Dear buyers! Unfortunately, we are currently unable to accept the application to Canada and are revoking the license. Keep an eye on the site to see if there are any updates from Canada.
ATC code:J ANTIMIBRICANTS FOR SYSTEMIC USE; J02 ANTIFUNGALS FOR SYSTEMIC USE; J02A ANTIFUNGALS FOR SYSTEMIC USE; J02A C Triazole derivatives; J02A C02 Itraconazole
Country of manufacture:Ukraine
Diabetics:Can
Delivery
USPS across the USA
Canada Post across Canada
Payment
Itracon capsules 100 mg No. 6
354.78 грн.
Description
Instructions for Itracon capsules 100 mg No. 6
Composition
active ingredient: itraconazole;
1 capsule contains itraconazole, pellets equivalent to itraconazole 100 mg;
excipients: hypromellose (hydroxypropylmethylcellulose (E 5)), sucrose;
capsule shell composition: gelatin, titanium dioxide (E 171), azorubine (E 122), indigo carmine (E 132).
Dosage form
Capsules.
Main physicochemical properties: hard gelatin capsules No. 0 or No. 1. The capsule body is pink, the cap is blue. The capsule contents are granules from almost white to cream color, spherical in shape.
Itraconazole is a triazole derivative with a broad spectrum of activity. In vitro studies have shown that itraconazole inhibits the synthesis of ergosterol in fungal cells. Ergosterol is an important component of the fungal cell membrane, and inhibition of its synthesis provides an antifungal effect.
For itraconazole, breakpoints have only been established for Candida spp. in superficial mycotic infections (CLSI M27-A2, breakpoints have not been established according to EUCAST methodology). The CLSI breakpoints are as follows: susceptible ≤ 0.125; susceptible dose-dependent 0.25–0.5 and resistant ≥ 1 μg/ml. Breakpoints have not been established for mycelial fungi.
In vitro studies have shown that itraconazole inhibits the growth of a wide range of fungi pathogenic to humans at concentrations usually ≤ 1 μg/ml. These include: dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum); yeasts (Candida spp., including C. albicans, C. tropicalis, C. parapsilosis and C. krusei, Cryptococcus neoformans, Malassezia spp., Trichosporon spp., Geotrichum spp.), Aspergillus spp.; Histoplasma spp., including H. capsulatum; Paracoccidioides brasiliensis; Sporothrix schenckii; Fonsecaea spp.; Cladosporium spp.; Blastomyces dermatitidis; Coccidiodes immitis; Pseudallescheria boydii; Penicillium marneffei and other species of yeasts and fungi.
Candida krusei, Candida glabrata, and Candida tropicalis are generally the least susceptible Candida species, and some isolates demonstrate resistance to itraconazole in vitro.
The main types of fungi that are not inhibited by itraconazole are zygomycetes (Rhizopus spp., Rhizomucor spp., Mucor spp., and Absidia spp.), Fusarium spp., Scedosporium proliferans, and Scopulariopsis spp.
Resistance to azoles develops slowly and is usually the result of multiple genetic mutations. Mechanisms that have been described include overexpression of ERG11, which encodes 14α-demethylase (the target enzyme), point mutations in ERG11 that result in reduced affinity of 14α-demethylase for itraconazole, and/or overexpression of a transporter that results in increased efflux of itraconazole from fungal cells (i.e., removal of itraconazole from its target). Cross-resistance among azoles has been observed within Candida species, but resistance to one member of the class does not necessarily imply resistance to other azoles. Itraconazole-resistant strains of Aspergillus fumigatus have been reported.
Pharmacokinetics.
General pharmacokinetic characteristics. Peak plasma concentrations after oral administration of itraconazole are reached within 2 to 5 hours. Due to nonlinear pharmacokinetics, itraconazole accumulates in plasma after multiple administration. Steady-state concentrations are generally reached within 15 days with Cmax values of 0.5 μg/ml, 1.1 μg/ml and 2.0 μg/ml after administration of 100 mg once daily, 200 mg once daily and 200 mg twice daily, respectively. The terminal half-life of itraconazole generally varies from 16 to 28 hours after a single dose and increases to 34-42 hours after multiple doses. After discontinuation of treatment, itraconazole concentrations decline to levels that are almost undetectable in plasma within 7-14 days, depending on the dose and duration of treatment. The mean plasma clearance of itraconazole after intravenous administration is 278 ml/min. Due to saturable hepatic metabolism, clearance of itraconazole decreases at higher doses.
