Expiration date: 09/2026

Structure and Composition:

1 capsule contains active substance: itraconazole 100 mg (Pellets of itraconazole - 0.464 g)

excipients: Hypromellose poloxamer (lutrol) wheat starch sucrose

hard gelatin capsule: gelatin, titanium dioxide, coloring agent quinoline yellow iron oxide, red iron oxide black dye sunset yellow azorubin

in blisters 5 or 6 pieces. In the paper cartons 1 (6 pcs.) or 3 (5 pcs.) packing.

Description pharmaceutical form:

Capsules number 0, two-colored: white hull, cover pink and brown. The contents of capsules - a spherical micro-granules from light yellow to yellowish-beige color.

Characteristic:

Synthetic triazole derivative.

Pharmacokinetics:

Suction. For oral application the maximum bioavailability of itraconazole observed when taking the capsules immediately after a meal. Plasma Cmax is achieved within 3-4 hours after ingestion.

Distribution. The equilibrium concentration of itraconazole in plasma within 3-4 hours after ingestion of 0.4 mg / ml (for receiving 100 mg 1 time per day), 1.1 ug / ml (when receiving 200 mg once a day 1) and 2 0 ug / ml (when receiving 200 mg 2 times a day). Chronic administration of the equilibrium concentration is achieved within 1-2 weeks. Binding to plasma proteins - 99.8%.

Itraconazole is well into and distributed in the tissues and organs. The concentration of drug in the lungs, kidneys, liver, spleen, bone, stomach, skeletal muscles of 2-3 times the corresponding plasma concentrations. The accumulation of the drug in the keratinous tissues, particularly the skin, approximately 4 times greater than the accumulation in the plasma, and elimination rate is dependent on the rate of regeneration of the epidermis. Unlike plasma concentration which is not detectable after 7 days after termination of therapy, a therapeutic concentration in the skin is maintained for 2-4 weeks after stopping the 4-week treatment course in the vaginal mucosa - 2 days after the end of 3- days of treatment at a dose of 200 mg / day for 3 days after 1-day treatment with 200 mg 2 times a day. A therapeutic concentration of the drug found in the nail keratin already 1 week after initiation of treatment and stored for 6 months after 3 months of therapy. Itraconazole is also defined in the sebum and to a lesser extent in perspiration.

Metabolism. Is metabolized in the liver with the formation of active metabolites, one of which - gidroksiitrakonazol - providing comparable with itraconazole antifungal effect in vitro.

Withdrawal. Elimination from the plasma is biphasic with the final T1 / 2 - 24-36 hours.

Excretion in the feces is from 3 to 18% of the dose, kidney - less than 0.03% of the dose approximately 35% of the dose excreted in urine as metabolites for 1 week.

Pharmacokinetics in special clinical situations

In patients with renal failure and certain immunocompromised patients (e.g. AIDS, organ transplantation, or in the case of neutropenia) may decrease the bioavailability of itraconazole. In patients with cirrhosis the bioavailability of itraconazole reduced, T1 / 2 is increased.

Description of the pharmacological actions:

It inhibits the synthesis of ergosterol membrane of fungi.

Active against dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum), yeasts, and yeast (Cryptococcus neoformans, Pityrosporum spp., Trichosporon spp., Geotrichum spp., Candida spp., Including C.albicans, C.glabrata and C.krusei), Aspergillus spp., Histoplasma spp., Paracoccidioides brasiliensis, Sporothrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatitidis, Pseudallescheria boydii, Penicillium marneffei, as well as other yeast and fungi.

Indications:

• Fungal infections, including systemic or tropical mycoses, including
  
• ringworm
  
• fungal keratitis
  
• onychomycosis caused by dermatophytes and / or yeasts and molds
  
• systemic mycoses: systemic aspergillosis and candidiasis, cryptococcosis (including cryptococcal meningitis), histoplasmosis, sporotrichosis, paracoccidioidomycosis, blastomycosis and other systemic mycoses
  
• kandidomikoz with skin lesions and / or mucous membranes, including vulvovaginal candidiasis
  
• deep visceral candidiasis
  
• chromophytosis.
  

Contraindications:

individual hypersensitivity to the drug or its components

concomitant use of drugs metabolized with the participation of isoenzyme CYP3A4 (terfenadine, astemizole, mizolastine, cisapride, dofetilide, quinidine, pimozide, Levo, sertindole), HMG-CoA reductase inhibitors, including simvastatin and lovastatin midazolam and triazolam for oral administration, preparations of ergot alkaloids (dihydroergotamine, ergometrine, ergotamine and metilergometrin) (see. also "Interactions").

