RUMIKOZ

Active material: Itraconazole
When ATH: J02AC02
CCF: Antifungal agent
ICD-10 codes (testimony): B35.0, B35.1, B35.2, B35.3, B35.4, B35.6, B36.0, B37.0, B37.1, B37.2, B37.3, B37.4, B37.6, B37.7, B37.8, B38, B39, B40, B41, B42, B44, B45, H19.2
When CSF: 08.01.01
Manufacturer: OAO Valenta PHARMACEUTICS (Russia)

Pharmaceutical form, composition and packaging

Capsules with a white body and pink cap brown, size №0; contents of capsules – spherical microgranules from light yellow to yellowish-beige.

Excipients: gipromelloza, poloxamer (lutrol), wheat starch, sucrose.

The composition of hard gelatin capsules: gelatin, Titanium dioxide, quinoline yellow, iron oxide red, iron oxide black, Yellow sunset, azoruʙin.

5 PC. – packings Valium planimetric (3) – packs cardboard.
6 PC. – packings Valium planimetric (1) – packs cardboard.

Pharmacological action

A synthetic antifungal drug broad spectrum, triazole derivative. It inhibits the synthesis of ergosterol cell membrane of fungi, which results in an antifungal effect of the drug.

Itraconazole active against dermatofitov (Trichophyton spp., Microsporum spp., Epidermophyton floccosum), yeasts and yeast (Cryptococcus neoformans, Pityrosporum spp., Trichosporon spp., Geotrichum spp., Candida spp., including Candida albicans, Candida glabrata, Candida krusei), Aspergillus spp., Histoplasma spp., P. brasiliensis, Sporothrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatidis, Pseudallescheria boydii, Penicillium marneffei, and also against yeasts and other fungi.

Pharmacokinetics

Absorption

When applying the maximum bioavailability of oral itraconazole observed when taking the capsules immediately after a meal. C_max plasma achieved for 3-4 hours after ingestion.

Distribution

Chronic administration of C_ss It reached within 1-2 weeks. C_ss Itraconazole plasma through 3-4 hours after administration of 0.4 ug / ml (100 upon receipt mg 1 time / day), 1.1 ug / ml (200 upon receipt mg 1 time / day) and 2 ug / ml (200 upon receipt mg 2 times / day).

Plasma protein binding is 99.8% Plasma protein.

Itraconazole is well into and distributed in the tissues and organs. The concentration of drug in the lung, kidney, liver, bones, stomach, spleen, in skeletal muscle 2-3 times greater than its concentration in plasma. The accumulation of itraconazole in keratinous tissues, especially in the skin, in 4 times its accumulation in plasma, and elimination rate is dependent on skin regeneration.

In contrast, the plasma concentrations of, which are not detectable within 7 days after stopping treatment, therapeutic concentrations persist in the skin for 2-4 weeks after stopping 4 weeks of treatment; in the vaginal mucosa – during 2 days after the 3-day course of treatment in a dose of 200 mg / day 3 days after the end of the 1-day course of treatment at a dose of 200 mg 2 times / day. Therapeutic concentrations in the nail keratin is determined by 1 week after initiation of treatment and stored for 6 months after 3 months of therapy. Itraconazole is also defined in the secretion of sebaceous and sweat glands.

Metabolism

It is metabolized in the liver with the formation of active metabolites, one of which – gidroksiitrakonazol is comparable to itraconazole in vitro antifungal activity.

Deduction

Withdrawal from the plasma is biphasic with a finite T_1/2 from 24-36 no.

Excretion in the feces is from 3% to 18% dose. Excretion in urine is less than 0.03%. About 35% the dose is excreted as metabolites in the urine within 1 of the week.

Pharmacokinetics in special clinical situations

In patients with renal insufficiency, and also in some patients with impaired immunity (eg, in AIDS, after organ transplantation or in case of neutropenia) may reduce the bioavailability of the drug.

In patients with cirrhosis the bioavailability of itraconazole reduced, T_1/2 itraconazole increased.