Absorption. Itraconazole is rapidly absorbed after oral administration. Peak plasma concentrations of unchanged drug after oral administration of capsules are reached within 2–5 hours. Absolute bioavailability of itraconazole is 55%. Maximum bioavailability when administered orally is observed immediately after ingestion of a high-calorie meal.
The concentration of itraconazole after administration of capsules is lower than after administration of oral solution at the same dose (see section "Special instructions").
Distribution. Itraconazole is largely bound to plasma proteins (99.8%), albumin being the major binding component (99.6% for the hydroxymetabolite). It also has a high affinity for lipids. Only 0.2% of itraconazole in the blood remains unbound. The apparent volume of distribution of itraconazole is quite large (>700 L), suggesting extensive tissue distribution: concentrations in the lungs, kidneys, liver, bones, stomach, spleen, and muscles were 2–3 times higher than those in plasma. Itraconazole accumulation in keratinized tissues, especially in the skin, was 4 times higher than that in plasma. Concentrations in cerebrospinal fluid are much lower than in plasma, but efficacy against infections localized in the cerebrospinal fluid has been demonstrated.
Biotransformation. Itraconazole is extensively metabolized in the liver to a large number of metabolites. In vitro studies indicate that CYP3A4 is the major enzyme involved in the metabolism of itraconazole. The major metabolite is hydroxyitraconazole, which has comparable antifungal activity to itraconazole in vitro. Plasma concentrations of hydroxyitraconazole are approximately 2-fold higher than those of itraconazole.
Excretion: Approximately 35% of itraconazole is excreted as inactive metabolites in the urine and approximately 54% in the feces within 1 week of a dose of oral solution. Renal excretion of itraconazole and the active metabolite hydroxyitraconazole after intravenous administration is less than 1% of the dose. Fecal excretion of unchanged drug varies from 3 to 18%.
Special categories of patients.
Hepatic impairment. Itraconazole is primarily metabolized in the liver. A pharmacokinetic study using a single dose of 100 mg itraconazole (1 capsule of 100 mg) was conducted in 6 healthy subjects and 12 cirrhotic subjects. A statistically significant decrease in mean Cmax (47%) and a 2-fold increase in the half-life of itraconazole (37±17 vs. 16±5 hours) were found in cirrhotic subjects compared to healthy subjects. Although total itraconazole concentrations based on AUC were comparable in both groups.
There are no data available on the long-term use of itraconazole in patients with cirrhosis.
Renal impairment. Data on the use of oral itraconazole in patients with renal impairment are limited. A pharmacokinetic study using a single dose of 200 mg itraconazole (4 capsules of 50 mg) was conducted in 3 groups of patients with renal impairment (uremia: n=7, hemodialysis: n=7, chronic ambulatory peritoneal dialysis: n=5). In uremic patients with a mean creatinine clearance of 13 mL/min × 1.73 m2, the AUC-based concentration was slightly reduced compared to healthy subjects. This study did not demonstrate any significant effect of hemodialysis or chronic ambulatory peritoneal dialysis on the pharmacokinetics of itraconazole (Tmax, Cmax, AUC0-8h). Plasma concentration versus time profiles showed significant intersubject variability in all 3 groups.
After a single intravenous dose, the mean terminal half-life values in patients with mild (CrCl 50–79 mL/min), moderate (CrCl 20–49 mL/min), and severe (CrCl ˂ 20 mL/min) renal impairment were similar to those in healthy volunteers (range 42–49 hours vs. 48 hours in renally impaired patients and healthy volunteers, respectively). Total itraconazole concentrations based on AUC were reduced in patients with moderate and severe renal impairment (by 30% and 40%, respectively) compared to healthy volunteers.
There are no data available on the long-term use of itraconazole in patients with renal impairment. Dialysis has no effect on the half-life or clearance of itraconazole or hydroxyitraconazole.
