Itraconazole, 100 mg capsules 14 pcs

Indications

Active ingredient

Composition

Each capsule contains itraconazole pellets (22%) – 0.460 g.

Content of the pellets:

The active ingredient: itraconazole – 0.100 g;

Auxiliary substances: Hypromellose (hydroxypropyl methylcellulose E-5) – 0.1472 g, butyl methacrylate, dimethylaminoethyl methacrylate and methyl methacrylate copolymer [1:2:1] (Eudragit E-100) – 0.0046 g, sucrose (sugar) – 0.2070 g.

Composition of the capsule shell:

casing: gelatin, titanium dioxide (E 171), azorubin (carmoisine) E 122;

caps: gelatin, titanium dioxide (E 171), indigo carmine – F D&C Blue 2 (E 132).

How to take, the dosage

Itraconazole should be taken immediately after eating for optimal absorption. The capsules should be swallowed whole.

Indication

Dose

Treatment duration

2nd course

Weeks free from taking Itraconazole

3rd course

Defections of the nail plates of the hands

1st course

Weeks free from taking Itraconazole

/p>

2nd course

Onychomycosis – continuous treatment

Dose

Duration of treatment

Foot nail plate lesions with or without hand nail plate lesions

200 mg per day

/p>

3 months

Excretion of Itraconazole from the skin and nail tissue is slower than from the plasma. Thus, optimal clinical and mycological effects are achieved 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 of treatment*

Remarks

Aspergillosis

200 mg once daily

2-5 months

Increase the dose to 200 mg 2 times daily in case of invasive or disseminated disease

Candida

100-200 mg once daily

3 weeks to 7 months

Increase the dose to 200 mg 2 times a day in the case of invasive or disseminated disease

Cryptococcal meningitis

200 mg 2 times daily

2 months to 1 year

Maintenance therapy – see Special Indications

Histoplasmosis

from 200 mg once daily to 200 mg twice daily

8 months

Blastomycosis

100 mg once daily to 200 mg twice daily

6 months

100 mg once daily

3 months

Paracoccidioidomycosis

100 mg once daily

6 months

There is no data on the efficacy of this dose for the treatment of paracoccidioidomycosis in AIDS patients

Chromomycosis

100-200 mg once daily

/td>

6 months

* – the duration of treatment may be adjusted depending on the effectiveness of the treatment.

Special patient groups

Children There are limited data on the use of Itraconazole in children. The use of Itraconazole in children is not recommended unless the expected benefits of treatment outweigh the potential risks.

Elderly patients. The data on the use of Itraconazole for the treatment of elderly patients are limited. It is recommended to use itraconazole preparation for treatment of patients in this category only if the expected benefits of treatment exceed the potential risks. When choosing the dose of the drug for treatment of elderly patients it is recommended to take into account the decrease of liver, kidney and heart function, which are more frequent in elderly patients, as well as the presence of concomitant diseases or taking other medications.

Hepatic disorders. The data on the use of oral itraconazole for the treatment of patients with hepatic impairment are limited. Caution should be exercised when prescribing the drug in this category of patients.

Renal dysfunction. The data on the use of oral itraconazole for the treatment of patients with impaired renal function are limited. In some patients with renal impairment, the exposure of itraconazole may be reduced. The drug should be administered with caution in this category of patients, in some cases it may be necessary to change the dose of the medicinal product.

Interaction

Itraconazole is primarily metabolized by CYP3A4 isoenzyme. Other drugs that are also metabolized with participation of this isoenzyme or change its activity can affect the pharmacokinetics of itraconazole. Similarly, itraconazole may affect the pharmacokinetics of drugs that are also metabolized with the participation of this isoenzyme. Itraconazole is a strong inhibitor of CYP3A4 isoenzyme and P-glycoprotein. If itraconazole is used together with other medicinal agents, it is recommended to read the instructions for use to clarify the way of metabolism of the drug and to decide if it is necessary to change the dose.

Drugs that may decrease plasma concentrations of itraconazole

Drugs that may decrease plasma concentrations of itraconazole Medicinal products which reduce the acidity of gastric juice (e.g., antacids, such as aluminum hydroxide, or products that inhibit the secretion of hydrochloric acid, such as H2-histamine receptor antagonists and proton pump inhibitors), impair the absorption of the drug Itraconazole. It is recommended to use these medicinal agents with caution in combination with itraconazole:

– Itraconazole is recommended to be taken together with acidic beverages (such as non-diet Coke) when using medicinal agents that reduce the acidity of gastric juice together.