Testimony

- Ringworm;

- Fungal keratitis;

- Onychomycosis, caused by dermatophytes and / or yeasts and molds;

- Systemic mycosis: systemic aspergillosis and candidiasis; kryptokokkoz, including cryptococcal meningitis (immunocompromised patients and patients with CNS cryptococcosis Rumikoz^® should be used only in cases, if the first-line treatment is not applicable in this case, are not effective or); histoplasmosis; sporotrichosis; Paracoccidioidomycosis; blastomycosis; other systemic or tropical mycoses;

- Candidiasis with skin lesions or mucous (incl. vulvovaginal candidiasis);

- Deep visceral candidiasis;

- Chromophytosis.

Dosage regimen

The drug is administered orally after meal.

Table 1.

The bioavailability with oral itraconazole may be reduced in some patients with impaired immunity, eg, in patients with neutropenic, AIDS patients or organ transplant. In such cases it may require doubling dose.

Onychomycosis, caused by dermatophytes and / or yeast, fungi

Pulse therapy

One course of pulse therapy is taken daily Rumikoza^® by 200 mg 2 times / day (by 2 caps. 2 times / day) during 1 of the week (table 2).

For the treatment of fungal infections of the nail plate brushes recommended 2 exchange rate.

For the treatment of fungal infections of the nail plate stop recommended 3 exchange rate.

The interval between courses, during which do not need to take the drug, is 3 of the week. Clinical results become apparent after treatment, as regrowth of the nail.

Table 2.

Continuous therapy

At defeat nail plates stop with defeat or without defeat of the nail plate brushes dose of 200 mg / day, duration of treatment – 3 Months.

Withdrawal Rumikoza^® of skin and nail tissue is slower, than from plasma. Thus, Optimal clinical and mycological effects are achieved through 2-4 weeks after the end of treatment for skin lesions and after 6-9 months after the end of treatment of nail diseases.

Systemic fungal infections

Recommended doses vary depending on the type of infection.

Table 3.

Side effect

From the digestive system: dyspepsia, nausea, vomiting, decreased appetite, abdominal pain, diarrhea, constipation, reversible increases in liver enzymes, hepatitis; rarely – severe liver toxicity, incl. Cases of acute hepatic failure with a fatal outcome.

From the central and peripheral nervous system: headache, dizziness, perifericheskaya neuropathy.

Allergic reactions: skin rash, itching, hives, angioedema; rarely – erythema multiforme exudative (Stevens-Johnson syndrome).

Dermatological reactions: alopecia, photosensitivity.

Other: menstrual irregularities, kaliopenia, edematous syndrome, congestive heart failure and pulmonary edema, staining of urine a dark color, giperkreatininemiя.

Contraindications

- Simultaneous with Rumikozom^® use of drugs, metabolized by the CYP3A4 isoenzyme, are capable of increasing QT interval (terfenadine, astemizol, mizolastin, cisapride, dofetilid, quinidine, pimozid, levomethadone, sertindole); HMG-CoA reductase, metabolized by the CYP3A4 isoenzyme (simvastatin, lovastatin); midazolam and triazolam (orally); preparations of ergot alkaloids (digidroergotamin, ergometrine, ergotamine and metilergometrin);

- Hypersensitivity to the drug.

FROM caution should use the drug in children, in patients with severe heart failure, with liver disease (incl. accompanied by hepatic insufficiency), in chronic renal failure.

Pregnancy and lactation

During pregnancy, the drug should be prescribed only, the potential benefit of therapy for the mother outweighs the potential risk to the fetus.

If necessary, use during lactation should stop breastfeeding.

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

Cautions

In the study of / in the dosage form of itraconazole observed transient asymptomatic decrease in left ventricular ejection fraction, normalize until the next infusion.

Detected, itraconazole has a negative inotropic effect. Cases of heart failure, associated with taking Rumikoza^®. Therefore, the drug is not administered to patients with chronic heart failure or with the presence of this disease in history, except, when the expected benefits of therapy far exceeds the potential risk.

Calcium channel blockers can have negative inotropic effect, which may exacerbate this effect itraconazole; itraconazole can slow down the metabolism of calcium channel blockers. With simultaneous use of itraconazole and calcium channel blockers requires caution.

Patients with renal insufficiency may reduce the bioavailability of itraconazole, in such cases may require dose adjustment.

