after eating. For vulvovaginal candidiasis, it is prescribed at a dose of 0.2 g 2 times a day for 1 day or at a dose of 0.2 g 1 time a day for 3 days. For chronic recurrent fungal vulvovaginitis - 0.1 g 2 times a day for 6-7 days, and then for 3-6 menstrual cycles, 0.1 g on the first day of the cycle. For pityriasis versicolor - 0.2 g once a day for 7 days. For dermatomycosis - 0.1 g 1 time per day for 15 days. In case of damage to highly keratinized areas, such as the skin of the hands and feet, an additional course of treatment is carried out at the same dose for 15 days. For oral candidiasis - 0.1 g once a day for 15 days. For fungal keratitis - 0.2 g once a day for 21 days. For onychomycosis - 0.2 g per day for 3 months or repeat courses of treatment using the pulse therapy method, prescribing itraconazole at a dose of 0.2 g 2 times a day for 1 week, followed by a break: for damage to the toenails (regardless depending on whether the fingernails are affected or not) 3 courses of treatment are carried out (1 week of taking itraconazole, then 3 weeks off). If the nails are affected only on the hands, 2 courses of treatment are carried out (1 week of taking itraconazole, 3 weeks off). For systemic aspergillosis, itraconazole is prescribed at a dose of 0.2 g once a day for 2–5 months; if necessary, the dose of itraconazole is increased to 0.2 g 2 times a day. For systemic candidiasis - 0.1-0.2 g once a day for 3 weeks - 7 months, if necessary, the dose is increased to 0.2 g 2 times a day. For systemic cryptococcosis (without signs of meningitis) - 0.2 g once a day; for maintenance therapy, itraconazole is prescribed at a dose of 0.2 g once a day for 2 months to 1 year. For cryptococcal meningitis - 0.2 g 2 times a day. For histoplasmosis - from 0.2 g once a day to 0.2 g 2 times a day for 8 months. For sporotrichosis - 0.1 g once a day for 3 months. For paracoccidioidosis (paracoccidioidomycosis) - at a dose of 0.1 g once a day for 6 months. For chromomycosis - 0.1–0.2 g once a day for 6 months. For blastomycosis - from 0.1 g 1 time per day to 0.2 g 2 times per day for 6 months. In some patients with impaired immunity (for example, with AIDS, after organ transplantation or with neutropenia), an increase in the dose of itraconazole may be required. For fungal and mixed infections of the vagina - intravaginally (vaginal suppositories), deeply 1 time per day before bedtime, course of treatment - 3 days.

Where to buy Itraconazole?

The drug is sold through pharmacies. You can buy Itraconazole in pharmacy chains only with a prescription from a doctor. The price of Itraconazole is determined individually depending on the pharmacy. Before use, you must carefully study the instructions for use, become familiar with the indications and contraindications, special instructions for use and any restrictions. It is also recommended to carefully check the expiration dates of the drug and not take Itraconazole after their expiration.

Take the drug strictly following the instructions and according to the treatment regimen prescribed by the doctor.

Side effects of the drug Itraconazole

Dyspepsia, nausea, abdominal pain, constipation, transient increase in transaminase activity in the blood serum, in some cases with long-term treatment - hepatitis (a clear cause-and-effect relationship with taking itraconazole has not been established); headache, dizziness, peripheral neuropathy; allergic reactions (skin itching, urticaria, angioedema, Stevens-Johnson syndrome); dysmenorrhea; in some cases, with long-term treatment, alopecia, hypokalemia, and edema are possible.