Index of drugs

Genital infections: vaginal and vulvar mycosis. Infections of the skin, mucous membranes or eyes: skin mycosis (eg athlete's foot, groin, torso and hand); dandruff versatile; oral candidosis; fungal corneal infection. Onychomycosis caused by dermatophytes and / or yeasts. Systemic mycoses: systemic aspergillosis and systemic candidiasis; cryptococcosis (including cryptococcal meningitis) in patients with cryptococcosis and impaired immunity, and in all patients with Cryptococcosis of the central nervous system (itraconazole is indicated only if first-line treatment is ineffective); histoplasmosis; blastomycosis; Sporotrichosis; paracoccidioidomycosis; other, rare, systemic or tropical fungal infections.

One capsule contains 100 mg of itraconazole. The product contains sucrose.

The drug is antifungal for general use with a wide range of action, a triazole derivative. Itraconazole disturbs the synthesis of ergosterol in fungal cells. Itraconazole inhibits the growth of many pathogenic fungi for humans, including: dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum); yeast (Candida spp., includingC. albicans, C. tropicalis, C. parapsilosis andC. krusei, Cryptococcus neoformans, Malassezia spp., Trichosporon spp., Geotrichum spp.); Aspergillus spp.; Histoplasma spp. includingH. capsulatum; Paracoccidioides brasiliensis; Sporothrix schenckii; Fonsaecaea spp.; Cladosporium spp; Blastomyces dermatitidis; Coccidiodes immitis; Pseudallescheria boydii; Penicillium marneffei and various other yeasts and fungi. Of yeastsCandida spp. the least sensitive to itraconazole areCandida krusei, Candida glabrata andCandida tropicalis, wherein some of the isolated strains show complete drug resistancein vitro. Basic fungi, the growth of which is not inhibited by Itraconazole, belong to the following species:Zygomycetes (Eg.Rhizopus spp., Rhizomucor spp., Mucor spp. andAbsidia spp.), Fusarium spp., Scedosporium spp. andScopulariopsis spp. Itraconazole is rapidly absorbed after oral administration. The maximum concentration of unchanged drug in plasma occurs after 2-5 h after administration. The drug accumulates in plasma after repeated administration. Steady-state is usually achieved within about 15 days. The absolute bioavailability is about 55%. It is the largest if the capsules are taken immediately after a heavy meal. Absorption of itraconazole capsules is reduced in patients with decreased gastric acidity, i.e. patients taking gastric acid-reducing drugs and patients with achlorhydria caused by certain diseases. In these patients, increased absorption of itraconazole after fasting is observed if itraconazole is administered with an acidic beverage (eg "non-gold" cola). Itraconazole is mostly bound to plasma proteins (99.8%), especially to albumin (the metabolite is 99.6% hydroxylated). It also has affinity for lipids. Only 0.2% of itraconazole in plasma is available as a free drug. It was found that the drug concentration in the lungs, kidneys, liver, bones, stomach, spleen and muscles is 2-3 fold greater than in the plasma, and itraconazole uptake by corneal tissues, especially through the skin, is up to 4 times greater. Cerebrospinal fluid concentrations are lower. Itraconazole is extensively metabolised in the liver mainly by CYP3A4. The main metabolite is hydroxyitraconazole, which has antiviral activity comparable to itraconazolein vitro. The plasma concentration of this metabolite is approximately 2-fold higher than that of itraconazole. Itraconazole is mainly excreted in the form of inactive urinary metabolites (35%) and faeces (54%). The elimination of the drug in the unchanged form is 3-18% of the dose. Final T_0,5 is 16-28 h after a single dose and increases to 34-42 h after multiple doses. The therapeutic concentration of itraconazole in the skin lasts for 2-4 weeks after the end of the 4-week treatment. Just 1 weektreatment is detected by itraconazole in the nail keratin, and the concentration of the drug persists in it for at least 6 months after the end of the 3-month treatment.

Hypersensitivity to the active substance or to any of the excipients. Co-administration of some drugs metabolised by CYP3A4 is contraindicated with itraconazole. Increased plasma concentrations of these medicinal products due to their concomitant use with itraconazole may increase or prolong both their therapeutic and adverse effects, to the extent that potentially serious risks can occur. For example, increased plasma concentrations of certain drugs may result in QT prolongation and ventricular tachyarrhythmias, including cardiac arrhythmiastorsade de pointesarrhythmia that can be life threatening. Itraconazole capsules should not be used in patients with known ventricular dysfunction, such as congestive heart failure (CHF) or congestive heart failure, except for the treatment of life-threatening infections or other serious infections. Itraconazole is contraindicated in pregnancy (except in life-threatening cases). Women of childbearing potential should use effective contraception during treatment with itraconazole. The use of such a method should continue until the menstrual bleeding after itraconazole is discontinued.

