COMPOSITION:

Active substance:

Itraconazole;

1 tablet contains 100 mg of itraconazole.

Additional ingredients:

Spherical sugar, microcrystalline cellulose, hydroxypropylmetylcellulose, lactose monohydrate, sodium starch glycolate (type A), croscarmellose sodium, low-substituted hydroxypropylcellulose, povidon K 30, magnesium stearate, colloidal anhydrous silica, Opadry II pink coating.

INDICATIONS:

Mycoses, caused by pathogenic agents sensitive to itraconazole:

vulvovaginal candidomycosis; dermatological/ophtalmological fungal diseases:

dermatomicosis, pityriasis versicolor, fungal keratitis, oral moniliasis; onychomycosis, caused by dermatophytes and/or yeasts; systemic mycosis: systemic aspergillosis, cryptococcosis (including cryptococcal meningitis): to patients with depressed immune system and to all patients with cryptococcosis of CNS Eszol® is administered only in case of ineffective treatment by other antifungal agents; histoplasmosis, sporotrichosis, paracoccidioidosis, blastomycosis and other systemic mycosis, which occur very rarely, and tropical mycosis.

DOSAGE:

It is used per oral. For optimal preparation absorption Eszol® tablets should be taken presently after intake of high-calorie food.

Tablets should be swallowed without chewing.

Vulvovaginal candidosis:

200 mg 2 times per day for 1 day or 200 mg 1 time per day for 3 days.

Dermatological/ophtalmological diseases:

– pityriasis versicolor:

200 mg 1 time per day for 7 days;

– dermatomicosis:

200 mg 1 time per day for 7 days or 100 mg 1 time per day for 15 days.

In affected areas with a high degree of keratinization (eg, hands epidermofitiya and tinea pedis) it is necessary to treat them with doses of 200 mg twice a day for 7 days or 100 mg per day for 30 days.

Oral moniliasis:

100 mg 1 time per day for 15 days.

Bioavailability of itraconazole in per oral administration can be reduced in some patients with immune system disorders, for example, in patients with neutropenia, AIDS patients or patients with transplant organs. In such cases, a double dose may be needed.

Fungal keratitis:

200 mg 1 time per day for 21 days.

Onychomycosis, caused by dermatophytes and/or yeasts:

Or continuous treatment:

2 tablets per day (200 mg per day) for 3 months.

Eszol® excretion out of skin tissues or nails is slower than those one out of plasma. Thus, optimal clinical and mycological effects are reached within 2 – 4 weeks after the treatment of skin infections and 6 – 9 months after the end of the treatment of nail plates infection.

Systemic mycosis:

* In combination with antibiotics with an action on anaerobic causative agent.

Dosage for patients with kidney function disorders and creatinine clearance less than 50 ml/min:

ADVERSE REACTIONS:

GIT:

Dyspepsia, nausea, abdominal pain, bloating, constipation, vomiting, diarrhea, dysgeusia.

CNS:

Headache, peripheral neuropathy, paresthesia, hypoesthesia, dizziness.

Skin:

Itch, rash, urticaria, angioneurotic edema, Stevens-Johnson syndrome, rhinitis, sinusitis, toxic epidermal necrolysis, erythema multiforme, exfoliative dermatitis, leukocytoclastic vasculitis, alopecia, photosensitivity.

Blood:

Leukopenia, neutropenia, thrombocytopenia.

Immune system:

Serum sickness, anaphylactic and anaphylactoid reactions.

Metabolic disorders:

Hypertriglyceridemia, hypokalemia.

Visual organ:

Visual impairment, including diplopia, a feeling of “gray fog”.

Hearing organ:

Ear noise, tinnitus, temporary or permanent hearing loss.

Hepatobiliary system:

Severe hepatotoxicity (including single cases of severe and fatal liver impairment), hepatitis, reverse growth of liver enzyme activity.

Musculoskeletal system: myalgia, arthralgia.

Urinary system:

Pollakiuria, urinary incontinence.

Reproductive system:

Menstrual disorders, erectile dysfunction.

General disorders:

Edema, upper respiratory tract infection, congestive heart failure and pulmonary edema.

Drug interactions:

In concurrent use with rifampicin, rifabutin and phenytoin a bioavailability of itraconazole and hydroxyitraconazole is significantly reduced, that leads to significant decreasing of the preparation effectiveness. Thus, a simultaneous use of itraconazole with these drugs, which are potent inducers of enzymes, is not recommended. Studies of interactions of itraconazole with other enzyme inducers, such as carbamazepine, phenobarbital and isoniazid, were not carried out, but similar interactions can be expected.

As itraconazole is degraded mainly by CYP3A4 enzyme, the potential inhibitors of this enzyme, for example, ritonavir, indinavir, clarithromycin and erythromycin, can increase the bioavailability of itraconazole, .

