Itraconazole - instructions for use, dose, side effects, contraindications

Excipients: sucrose 117.05 g, sugar grits (sucrose, starch syrup) 347.19 g, hypromellose 280.53 g,methyl parahydroxybenzoate 0.165 g, sodium propyl parahydroxybenzoate 0.015 g, butyl methacrylate, dimethylaminoethyl methacrylate and methyl methacrylate copolymer [1: 2: 1] (eudragit E 100) 35.05 g

Description:

Capsules number 0, body - transparent natural gelatin, lid - opaque blue.

The contents of the capsules are white or almost white spherical pellets.

Pharmacotherapeutic group:Antifungal agent

ATX: & nbsp

J.02.A.C.02 Itraconazole

Pharmacodynamics:

Itraconazole - a synthetic antifungal mediumwide spectrum of action, a triazole derivative. The mechanism of action of itraconazole is the inhibition of the biosynthesis of ergosterol, the main component of the fungal cell membrane involved in maintaining the structural integrity of the membrane. Disruption of the synthesis of ergosterol leads to a change in membrane permeability and cell lysis, which determines the antifungal effect of the drug.

Itraconazole is active against infections caused by fungi:

- dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum);

- yeast-like mushrooms (Candida spp., including C. albicans, FROM. tropicalis, C. parapsilosis, 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; Coccidioides immitis, Pseudallescheria boydii; Penicillium marneffei and by many other.

Candida krusei, Candida glabrata and Candida tropicalis - are the least sensitive to the effects of itraconazole species Candida.

The main types of fungi, development of which not suppressed itraconazole, are the Zygomycetes (Rhizopus spp., Rhizomucor spp., Mucor spp. and Absidia spp.), Fusarium spp., Scedosporium spp. and Scopulariopsis spp.

Resistance to azoles develops slowly and is often the result of several genetic mutations. The described mechanisms of development of resistance include overexpression of the gene ERG11, which encodes the enzyme 14α-demethylase, which is the main target of azoles, and point mutations ERG11, leading to a decrease in the binding of enzymes to azoles and / or activation of transport systems, which leads to an increase in the excretion of azoles. Cross-resistance was observed Candida spp. to preparations of the azole group, although resistance to one drug of this group does not necessarily mean the presence of resistance to other preparations of the azole group. Stresses have been reported Aspergillus fumigates, resistant to itraconazole.

Pharmacokinetics:

Due to nonlinear pharmacokinetics itraconazole accumulates in the blood plasma at multiple admission.The equilibrium concentration of itraconazole is usually achieved within about 15 days, with the values of the maximum concentration of itraconazole and AUC (the area under the curve "concentration-time") with multiple admission is 4-7 times higher than with a single admission. The maximum equilibrium concentration of itraconazole in plasma is about 2 μg / ml for nThe use of 200 mg of itraconazole 1 once a day. The final half-life is usually 16-28 hours with a single dose and 34-42 hours with multiple administration. The concentration of itraconazole in blood plasma is reduced to a practically undetectable value within 7-14 days, after the cessation of therapy, depending on the prescribed dose and duration of treatment.

Absorption

After oral administration itraconazole quickly absorbed. The maximum concentration of unchanged itraconazole in the plasma is reached within 2-5 hours after oral administration. The absolute bioavailability of itraconazole is about 55%. When administered orally, the maximum bioavailability of itraconazole is noted when taking capsules immediately after meals.

Distribution

Itraconazole binds 99.8% to plasma proteins, mainly with albumin (hydroxyitraconazole binds to albumin by 99.6%). Also affinity for lipids is noted. In unbound form, only 0.2% of itraconazole remains in the plasma. Apparent volume of distribution> 700 liters, which indicates its significant distribution in tissues. Concentrations in the lungs, kidneys, bones, stomach, spleen and muscles are 2-3 times higher than the corresponding concentrations in the plasma, while the concentration of itraconazole in tissues containing keratin, especially in the skin, is about 4 times higher than the concentration in the plasma. Concentration in cerebrospinal fluid is much lower than in plasma, however, itraconazole has been shown to be effective against infectious agents present in cerebrospinal fluid.

