Kanditral - instructions for use, dose, side effects, contraindications

Excipients: hypromellose (hydroxypropylmethylcellulose E-5), methyl methacrylate, dimethylaminoethyl methacrylate and butyl methacrylate copolymer (eudragit E-100), sucrose.

Hard gelatin capsule No. 0: gelatin, purified water, methyl parahydroxybenzoate, propyl parahydroxybenzoate, sodium lauryl sulfate, dyes:

cap capsule - titanium dioxide, iron dye oxide black (for the application of the company logo "G");

capsule body - Crimson dye (Ponce 4R), dye azorubin (carmozine), titanium dioxide (for the inscription "canditral").

Description:

Hard gelatin capsules No. 0 with a red body and a white lid with a black company logo on the lid and the inscription "canditral"white on the body.The contents of the capsules are spherical microgranules from white to white with a beige shade of color.

Pharmacotherapeutic group:Antifungal agent

ATX: & nbsp

J.02.A.C.02 Itraconazole

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.

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, as well as 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 the maximum concentration in the blood plasma is 3-4 hours.

Distribution

The equilibrium concentration of itraconazole in plasma 3-4 hours after taking the drug is 0.4 μg / ml (with 100 mg once daily), 1.1 μg / ml (with 200 mg once daily) and 2, 0 μg / ml (with taking 200 mg twice a day). 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 determined in the secretion of the sebaceous and sweat glands.

Metabolism

Metabolized by the liver with the formation of active metabolites, one of which - hydroxyitraconazole - has an antifungal action comparable to itraconazole in vitro.

Excretion

Excretion from the plasma is biphasic with a finite half-life of 24-36 hours. 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 mycoses:

systemic aspergillosis and candidiasis;
cryptococcosis, including cryptococcal meningitis (patients with immunodeficiency and patients with cryptococcosis of the central nervous system Kanditral® should be appointed only if the first-line drugs are not applicable or ineffective in this case);
histoplasmosis;
sporotrichosis;
paracoccidioidomycosis;
blastomycosis;
other systemic or tropical mycoses;

- Candidomycosis with skin and mucous membranes, including vulvovaginal candidiasis;

- deep visceral candidiasis;

- pityriasis lichen.

Contraindications:

- Individual hypersensitivity to the drug or its components;

- simultaneous with the drug Kanditral® reception of the following medicines:

preparations metabolized by the enzyme CYP3A4, which can increase the QT interval (terfenadine, astemizole, misolastine, cisapride, dofetilide, quinidine, pimozide, levomethadone, sertindole);
inhibitors of reductase HMG-CoA, cleaved by the enzyme CYP3A4 (simvastatin, lovastatin);
midazolam and triazolam (for oral administration);
preparations of ergot alkaloids (dihydroergotamine, ergometrine, ergotamine and methylergomethrin);

- Children's age up to 3 years.

Carefully:

Childhood age, severe heart failure, liver disease (including those accompanied by liver failure), chronic renal failure.

Pregnancy and lactation:

Pregnant women should be prescribed Candidral® only in life-threatening situations if the expected benefit for a woman exceeds the potential risk to the fetus.

When appointing during lactation it is necessary to stop breastfeeding.

Dosing and Administration:

Inside, after eating.

Indication	Dose	Duration
Vulvovaginal candidiasis	200 mg twice daily	1 day
	or	or
	200 mg once a day	3 days
Peregrine lichen	200 mg once a day	7 days
Dermatomycosis of smooth skin	200 mg once a day	7 days
	or	or
	100 mg 1 syrup	15 days
Defeats high-keratinized areas of the skin, such as hands and feet	200 mg twice daily	7 days
	or	or
	100 mg once a day	30 days
Oral candidiasis	100 mg once a day	15 days
Fungal keratitis	200 mg once a day	21 day It is possible to correct 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. For treatment fungal lesion of nail plates of brushes two courses are recommended. For treatment 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 onychomycosis	1st week	2nd ned.	3rd ned.		4th week	5th week	6th ned.	7th ned.	8th week	9th week
Lesions of the nail plates of the feet with or without defeat of the nail plates of the brushes	1st course	Weeks free from taking Canditral ®				2 nd course	Weeks free from taking Canditral ®			3rd course
Lesion of the nail plates of brushes	1st course	Weeks free from taking Canditral ®				2 nd course
Continuous treatment				Doses			Duration treatment
Lesions 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 once a day	2-5 months	In the case of an invasive or disseminated disease, the dose should be increased to 200 mg twice a day
Candidiasis	100-200 mg once a day	from 3 weeks to 7 months	In the case of an invasive or disseminated disease, the dose should be increased to 200 mg twice a day
Cryptococcosis (except meningitis)	200 mg once a day	from 2 months to 1 year
Cryptococcal meningitis	200 mg twice daily	from 2 months to 1 year	Supportive therapy - seesection "Special instructions"
Histoplasmosis	from 200 mg once a day to 200 mg twice a day	8 months
Blastomycosis	from 100 m g once a day to 200 mg twice a day	6 months
Sporotrichosis	100 mg once a day	3 months
Paracoccidioidomycosis	100 mg once a day	6 months
Chromomycosis	100-200 mg once a day	6 months