At low acidity of gastric absorption of itraconazole is broken. Patients, receiving antacids (eg, aluminum hydroxide), It recommended to take them no earlier than 2 h after administration Rumikoza^®. Patients with achlorhydria, as well as patients, receiving histamine H₂-receptors or proton pump inhibitors, It advised to take itraconazole with acid drink.

In very rare cases, the application Rumikoza^® developed severe liver toxicity, sometimes with acute liver failure and death. This has been observed in patients with pre-existing liver disease, and in patients, receiving other medications, possessing hepatotoxic. Several such cases have arisen in the first month of therapy, and some – in the first week of treatment. In this connection, it is recommended to regularly monitor liver function in patients, receiving Rumikoz^®.

Treatment should be discontinued in case of neuropathy, which may be associated with taking Rumikoza^®.

There is no evidence of cross-hypersensitivity to itraconazole and other azole antifungal drugs. Rumikoz^® should be used with caution in patients with hypersensitivity to other azole antifungal agents.

In patients with impaired immunity (AIDS, state after organ transplantation, neutropenia) You may need to increase the dose Rumikoza^®.

Use in Pediatrics

Rumikoz^® should not be given to children, except, when the expected benefits of therapy exceeds potential risk.

Effects on ability to drive vehicles and management mechanisms

Effects on ability to drive the car and work with the technique was not observed.

Overdose

Data on cases of drug overdose Rumikoz^® no.

Treatment: Accidental overdose supportive measures should be used. During the first hour to gastric lavage and, if necessary, assign activated carbon. Itraconazole is not removed from the body by hemodialysis. There is no specific antidote.

Drug Interactions

Drugs, affecting absorption of itraconazole

Preparations, reduce gastric acidity, reduce the absorption of itraconazole.

Drugs, affecting the metabolism of itraconazole

Itraconazole osnovnom metaboliziruetsya izofermentom CYP3A4. In an application with rifampicin, rifaʙutinom, phenytoin, karʙamazepinom, izoniazidom, It is a potent inducer of CYP3A4, bioavailability of itraconazole and hydroxy-itraconazole greatly reduced, which leads to a significant reduction in the effectiveness of the drug (simultaneous use Rumikoza^® with these drugs is not recommended).

Potent inhibitors of CYP3A4 enzyme, such as ritonavir, indinavir, clarithromycin and эritromitsin, may increase the bioavailability of itraconazole.

Effect of itraconazole on the metabolism of other drugs

Itraconazole is able to inhibit CYP3A4-mediated drug metabolism, which could lead to an increase or prolong their actions, incl. side effects. After stopping treatment with Rumikoz^® itraconazole concentration in plasma slowly decreases, depending on the dose and duration of treatment. This should be considered when necessary combination therapy.

Preparations, which can not be administered concurrently with itraconazole

Calcium channel blockers, in addition to possible pharmacokinetic interactions, associated with the general metabolism of CYP3A4-mediated, are able to exert a negative inotropic effect, which can amplify the same effect, shown by itraconazole.

Preparations, in which the assignment must monitor their concentrations in plasma, action, side effects

- Oral anticoagulants;

- HIV protease inhibitors (ritonavir, indinavir, saquinavir);

- Anticancer drugs (vinca alkaloids, busulfan, docetaxel, trimetrexate);

- Calcium channel blockers (digidropiridin, verapamil), metabolized by the CYP3A4 isoenzyme;

- Immunosuppressive agents (cyclosporine, tacrolimus, sirolimus);

- HMG-CoA reductase, metabolized by the CYP3A4 isoenzyme;

- Some GCS (ʙudezonid, dexamethasone and methylprednisolone);

- Other preparations: Digoxin, Carbamazepine, buspirone, alfentanil, alprazolam, ʙrotizolam, midazolam for the on / in the, rifabutin, eʙastin, reboxetine, cilostazol, disopyramide, Eletriptan, galofantrin, repaglinide.

If necessary, the simultaneous application of Rumikozom^® may require dose reduction of these drugs.

The interactions between itraconazole and zidovudine, fluvastatin is not detected.

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

Studies in vitro have shown no interaction between itraconazole and propranolol, imipramine, diazepamom, cimetidine, Indomethacin, tolʙutamidom, sulfamethazine upon binding to plasma proteins.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children, dry, dark place at a temperature no higher than 25 ° C. Shelf life – 2 year.