Composition, form of production and packaging
Hard gelatin capsules, size No. 0, with a red body and a white lid, with a black company logo on the lid and an inscription "canditral" white on the body; the contents of the capsules are spherical microgranules from white to white with a beige shade of color.
1 caps.
itraconazole in the form of pellets 470 mg,
which corresponds to the content of itraconazole 100 mg
Excipients: hypromellose (hydroxypropylmethylcellulose E5), eudragit E-100 (copolymer of methyl methacrylate, dimethylaminoethyl methacrylate and butyl methacrylate), sucrose.
Capsule composition: gelatin, purified water, methyl parahydroxybenzoate, propyl parahydroxybenzoate, sodium lauryl sulfate.
Dyestuff caps capsules: titanium dioxide, iron oxide black (for applying the logo of the firm "G").
Dyes of capsule body: dye crimson (Ponso 4R), azorubin (carmosein), titanium dioxide (for the inscription "canditral").
4 things. - packings of cellular contour (1) - packs cardboard.
6 pcs. - packings of cellular contour (1) - packs cardboard.
7 pcs. - packings of cellular contour (1) - packs cardboard.
7 pcs. - packings cellular planimetric (2) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2010.
PHARMACHOLOGIC EFFECT
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.Itraconazole is active against dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum); yeast-like fungi and yeast (Cryptococcus neoformans, Pityrosporum spp., Trichosporon spp., Geotrichum spp., Candida spp., including Candida albicans, Candida glabrata and Candida krusei); Aspergillus spp., Histoplasma spp., Paracoccidioides brasiliensis, Sporothrix schenckii, Fonsecaea spp., Cladosporium spp., Blastomyces dermatitidis, Pseudallescheria boydii, Penicillium marneffei , and other yeast and mold fungi.
PHARMACOKINETICS
Suction
When administered orally, the maximum bioavailability of itraconazole is noted when taking capsules immediately after meals. The time to reach C max is 3-4 h.
Distribution
The equilibrium concentration of itraconazole in the plasma 3-4 hours after taking the drug is 0.4 Ојg / ml (with 100 mg once a day), 1.1 Ојg / ml (with 200 mg once daily) and 2.0 Ојg / ml (with taking 200 mg twice daily). At long reception the equilibrium concentration is reached within 1-2 weeks. The connection with plasma proteins is 99.8%.
Itraconazole penetrates well and is distributed in tissues and organs. The concentration of the drug in the lungs, kidneys, liver, spleen, stomach, bones, skeletal muscles is 2-3 times higher than its concentration in the plasma. Accumulation of itraconazole in keratin tissues, especially in the skin, is 4 times higher than in plasma, and the rate of excretion depends on the regeneration of the epidermis. In contrast to plasma concentrations that are not detectable within 7 days after cessation of treatment, the therapeutic concentration of itraconazole in the skin persists for 2-4 weeks after the cessation of the 4-week course of treatment; in the mucous membrane of the vagina - within 2 days after the end of the 3-day course of treatment at a dose of 200 mg per day and 3 days after the end of a one-day course of treatment at a dose of 200 mg twice a day. The therapeutic concentration of the drug in the nail keratin is determined 1 week after the start of treatment and is maintained for 6 months after the completion of the 3-month course of therapy. Itraconazole is also defined in the secretion of the sebaceous and sweat glands.
Metabolism
Metabolized by the liver with the formation of active metabolites, one of which - hydroxy-itraconazole - has an antifungal action comparable to itraconazole - in vitro.
Excretion
Excretion from the plasma is biphasic with a finite half-life from 24 to 36 h.
Excretion with feces is from 3 to 18% of the dose. Kidney excretion - less than 0.03% of the dose. Approximately 35% of the dose is excreted as metabolites in urine for 1 week.