Metabolism

CYP3A4 is the main isoenzyme involved in the metabolism of itraconazole. Itraconazole is subject to active metabolism in the liver with the formation of a variety of metabolites. The main metabolite is hydroxyitraconazole, which in vitro has antifungal activity comparable to itraconazole.The concentrations of hydroxyitraconazole in plasma are about 2 times higher than the concentration of itraconazole.

Excretion

Approximately 35% of itraconazole is excreted as inactive metabolites by the kidneys within one week and about 54% by the intestine.

Since the redistribution of itraconazole from tissues containing keratin is insignificant, the removal of itraconazole from these tissues is associated with the regeneration of the epidermis. Unlike blood plasma, the concentration of itraconazole to the skin persists for 2 to 4 weeks after discontinuation of 4-weektreatment, and concentration in the nail keratin, where itraconazole can be detected as early as 1 week after the start of treatment, is maintained for at least six months after the end of the 3-month course of treatment.

Impaired liver function

Itraconazole is predominantly metabolized in the liver. In patients with cirrhosis of the liver with a single dose of 100 mg of itraconazole, the average maximum concentration of itraconazole in the blood plasma was significantly lower than in healthy volunteers. Data on the long-term use of itraconazole in patients with cirrhosis are absent.

Impaired renal function

Data on the oral use of itraconazole for the treatment of patients with impaired renal function are limited. Dialysis does not affect the half-life or clearance of itraconazole or hydroxyitraconazole.

Indications:

Fungal infections caused by itraconazole-sensitive pathogens:

- damage to the skin and mucous membranes:

vulvovaginal candidiasis;
colored lichen;
dermatomycosis;
Candidiasis of the oral mucosa;
fungal keratitis;

- onychomycosis caused by dermatophytes and / or yeast-like fungi;

- systemic mycoses:

systemic aspergillosis and candidiasis;
cryptococcosis (including cryptococcal meningitis): in patients with immunodeficiency and in all patients with cryptococcosis of the central nervous system itraconazole It should be used only if the first-line drugs are not applicable or ineffective;
histoplasmosis;
blastomycosis;
sporotrichosis;
paracoccidioidomycosis;
other seldom occurring systemic or tropical mycoses.

Contraindications:

- Hypersensitivity to itraconazole or excipients.

- simultaneous reception of preparations of substrates isoenzyme CYP3A4 (see para.section "Interaction with other drugs");

- simultaneous administration of midazolam (oral) and triazolam;

- simultaneous use of preparations of ergot alkaloids, such as dihydroergotamine, ergometrine, ergotamine and methylergomethrin;

- simultaneous use of eletriptan, nisoldipine;

- chronic heart failure, currently or in history (except for life-threatening or other dangerous infections. See "Special instructions");

- intolerance to fructose, sugarase / isomaltase deficiency, glucose-galactose malabsorption;

- children under 3 years;

- pregnancy and the period of breastfeeding.

Carefully:

- With cirrhosis of the liver;

- with severe violations of the liver and kidneys;

- with increased sensitivity to other azoles;

- with simultaneous use with drugs that can increase or decrease the concentration of itraconazole in blood plasma or with simultaneous use with drugs, the concentration of which in the plasma can vary (see section "Interaction with other drugs");

- in children older than 3 years and elderly patients.

Pregnancy and lactation:

Pregnancy

The drug is contraindicated in pregnancy.

Women of childbearing age who receive itraconazole, it is necessary to use reliable methods of contraception throughout the course of treatment until the onset of the first menstruation after its completion.

Breastfeeding period

Because the itraconazole can penetrate into breast milk, with need use of the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Inside, right after eating. Capsules should be swallowed whole.