Children. Data on the use of oral itraconazole in children are limited. Clinical pharmacokinetic studies in children and adolescents aged 5 months to 17 years were conducted with itraconazole capsules, oral solution, and intravenous solution. Individual doses with the capsules and oral solution ranged from 1.5 to 12.5 mg/kg/day, administered once or twice daily. A single dose of 2.5 mg/kg was administered intravenously as an infusion or 2.5 mg/kg as infusions once or twice daily. There was no significant age-related relationship between itraconazole AUC and total clearance, but there was a weak relationship between age, volume of distribution, Cmax, and terminal elimination. Apparent clearance and volume of distribution were weight-related.
Indication
Vulvovaginal candidiasis;
lichen planus;
dermatophytosis caused by itraconazole-sensitive pathogens (Trichophyton spp., Microsporum spp., Epidermophyton floccosum), e.g. tinea pedis, inguinal tinea, tinea corporis, tinea corporis of the hands;
oropharyngeal candidiasis;
onychomycoses caused by dermatophytes and/or yeasts;
systemic mycoses (in cases where first-line antifungal therapy cannot be used or in case of ineffectiveness of treatment with other antifungal drugs, which may be due to the existing pathology, insensitivity of the pathogen or toxicity of the drug):
aspergillosis and candidiasis;
Cryptococcosis (including cryptococcal meningitis): treatment of immunocompromised patients with cryptococcosis and all patients with cryptococcosis of the central nervous system (CNS);
maintenance therapy in patients with AIDS to prevent recurrence of an existing fungal infection.
Itraconazole can also be prescribed for the prevention of fungal infections in patients with prolonged neutropenia in cases where standard therapy is insufficient.
Contraindication
Itracon® capsules are contraindicated in patients with known hypersensitivity to the active substance or to any of the excipients.
Concomitant use of Itracon® and CYP3A4 substrates is contraindicated. These include:
Antibacterials for systemic use; Antimycobacterials; Antimycotics for systemic use
Isavuconazole
Anthelmintics; Antiprotozoal agents
Halofantrine
Antihistamines for systemic use
Astemizole
Mizolastine
Terfenadine
Antineoplastic agents
Irinotecan
Venetoclax (in patients with chronic lymphocytic leukemia during the initiation and dose titration phase of venetoclax)
Antithrombotic agents
Dabigatran
Ticagrelor
Antiviral drugs for systemic use
Ombitasvir/Paritaprevir/Ritonavir (with or without dasabuvir)
Drugs affecting the cardiovascular system (drugs acting on the renin-angiotensin system; antihypertensives; beta-blockers; calcium channel blockers; cardiac therapy; diuretics)
Aliskiren
Eplerenone
Quinidine
Bepridil
Finerenone
Ranolazine
Disopyramide
Ivabradine
Sildenafil (pulmonary hypertension)
Dofetilide
Lercanidipine
Dronedarone
Nisoldipine
Drugs affecting the gastrointestinal tract, including antidiarrheals, intestinal anti-inflammatory/anti-infectives; antiemetics and antinausea drugs; constipation drugs; drugs for functional gastrointestinal disorders
Cisapride
Domperidone
Naloxegol
Lipid-regulating agents
Lovastatin
Lomitapide
Simvastatin
Psychoanaleptics; Psycholeptics (e.g. antipsychotics, anxiolytics and hypnotics)
Lurasidone
Pimozide
Sertindole
Midazolam (oral)
Quetiapine
Triazolam
Urological products
Avanafil
Darifenacin
Solifenacin (in patients with severe renal impairment or moderate to severe hepatic impairment)
Dapoxetine
Fesoterodine (in patients with moderate or severe renal or hepatic impairment)
Vardenafil (in patients over 75 years of age).
Various medicines and other substances
Colchicine (in patients with renal or hepatic insufficiency)
Eliglustat (in patients with CYP2D6 poor metabolizers (PM), intermediate metabolizers (IM), or extensive metabolizers (EM) taking a strong or moderate CYP2D6 inhibitor).
Itracon capsules are contraindicated in patients with ventricular dysfunction, such as congestive heart failure, or a history of congestive heart failure, except for the treatment of life-threatening infections (see section "Special warnings and precautions for use").