Itrakonazole may inhibit the metabolism of drugs, which are degraded by such enzymes as CYP3A4 cytochrome. Calcium channel blockers can produce a negative inotropic effect, which may enhance similar effect of itraconazole, itraconazole may decrease the metabolism of calcium channel blockers.

It is necessary to be caution in concurrent use of itraconazole and calcium channel blockers.

Medicines in administration of which it is necessary to monitor the level of their concentrations in plasma, their actions and side effects (in case of their concurrent use with itraconazole the dose of these medicines should be reduced, if necessary): oral anticoagulants, HIV protease inhibitors, such as ritonavir, indinavir, saquinavir, some antitumoral drugs, such as alkaloids of pink periwinkle (Vinca), busulfan, docetaxel and trimetrexate, calcium channel blockers, which are degraded by CYP3A4 enzymes, such as dihydropyridine and verapamil, certain immunosuppressive agents: tacrolimus, rapamicine (also known as sirolimus), some glucocorticosteroids, such as budesonide, dexamethasone, methylprednisolone, digoxin (because of inhibition of P-glycoprotein), other drugs: carbamazepine, buspirone, alfentanil, fentanyl, cilostazol, dizopiramidum, halofantrine, alprazolam, brotizolam, midazolam IV, rifabutin, ebastine, reboxetine, repaglinide, loperamide.

Itraconazole interaction with zidovudine and fluvastatin is not established.

It was not observed itraconazole effect on metabolism of ethynilestradiol and norethisterone.

Pregnancy and lactation:

Clinical experience of Eszol® preparation use for the treatment of pregnant women is limited, so during pregnancy the preparation can be used only in case of systemic mycosis, which is life threatening and when the expected benefit to a mother overweights the potential risk to a fetus.

Women of childbearing age during Eszol® preparation treatment are recommended to use effective contraception.

If necessary the treatment by Eszol® preparation during lactation, a breast feedingshould be stopped.

Children:

As there is no enough clinical data concerning Eszol® tablets administration to children, it is not recommended to administer the preparation to patients of this age group.

PRECAUTIONS

The product contains sugar, that should be considered when it is administered to insular patients.

Use with other medicines:

In reduced gastric acidity Eszol® preparation absorption in intestinal tract is impaired. Patients who concurrently use Eszol® preparation and medicines for acidity reducing (such as aluminum hydroxide), must adhere to at least two-hours break between intakes of these medicines. Patients with achlorhydria, such as AIDS patients or those who use H2-blockers or proton pump inhibitors, are recommended to take Eszol® tablets with drinks like cola.

Taking into consideration pharmacokinetic characteristics of the preparation, Eszol® tablets are not recommended for the first therapy of emergency states caused by systemic fungal infections.

In AIDS patients who were treated for systemic mycoses, such as sporotrichosis, blastomycosis, histoplasmosis or cryptococcosis (including cryptococcal meningitis) and who are in the group of risk relapse, a necessity of supporting treatment should be considered by a doctor.

Women of reproductive age, who take Eszol® tablets, must use an effective contraception throughout the treatment course up to the first menstruation after its discontinuation.

Heart dysfunction:

It is known that Eszol® has a negative inotropic effect. It was reported about cases of chronic heart failure associated with the use of Eszol® preparation. Patients with chronic heart failure or present disease in anamnesis should not use the preparation with the exception of cases when the expected benefit greatly outweighs the potential risk. In individual assessment of benefit/risk it is necessary to take into account such factors as indications, dosage regimen and individual risk factors of chronic heart failure development. Risk factors include the presence of cardiac diseases, such as coronary heart disease or valve affection; severe lung diseases, such as obstructive lung disease; kidney insufficiency or other diseases accompanied by edema. Such patients should be informed about symptoms of chronic heart failure. Treatment should be provided with caution. During the treatment it is necessary to control symptoms of chronic heart failure. In case of appearance of these symptoms during the treatment course Eszol® preparation use should be discontinued.

It is necessary to be careful while concurrent use of Eszol® preparation and calcium channel blockers.

Hepatic dysfunction:

During Eszol® preparation cases of severe hepatotoxicity, including acute and fatal liver impairment, are rare. Observed side effects were in patients with liver disease in anamnesis or in those which were treated for systemic indications and/or took hepatotoxic medicines. Several of these cases were observed during the first month of the treatment, including in the first weeks. Therefore, it is desirable to monitor liver function in patients who take Eszol®. Patients should be warned about a necessity of urgent visit to a doctor in cases of signs or symptoms of hepatitis,

such as: Anorexia, nausea, vomiting, fatigue, abdominal pain or dark-colored urine. In case of these symptoms occurence it is necessary to discontinue the treatment immediately and to examine liver function. Patients with increased level of liver enzymes, liver disease in active form or those who have had cases of liver toxicity during the usage of other medicines, it is recommended not to start the treatment, with the exception of cases when the expected result outweighs the risk of disorders development. In such cases, a monitoring of liver enzymes is necessary.