Indication				Dose				Duration of treatment
Vulvovaginal candidiasis			200 mg twice daily or 200 mg once daily					1 day or 3 days
Multicolored lichen			200 mg once a day					7 days
Dermatomycosis smooth skin			200 mg once a day or 100 mg once a day					7 days or 15 days
Defeats high-keratinized areas of the skin, such as hands and feet			200 mg 2 times a day or 100 mg once a day					7 days or 30 days
Candidiasis of the oral mucosa			100 mg once a day					15 days
Bioavailability of itraconazole for oral administration may be reduced in some patients with impaired immunity, for example, in patients with neutropenia, AIDS patients or organ transplants.Therefore, a double dose increase may be required.
Fungal keratitis			200 mg once a day					21 day Duration of treatment can be adjusted depending on the improvement of the clinical picture
Onychomycosis caused by dermatophytes and / or yeast-like and mold fungi
Onychomycosis - pulse therapy	Doses and duration of treatment
	One course of pulse therapy is a daily intake of 2 capsules of the drug 2 times a day for 1 week. For treatment of fungal lesions of the nail plates of the brushes, 2 courses are recommended. For treatment of fungal lesions of the nail plates of the feet, 3 courses are recommended. The gap between the courses during which you do not need to take the drug is 3 weeks. Clinical results will become evident after the end of treatment, as the nails grow.
Localization onychomycosis	1st week	2 nd week		3rd week	4th week	5th week	6th week		7th week	8th week	9th week
Lesion of the nail plates of the toes with or without defeat of the nail plates of the fingers	1st year	Weeks free from taking the drug				2 nd year	Weeks free from taking the drug				3rd year
Defeat nail records brushes	1st year	Weeks free from taking the drug				2 nd year
Onychomycosis continuous treatment		Dose					Duration of treatment
Lesions of the nail plates of the feet with or without defeat of the nail plates of the brushes		200 mg per day					3 months

The removal of itraconazole from the skin and nail tissue is slower than from the plasma. Thus, optimal clinical and mycological effects are achieved after 2-4 weeks after the end of treatment for skin infections and 6-9 months after the end of treatment for nail infections.

Systemic mycoses
Indication	Dose	Average Duration treatment *	Remarks
Aspergillosis	200 mg once a day	2-5 months	Increase the dose to 200 mg twice a day for invasive or disseminated disease
Candidiasis	100-200 mg once a day	from 3 weeks to 7 months	Increase the dose to 200 mg twice a day for invasive or disseminated disease
Cryptococcosis (except meningitis)	200 mg once a day	from 2 months to 1 year
Cryptococcal meningitis	200 mg twice daily	from 2 months to 1 year	Maintenance therapy, see section "Special instructions"
Histoplasmosis	from 200 mg once a day to 200 mg twice a day	8 months
Blastomycosis	from 100 m g once a day to 200 mg twice a day	6 months
Sporotrichosis	100 mg once a day	3 months
Paracoccidioidomycosis	100 mg once a day	6 months	Data on the effectiveness of this dose for the treatment of paracoccidioidomycosis in AIDS patients are absent
Chromomycosis	100-200 mg once a day	6 month

* Duration of treatment can be adjusted depending on the effectiveness of treatment.

Clinical data on the use of itraconazole in children It is not enough, it is recommended to use the drug for children over 3 years only if the possible benefit exceeds the potential risk.

Data on the use of itraconazole in elderly patients are limited, it is recommended to apply the drug in this category of patients only if the possible benefit exceeds the potential risk. When choosing a dose of the drug for the treatment of elderly patients, it is recommended to take into account the decrease in the function of the liver, kidney and heart, more common in old age, as well as the presence of concomitant diseases or the intake of other medicines.

Impaired liver function

Data on the use of itraconazole for the treatment of a patientwith liver dysfunction are limited. Care should be taken when using the drug in this category of patients.

Impaired renal function

Data on the use of itraconazole for the treatment of patients with impaired renal function are limited. Care should be taken when using the drug in this category of patients, in some cases, a change in the dose of the drug may be required.

Side effects:

Side effects of the drug are systematized relative to each of the organ systems depending on the frequency of occurrence, using the following classification:

Very often (≥1 / 10)

Often (≥1 / 100, <1/10)

Infrequently (≥1 / 1000, <1/100)

Rarely (≥1 / 10000, <1/1000)

Very rarely (<1/10000), including isolated cases

The frequency is unknown (can not be calculated from the available data)

Infectious and parasitic diseases:

Infrequently: rhinitis, sinusitis, infections of the upper respiratory tract.

Violations of the blood and lymphatic system:

Rarely: leukopenia.

Very rarely: neutropenia, thrombocytopenia.

Immune system disorders:

Very rarely: serum sickness, angioedema, anaphylactic and anaphylactoid reactions.