Pharmacokinetics in special clinical cases
In patients with renal insufficiency, as well as in some patients with impaired immunity (eg, in AIDS, after organ transplantation or in case of neutropenia), the bioavailability of itraconazole may decrease. In patients with cirrhosis of the liver, the bioavailability of itraconazole is reduced, the half-life is increased.
INDICATIONS
- dermatomycosis;
- fungal keratitis;
- onychomycosis caused by dermatophytes and / or yeast and mold fungi;
- Systemic fungal infections:
- systemic aspergillosis and candidiasis;
- cryptococcosis, including cryptococcal meningitis (for patients with immunodeficiency and for patients with cryptococcosis of the central nervous system, Kanditral should be prescribed only if the first-line drugs are not applicable or effective in this case);
- Histoplasmosis;
- sporotriosis;
- Paracoccidioidomycosis;
- blastomycosis;
- other systemic or tropical mycoses;
- Candidomycosis with skin and mucous membranes, including vulvovaginal candidiasis;
- deep visceral candidiasis;
- Peregrine lichen.
DOSING MODE
Inside, after eating.
Indication Dose Duration
Vulvovaginal candidiasis 200 mg 2 times a day or 200 mg 1 time per day 1 day or 3 days
Pityriasis lichen 200 mg 1 time per day 7 days
Dermatomycosis smooth skin 200 mg 1 time per day or 100 mg 1 time per day 7 days or 15 days
Lesions of highly keratinized areas of the skin such as hands and feet 200 mg 2 times per day or 100 mg 1 time per day 7 days or 30 days
Oral candidiasis 100 mg 1 time per day 15 days
Fungal keratitis 200 mg 1 time per day 21 days Possible correction of the duration of treatment, taking into account the positive dynamics of the clinical picture
Bioavailability of the drug for oral administration can be reduced in some patients with impaired immunity, for example, in patients with neutropenia, AIDS patients or patients with transplanted organs. In these cases, a double dose increase may be required.
Onychomycosis caused by dermatophytes and / or yeast, mold fungi
Doses and duration of treatment
Pulse therapy One course: daily intake of 200 mg 2 times (2 capsules 2 times a day) for one week. Two courses are recommended for the treatment of fungal involvement of the nail plates of the brushes . For the treatment of fungal lesions of the nail plates of the feet , three courses are recommended. The interval between the courses, during which you do not need to take the drug, is 3 weeks. Clinical results will become evident after the end of treatment, as the nails grow.
Localization of onychomycosis 1st week. 2 nd week. 3rd week. 4 th week. 5 th week. 6 th week. The 7th week. 8th week. 9 th week.
The defeat of the nail plates of the feet with or without defeat of the nail plates of the 1st Week, free from the 2nd Week, the 3rd
course of admission Kanditral course free course
from admission
Canditral В®
Defeat of the 1st week, free from the 2nd
Nail course of admission Kanditral course
plates of brushes
Continuous treatment Doses Duration of treatment
Lesion of the nail plates of the feet with or without defeat of the nail plates of the brushes 200 mg per day 3 months
The removal of itraconazole from the skin and nail tissue is slower than from the plasma. Thus, the optimal clinical and mycological effect is achieved in 2-4 weeks after the end of treatment for skin diseases and 6-9 months after the end of treatment of nail diseases.
Systemic mycoses
Indication Dose Average duration Remarks
Aspergillosis 200 mg 1 time per day 2-5 months In the case of an invasive or disseminated disease dose is recommended to increase to 200 mg 2 times a day
Candidiasis 100-200 mg 1 time a day from 3 weeks to 7 months In the case of an invasive or disseminated disease dose is recommended to increase to 200 mg 2 times a day
Cryptococcosis (except for meningitis) 200 mg 1 time per day from 2 months to 1 year
Cryptococcal meningitis 200 mg twice daily for 2 months to 1 year Maintenance therapy - see section "Special instructions"
Histoplasmosis from 200 mg 1 time per day to 200 mg 2 times a day 8 months
Blastomycosis from 100 mg 1 time per day to 200 mg 2 times a day 6 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 a day 6 months
SIDE EFFECT
On the part of the gastrointestinal tract : dyspepsia, nausea, vomiting, decreased 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, itchy skin, hives, angioedema, rarely - multiforme exudative erythema (Stevens-Johnson syndrome).