Precautions: infancy (as clinical data itraconazole capsules in children insufficient itraconazole recommended only if the potential benefit outweighs the potential risk) severe heart failure of liver disease (including hepatic insufficiency accompanied) chronic renal failure.

Application of pregnancy and breastfeeding:

During pregnancy, the drug should be used only in life-threatening cases, if the expected benefit to the woman outweighs the potential risk to the fetus.

In the appointment during lactation should stop breastfeeding.

Side effect:

On the part of the digestive tract: dyspepsia, nausea, vomiting, loss of appetite, abdominal pain, diarrhea, constipation.

On the part of the hepatobiliary system: reversible increases in liver transaminases, hepatitis rarely - severe liver toxicity, including acute liver failure with fatal consequences.

From the nervous system: headache, dizziness, peripheral neuropathy.

Allergic reactions: skin rash, pruritus, urticaria, angioneurotic edema, rarely - exudative erythema multiforme (Stevens-Johnson syndrome).

With the Skin: alopecia, photosensitivity.

Other: menstrual disorders, hypokalemia, edema syndrome, congestive heart failure and pulmonary edema, hypercreatininemia, staining of urine in a dark color.

Drug Interactions:

Drugs affecting the absorption of itraconazole

Drugs that reduce gastric acidity, reduce the absorption of itraconazole.

Drugs affecting the metabolism of itraconazole

Itraconazole mostly cleaved by the enzyme CYP3A4. With simultaneous use of itraconazole with rifampicin, rifabutin, phenytoin, carbamazepine, isoniazid, is a potent inducer of CYP3A4, itraconazole bioavailability and gidroksiitrakonazola greatly reduced, which leads to a substantial decrease in efficacy. Concomitant use with these drugs Rumikoza which are potential inducers of hepatic enzymes, it is not recommended.

Potent inhibitors of the enzyme CYP3A4 (for example ritonavir, indinavir, clarithromycin, erythromycin) may increase the bioavailability of itraconazole.

Effect of itraconazole on the metabolism of other drugs

Itraconazole can inhibit the metabolism of drugs, biotransformed involving CYP3A4 enzyme, which may lead to an increase or prolongation of their actions, including side effects. After the cessation of treatment plasma levels of itraconazole gradually reduced depending on the dose and duration of treatment (see., "Pharmacokinetics").

Drugs are at the same time appoint Rumikoz drug is not recommended:

- Calcium channel blockers (CCBs) - in addition to possible pharmacokinetic interactions associated with common pathway of metabolism by CYP3A4 enzyme, BPC may have a negative inotropic effect, which is enhanced by concomitantly with itraconazole.

Along with itraconazole should not be administered terfenadine, astemizole, mizolastine, cisapride, midazolam, and triazolam (oral), dofetilide, quinidine, pimozide, Levo, sertindole, inhibitors of HMG-CoA reductase inhibitors (simvastatin, lovastatin), preparations of ergot alkaloids.

Formulations with concomitant administration of itraconazole which is recommended to monitor their concentrations in plasma, and side effects of the action and, if necessary, reduce the dose:

• Oral anticoagulants
  
• HIV protease inhibitors: ritonavir, indinavir, saquinavir
  
• Anticancer drugs: vinca alkaloids, busulfan, docetaxel, trimetrexate
  
• BPC, metabolized by the enzyme of CYP3A4, such as verapamil and derivatives of dihydropyridine
  
• Immunosuppressive agents: cyclosporine, tacrolimus, sirolimus
  
• Some digestive enzymes CYP3A4 inhibitors of HMG-CoA reductase inhibitors (atorvastatin)
  
• Some corticosteroids (budesonide, dexamethasone and methylprednisolone)
  
• Other medicines: digoxin, carbamazepine, buspirone, alfentanil, alprazolam, brotizolam, midazolam for / in the introduction, rifabutin, ebastine, reboxetine, cilostazol, disopyramide, eletriptan, halofantrine, repaglinide.
  

The interactions between itraconazole and zidovudine and fluvastatin is not revealed.

There was no effect of itraconazole on the metabolism of ethinyl estradiol and norethisterone.

in vitro studies demonstrated no interaction between itraconazole and other drugs such as imipramine, propranolol, diazepam, cimetidine, indometacin, tolbutamide and sulfamethazine upon binding to plasma proteins.

Dosage and administration:

Inside, after eating capsules should be swallowed whole.

Table 1

Indication	????	????????????????? ??????????, ???
Vulvovaginal candidiasis	200 mg 2 times a day 200 mg 1 time per day	1 3
Chromophytosis	200 mg 1 time per day	7
Dermatomycoses smooth skin	200 mg 1 time per day 100 mg 1 time per day	7 15
Fungal keratitis	200 mg 1 time per day	21 You can correct the duration of treatment, taking into account the positive dynamics of clinical
Oral candidiasis	100 mg 1 time per day	15
Lesions highly keratinized areas of skin, such as hands and feet	200 mg 1 time per day 100 mg 1 time per day	7 30

The bioavailability of itraconazole when given orally can be reduced in some patients with impaired immune systems, such as in patients with neutropenia, patients with AIDS or undergoing organ transplantation. In such cases it may require doubling the dose.