Metabolic disorders:

Very rarely: hypertriglyceridemia, hypokalemia.

Disturbances from the nervous system:

Infrequent: headache, dizziness, paresthesia.

Rarely: hypoesthesia.

Very rarely: peripheral neuropathy.

Disturbances on the part of the organ of sight:

Rarely: blurred vision.

Very rarely: diplopia.

Hearing disorders and labyrinthine disorders:

Rarely: ringing in the ears.

Very rarely: persistent or temporary hearing loss.

Disorders from the cardiovascular system:

Very rarely: chronic heart failure, hypertension, arterial hypotension.

Respiratory system disorders:

Very rarely: pulmonary edema, dyspnea.

Disorders from the digestive system:

Often: pain in the abdomen, nausea.

Infrequent: vomiting, diarrhea, constipation, indigestion, dysgeusia, flatulence.

Very rarely: pancreatitis.

Disorders from the hepatobiliary system:

Infrequently: hyperbilirubinemia, increased activity of "liver" transaminases.

Very rarely: severe toxic liver damage (including several cases of acute hepatic insufficiency with a lethal outcome), hepatitis.

Disturbances from the skin and subcutaneous tissues:

Often: rash.

Infrequently: urticaria, itching, hypersensitivity, alopecia.

Very rarely: toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, polymorphic erythema, exfoliative dermatitis, leukocytoclastic vasculitis, photosensitivity.

Musculoskeletal system disorders:

Very rarely: myalgia, arthralgia.

Disorders from the kidneys and urinary tract:

Rarely: pollakiuria.

Very rarely: urinary incontinence.

Disorders from the reproductive system:

Infrequent: violation of the menstrual cycle.

Rarely: erectile dysfunction.

Laboratory indicators and instrumental studies:

Very rarely: increased activity of creatine phosphokinase of blood.

General disorders:

Infrequent: edematic syndrome.

Very rarely: hyperthermia.

Overdose:

Symptoms, observed with an overdose of itraconazole, were comparable to dose-related adverse reactions observed with the use of conventional doses of the drug.

Treatment: there is no specific antidote. In case of an overdosage, supportive therapy should be carried out, gastric lavage with sodium bicarbonate solution,give Activated carbon. Itraconazole It is not removed from the body during hemodialysis.

Interaction:

Itraconazole is mainly metabolized by isoenzyme CYP3A4. Other drugs that are also metabolised involving this isozyme or alter its activity, can affect the pharmacokinetics of itraconazole. Similarly, itraconazole can affect the pharmacokinetics of drugs that are also metabolized with the participation of this isoenzyme. Itraconazole refers to strong inhibitors of isoenzyme CYP3A4 and P-glycoprotein. With simultaneous application of itraconazole with other drugs encouraged to read the instructions for use to determine the metabolism of the drug and the method solve the problem of the need to change the dose.

Drugs that can reduce the concentration of itraconazole in the blood plasma

Drugs that reduce the acidity of gastric juice (for example, antacids such as aluminum hydroxide or agents that inhibit acid secretion, such as H2-antagonists, histamine receptors and proton pump inhibitors) violate absorption of itraconazole.These medications should be used with caution in combination with the drug Itraconazole.

- Itraconazole it is recommended to take together with drinks containing cola, when combined use of drugs that reduce the acidity of gastric juice.

- It is recommended to take medicines that neutralize hydrochloric acid (for example, aluminum hydroxide), at least 1 hour before or 2 hours after taking the drug Itraconazole.

- With the joint administration of medicines, it is recommended to monitor the antifungal activity of itraconazole and increase the dose of the drug if necessary.

Combined use of itraconazole with strong isoenzyme inducers CYP3A4 can reduce the bioavailability of itraconazole and hydroxyitraconazole to such an extent that the efficacy of the drug will be greatly reduced:

Antibacterial agents: isoniazid, rifabutin, rifampicin.
Anticonvulsants: carbamazepine, phenobarbital, phenytoin.
Antiviral drugs: efavirenz, nevirapine.

Thus, the use of strong isoenzyme inducers CYP3A4 together with itraconazole is not recommended. It is recommended to avoid the use of these medicines for two weeks before the onset of itraconazole and during treatment with the drug, unless the expected benefit exceeds the potential risk associated with a decrease in the effectiveness of itraconazole. With the joint administration of medicines, it is recommended to monitor the antifungal activity of itraconazole and increase the dose of the drug if necessary.

