Itraconazole

When ATH:
J02AC02

Characteristic.

Antimycotic means of a group of triazole derivatives. White or slightly yellowish powder. Insoluble in water, very little is soluble in alcohols, easily soluble in dihlormetane. Lipophilic, distribution coefficient (octanol/water at pH 8,1) - 5,66. Molecular weight - 705,64.

Pharmacological action.
Broad spectrum antifungal.

Application.

Mycosis of the skin, mucous membrane of the mouth and eyes; onychomycosis, caused by dermatophytes, yeasts and molds; candidiasis with the defeat of the skin and mucous membranes, incl. vulvovaginal candidiasis; chromophytosis; systemic mycosis, incl. aspergillosis (resistance or poor tolerability amphotericin b), kryptokokkoz (incl. cryptococcal meningitis), histoplasmosis, sporotrichosis, Paracoccidioidomycosis, blastomycosis.

Contraindications.

Hypersensitivity.

Restrictions apply.

Congestive heart failure, incl. history (use only in cases, the expected benefit outweighs the potential risk), cirrhosis of the liver, renal failure, childhood (safety and effectiveness in children have not identified).

Pregnancy and breast-feeding.

Application of pregnancy is possible only in systemic mikozah in cases, When the expected effect outweighs the potential risk to the fetus.

Nursing mothers should abandon breastfeeding (itraconazole enters breast milk).

Side effects.

From the digestive tract: dyspepsia, nausea, abdominal pain, anorexia, vomiting, constipation, increased activity of liver transaminases, hepatitis, in very rare cases — heavy toxic liver damage, incl. a case of acute hepatic failure fatal.

From the nervous system and sensory organs: headache, dizziness, peripheral neuropathy, fatiguability, drowsiness.

Cardio-vascular system and blood (hematopoiesis, hemostasis): arterial hypertension. Reported cases of chronic heart failure, associated with the acquisition of itraconazole.

With the genitourinary system: dysmenorrhoea, edematous syndrome, albuminuria, staining of urine a dark color.

Allergic reactions: itching, rash, hives, angioedema, Syndrome Stevens - Johnson.

Other: alopecia, kaliopenia, pulmonary edema, decreased libido, impotence.

Cooperation.

Incompatible with terfenadine, astemizolom, cizapridom, lovastatin, oral forms midazolama and triazolama. Enhances and/or prolong the action of oral anticoagulants (incl. varfarina), cyclosporine, digoksina, methylprednisolone, vinchristina, calcium channel blockers. Rifampicin and phenytoin reduce bioavailability itrakonazola, inhibitors zitohroma CYP3A4 (ritonavir, indinavir, clarithromycin) increase its bioavailability. Antacids reduce absorption of itraconazole (interval, separating their admission, must be at least 2 no).

Overdose.

Treatment: gastric lavage, administration of activated charcoal, simptomaticheskaya therapy. Is not removed during dialysis. No specific antidote.

Dosing and Administration.

Inside, after meal (capsules), fasting (oral solution). Onychomycosis is 200 mg 1 once a day for 3 months or 200 mg 2 twice a day for 1 weeks, followed by a break 3 Sun; onihomicose 3 treatment, brushes- 2 exchange rate; vulvowaginalny candidiasis-on 200 mg 2 times during 1 day or 200 mg 1 once a day for 3 days; Tinea Versicolor- 200 mg 1 once a day for 7 days; dermatomikozy and candidiasis of the oral cavity is 100-200 mg 1 Once a day for 7-15 days (If necessary, repeat); gribkovi keratit- 200 mg 1 once a day for 21 day; mikozy system — for 100-200 mg 1-2 times a day for 2-12 months (depending on the pathogen).

Precautions.

In patients with impaired immunity (AIDS, state after organ transplantation, neutropenia) You may need to increase the dose (as a result of reduced bioavailability of itraconazole).

In appointing patients with chronic heart failure require individual assessment ratio of benefits and risks, taking into account such factors as the seriousness of the evidence, dosing regimen, individual risk factors (the presence of heart disease, incl. CHD, defeat valves), chronic obstructive pulmonary disease, renal failure. If you experience signs or symptoms of congestive heart failure, as well as neuropathy treatment itrakonazolom should be discontinued.

During treatment itrakonazolom it is necessary to monitor liver function (especially in the long admission). With the increased level transaminaz shall appoint, If the effect of therapy outweighs the potential risk to liver. In patients with cirrhosis of the liver and/or kidney dysfunction must be monitored itrakonazola concentration in the plasma and adjust dose.

Women of childbearing age should use adequate contraception throughout treatment, until the onset of first menstruation after its completion.

