Rumicose, capsules 100 mg 15 pcs

Rumicose is a broad-spectrum antifungal.

Pharmacodynamics

A broad-spectrum synthetic antifungal agent, a triazole derivative.

Inhibits the synthesis of ergosterol which is an important component of the cell membrane of fungi.

It is active against dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum), yeast-like fungi and yeasts (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 and other yeasts and molds.

Pharmacokinetics

Absorption

In oral administration maximum bioavailability of itraconazole is observed when taking capsules immediately after meals. Tmax in plasma is 3-4 hours after oral administration.

Distribution

The plasma Css of itraconazole is 0.4 µg/ml (when taking 100 mg once daily), 1.1 µg/ml (when taking 200 mg once daily) and 2 µg/ml (when taking 200 mg twice daily). With prolonged use Css is achieved within 1-2 weeks. Binding to plasma proteins is 99.8%.

Itraconazole penetrates and distributes well in tissues and organs. Concentration of the drug in lungs, kidneys, liver, spleen, bones, stomach, skeletal muscles is 2-3 times higher than the corresponding concentration in plasma. Accumulation of the drug in keratinous tissues, especially in skin, is about 4 times higher than in plasma, and the excretion rate depends on the rate of epidermal regeneration. Unlike plasma concentration, which is undetectable as early as 7 days after discontinuation of therapy, therapeutic concentration in skin is maintained for 2-4 weeks after discontinuation of 4-week treatment course; in vaginal mucosa – for 2 days after 3-day treatment course in a dose of 200 mg once a day and for 3 days after 1-day treatment course in a dose of 200 mg twice a day. Therapeutic concentration of the drug in nail keratin is determined 1 week after the start of treatment and maintained for 6 months after the completion of 3-month course of therapy. Itraconazole is also determined in the secretion of sebaceous and sweat glands.

Metabolism

Metabolized in the liver with the formation of active metabolites, one of which – hydroxyitraconazole – has comparable with itraconazole antifungal effect in vitro.

Elimation

Elimation from plasma is biphasic with a final T1/2 of 24-36 hours.

Elevation in the feces is 3 to 18% of the dose, by the kidneys less than 0.03% of the dose; approximately 35% of the dose is excreted as metabolites in the urine within 1 week.

Pharmacokinetics in special clinical cases

In patients with renal insufficiency, as well as in some patients with impaired immunity (e.g., AIDS, after organ transplantation, neutropenia) the bioavailability of itraconazole may decrease. In patients with liver cirrhosis the bioavailability of itraconazole is decreased, T1/2 is increased.

Indications

ringworm;
fungal keratitis;
onychomycosis caused by dermatophytes and/or yeasts and molds;
systemic mycoses:
systemic aspergillosis and candidiasis;
cryptococcosis, including cryptococcal meningitis (patients with immunodeficiency and patients with cryptococcosis of the central nervous system should be prescribed Rumikoz® only in cases where first-line treatment drugs are not applicable in this case or are not effective);
histoplasmosis;
sporotrizosis;
paracoccidioidomycosis;
blastomycosis;
other systemic or tropical mycoses;
candidomycosis with damage to the skin and mucous membranes, including vulvovaginal candidiasis;
deep visceral candidiasis;
pityriasis versicolor.

Pharmacological effect

Rumicosis is a broad-spectrum antifungal.

Pharmacodynamics

A synthetic broad-spectrum antifungal agent, a triazole derivative.

Inhibits the synthesis of ergosterol, which is an important component of the cell membrane of fungi.

Active against dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum), yeast-like fungi and yeasts (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 yeasts and molds.

Pharmacokinetics

Suction

When administered orally, maximum bioavailability of itraconazole is observed when capsules are taken immediately after meals. Tmax in plasma is 3–4 hours after oral administration.

Distribution

Css of itraconazole in plasma 3-4 hours after taking the drug is 0.4 μg/ml (when taking 100 mg 1 time per day), 1.1 μg/ml (when taking 200 mg 1 time per day) and 2 μg/ml (when taking 200 mg 2 times a day). With long-term use, Css is achieved within 1–2 weeks. Plasma protein binding – 99.8%.