Drugs that can cause an increase in the concentration of itraconazole in the blood plasma

Application of strong isoenzyme inducers CYP3A4 concomitantly with itraconazole may increase the bioavailability of itraconazole. Strong inhibitors of isoenzyme CYP3A4:

Antibacterials: ciprofloxacin, clarithromycin, erythromycin.
Antiviral drugs: darunavir in combination with ritonavir, fosamprenavir in combination with ritonavir, indinavir, ritonavir.

These medications should be used with caution.together with itraconazole. It is recommended that the condition of patients receiving itraconazole together with strong inhibitors of isoenzyme CYP3A4, for the timely detection of symptoms and signs of increased or prolonged pharmacological effects of itraconazole, if necessary, a reduction in the dose of itraconazole is possible.

Drugs, the concentration of which in the blood plasma may increase when combined with itraconazole

Itraconazole and its main metabolite hydroxyitraconazole can disrupt the metabolism of drugs metabolized by the isoenzyme CYP3A4 and to prevent transportation of drugs under the action of P-glycoprotein. This can lead to an increase in the plasma concentration of these drugs and / or their active metabolites when taken together with itraconazole. An increase in plasma concentration may cause an increase or prolongation of both the therapeutic and undesirable effects of these drugs. Reception together with itraconazole medications metabolized by isoenzyme CYP3A4 and able to lengthen the interval QT the electrocardiogram may be contraindicated, as this may lead to the development of ventricular tachyarrhythmias, including arrhythmia type "pirouette", which is a potentially life-threatening condition. After discontinuation of treatment, the plasma concentration of itraconazole decreases to almost indeterminate within 7 to 14 days, depending on the dose of the drug and the duration of treatment. Life threatening cardiac arrhythmias and / or sudden death were noted in patients with simultaneous use of methadone. In patients with cirrhosis of the liver or those who simultaneously take enzyme inhibitors CYP3A4, the decrease in drug concentration may be even slower. This is especially important at the time of initiation of therapy with the use of drugs, the metabolism of which is affected itraconazole.

Interacting medicines are divided into the following categories:

"Contraindicated": under no circumstances should this drug be used in combination with itraconazole and within two weeks after stopping itraconazole.

"Not recommended": it is recommended to avoid the use of this drug during treatment and for two weeks after discontinuing itraconazole, unless the expected benefit exceeds the potential risk associated with the therapy. If it is impossible to avoid using this combination of drugs, it is recommended to monitor the condition patient for the timely detection of symptoms and signs of increased or prolonged effects of drugs or the development of side effects, if necessary, le ix possible to stop or reduce the dose of drugs. If possible, it is recommended to control the plasma concentrations of drugs.

"Use with caution": careful monitoring should be carried out when the drug is used together with itraconazole. With joint the use of medicines is recommended to monitor the patient's condition for the timely detection of symptoms and signs of increased or prolonged effects of drugs or the development of side effects, if necessary, treatment can be interrupted or reduced by a dose of medicinalmeans. If possible, it is recommended to monitor the plasma concentration of drugs.

Below are examples of drugs whose plasma concentration may increase under the action of itraconazole.