Onychomycosis: Pulse therapy or continuous treatment.

Pulse therapy (see. Table. 2). One course of pulse therapy is a daily intake of 2 capsules. Two times a day (200 mg, 2 times daily) for 1 week.

For the treatment of fungal infections of the nail plate toes recommended 3 courses.

For the treatment of fungal infections of the nail plate of fingers is recommended 2 courses.

The interval between courses is 3 weeks. Clinical results become apparent after treatment as regrowth of the nail.

Table 2

Localization of onychomycosis	1st week	2nd week	3nd week	4th week	5th week	6th week	7th week	8th week	9th week
Nail plate toes with defeat or without defeat nail plates of fingers	1st course	The break between courses			2nd course	The break between courses			3rd course
Nail plate of fingers	1st course	The break between courses			2nd course	-

Continuous treatment - 2 caps. per day (200 mg 1 time per day) for 3 months. The optimum therapeutic effect is attained 2-4 weeks after the end of treatment for skin lesions, and after 6-9 months - when the affected nail.

Systemic mycoses: recommended dosages vary depending on the type of infection (Table 3..).

Table 3

Indication	Dose	The average duration of treatment	Note
Aspergillosis	200 mg 1	2–5 month	Increase the dose to 200 mg 2 times a day in case of invasive or disseminated disease
Candidiasis	100–200 mg 1 time per day	from 3 weeks to 7 months
Cryptococcosis (except meningitis) Cryptococcal meningitis	200 mg 1 time per day 200 mg 2 time per day	from 2 months to 1 year	Supportive therapy (cases of meningitis) - 200 mg 1 time per day
Histoplasmosis	200 mg 1-2 time per day	8 months
Sporotrichosis	100 mg 1 time per day	3 months
Paracoccidioidomycosis	100 mg 1 time per day	6 months
Chromomycosis	100-200 mg 1 time per day	6 months
Blastomycosis	100 mg 1 time per day — 200 mg 1 time per day	6 months

Overdose:

Data not available.

In case of accidental overdose, supportive measures should be used - gastric lavage within the first hour, if necessary - the appointment of activated carbon.

Itraconazole not appear in hemodialysis.

There is no specific antidote.

Precautionary measures:

Women of childbearing potential taking itraconazole, you must use adequate contraception methods during the course of treatment until the onset of the first menstrual period after its completion.

In the study of / in the dosage form of itraconazole, conducted in healthy volunteers noted a transient asymptomatic decrease in left ventricular ejection fraction, normalized to the next infusion. The clinical relevance of the data obtained for the oral formulations is unknown.

It found that itraconazole has a negative inotropic effect. It reported cases of heart failure associated with taking Rumikoza. The drug should not be taken in patients with chronic heart failure, including history, except in cases where the potential benefit significantly outweighs the potential risk.

Calcium channel blockers can have negative inotropic effects which may enhance this effect of itraconazole itraconazole may decrease the metabolism of BPC. At the same time taking itraconazole and BPC must be careful.

In renal failure may require dose adjustment.

At low acidity of the stomach breaks down the absorption of itraconazole. Patients taking antacids (eg, aluminum hydroxide), it is recommended to use them no earlier than 2 hours after taking itraconazole. Patients with achlorhydria or applying H2-antihistamines or proton pump inhibitors, are advised to take itraconazole capsules with acidic beverages.

It is recommended to regularly monitor liver function in patients receiving treatment with itraconazole. Patients should be warned of the need to immediately contact a doctor in case of symptoms, suggesting the occurrence of hepatitis: anorexia, nausea, vomiting, weakness, abdominal pain, and dark urine. When these symptoms should immediately discontinue treatment and to conduct a study of liver function.

Patients with elevated liver enzymes or liver disease in the active phase, as well as in transferring toxic liver injury should not be used during treatment with itraconazole taking other drugs, except in cases where the expected benefit justifies the risk of liver damage. In these cases, during treatment is necessary to control the activity of liver enzymes.

If abnormal liver function Dose adjustment is possible if the duration of receiving more than 1 month is necessary to monitor liver function.

In the event of neuropathy, which may be associated with the reception of itraconazole, treatment should cease.

Itraconazole should be used with caution in patients with hypersensitivity to other azole antifungal agents.

Patients with impaired immunity (AIDS, conditions after organ transplantation, neutropenia) may need to increase the dose.