Itracon® capsules should not be used during pregnancy, except for the treatment of life-threatening conditions (see section “Use during pregnancy or breastfeeding”).
Women of reproductive age should use effective methods of contraception during treatment with Itracon® capsules, as well as until the end of the menstrual cycle after the end of treatment.
Interaction with other medicinal products and other types of interactions
Examples of medicinal products that may affect itraconazole plasma concentrations are listed by medicinal product class in Table 1 below. Examples of medicinal products whose plasma concentrations may be affected by itraconazole are listed in Table 2 below. Due to the large number of interactions, potential changes in the safety or efficacy of the interacting medicinal products are not included. Please refer to the prescribing information of the interacting medicinal products for further information. The interactions described in these tables are classified as contraindicated, not recommended or should be used with caution with itraconazole, taking into account the extent of the increase in concentration and the safety profile of the interacting medicinal products (see also sections “Special instructions” and “Contraindications” for further information). The potential for drug interactions listed below was assessed based on human pharmacokinetic studies with itraconazole and/or human pharmacokinetic studies with other strong CYP3A4 inhibitors (e.g. ketoconazole) and/or in vitro data:
"Contraindicated": Under no circumstances should it be used simultaneously with itraconazole and within two weeks after stopping treatment with itraconazole.
"Not recommended": The use of these drugs concomitantly and within 2 weeks of stopping itraconazole treatment should be avoided unless the benefit of treatment outweighs the potential risk of adverse reactions. If concomitant use cannot be avoided, clinical monitoring for signs or symptoms of increased, prolonged or adverse reactions of the concomitant drug is recommended and, if necessary, its dosage should be reduced or discontinued. Plasma concentrations of the concomitant drug should be monitored as appropriate.
"Use with caution": Close monitoring is recommended when co-administered with itraconazole. Such patients should be closely observed for signs or symptoms of increased, prolonged, or adverse reactions to the concomitant drug and the dose should be reduced if necessary. Monitoring of the plasma concentration of the concomitant drug is recommended if necessary.
The interactions listed in these tables have been characterized in studies conducted with the recommended doses of itraconazole. However, the extent of the interaction may depend on the dose of itraconazole administered. Stronger interactions may be observed with higher doses or shorter dosing intervals. Extrapolation of the results to other dosing scenarios or other drugs should be done with caution.
After discontinuation of treatment, itraconazole plasma concentrations decline to almost undetectable levels within 7 to 14 days, depending on the dose and duration of treatment. In patients with cirrhosis of the liver or in patients receiving concomitant CYP3A4 inhibitors, the decline in plasma concentrations should be even more gradual. This is especially true for drugs whose metabolism is affected by itraconazole. (See Pharmacodynamics).
Table 1: Examples of drugs that may affect itraconazole plasma concentrations, presented by drug class.
Drugs (single dose oral (PO), unless otherwise specified) within the class
Expected/potential effect on itraconazole levels
(↑ = increase; ↔ = no change; ↓ = decrease)
Clinical commentary
(see above for additional information, as well as the sections "Contraindications" and "Peculiarities of use")
Antibacterials for systemic use; antimycobacterials
Isoniazid
Although isoniazid has not been directly studied, it is likely that it reduces itraconazole concentrations.
Not recommended
Rifampicin PO 600 mg once/day
AUC of itraconazole ↓
Not recommended
Rifabutin PO 300 mg once daily
Itraconazole Cmax ↓ 71%, AUC ↓ 74%
Not recommended
Ciprofloxacin PO 500 mg twice daily
Itraconazole Cmax ↑ 53%, AUC ↑ 82%
Use with caution.
Erythromycin 1 g
Itraconazole Cmax ↑ 44%, AUC ↑ 36%
Use with caution.
Clarithromycin PO 500 mg twice daily
Itraconazole Cmax ↑ 90%, AUC ↑ 92%
Use with caution.
Antiepileptic drugs
Carbamazepine, phenobarbital
Although these drugs have not been directly studied, they are likely to reduce itraconazole concentrations.