Cooperation

Active substance	Description of interaction
Akarʙoza	FMR: synergism. Against the backdrop of itraconazole significantly amplifies the effect and may develop severe hypoglycemia.
Algeldrat + Magnesium hydroxide	FKV. Slows absorption (the interval between doses should be at least 2 no).
Amlodipine	FKV. FMR. Against the backdrop of itraconazole (blocks biotransformation) enhances the effect of, incl. side (swelling, the weakening of the heart rate, etc.).
Amphotericin B	FMR: antagonizm. Against the background of declining effect of itraconazole.
Buspirone	FKV. Against the backdrop of itraconazole (blocks biotransformation) increases plasma concentration.
Busulfan	FKV. Against the backdrop of itraconazole (blocks biotransformation) may increase the risk of manifestations of toxicity.
Warfarin	FKV: synergism. Against the backdrop of itraconazole (blocks biotransformation) is enhanced and/or extended effect.
Verapamil	FKV. FMR. Against the backdrop of itraconazole, blocking biotransformation, enhances the effect of, incl. side (swelling, the weakening of the heart rate, etc.).
Vynblastyn	FKV. Against the background of reduced biotransformation of itraconazole, amplified and prolonged effect.
Vynkrystyn	FKV. FMR. Against the backdrop of itraconazole (CYP3A4 inhibitor) effect and increases the likelihood of side effects; combined use is contraindicated.
Glimepiride	FMR: synergism. Against the backdrop of itraconazole significantly amplifies the effect and may develop severe hypoglycemia.
Glipizide	FMR: synergism. Against the backdrop of itraconazole significantly amplifies the effect and may develop severe hypoglycemia.
Digoxin	FKV. FMR. Against the background of the itrakonazola concentration in the plasma increases, reduced clearance and/or volume of distribution and increases the risk of toxic manifestations.
Docetaxel	FKV. Against the background of the itrakonazola blocked biotransformation and amplified effect.
Isoniazid	FKV. Reduces plasma levels and significantly reduces the effect of; co-administration is not recommended.
Carbamazepine	FKV. Accelerating the degradation and reduces content in the blood. Against the backdrop of itraconazole (inhibits CYP3A4) oppressed biotransformation and increases plasma concentration.
Clarithromycin	FKV. Inhibiting cytochrome CYP3A4, increases the bioavailability and concentration in plasma.
Clonazepam	FKV. Against the backdrop of itraconazole (CYP3A4 inhibitor) zamedlyaetsya biotransformation; the combined appointment of caution.
Magnesium oxide	FKV. Oŝelačivaâ gastric contents, reduces the absorption of; should not be taken before 2 hours after itraconazole.
Methylprednisolone	FKV. FMR. Against the backdrop of itraconazole (CYP3A4 inhibitor) zamedlyaetsya biotransformation, reduced clearance, toxic effects may occur.
Midazolam	FKV. FMR. Against the backdrop of itraconazole (CYP3A4 inhibitor) increases (in 2-10 times) FROMmax, AUC and reduced clearance, amplified effect is extended; concomitant use is contraindicated.
Natriya carbonate	FKV. Oŝelačivaâ gastric contents, reduces the absorption of; should not be taken before 2 hours after itraconazole.
Nevirapine	FKV. Speeds (According to èkperimental′nym data) biotransformation and significantly reduces the bioavailability; co-administration is not recommended.
Nimodipine	FKV. FMR. Against the backdrop of itraconazole, blocking biotransformation, enhances the effect of, incl. side (swelling, the weakening of the heart rate, etc.).
Nifedipine	FKV. FMR. Against the backdrop of itraconazole, blocking biotransformation, enhances the effect of, incl. side (swelling, the weakening of the heart rate, etc.).
Pantoprazole	FKV. Reduces plasma concentration.
Rabeprazole	FKV. Reduces plasma concentration.
Ritonavir	FKV. As CYP3A4 inhibitor increases the (mutually) bioavailability and AUC; When combined may require lower doses.
Rifabutin	FKV. Speeds up biotransformatia and greatly reduces plasma levels of itraconazole and its active metabolite gidroksiitrakonazola; co-administration is not recommended.
Rifampicin	FKV. Speeds up biotransformatia and significantly reduces the level of itraconazole and its active metabolite in plasma gidroksiitrakonazola; co-administration is not recommended.
Simvastatin	FKV. FMR. Against the backdrop of itraconazole (CYP3A4 inhibitor) zamedlyaetsya biotransformation, increases in the level of plasma and increases the risk of toxic lesions of skeletal muscles, myopathies, rhabdomyolysis.
Sirolimus	FKV. Against the backdrop of itraconazole, blocking biotransformation, increased plasma concentration.
Felodipine	FKV. Against the backdrop of itraconazole (CYP3A4 inhibitor) increases the AUC, Cmax, T1/2 and enhances the effect of, incl. side.
Phenobarbital	FKV. Enhances biotransformatia, reduces the level of plasma.
Celecoxib	FKV. Against the backdrop of itraconazole (CYP2S9 inhibitor) slows biotransformation and increases concentration in plasma; with a joint appointment caution.
Cyclosporine	FKV. FMR. Against the backdrop of itraconazole (inhibitor of CYP3A) zamedlyaetsya biotransformation, increasing concentration in the tissues, It increases the likelihood of renal impairment; combined use is contraindicated.
Esomeprazole	FKV. Reduces plasma concentration.