– It is recommended to take medicines that neutralize hydrochloric acid (such as aluminum hydroxide) at least 1 hour before or 2 hours after taking Itraconazole.

When co-administering medications, it is recommended that the antifungal activity of itraconazole be monitored and the dose of the drug be increased as needed.

The co-administration of itraconazole with strong inducers of CYP3A4 isoenzyme may decrease the bioavailability of itraconazole and hydroxyitraconazole to the extent that the effectiveness of the medicine will be reduced. Examples include the following drugs:

– Antibacterials: isoniazid, rifabutin, rifampicin.

– Anticonvulsants: carbamazepine, phenobarbital, phenytoin.

– Antiviral drugs: efavirenz, nevirapine.

Hence, the use of strong inducers of CYP3A4 isoenzyme in combination with itraconazole is not recommended. It is recommended to avoid taking these medicinal agents for 2 weeks before starting to take itraconazole and during treatment with the drug, except in cases when the expected benefits exceed the potential risk associated with a decrease in the effectiveness of itraconazole. It is recommended to monitor the antifungal activity of itraconazole during concomitant use of the medicinal product, and to increase the dose of the drug if necessary.

Drugs which may cause increase in plasma concentration of itraconazole

The simultaneous use of itraconazole and strong CYP3A4 isoenzyme inhibitors may lead to increased bioavailability of itraconazole. Examples of strong inhibitors of CYP3A4 isoenzyme:

– Antibacterial drugs: ciprofloxacin, clarithromycin, erythromycin.

– Antiviral drugs: darunavir, ritonavir-enhanced, fosamprenavir, ritonavir-enhanced, indinavir, ritonavir and telaprevir.

These medications are recommended with caution when used with itraconazole. It is recommended to monitor closely the condition of patients taking itraconazole together with strong CYP3A4 isoenzyme inhibitors, for timely detection of symptoms and signs of enhancement or prolongation of pharmacological effects of itraconazole, if necessary, itraconazole dose reduction is possible. If possible, it is recommended to monitor the plasma concentration of itraconazole.

Drugs the plasma concentrations of which may increase when combined with itraconazole

Itraconazole and its main metabolite hydroxyitraconazole may interfere with the metabolism of drugs metabolized by CYP3A4 isoenzyme and inhibit the transportation of drugs by P-glycoprotein. This may lead to increased plasma concentrations of these drugs and/or their active metabolites when co-administered with itraconazole. The increase of plasma concentration, in turn, can cause intensification or prolongation of both therapeutic and undesirable effects of these drugs, which can result in potentially life-threatening conditions. Thus, increased concentrations of some drugs (terfenadine, astemizole, bepridil, misolastin, cisapride, dofetilide, quinidine, pimozide, sertindol, levometadone) may lead to increased QT interval and ventricular tachyarrhythmias, including cases of ventricular pirouette tachycardia, which are considered potentially life-threatening conditions. After discontinuation of treatment, plasma concentrations of itraconazole decrease to near indeterminate levels within 7 to 14 days, depending on the drug dose and duration of treatment. In patients with cirrhosis or those who concomitantly take CYP3A4 enzyme inhibitors the decrease in drug concentration may be even slower. This is especially important during the initiation of therapy with the use of drugs, metabolism of which is affected by itraconazole.

The concomitant medications fall into the following categories:

– “Contraindicated”: Under no circumstances should this medication be used in combination with itraconazole and for 2 weeks after stopping itraconazole.

“Not recommended”: It is recommended to avoid the use of this medicine during treatment and for 2 weeks after discontinuation of itraconazole, unless the expected benefits exceed the potential risks associated with the current therapy. If it is impossible to avoid using this combination of medicinal agents, it is recommended to monitor the patient’s condition for timely detection of symptoms and signs of intensification or prolongation of drug effects or development of side effects; if necessary, the treatment may be interrupted or the dose of medicinal agents may be reduced. If possible, it is recommended that plasma concentrations of the drugs be monitored.

– Use with caution: Close monitoring should be done when using the drug together with itraconazole. When concomitant use of the medicinal products it is recommended to monitor the patient’s condition for timely detection of symptoms and signs of intensification or prolongation of drug effects or development of side effects; if necessary, treatment may be interrupted or the dose of the medicinal products may be reduced. If possible, it is recommended to monitor the plasma concentration of the drugs.

