4-[4-[4-[4-[ [2-(2,4-dichlorophenyl)- 2-(1H-1,2,4-triazol-1-ylmethyl)- 1,3-dioxolan-4-yl]methoxy]phenyl] piperazin-1-yl]phenyl]- 2-(1-methylpropyl)-2,4-dihydro-1, 2,4-triazol- 3-one

Absorption
Absolute bioavailability 55%. The mean C max at steady state is approximately 2,282 ng/mL (capsules) and 1,963 ng/mL (oral solution). The mean T max at steady state is approximately 4.6 h (capsules) and 2.5 h (oral solution).

Distribution
99.8% of itraconazole and 99.5% of hydroxyitraconazole are protein bound.

Metabolism
The active metabolite is hydroxyitraconazole. Metabolized predominantly by CYP-450 3A4 isoenzyme, resulting in several metabolites.

Elimination
The mean t ½ at steady state is approximately 64 h (capsules) and 39.7 h (oral solution). Approximately 40% is excreted in the urine as inactive metabolites, and 3% to 18% is excreted in the feces as the parent drug.

Special Populations
Renal Function Impairment

Bioavailability is slightly reduced.

Hepatic Function Impairment

Prolonged t ½ . Monitor closely. Reduced C max 147% (capsules).

Alfentanil, alfuzosin, almotriptan, alprazolam, aripiprazole, atorvastatin, bosentan, buspirone, busulfan, carbamazepine, cerivastatin, cilostazol, cinacalcet, conivaptan, cyclophosphamide, cyclosporine, diazepam, digoxin, disopyramide, docetaxel, eletriptan, fentanyl, gefitinib, halofantrine, haloperidol, protease inhibitors, quetiapine, risperidone, sildenafil, sirolimus, tacrolimus, tadalafil, tolterodine, trimetrexate, vardenafil, venlafaxine, warfarin, zolpidem
Levels may be elevated by itraconazole, increasing the risk of adverse reactions.

Antacids, carbamazepine, grapefruit juice, H 2 -receptor antagonists (eg, cimetidine), isoniazid, orange juice, phenobarbital, phenytoin, proton pump inhibitors
Plasma levels of itraconazole may be decreased.

Calcium blockers (eg, amlodipine, felodipine, nifedipine, verapamil)
Edema has occurred with concomitant dihydropyridine calcium blockers.

Cisapride, dofetilide, eplerenone, ergot alkaloids, levacetylmethadol, lovastatin, nisoldapine, oral midazolam, pimozide, quinidine, ranolazine, simvastatin, triazolam
Serious CV events may occur. Coadministration is contraindicated.

Corticosteroids (eg, budesonide, dexamethasone, methylprednisolone)
The metabolism of these corticosteroids may be inhibited, resulting in increased toxicity.

Didanosine (buffered)
May decrease therapeutic effects of itraconazole. Administer itraconazole 2 h or more before didanosine.

HMG-CoA reductase inhibitors
Coadministration may increase risk of rhabdomyolysis. Lovastatin and simvastatin coadministration is contraindicated.

Hypoglycemic agents
Hypoglycemia may occur. Monitor blood glucose.

Macrolide antibiotics (eg, clarithromycin, erythromycin), protease inhibitors (eg, indinavir, ritonavir)
Plasma levels of itraconazole may be increased.

Nevirapine, phenytoin, rifamycins
Reduced plasma levels of itraconazole may occur. Avoid use if possible.

Phenytoin, rifamycins, vinca alkaloids
Levels may be elevated by itraconazole, increasing the risk of adverse reactions. Avoid use if possible.