Class of medicinal products	Contraindicated	Not recommended	Use with caution
Alpha-blockers		Tamsulosin
Narcotic drugs analgesics	Levacetylmethadol (levometadil) Methadone	Fentanyl	Alfentanil Buprenorphine for intravenous and sublingual administration Oxycodone
Antiarrhythmic facilities	Disopyramide Dofetilide Dronedaron Quinidine		Digoxin
Anti-tuberculosis facilities		Rifabutin¹
Anticoagulants and antiplatelet agents		Rivaroxaban	Coumarins, Cilostazol, Dabigatran
Anticonvulsant drugs		Carbamazepine¹
Antidiabetic drugs			Repaglinide, Saxaglyptine
Anthelmintic and antiprotozoal facilities	Halofantrine		Praziquantel
Antihistamines drugs	Astemizole, Misolastine, Terfenadine		Ebastin
Medications against migraine	Ergot alkaloids, such as dihydroergotamine, ergometrine (ergonovine), ergotamine methylergomethrin (methylergonovine)		Eletriptan
Antineoplastic drugs	Irynotekan	Dasatinib, Nilotinib, Trabecectin	Bortezomib, Buzulfan, Docetaxel, Erlotinib, Ixabepilone, Lapatinib, Trimetrexate, Vinca alkaloids
Neuroleptics, anxiolytics and hypnotics	Lurasidon, midazolam for oral administration, pimozide, sertindole, triazolam		Alprazolam, Aripiprazole, Brotisolam, Buspiron, Haloperidol, Midazolam for intravenous administration, Perosporone, Quetiapine, Ramelteon, Risperidone
Antiviral drugs drugs			Maraviroc, Indinavir², Ritonavir², Saquinavir
Beta-blockers			Nadolol
Blocks of "slow" calcium channels	Bepridil, Felodipine, Lercanidipine, Nisoldipin		Other dihydropyridines, including verapamil
Other drugs acting on the cardiovascular system	Ivabradin, Ranolazine	Aliskiren
Diuretics	Eplerenone
Drugs affecting the organs of the gastrointestinal tract	Cisapride		Aprepitant, Domperidone
Immunosuppressants		Everolimus	Budesonide, Ciclesonide, Cyclosporine, Dexamethasone, Fluticasone, Methylprednisolone, Rapamycin (sirolimus), Tacrolimus, Temsirolimus
Drugs regulating lipid metabolism	Lovastatin, Simvastatin Atorvastatin
Drugs used to treat diseases of the respiratory system		Salmeterol
SSRIs, tricyclics and others antidepressants			Reboxetine
Preparations used in urology		Vardenafil	Fesoterodine, Imidafenacin, Sildenafil, Solifenacin, Tadalafil, Tolterodin
Other	Colchicine in patients with impaired hepatic or renal function	Colchicine	Alitretinoin (dosage forms for oral administration reception), Cinakaltset, MozaWaptan, Tolvaptpan

¹- See also the section "Drugs that can help reduce the plasma concentration of itraconazole."

²- See also the section on "Drugs that can increase the plasma concentration of itraconazole."

Drugs whose plasma concentration may be reduced by itraconazole

Simultaneous use of itraconazole with a non-steroidal anti-inflammatory drug meloxicam can reduce the concentration in the plasma meloxicam. It is recommended to use caution meloxicam simultaneously with itraconazole, as well as carefully monitor the clinical condition of the patient and the occurrence of side effects. If necessary, the dose of meloxicam should be adjusted.

Children

Drug interactions are studied only in adults.

Special instructions:

Influence on heart activity

Itraconazole has a negative inotropic effect. Cases of chronic heart failure associated with itraconazole administration have been reported. At a daily dose of 400 mg itraconazole, a more frequent occurrence of heart failure was observed; at lower daily doses, no such regularity was revealed. The risk of chronic heart failure is presumably proportional to the daily dose. A drug Itraconazole Do not take patients with chronic heart failure or the presence of this symptom complex in an anamnesis, unless the possible benefit far exceeds the potential risk. When assessing the benefit / risk ratio individually, one should take into account such factors as the severity of the indications,dosing regimens and individual risk factors for heart failure (coronary heart disease, valve lesions, obstructive pulmonary disease, renal failure and other diseases accompanied by edema). Patients should be informed about the signs and symptoms of chronic heart failure and follow their appearance during the course of treatment. If these symptoms appear, itraconazole should be taken to cease.

Drug Interactions

Simultaneous administration of certain drugs with itraconazole may lead to a change in the effectiveness of itraconazole and / or concomitant medications, the occurrence of life-threatening adverse reactions and / or sudden death (see "Interactions with Other Drugs").

Cross-Hypersensitivity

Data on the presence of cross-hypersensitivity between itraconazole and other antifungal agents with an azole structure (from the azole group) are not available. In the presence of hypersensitivity to other azoles, caution should be exercised itraconazole.