The following are examples of medications that can increase plasma concentrations with itraconazole. The drugs are divided into classes, and recommendations are also given for combined use with itraconazole:

Drug class

Contraindicated

Not recommended

Use with caution

Alpha-adrenoblockers

Tamsulosin

Narcotic analgesics

Levacetylmethadol (levomethadil), methadone

Fentanyl

Alfentanil, buprenorphine for intravenous and sublingual administration, oxycodone, sufentanil

Antiarrhythmic agents

Disopyramide, dofetilide, dronedarone, quinidine

Digoxin

Antibacterials

Telithromycin in patients with severe renal or hepatic impairment

Telithromycin in patients with severe renal or hepatic impairment

Rifabutina

Telithromycin

Anticoagulants and antiaggregants

Ticagrelor

Apixaban, rivaroxaban

Coumarins, cilostazol, dabigatran

Anticonvulsants

/td>

Carbamazepinea

Antidiabetic drugs

Repaglinide, saxagliptin

Anthelminthic and antiprotozoal agents

Astemizole, misolastin, terfenadine

Bilastin, ebastine

Migraine medications

Etrone alkaloids such as dihydroergotamine, ergometrine (ergonovine), ergotamine, methyl ergometrine (methyl ergonovine), eletriptan

Antitumor drugs

Irinotecan

Axitinib, dafrafenib, dasatinib, ibrutinib, nilotinib sunitinib, trabectedin

Neuroleptics, anxiolytics, and hypnotics

Lurazidone, oral midazolam, pimozide, sertindol, triazolam

Lurazidone, oral midazolam, pimozide, sertindol, triazolam

Alprazolam, aripiprazole, brotizolam, buspirone, haloperidol, intravenous midazolam, perosapine, quetiapine, ramelteon, risperidone

Antiviral drugs

Simeprevir

Maraviroc, indinavirb, ritonavirb, saquinavir

Beta-adrenal blockers

Special Instructions

In a study of itraconazole in intravenous dosage form, a transient asymptomatic decrease in left ventricular ejection fraction was observed, which normalized before the next infusion of the drug. The clinical significance of these findings for oral dosage forms is unknown.

Itraconazole has a negative inotropic effect. There have been reported cases of chronic heart failure associated with taking itraconazole. At a daily dose of 400 mg of itraconazole, a more frequent occurrence of heart failure was observed; no such pattern was found at lower daily doses. The risk of chronic heart failure is presumably proportional to the daily dose. The drug should not be used in patients with chronic heart failure or with the presence of this symptom complex in the anamnesis, except in cases when the possible benefit significantly exceeds the potential risk. In individual assessment of the benefit-risk ratio such factors as severity of indications, dosage regimen and individual risk factors of heart failure (coronary heart disease, valve lesions, obstructive pulmonary disease, renal failure and other diseases accompanied by edema) should be taken into account. Such patients should be informed about signs and symptoms of chronic heart failure and follow their appearance during the treatment. If such signs appear, the drug should be discontinued.

Life-threatening cardiac arrhythmias and/or sudden death have been reported in patients with concomitant use of methadone.

Medication interactions: simultaneous use of some medicinal products with itraconazole can lead to changes in the effectiveness of itraconazole and/or concomitant drugs, occurrence of life-threatening adverse reactions and/or sudden death. Drugs that should not be taken concomitantly with itraconazole, not recommended for concomitant use and/or recommended for concomitant use with itraconazole with caution are listed in section “Interaction with other medicinal products”.

Cross hypersensitivity: there are limited data on the presence of cross-sensitivity between itraconazole and other antifungal agents with azole structure (from the group of azoles). In the presence of hypersensitivity to other azoles, itraconazole should be used with caution.

Interchangeability: interchangeable use of itraconazole in the form of capsules and in the form of oral solution is not recommended, due to the fact that exposure to itraconazole is higher when used in the form of oral solution than in the form of capsules, even when the same doses of itraconazole are taken.

Decreased gastric acidity: absorption of itraconazole from capsules is impaired when gastric acidity is decreased. In patients with decreased gastric acidity due to a disease (e.g., in patients with achlorhydria) or due to taking medications (e.g., drugs that inhibit gastric secretion), itraconazole is recommended to take it simultaneously with acidic beverages (such as non-dietic cola). The antifungal activity of the drug should be monitored and the dose of itraconazole should be increased if necessary.