In a study involving healthy volunteers who received itraconazole intravenously, a transient asymptomatic decrease in left ventricular ejection fraction was observed. These disorders resolved before the Next intravenous infusion. It is not known if the described phenomenon is of clinical significance in relation to oral forms of the drug. Itraconazole has an inotropic negative effect. Cases of congestive heart failure have been reported in association with itraconazole. The risk of heart failure may increase with the daily dose of itraconazole. Itraconazole should not be used in patients with a history of congestive heart failure or congestive heart failure, unless the expected benefit clearly outweighs the risk. In determining the risk-benefit ratio for each patient, factors such as the severity of the indication to use the drug, the dosing regimen (ie the total daily dose) and the occurrence of individual risk factors for congestive heart failure: coronary heart disease, should be taken into account. valve defects, serious lung diseases such as chronic obstructive pulmonary disease, as well as renal failure and other diseases with edema. If the patient is at risk of developing congestive heart failure, he should be informed about possible signs and symptoms. Treatment should be carried out carefully, observing in particular that there are no signs and symptoms of congestive heart failure. If such symptoms occur, itraconazole should be discontinued. Because of the increased risk of congestive heart failure, caution should be exercised when itraconazole and Calcium antagonists are used. There are no data on the occurrence of cross-sensitivity to itraconazole and other azole antifungals. Caution should be exercised when prescribing itraconazole to patients who are hypersensitive to other azoles. Treatment with the preparation should be discontinued if there are symptoms of neuropathy that can be associated with the use of the drug. Transient or permanent hearing loss has been reported in patients receiving itraconazole. Hearing loss usually disappears after discontinuation of therapy, but may persist in some patients. If it is suspected that systemic yeast is caused by strainsCandida resistant to Fluconazole, it can not be assumed that they will be sensitive to itraconazole - a sensitivity test should be performed before treatment with itraconazole. Due to the risk of hepatotoxicity in patients treated with itraconazole, monitoring of liver function should be considered. Patients should be advised to immediately inform their doctor if they experience signs of hepatitis. If the patient reports these symptoms, treatment with itraconazole should be discontinued immediately and hepatic function should be assessed.Available data on the oral use of itraconazole in patients with impaired liver function are limited. Caution should be exercised when using the drug in this group of patients. It is recommended that patients with impaired liver function should be carefully monitored during treatment with itraconazole. When deciding to initiate treatment with itraconazole concurrently with other drugs metabolised by CYP3A4, an extended T_0,5 in patients with liver cirrhosis. In patients with increased or abnormal liver enzymes, active liver disease, and in patients who have experienced symptoms of hepatic toxicity after treatment with other medicinal products, itraconazole should not be used unless there is a serious or life-threatening condition and the expected benefits of treatment outweighs the risk. Monitoring of liver function is recommended in patients with previous hepatic impairment or toxic effects of other liver medications. Caution should be exercised in patients with renal insufficiency. Absorption of itraconazole after oral administration is less pronounced if gastric acidity is reduced. In patients with reduced gastric acidity resulting from the disease (eg patients with achlorhydria) or from the use of medicines (eg patients taking drugs to reduce gastric acidity), it is recommended to administer the preparation with acidic beverages ("cola" unnatural). The antifungal activity should be monitored and the dose should be increased if necessary. In some immunocompromised patients (eg neutropenic patients, AIDS, organ transplantation), oral bioavailability of itraconazole may be reduced. It is not recommended to initiate treatment of systemic fungal diseases that directly threaten life with itraconazole capsules. If a patient with AIDS, treated for systemic mycoses such as sporotrichosis, blastomycosis, histoplasmosis or cryptococcosis (a form with or without meningitis), there is a risk of recurrent infection, consideration should be given to maintenance treatment. Due to limited data in children and the elderly, the preparation can only be used if the expected benefits outweigh the risks. The product contains sucrose - should not be used in patients with rare inherited disorders associated with fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency.

Do not use during pregnancy, except in life-threatening situations where the expected benefit to the mother outweighs the risk of fetal defects (fetal malformations have been reported: deformities within the skeleton, urogenital tract, cardiovascular and eye systems, and chromosomal aberrations and multiple malformations, however, the causal relationship between the occurrence of defects and the use of itraconazole has not been established, epidemiological data on the use of itraconazole during the first trimester of pregnancy, mainly in patients treated for a short time due to vaginal candidiasis and vulva, showed no increased risk of malformation ). Women of childbearing age who are treated with itraconazole should use effective contraception until the first menstrual period after the end of treatment. A very small amount of itraconazole is excreted in human milk. When breastfeeding, the expected benefits of itraconazole should be weighed against the risk; in case of any doubts, the patient should not breastfeed.