Itraconazole penetrates well and is distributed in tissues and organs. The concentration of the drug in the lungs, kidneys, liver, spleen, bones, stomach, and skeletal muscles is 2–3 times higher than the corresponding concentration in plasma. The accumulation of the drug in keratin tissues, especially in the skin, is approximately 4 times higher than the accumulation in plasma, and the rate of elimination depends on the rate of regeneration of the epidermis. In contrast to plasma concentrations, which are undetectable 7 days after cessation of therapy, therapeutic skin concentrations persist for 2–4 weeks after cessation of a 4-week course of treatment; in the vaginal mucosa – within 2 days after the end of a 3-day course of treatment at a dose of 200 mg 1 time per day and within 3 days after the end of a 1-day course of treatment at a dose of 200 mg 2 times a day. The therapeutic concentration of the drug in nail keratin is determined 1 week after the start of treatment and remains for 6 months after completion of the 3-month course of therapy. Itraconazole is also detected in the secretions of the sebaceous and sweat glands.

Metabolism

Metabolized in the liver to form active metabolites, one of which, hydroxyitraconazole, has an antifungal effect comparable to itraconazole in vitro.

Removal

Elimination from plasma is biphasic with a final T1/2 of 24–36 hours.

Excretion with feces ranges from 3 to 18% of the dose, by the kidneys – less than 0.03% of the dose; approximately 35% of the dose is excreted as metabolites in the urine within 1 week.

Pharmacokinetics in special clinical situations

In patients with renal failure, as well as some patients with compromised immunity (for example, AIDS, after organ transplantation, neutropenia), the bioavailability of itraconazole may be reduced. In patients with liver cirrhosis, the bioavailability of itraconazole is reduced, T1/2 is increased.

Special instructions

Women of childbearing age taking Rumikoz® must use adequate contraception throughout the course of treatment until the first menstrual period after its completion.

When studying the IV dosage form of itraconazole, a transient asymptomatic decrease in left ventricular ejection fraction was noted, which normalized until the next infusion of the drug.

Itraconazole has been found to have a negative inotropic effect. Cases of heart failure associated with taking Rumikoz® have been reported. Rumikoz® should not be taken by patients with chronic heart failure or a history of this disease, unless the possible benefit significantly outweighs the potential risk.

CCBs may have a negative inotropic effect, which may enhance this effect of itraconazole; itraconazole may reduce the metabolism of CCBs. Caution should be exercised when taking itraconazole and CCBs concomitantly.

In patients with renal impairment, the bioavailability of itraconazole may be reduced, which may require dose adjustment.

With reduced gastric acidity, the absorption of itraconazole is impaired. For patients taking antacid medications (for example, aluminum hydroxide), it is recommended to use them no earlier than 2 hours after taking Rumikoz®. Patients with achlorhydria or using H2-blockers of histamine receptors or proton pump inhibitors are recommended to take Rumikoz® capsules with acidic drinks.

In very rare cases, when using the drug Rumikoz®, severe toxic liver damage developed, incl. cases of acute liver failure with fatal outcome. This occurred in patients who already had liver disease, as well as in patients receiving other drugs that have hepatotoxic effects. Several such cases occurred in the 1st month of therapy, and some in the 1st week of treatment. In this regard, it is recommended to regularly monitor liver function in patients receiving itraconazole therapy.

Treatment should be discontinued if neuropathy occurs, which may be associated with taking Rumikoz® capsules.

There is no evidence of cross-hypersensitivity to itraconazole and other azole antifungals. Rumikoz® capsules should be administered with caution to patients with hypersensitivity to other azoles.

In patients with compromised immunity (AIDS, after organ transplantation, neutropenia), an increase in the dose of Rumikoz® may be required.

Impact on the ability to drive vehicles and operate machinery. Not observed.

Active ingredient

Itraconazole

Composition

One capsule contains:

Active ingredient:

itraconazole pellets – 464.00 mg,

itraconazole – 100.00 mg,

sugar pellets (sucrose – 80.0-91.5%, corn starch – 8.5-20.0%, water – maximum 1.5%) – 207.44 mg,

Poloxamer 188 (Lutrol) – 25.94 mg,

Poloxamer 188 (Lutrol) micronized – 0.51 mg,

hypromellose – 130.11 mg.

Composition of the capsule shell:

body: titanium dioxide E 171, gelatin;

cap: titanium dioxide E 171, azorubine dye E 122, sunset yellow dye E 110, quinoline yellow dye E 104, iron oxide red dye E 172, iron oxide black dye E 172, gelatin.

Pregnancy

Pregnant women should be prescribed Rumikoz® only in life-threatening cases if the expected benefit to the woman outweighs the potential risk to the fetus.