Impact on liver function: In very rare cases severe toxic liver damage developed during the use of the drug, including several cases of acute hepatic failure with fatal outcome. In most cases this occurred in patients who already had liver disease, in patients with other severe diseases to whom the drug was prescribed for the treatment of systemic diseases, as well as in patients who received other drugs with hepatotoxic effects. However, some patients had no comorbidities or obvious risk factors for liver damage. Several such 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 itraconazole therapy. In case of symptoms suggestive of hepatitis occurrence, namely: anorexia, nausea, vomiting, weakness, abdominal pain and darkened urine, it is necessary to stop treatment immediately and conduct liver function tests. Patients with increased “liver” enzymes activity or active liver disease, or in patients with past toxic liver injury caused by taking other drugs should not be treated with itraconazole, except in cases when the expected benefits justify the risk of liver damage. In such cases, it is necessary to monitor the activity of “liver” enzymes during treatment. Itraconazole is mainly metabolized in the liver. As the total half-life of itraconazole in patients with liver dysfunction is slightly prolonged, itraconazole plasma concentrations should be controlled and the dose of the medicine adjusted, if necessary.

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

Patients with immunodeficiency: bioavailability of itraconazole in per oral administration may be reduced in some patients with impaired immunity, such as patients with neutropenia, patients with AIDS or patients who underwent surgery for organ transplantation.

Patients with systemic fungal infections that are life-threatening: Due to the pharmacokinetic characteristics of itraconazole, its use is not recommended for initiating treatment of systemic mycoses that are life-threatening in patients.

AIDS patients: The treating physician should evaluate the need for maintenance therapy in AIDS patients previously treated for systemic fungal infections such as sporotrichosis, blastomycosis, histoplasmosis, or cryptococcosis (both meningeal and nonmeningeal) who are at risk for relapse.

Pediatric use: Because there is insufficient clinical data on the use of itraconazole in children, it is recommended that the drug be administered to children only if the possible benefit of treatment outweighs the potential risk.

Women of childbearing age who are taking itraconazole should use adequate contraception for the duration of treatment until their first menstrual period after treatment ends.

The treatment should be stopped if peripheral neuropathy occurs, which may be associated with the use of Itraconazole.

In systemic candidiasis suspected to be caused by fluconazole-resistant strains of Candida, sensitivity to itraconazole cannot be assumed, therefore, it is recommended to check sensitivity before starting itraconazole therapy.

Hearing loss: Temporary or permanent hearing loss has been reported in patients taking itraconazole. In some cases, hearing loss occurred while concomitant use with quinidine (see sections “Contraindications” and “Interaction with other medicinal products”). Hearing usually returns after therapy with Itraconazole, but some patients have irreversible hearing loss.

Confertility: animal studies have shown no reproductive toxicity in itraconazole.

Mucoviscidosis (cystic fibrosis): In patients with cystic fibrosis (cystic fibrosis) a variability in plasma concentration of itraconazole was observed when using itraconazole in the form of oral solution at a dose of 2.5 mg/kg 2 times daily. As a consequence, the therapeutic equilibrium plasma concentration of itraconazole may not be reached. Equilibrium concentrations of >250 ng/ml were achieved in approximately 50% of patients over the age of 16 years and were not achieved in any patient younger than 16 years. If there is no response to therapy with Itraconazole, consideration should be given to switching to an alternative therapy.

Influence on ability to drive vehicles, mechanisms

There have been no studies on the effect of itraconazole on the ability to drive vehicles and operate machinery. It is necessary to take into account the possibility of adverse reactions, such as dizziness, visual impairment and hearing loss (see “Adverse effects”). If the adverse events described above occur, you should refrain from performing the indicated activities.

Synopsis

Contraindications

– levacetylmethadol, methadone;

– disopyramide, dofetilide, dronedarone, quinidine;

– telithromycin in patients with severe renal or hepatic impairment;

– ticagrelor;

– halofantrine;

– astemizole, misolastin, terfenadine;

– ergot alkaloids: dihydroergotamine, ergometrine (ergonovine), ergotamine, methyl ergometrine (methyl ergonovine), eletriptan;

– irinotecan;

– lurazidone, oral midazolam, pimozide, sertindol, triazolam;

-bepridil, felodipine, lercanidipine, nisoldipine;

– ivabradine, ranolazine;

– eplerenone;

– cisapride, domperidone;

p> – lovastatin, simvastatin, atorvastatin;

Fesoterodine in patients with moderate to severe renal or hepatic impairment, solifenacin in patients with severe renal impairment and moderate to severe hepatic impairment;

– Colchicine in patients with impaired hepatic or renal function.

With caution

In cirrhosis; severe hepatic and renal dysfunction; hypersensitivity to azoles; in elderly patients; in children.

Side effects

Overdose

The symptoms observed in itraconazole overdose were comparable to the dose-dependent adverse reactions observed with normal doses of the drug.

Treatment

There is no specific antidote. In case of overdose, supportive therapy should be carried out, gastric lavage with sodium bicarbonate solution, give activated charcoal. Itraconazole is not eliminated from the body by hemodialysis.

Pregnancy use

Similarities