Data from clinical trials. Adverse reactions reported in ≥1% of patients: headache, nausea, abdominal pain. Adverse reactions reported in <1% of patients: rhinitis, sinusitis, upper respiratory tract infection, leukopenia, hypersensitivity, disturbed taste, hypoaesthesia, paresthesia, tinnitus, constipation, diarrhea, indigestion, bloating, vomiting, liver dysfunction, hyperbilirubinaemia, pruritus, rash, urticaria, polyuria, erectile dysfunction, menstrual disorders, edema. Adverse reactions observed after the medicine has been placed on the market.Very rare: serum sickness syndrome, angioneurotic edema, anaphylactic reaction, hypertriglyceridemia, visual disturbances (including double and blurred vision), transient or permanent hearing loss, congestive heart failure, dyspnea, pancreatitis, severe hepatotoxicity (including several deaths from due to acute hepatic failure), toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized pustular exanthema, erythema multiforme, exfoliative dermatitis, leukoclastic vasculitis, alopecia, photosensitivity, elevated creatine phosphokinase.Children and youth. The most commonly reported adverse reactions in children and adolescents were headache (3%), vomiting (3%), abdominal pain (2.4%), diarrhea (2.4%), liver dysfunction (1.2%), hypotension (1.2%), nausea (1.2%) and urticaria (1.2%). The nature of adverse reactions is generally similar in children and adolescents as well as in adult patients, but the incidence is greater in children and adolescents.

Orally.Genital infections. Candidiasis of vulva and vagina: 200 mg 2 times daily for 1 day or 200 mg once daily for 3 days.Infections of the skin, mucous membranes or eyes. Skin mycosis: 200 mg once daily for 7 days or 100 mg once daily for 15 days. Infections of the area with increased keratinisation, such as athlete's foot and palm mycosis: 200 mg 2 times a day for 7 days or 100 mg once a day for 30 days. Dandruff versatile: 200 mg once a day for 7 days. Oral candidiasis: 100 mg once a day for 15 days. In some patients with immunosuppression (eg in patients with neutropenia, AIDS or organ transplantation), there may be a reduction in the bioavailability of the drug - it may be necessary to double the dose. Fungal inflammation of the cornea: 200 mg once daily for 21 days (the length of treatment should be adjusted according to the clinical response).Onychomycosis caused by dermatophytes and / or yeasts. Recurring treatment. Consists of taking 200 mg 2 times a day for 1 week. The periods of taking the drug (cycles) are separated by a 3-week break, during which the medicine is not taken. Two cycles are used in the treatment of onychomycosis of the hands. In the treatment of onychomycosis of the feet (or onychomycosis of the feet together with the nails of the hands), 3 cycles are used. The response to the treatment becomes visible after the treatment and regrowth of the nails.Continuous treatment. Treatment of toenail onychomycosis or with hand nails: 200 mg once a day for 3 months. Elimination of itraconazole from the skin and nails takes place more slowly than from the plasma. Optimal treatment results in terms of clinical symptoms and results of mycological tests are obtained within 2-4 weeks after the end of treatment of skin infections and 6-9 months after the end of treatment of nail infections.Systemic mycoses. Aspergillosis: 200 mg once daily for 2-5 months; increase the dose to 200 mg 2 times a day if the changes are deep or scattered. Candidiasis: 100-200 mg once daily for 3 weeks-7 months; increase the dose to 200 mg 2 times a day if the changes are deep or scattered. Cryptococcosis (without meningitis): 200 mg once a day for 2 months-1 year (if you have a risk of relapse from an AIDS patient, you should consider maintaining maintenance treatment). Cryptococcal meningitis: 200 mg 2 times a day for 2 months-1 year (if the patient with AIDS is at risk of relapse, consideration should be given to maintenance treatment). Histoplasmosis: from 200 mg once daily to 200 mg twice daily for 8 months Blastomycosis: from 100 mg once a day to 200 mg twice daily for 6 months. Lymphoid-cutaneous and cutaneous comorphicosis: 100 mg once a day for 3 months Paracocidioidomycosis: 100 mg once daily for 6 months; no data on the efficacy of the preparation in the treatment of paracoccinidio- phicosis in AIDS patients. Chromomycosis: 100-200 mg once daily for 6 months. In children and elderly patients, the preparation can only be used if the expected benefits outweigh the risks (limited data). It is recommended that during the dose selection in elderly patients, a higher incidence of hepatic, renal or cardiac dysfunction and the presence of other diseases or the use of other medications should be considered. Caution should be exercised in patients with hepatic impairment.In patients with renal insufficiency exposure to itraconazole may be lower - caution should be exercised and dose modification considered. For the best absorption of the active substance, the preparation should be administered immediately after a full meal. The capsules should be swallowed whole.