Bioavailability of the preparation while per oral administration in patients with liver cirrhosis is insignificantly decreased, therefore a dosage adjustment may be required.

Kidney dysfunction: Bioavailability of Eszol® preparation while per oral use in patients with renal failure can be reduced. In this case it may be considered a dosage adjustment.

Neuropathy:

The treatment should be discontinued in case of neuropathy ocurence, which may be associated with the use of Eszol® tablets.

Elderly patients:

As clinical data on the use of Eszol® preparation in elderly patients is not enough, then the preparation can be administered to such patients only when the expected benefit of the treatment greatly outweighs the potential risk.

Prophylaxis in patients with neutropenia:

Diarrhea was the most frequent side effect of Eszol® preparation in clinical studies. Such a disorder of the digestive tract may lead to a lower absorption and can change a microbiological flora, potentially promoting fungal colonization. It is necessary to be cautious when discontinuing the treatment in such cases.

Cross sensitivity:

There is no information about presence of cross sensitivity between Eszol® preparation and other azole antifungal agents. However, caution should be taken when the preparation is administered to patients with hypersensitivity to other azole agents.

Hearing loss:

In administration of Eszol® preparation it was observed a temporary or permanent hearing loss in patients who took Eszol®. In some cases hearing loss occurred while concurrent use with chinidin, which is contraindicated (see “Contraindications”). Hearing is usually renewed after the preparation discontinuation, however, in some patients hearing loss was irreversible.

Overdose:

There are no reports about overdose. If there was an accidental overdose, supportive measures should be taken. During the first hour after intake it is necessary to cleanse a stomach. If it is reasonably, an activated carbon may be used. Eszol® can not be excreted via hemodialysis. There is no specific antidote.

Ability to influence reaction velocity while driving or operating any other mechanisms.

Taking into consideration that in administration of the preparation to sensitive patients CNS and visual organs side effects may occur, therefore, it is necessary to avoid driving a car and operating other machines while the preparation use.

CONTRAINDICATIONS:

Fusys® should not be administered in individual hypersensitivity to Fluconazole or other agents similar to azole substance by chemical structure.

Concurrent usage of Terfenadine is contraindicated in patients who use Fusys®. Cisapride is contraindicated in patients who receive Fusys®. Children age less than 7 years old. Lactation and pregnancy periods.

PHARMACOLOGICAL PROPERTIES:

Pharmacodynamics:

Eszol® is a synthetical antifungal agent, which is active against a wide specter of pathogenic organisms. Mechanism of action of Eszol® is related to inhibition of ergosterol synthesis – an important component of fungal cell membrane. The following agents are sensitive to Eszol®: dermatophytes (Trichophyton, Microsporum, Epidermophyton flocosum), yests and yest-like fungi (Cryptococcus noeformans, Pityrosporum, Candida, including Cadida albicans, Candida glabrata, Candida krusei) and also Aspergillus, Histoplasma, Fonsecaea, Cladosporuim, Paracoccidioides basiliensis, Sporothrix schenckii, Blastomyces dermatitidis and other microorganisms.

Clinical effect, which is reached while Eszol® usage, becomes entirely apparent after 2 – 4 weeks of the treatment discontinuation. In a case of skin mycosis – in 6 – 9 weeks after the end of the treatment.

Pharmacokinetics:

Plasma peak of itraconazole concentrations is about 1 μg equiv/ml is reached in 1.5 – 3 hours after intake. Half-life in men is approximately 20 hours. In per oral use immediately after meal the peak concentration doubles every 3 – 4 hours.

Peak concentrations of itraconazole in keratinized tissues, especially in skin, 3 times higher than concentrations in plasma. Therapeutic concentrations in skin are remained up to 2 – 4 weeks after the therapy discontinuation, because the excretion more depends on epidermal regeneration than on redistribution in systemic ring.

Itrakonazole is extensively metabolized by liver with the formation of a large number of metabolites, which are 40% of the dose. Active substance excretion with faeces varies from 3 to 18% of the dose, and its excretion with the urine is less than 0,03%.

PHARMACEUTICAL CHARACTERISTICS:

General physic-chemical properties:

Capsule-shaped, pink, coated tablets with “ITR 100” logo on one side.

Shelf-life:

2 years.

Storage:

Store in a dry, protected from light place, at the temperature not more than 25 С.

Keep it out of reach of children.

Package:

4 or 10 tablets are in blisters, 1 blister is in a carton box

Conditions of supply:

By prescription<