Itrazole capsules 100mg №42

Tradename:

Itrazole

International non-proprietary name:

itraconazole

Dosage Form:

capsules

Composition

One capsule contains 100 mg of itraconazole in microgranules (pellets) containing the active substance Itraconazole 100 mg and excipients: sucrose, starch, hydroxypropylmethylcellulose, poloxamer.

Description:

White capsules. Capsule contents: spherical microgranules from light yellow to yellowish-beige.

Pharmacotherapeutic group

Antifungal agent

Pharmacological properties

Pharmacodynamics
Itraconazole is a broad-spectrum synthetic antifungal agent derived from triazole. Inhibits the synthesis of ergosterol of the cell membrane of fungi, which causes the antifungal effect of the drug. Itraconazole is active against infections caused by dermatophytes (Trichophyton spp., Microsporum s.p., Epydermophyton floccosum), yeast-like fungi and yeast (Cryptococcus neoformans, Pityrosporum spp., Candida spp., Including C.albicans, C., C., C. albicans, C., C., C., C., etc., C. Aspergillus spp., Histoplasma spp., Histoplasma spp., Paracoccidioides brasiliensis, Sporthrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatitidis, as well as other yeast and mold fungi.
Pharmacokinetics

Absorbed from the digestive tract quite fully. Taking itraconazole in capsules immediately after a meal increases bioavailability. C_max in plasma is reached within 3-4 hours after ingestion. C_ss when taking 100 mg of the drug 1 time per day - 0.4 mcg / ml; when taking 200 mg 1 time per day - 1.1 mcg / ml, 200 mg 2 times per day - 2 mcg / ml.

C time_ss in plasma with prolonged use - 1-2 weeks. Communication with plasma proteins - 99.8%.

It penetrates well into tissues and organs (including the mucous membrane of the vagina) and is contained in the secretions of the sebaceous and sweat glands. The concentration of itraconazole in the lungs, kidneys, liver, bones, stomach, spleen, skeletal muscle is 2-3 times its concentration in plasma; in the tissues containing keratin - 4 times.

The therapeutic concentration of itraconazole in the skin persists for 2-4 weeks after stopping the 4-week course of treatment. The therapeutic concentration in the keratin of the nails is reached 1 week after the start of treatment and lasts for 6 months after the completion of the 3-month course of treatment. Low concentrations are found in the sebaceous and sweat glands of the skin.

Metabolized in the liver to form active metabolites, incl. hydroxyitraconazole. It is an inhibitor of isoenzymes CYP3A4, CYP3A5 and CYP3A7.

Removal from plasma is two-phase: by the kidneys for 1 week (35% in the form of metabolites, 0.03% in the unchanged form) and through the intestine (3-18% in the unchanged form). T_1/2 - 1-1.5 days. Not removed during dialysis.

Indications for use 

• 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 or tropical mycoses.
• Candidomycosis with damage to the skin or mucous membranes, including vulvovaginal candidiasis;
• deep visceral candidiasis;
• pityriasis versicolor.

Contraindications

• individual hypersensitivity to the drug or its constituent parts;
• simultaneous administration of drugs metabolized by the CYP3A4 enzyme: terfenadine, astemizole, mizolastin, cisapride, dofetilide, quinidine, pimozide, HMG-CoA reductase inhibitors, such as Simvastatin and lovastatin, triazolam and midazolam (see symvastatin and lovastatin, triazolam and midazolam)
• pregnancy;
• lactation period;
• children's age (up to 3 years)

Carefully

Severe heart failure, liver diseases (including those accompanied by liver failure). It is recommended to use Itrazole^® in children over 3 years of age only if the potential benefit outweighs the potential risk.

Dosage and administration

Inside, after eating.

The oral bioavailability of itraconazole can be reduced in some immunocompromised patients, for example, in patients with neutropenia,AIDS patients or with transplanted organs. Therefore, it may be necessary to double the dose.

Onychomycosis
Pulse therapy (see table)
One course of pulse therapy consists in daily intake of 2 capsules Itrazole^® twice a day (200 mg twice a day) for one week. For the treatment of fungal infections of the nail plate brushes two courses are recommended. For the treatment of fungal infections of the nail plate foot, three courses are recommended (see table). The interval between courses, during which you do not need to take the drug, is 3 weeks.
Clinical results will become apparent after the end of treatment, as nails grow back.

OR
Continuous treatment:
Two capsules per day (200 mg once a day) for 3 months.

Withdrawal Itrazole^® from the skin and nail tissue is slower than from 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 the treatment of nail infections.

Systemic mycoses (recommended dosages vary depending on the type of infection)

Application in pediatrics. It is recommended to use Itrazole^® in children over 3 years of age only if the potential benefit outweighs the potential risk.

Side effects

From the digestive tract: dyspepsia, nausea, abdominal pain and constipation, reversible increase in liver enzymes, cholestatic jaundice, hepatitis, anorexia. In very rare cases when using Itrazole^® developed severe toxic liver damage, including case of acute liver failure with a fatal outcome

From the side of the central nervous system: headache, fatigue, dizziness, peripheral neuropathy.

From the CCC: congestive heart failure and pulmonary edema.

From other organs and systems: menstrual irregularities, allergic reactions (such as itching, rash, urticaria and angioedema), Stevens-Johnson syndrome, alopecia, hypokalemia, edema, dark urine staining, hypercreatininemia.

Overdraft

No data available. During the first hour, carry out gastric lavage and, if necessary, prescribe Activated carbon, symptomatic treatment. Itraconazole is not excreted by hemodialysis. There is no specific antidote.

Interaction with other drugs
Drugs that affect the metabolism of itraconazole.
The interaction of itraconazole with rifampicin, rifabutin and phenytoin was studied. The simultaneous use of itraconazole with these drugs, which are potential inducers of hepatic enzymes, is not recommended. Studies of the interaction with other hepatic enzyme inducers, such as Carbamazepine, phenobarbital and isoniazid, have not been conducted, however, similar results can be suggested.
Since itraconazole is mainly metabolized by the CYP 3A4 enzyme, potential inhibitors of this enzyme can increase the bioavailability of itraconazole. Examples include ritonavir, indinavir, Clarithromycin and Erythromycin .

The effect of itraconazole on the metabolism of other drugs.
Itraconazole can inhibit the metabolism of drugs cleaved by CYP3A4 enzyme.The result of this may be an increase or prolongation of their actions, including side effects.

Drugs that can not be prescribed simultaneously with itraconazole:

• Terfenadine, astemizol, mizolastine, cisapride, triazolam and midazolam, dofetilide, quinidine, pimozide, HMG-CoA reductase inhibitors such as simvastatin and lovastatin.
• Calcium channel blockers may have a negative inotropic effect, which may enhance the same effect exerted by itraconazole. At the same time taking itraconazole and Calcium channel blockers, care must be taken, since the metabolism of calcium channel blockers can be reduced.

Drugs, the appointment of which is necessary to monitor their concentration in plasma, action, side effects.
In the case of simultaneous administration with itraconazole, the dose of these drugs, if necessary, should be reduced.

• Oral anticoagulants;
• HIV protease inhibitors such as ritonavir, indinavir, saquinavir;
• Some