From the skin: alopecia, photosensitivity
Other: disorders of the menstrual cycle, hypokalemia, edematous syndrome, congestive heart failure and pulmonary edema, hypercreatinemia, staining of urine in a dark color.
CONTRAINDICATIONS
- individual hypersensitivity to the drug or its components;
- simultaneous with the drug Kanditral reception of the following medicines:
- drugs metabolized by the enzyme CYP3A4, which can increase the QT interval (terfenadine, astemizole, misolastine, cisapride, dofetilide, quinidine, pimozide, levomethadone, sertindole);
- HMG-CoA reductase inhibitors, cleavable by the enzyme CYP3A4 (simvastatin, lovastatin);
- midazolam and triazolam (for oral administration);
- preparations of ergot alkaloids (dihydroergotamine, ergometrine, ergotamine and methylergometrine);
- Children's age up to 3 years.
With caution: children's age, severe heart failure, liver disease (including those accompanied by hepatic insufficiency), chronic renal failure.
PREGNANCY AND LACTATION
The use of the drug during pregnancy is possible only if the intended benefit for the mother exceeds the potential risk to the fetus.
If you need to use the drug during lactation, you should decide whether to stop breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution take the drug for chronic kidney failure.
In patients with renal insufficiency, the bioavailability of itraconazole can be reduced, which may require dose adjustment.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution take the drug for liver diseases (including those accompanied by liver failure).
In very rare cases, the use of Canditral developed severe toxic liver damage, including cases of acute hepatic insufficiency with a fatal outcome. This happened with patients who already had liver diseases, as well as patients who received other drugs that have a hepatotoxic effect. Several such cases occurred in the first month of therapy, and some in the first week of treatment. In this regard, it is recommended to regularly monitor liver function in patients receiving itraconazole therapy.
APPLICATION FOR CHILDREN
Contraindicated in children up to 3 years. With caution: children older than 3 years.
SPECIAL INSTRUCTIONS
Women of childbearing age who take Canditral should use adequate contraceptive measures throughout the course of treatment until the onset of the first menstrual period after it is completed.
When examining the intravenous drug form of the drug Itraconazole, there was a transient asymptomatic decrease in the left ventricular ejection fraction normalized until the next infusion of the drug.
Itraconazole has been found to have a negative inotropic effect. There have been reports of cases of heart failure associated with taking Canditral. Canditral should not be taken to patients with chronic heart failure or having a history of the disease, unless the potential benefit far exceeds the potential risk.
Calcium channel blockers can have a negative inotropic effect, which can enhance the similar effect of itraconazole; Itraconazole can reduce the metabolism of calcium channel blockers. Caution should be exercised when concomitantly taking itraconazole and calcium channel blockers.
In patients with renal insufficiency, the bioavailability of itraconazole can be reduced, which may require dose adjustment.
With a reduced acidity of the stomach, the absorption of itraconazole is disrupted. Patients taking antacid preparations (for example, aluminum hydroxide) are recommended to use them not earlier than 2 hours after taking Canditral. Patients with achlorhydria or using H2-histamine blockers or proton pump inhibitors are advised to take Canditral capsules with acidic drinks.
In very rare cases, the use of Canditral developed severe toxic liver damage, including cases of acute hepatic insufficiency with a fatal outcome. This happened with patients who already had liver diseases, as well as patients who received other drugs that have a hepatotoxic effect. Several such cases occurred in the first month of therapy, and some in the first week of treatment. In this regard, it is recommended to regularly monitor liver function in patients receiving itraconazole therapy.