When prescribed during lactation, breastfeeding must be stopped.

Contraindications

individual hypersensitivity to the drug or its components;
simultaneous use of the following drugs with the drug Rumikoz®:
drugs metabolized by the CYP3A4 enzyme that can increase the QT interval (terfenadine, astemizole, mizolastine, cisapride, dofetilide, quinidine, pimozide, levomethadone, sertindole);
HMG-CoA reductase inhibitors cleaved by the CYP3A4 enzyme (simvastatin, lovastatin);
midazolam and triazolam (for oral administration);
ergot alkaloid preparations (dihydroergotamine, ergometrine, ergotamine and methylergometrine).

With caution: children’s age; severe heart failure; liver diseases (including those accompanied by liver failure); chronic renal failure.

Side Effects

From the gastrointestinal tract: dyspepsia, nausea, vomiting, loss of appetite, abdominal pain, diarrhea, constipation.

From the hepato-biliary system: reversible increase in the activity of “liver” transaminases, hepatitis; very rarely – severe toxic liver damage, including acute liver failure with a fatal outcome.

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

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

Skin disorders: alopecia, photosensitivity.

Other: menstrual irregularities, hypokalemia, edema syndrome, congestive heart failure and pulmonary edema, hypercreatinemia, dark urine color.

Interaction

Drugs that affect the absorption of itraconazole

Drugs that reduce gastric acidity reduce the absorption of itraconazole.

Drugs that affect the metabolism of itraconazole

Itraconazole is primarily broken down by the enzyme CYP3A4. With the simultaneous use of itraconazole with rifampicin, rifabutin, phenytoin, carbamazepine, isoniazid, which are powerful inducers of CYP3A4, the bioavailability of itraconazole and hydroxyitraconazole is significantly reduced, which leads to a significant decrease in the effectiveness of the drug. The simultaneous use of Rumikoz® with these drugs, which are potential inducers of liver enzymes, is not recommended.

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

The effect of itraconazole on the metabolism of other drugs

Itraconazole may inhibit the metabolism of drugs metabolized by the CYP3A4 enzyme. The result of this may be an intensification or prolongation of their action, incl. and side effects.

After discontinuation of treatment with Rumikoz®, the plasma concentration of itraconazole decreases gradually, depending on the dose and duration of treatment (see “Pharmacokinetics”). This must be taken into account when discussing the inhibitory effect of itraconazole on concomitant drugs.

Medicines that are not recommended to be prescribed simultaneously with Rumikoz®

BKK. In addition to a possible pharmacokinetic interaction associated with a common metabolic pathway involving the CYP3A4 enzyme, CCBs may have a negative inotropic effect, which is enhanced when taken concomitantly with Rumikoz®.

Drugs, when administered concomitantly, it is recommended to monitor their plasma concentrations, effects, and side effects. If necessary, the dose of these drugs should be reduced:

oral anticoagulants;
HIV protease inhibitors (ritonavir, indinavir, saquinavir);
some antitumor drugs (vinca rosea alkaloids, busulfan, docetaxel, trimetrexate);
CCBs cleaved by the CYP3A4 enzyme (verapamil and dihydropyridine derivatives);
some immunosuppressive drugs (cyclosporine, tacrolimus, sirolimus (also known as rapamycin);
some HMG-CoA reductase inhibitors cleaved by the CYP3A4 enzyme (atorvastatin);
some corticosteroids (budesonide, dexamethasone and methylprednisolone);
other drugs: digoxin, carbamazepine, buspirone, alfentanil, alprazolam, brotizolam, midazolam for intravenous administration, rifabutin, ebastine, reboxetine, cilostazol, disopyramide, eletriptan, halofantrine, repaglinide.

No interaction was found between itraconazole, zidovudine and fluvastatin.

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

In vitro studies have demonstrated the absence of interaction between itraconazole and drugs such as imipramine, propranolol, diazepam, cimetidine, indomethacin, tolbutamide and sulfamerazine when bound to plasma proteins.

Overdose

No data available.

Treatment: in case of accidental overdose, gastric lavage should be performed within the first hour, and, if necessary, activated charcoal should be prescribed.

Itraconazole is not eliminated by hemodialysis.

There is no specific antidote for the drug.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf life

3 years. Do not use after expiration date.

Manufacturer

Valenta Pharm JSC, Russia