Not recommended
Phenytoin PO 300 mg once/day
Itraconazole Cmax ↓ 83%, AUC ↓ 93%
Cmax of hydroxy-itraconazole ↓ 84%, AUC ↓ 95%
Not recommended
Antitumor agents
Idelalisib
Although idelalisib has not been directly studied, it is likely to increase itraconazole concentrations.
Use with caution.
Antiviral drugs for systemic use
Ombitasvir/paritaprevir/ritonavir (with or without dasabuvir)
Although these drugs have not been directly studied, they are likely to increase itraconazole concentrations.
Although itraconazole has not been directly studied, it is likely to increase the concentrations of these agents.
Contraindicated
Eletriptan, Fentanyl
Although itraconazole has not been directly studied, it is likely to increase the concentrations of these agents.
Not recommended
Alfentanil,
Buprenorphine (intravenous and sublingual), cannabinoids, methadone, sufentanil
Although itraconazole has not been directly studied, it is likely to increase the concentrations of these agents.
Use with caution.
Oxycodone PO 10 mg
Oxycodone PO: Cmax ↑ 45%, AUC ↑ 2.4 times
Use with caution.
Oxycodone IV 0.1 mg/kg
Oxycodone IV: AUC ↑ 51%
Use with caution.
Antibacterial agents for systemic use; antimycobacterial agents;
Antimycotics for systemic use
Isavuconazole
Although itraconazole has not been directly studied, it is likely to increase the concentration of isavuconazole.
Contraindicated
Bedaquiline
Although itraconazole has not been directly studied, it is likely to increase bedaquiline concentrations.
Not recommended
Rifabutin PO 300 mg once daily
Rifabutin concentration ↑ (extent unknown)
Not recommended
Clarithromycin PO 500 mg twice daily
Clarithromycin concentration ↑
Use with caution.
Delamanid
Although itraconazole has not been directly studied, it is likely to increase delamanid concentrations.
Use with caution.
Antiepileptic drugs
Carbamazepine
Although itraconazole has not been directly studied, it is likely to increase carbamazepine concentrations.
Not recommended
Anti-inflammatory and antirheumatic drugs
Meloxicam 15 mg
Cmax of meloxicam ↓ 64%, AUC ↓ 37%
Use with caution.
Anthelmintics; Antiprotozoal agents
Halofantrine
Although itraconazole has not been directly studied, it is likely to increase halofantrine concentrations.
Contraindicated
Artemether-lumefantrine, praziquantel
Although itraconazole has not been directly studied, it is likely to increase the concentrations of these agents.
Use with caution.
Quinine 300 mg
Cmax of quinine ↔, AUC ↑ 96%
Use with caution.
Antihistamines for systemic use
Astemizole, Mizolastine, Terfenadine
Although itraconazole has not been directly studied, it is likely to increase the concentrations of these agents.
Contraindicated
Ebastine 20 mg
Ebastine Cmax ↑ 2.5 times, AUC ↑ 6.2 times
Cmax of carabastin ↔, AUC ↑ 3.1 times
Not recommended
Bilastine, rupatidine
Use with caution.
Antitumor agents
Irinotecan
Although itraconazole has not been directly studied, it is likely to increase the concentrations of irinotecan and its active metabolite.
Contraindicated
Venetoclax
Although itraconazole has not been directly studied, it is likely to increase venetoclax concentrations.
Contraindicated in patients with chronic lymphocytic leukemia during the initiation and titration phase of venetoclax. Not recommended unless the expected benefit outweighs the risk. Refer to venetoclax prescribing information.
Although itraconazole has not been studied directly, it is likely to increase the concentrations of these agents, with the exception of cabazitaxel and regorafenib. No statistically significant change in the bioavailability of cabazitaxel was found, but high variability was observed.
Regorafenib AUC is expected to decrease (based on active fraction estimate)
Although itraconazole has not been studied directly, it is likely to increase the concentrations of these agents.
Contraindicated
Aliskiren 150 mg
Cmax of aliskiren ↑ 5.8 times, AUC ↑ 6.5 times
Contraindicated
Quinidine 100 mg
Cmax of quinidine ↑ 59%, AUC ↑ 2.4 times
Contraindicated
Felodipine 5 mg
Cmax of felodipine ↑ 7.8 times, AUC ↑ 6.3 times
Not recommended
Riociguat,
Tadalafil (pulmonary hypertension)
Although itraconazole has not been studied directly, it is likely to increase the concentrations of these agents.