Pediatric Use

Candidral® should not be given to children unless the expected benefit exceeds the potential risk.

Side effects:

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

From the hepatobiliary system: a 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, skin itching, 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 the dark Colour.

Overdose:

No data available. In case of an accidental overdose, a gastric lavage should be performed within the first hour, Activated carbon. Hemodialysis is ineffective. There is no specific antidote.

Interaction:

Medicines that affect the absorption of itraconazole

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

Medicines affecting the metabolism of itraconazole

Itraconazole is mainly digested with an enzyme CYP3A4. When used simultaneously with rifampicin, rifabutin, phenytoin, carbamazepine, isoniazid, which are potent inducers of the enzyme CYP3A4, bioavailability of itraconazole and hydroxyitraconazole 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 liver enzymes, is not recommended.

Powerful enzyme inhibitors CYP3A4, such as ritonavir, indinavir, clarithromycin and erythromycin, can increase the bioavailability of itraconazole.

Effect of itraconazole on the metabolism of other drugs

Itraconazole can inhibit the metabolism of enzyme-cleavable drugs CYP3A4. The result of this may be an increase or prolongation of their action, including side effects. After the termination of treatment with the drug Kanditral®, the concentration of itraconazole in the plasma decreases gradually depending on the dose and duration of treatment (see the 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 simultaneously with the drug Kanditral® 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 may 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 anticancer drugs (vinca alkaloids pink, busulfan, docetaxel, trimetrexate);
enzyme-cleavable CYP3A4 calcium channel blockers (verapamil and dihydropyridine derivatives);
some immunosuppressive agents (ciclosporin, tacrolimus, sirolimus (also known as rapamycin);
some enzyme-cleavable CYP3A4 inhibitors of reductase HMG-CoA (atorvastatin);
some glucocorticosteroids (budesonide, dexamethasone and methylprednisolone);
other drugs: digoxin, carbamazepine, buspirone, alfentanil, alprazolam, brotisolam, midazolam for intravenous administration, rifabutin, ebastine, 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.

Research in vitro demonstrated the lack of interaction between itraconazole and such drugs as imipramine, propranolol, diazepam, cimetidine, indomethacin, tolbutamide and sulfamethasine when bound to plasma proteins.

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 completion.

- When studying 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.

- It was found that itraconazole has a negative inotropic effect. There have been reports of cases of heart failure associated with the use of 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-gistamine blockers or proton pump inhibitors, it is recommended to take Canditral ® capsules with acidic beverages.

- 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 capsitals of Canditral ®.

- There is no evidence of cross-sensitivity to itraconazole and other azole antifungal agents. Canditral® in capsules should be administered with caution to patients with hypersensitivity to other azoles.

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

Effect on the ability to drive transp. cf. and fur:

Not observed.

Form release / dosage:

Capsules, 100 mg.

Packaging:

For 4, 6 or 7 capsules in a contour cell package.

1 contour pack of 4, 6, 7 capsules or 2 contour packs of 7 capsules together with instructions for use are placed in a cardboard box.

Storage conditions:

In dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years and 6 months.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-000125/09

Date of registration:14.01.2009

Expiration Date:Unlimited

The owner of the registration certificate:Glenmark Pharmaceuticals Co., Ltd.Glenmark Pharmaceuticals Co., Ltd. India

Manufacturer: & nbsp

GLENMARK PHARMACEUTICALS, Ltd. India

Representation: & nbspGLENMARK PHARMACEUTICALS LTD. GLENMARK PHARMACEUTICALS LTD. India

Information update date: & nbsp21.11.2017

Illustrated instructions

Instructions

Kanditral® (Canditral®)