Reduced acidity of gastric juice

With reduced acidity of gastric juice, the absorption of itraconazole from the capsules is impaired. Patients taking antacid preparations (for example, aluminum hydroxide), it is recommended to use them not earlier than 2 hours after taking the drug. Patients with achlorhydria or using blockers H₂-gistaminovyh receptors or proton pump inhibitors, it is recommended to take the drug Itraconazole with drinks containing cola. It is necessary to monitor the antifungal activity of the drug and increase the dose of itraconazole if necessary.

Effects on liver function

In very rare cases, with the use of itraconazole, severe toxic liver damage developed, including several cases of acute hepatic insufficiency with a fatal outcome. In most cases, this was the case with patients who already had liver disease in patients with other serious illnesses that the drug was assigned to treat systemic diseases, as well as patients receiving other drugs with hepatotoxic effect.However, in some patients there were no concomitant diseases or obvious risk factors for liver damage. In this regard, it is recommended to regularly monitor liver function in patients receiving itraconazole therapy. In case of symptoms suggesting the onset of hepatitis, namely: anorexia, nausea, vomiting, weakness, abdominal pain and darkening of urine, it is necessary to immediately stop treatment and conduct a study of liver function. Patients with an increase in the activity of "hepatic" enzymes or liver disease in the active phase, or with transferred toxic liver damage due to the use of other drugs should not use the drug Itraconazole Except where the expected benefit justifies the risk of liver damage. In such cases it is necessary during the treatment to monitor the activity of "liver" enzymes. Itraconazole mainly metabolized in the liver. Since in patients with impaired hepatic function, the half-life of itraconazole is slightly increased, it is recommended to monitor the concentrations of itraconazole in plasma and, if necessary, adjust the dose of the drug.

Renal impairment

Data on the use of the drug in patients with impaired renal function are limited, in some patients with impaired renal function, exposure to itraconazole may be lowered. Therefore, in such patients, the drug should be taken with caution. It is recommended to monitor the concentrations of itraconazole in the plasma and, if necessary, adjust the dose of the drug.

Patients with immunodeficiency

The bioavailability of itraconazole for oral administration may be reduced in some patients with impaired immunity, for example, in patients with neutropenia who have AIDS or who underwent an organ transplant operation.

Patients with systemic fungal infections that are life threatening

It is not recommended for the beginning of treatment of systemic mycoses, which are a threat to the life of patients, to apply itraconazole for oral administration (capsule).

AIDS patients

The attending physician should assess the need to prescribe maintenance therapy for people with AIDS who have previously been treated for systemic fungal infections, such as sporotrichosis, blastomycosis, histoplasmosis, or cryptococcosis (both meningeal and non-meningeal),who have a risk of recurrence.

Application in pediatric practice

Because clinical data on the use of itraconazole in children is not enough, it is recommended to use the drug for children over 3 years only if the possible benefit exceeds the potential risk.

Women of childbearing age, host itraconazole, it is necessary to use reliable methods of contraception throughout the course of treatment until the onset of the first menstruation after its completion.

Treatment should be discontinued when peripheral neuropathy, which can be associated with the administration of itraconazole.

Hearing Loss

A temporary or persistent hearing loss has been reported in patients taking itraconazole. In some cases, hearing loss occurred against a background of simultaneous administration with quinidine. Hearing usually recovers after the end of therapy with the drug, but in some patients hearing loss is irreversible.

Effect on the ability to drive transp. cf. and fur:

Studies to study the effect of the drug on the ability to drive vehicles and work with mechanisms have not been carried out.When using the drug, there may be side effects such as dizziness, blurred vision and hearing loss. When these undesirable phenomena appear, one should refrain from performing these activities.

Form release / dosage:

Capsules, 100 mg.

Packaging:

5, 10 capsules in a contour cell packaging from polyvinylchloride film and aluminum foil foil lacquered.

By 5, 10, 15, 20, 30, 50 or 100 capsules in cans of polyethylene terephthalate for medicines or cans of polymeric drugs.

One jar or 1, 2, 3, 4, 5, 6 or 10 contour squares, together with the instructions for use, are placed in a cardboard package (bundle).

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002620

Date of registration:11.09.2014 / 08.10.2015

Expiration Date:11.09.2019

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

OZON PHARM, LLC Russia

Information update date: & nbsp28.11.2017

Illustrated instructions

Instructions

Itraconazole (Itraconazole)