Treatment should be discontinued when neuropathy occurs, which may be associated with the administration of Kanditral capsules.
There is no evidence of cross-sensitivity to itraconazole and other azole antifungal agents. Canditral capsules should be given with caution to patients with hypersensitivity to other azoles.
Patients with impaired immunity (AIDS, after organ transplantation, neutropenia) may need an increase in the dose of Canditral.
Pediatric Use
Kanditral should not be given to children, unless the expected benefit exceeds the possible risk.
Impact on the ability to drive a car and work with machinery
Not observed.
OVERDOSE
No data available.
In case of an accidental overdose, a gastric lavage should be performed within the first hour, and an activated charcoal should be prescribed. Hemodialysis is not effective. There is no specific antidote.
DRUG INTERACTION
Medicines that affect the absorption of itraconazole:
Drugs that reduce the acidity of gastric juice reduce the absorption of itraconazole.
Medicines that affect the metabolism of itraconazole:
Itraconazole is mainly cleaved by the enzyme CYP3A4. With simultaneous use with rifampicin, rifabutin, phenytoin, carbamazepine, isoniazid, which are powerful inducers of the enzyme CYP3A4, the bioavailability of itraconazole and hydroxy-itraconazole is significantly reduced, which leads to a significant decrease in the effectiveness of the drug. The simultaneous use of Canditral with these drugs, which are potential inducers of hepatic enzymes, is not recommended.
Powerful inhibitors of the enzyme CYP3A4, such as ritonavir, indinavir, clarithromycin and erythromycin, can increase the bioavailability of itraconazole.
The effect of itraconazole on the metabolism of other drugs:
Itraconazole can inhibit the metabolism of drugs cleavable by the enzyme CYP3A4. The result of this may be an increase or prolongation of their action, including side effects. After cessation of treatment with the drug Kanditral, the concentration of itraconazole in the plasma decreases gradually depending on the dose and duration of treatment (see section Pharmacokinetics). This need to be taken into account when discussing the inhibitory effect of itraconazole on concomitant medications.
Examples of such medicines are:
Medicines prescribed at the same time as Canditral are not recommended:
- calcium channel blockers - in addition to the possible pharmacokinetic interaction associated with a common metabolic pathway involving the enzyme CYP3A4, calcium channel blockers can have a negative inotropic effect, which is enhanced by simultaneous administration with the drug Kanditral.
Preparations, with the simultaneous appointment of which is recommended to monitor their concentration in the plasma, the effect, side effects. If necessary, the dose of these drugs should be reduced:
- oral anticoagulants;
- HIV protease inhibitors (ritonavir, indinavir, saquinavir);
- Some antitumor drugs (vinca alkaloids pink, busulfan, docetaxel, trimetrexate);
- cleavable by the enzyme CYP3A4 calcium channel blockers (verapamil and dihydropyridine derivatives);
- Some immunosuppressive agents (ciclosporin, tacrolimus, sirolimus (also known as rapamycin);
- Some CYP3A4 cleavage inhibitors of HMG-CoA reductase (atorvastatin);
- Some glucocorticosteroids (budesonide, dexamethasone and methylprednisolone);
- Other drugs: digoxin, carbamazepine, buspirone, alfentanil, alprazolam, brotisolam, midazolam for iv administration, rifabutin, ebastin, reboxetine, cilostazol, disopyramide, eletriptan, halofantrine, repaglinide.
Interactions between itraconazole zidovudine and fluvastatin were not found.
There was no effect of itraconazole on the metabolism of ethinylestradiol and norethisterone.
In vitro studies have demonstrated the lack of interaction between itraconazole and such drugs as imipramine, propranolol, diazepam, cimetidine, indomethacin, tolbutamide and sulfamerazine when bound to plasma proteins.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in a dry, protected from light at a temperature of no higher than 25 В° C. Keep out of the reach of children.
Shelf life 2 years 6 months. Do not use after expiry date.