Not recommended
Bosentan, diltiazem, guanafacin,
Other dihydropyridines (e.g. amlodipine, isradipine, nifedipine, nimodipine), verapamil
Although itraconazole has not been studied directly, it is likely to increase the concentrations of these agents.
Use with caution.
Digoxin 0.5 mg
Digoxin Cmax ↑ 34%, AUC ↑ 68%
Use with caution.
Nadolol 30 mg
Use with caution.
Corticosteroids for systemic use; Drugs for the treatment of obstructive airway diseases
Ciclesonide, salmeterol
Although itraconazole has not been directly studied, it is likely to increase the concentrations of salmeterol and the active metabolite ciclesonide.
Not recommended
Budesonide 1 mg once
Budesonide Cmax ↑ 65%, AUC ↑ 4.2-fold;
Budesonide concentration (other forms) ↑
Use with caution.
Dexamethasone IV 5 mg Dexamethasone PO 4.5 mg
Dexamethasone IV: Cmax ↔, AUC ↑ 3.3 times Dexamethasone PO: Cmax ↑ 69%, AUC ↑ 3.7 times
Use with caution.
Fluticasone 1 mg twice daily
Fluticasone concentration ↑
Use with caution.
Methylprednisolone 16 mg
Cmax of methylprednisolone PO ↑ 92%, AUC ↑ 3.9 times
AUC of methylprednisolone IV ↑ 2.6 times
Use with caution.
Fluticasone nasal
Although itraconazole has not been studied directly, it is likely to increase the concentration of nasally administered fluticasone.
Use with caution.
Drugs used for diabetes
Repaglinide 0.25 mg
Repaglinide Cmax ↑ 47%, AUC ↑ 41%
Use with caution.
Saxagliptin
Although itraconazole has not been directly studied, it is likely to increase saxagliptin concentrations.
Use with caution.
Drugs affecting the gastrointestinal tract, including antidiarrheals, intestinal anti-inflammatory/anti-infectives; antiemetics and antinausea drugs; drugs for constipation; drugs for functional gastrointestinal disorders
Cisapride, naloxegol
Although itraconazole has not been studied directly, it is likely to increase the concentrations of these agents.
Contraindicated
Domperidone 20 mg
Cmax of domperidone ↑ 2.7 times, AUC ↑ 3.2 times
Contraindicated
Aprepitant, loperamide, netupitant
Although itraconazole has not been studied directly, it is likely to increase the concentrations of these agents.
Use with caution.
Immunosuppressants
Sirolimus (rapamycin)
Although itraconazole has not been directly studied, it is likely to increase sirolimus concentrations.
Not recommended
Cyclosporine, tacrolimus
Although itraconazole has not been studied directly, it is likely to increase the concentrations of these agents.
Use with caution.
Tacrolimus IV 0.03 mg/kg once/day
Tacrolimus IV concentration ↑
Use with caution.
Lipid-regulating agents
Lomitapide
Although itraconazole has not been directly studied, it is likely to increase lomitapide concentrations.
Contraindicated
Specifications
Characteristics
Active ingredient
Itraconazole
Adults
Can
ATC code
J ANTIMIBRICANTS FOR SYSTEMIC USE; J02 ANTIFUNGALS FOR SYSTEMIC USE; J02A ANTIFUNGALS FOR SYSTEMIC USE; J02A C Triazole derivatives; J02A C02 Itraconazole
Country of manufacture
Ukraine
Diabetics
Can
Dosage
100 мг
Drivers
With caution
For allergies
With caution
For children
It is impossible.
Form
Capsules
Method of application
Inside, solid
Nursing
By doctor's prescription
Pregnant
By doctor's prescription
Producer
Farmak JSC
Quantity per package
6 pcs
Trade name
Itracon
Vacation conditions
By prescription
Reviews
There are no reviews for this product.
Write a review
There are no reviews for this product, be the first to leave your review.
Answers & questions
Add your question and we will answer as soon as possible.
Ask a question
Add your question and we will answer as soon as possible.
No questions about this product, be the first and ask your question.
