No

Antifungal Agent, Oral

Dental: Treatment of susceptible fungal infections in immunocompromised and immunocompetent patients including blastomycosis and histoplasmosis; also has activity against Aspergillus, Candida, Coccidioides, Cryptococcus, Sporothrix and chromomycosis

Medical: Treatment of susceptible fungal infections in immunocompromised and immunocompetent patients including blastomycosis and histoplasmosis; indicated for aspergillosis, and onychomycosis of the toenail; treatment of onychomycosis of the fingernail without concomitant toenail infection via a pulse-type dosing regimen; has activity against Aspergillus, Candida, Coccidioides, Cryptococcus, Sporothrix, tinea unguium

Oral solution (not capsules) is marketed for oral and esophageal candidiasis

Useful in superficial mycoses including dermatophytoses (eg, tinea capitis), pityriasis versicolor, sebopsoriasis, vaginal and chronic mucocutaneous candidiases; systemic mycoses including candidiasis, meningeal and disseminated cryptococcal infections, paracoccidioidomycosis, coccidioidomycoses; miscellaneous mycoses such as sporotrichosis, chromomycosis, leishmaniasis, fungal keratitis, alternariosis, zygomycosis

Intravenous solution is indicated in the treatment of blastomycosis, histoplasmosis (nonmeningeal), and aspergillosis (in patients intolerant or refractory to amphotericin B therapy)

C

Known hypersensitivity to other azoles; concurrent administration with astemizole, cisapride, lovastatin, midazolam, simvastatin, or triazolam

Rare cases of serious cardiovascular adverse event, including death, ventricular tachycardia and torsade de pointes have been observed due to increased terfenadine and cisapride concentrations induced by itraconazole; patients who develop abnormal liver function tests during itraconazole therapy should be monitored and therapy discontinued if symptoms of liver disease develop

Listed incidences are for higher doses appropriate for systemic fungal infections

1% to 10%:

Cardiovascular: Edema (3.5%), hypertension (3.2%)

Central nervous system: Headache (4%), fatigue (2% to 3%), malaise (1.2%), fever (2.5%)

Dermatologic: Rash (8.6%)

Endocrine & metabolic: Decreased libido (1.2%), hypertriglyceridemia

Gastrointestinal: Abdominal pain (1.5%), vomiting (5%), diarrhea (3%)

Hepatic: Abnormal LFTs (2.7%), hepatitis

<1%: Dizziness, somnolence, pruritus, hypokalemia, anorexia, impotence, adrenal suppression, gynecomastia, albuminuria

Overdoses are well tolerated

Following decontamination, if possible, supportive measures only are required; dialysis is not effective

CYP3A3/4 enzyme substrate; CYP3A3/4 enzyme inhibitor

Decreased serum levels with carbamazepine, didanosine, isoniazid, phenobarbital, phenytoin, rifabutin, and rifampin; may cause a decreased effect of oral contraceptives; alternative birth control is recommended

Decreased/undetectable serum levels with rifampin - should not be administered concomitantly with rifampin

Absorption requires gastric acidity; therefore, antacids, H₂-antagonists (cimetidine and ranitidine), proton pump inhibitors like omeprazole, and sucralfate significantly reduce bioavailability resulting in treatment failures and should not be administered concomitantly; amphotericin B or fluconazole should be used instead

Increased toxicity:

Itraconazole may increase protease inhibitors' serum concentrations.

May increase cyclosporine or tacrolimus levels (by 50%) when high doses are used

Itraconazole increases serum levels of lovastatin (possibly 20-fold) and other HMG-CoA inhibitors due to inhibition of CYP3A4

May increase phenytoin serum concentration

May inhibit warfarin's metabolism

May increase digoxin serum levels

May increase astemizole, busulfan, cisapride, terfenadine, and vinca alkaloid levels - concomitant administration is not recommended due to increased risk of cardiotoxicity

Itraconazole may increase astemizole levels resulting in prolonged Q-T intervals - concomitant administration is contraindicated

Itraconazole may increase levels of cisapride - concomitant administration is contraindicated due to increased risk of cardiotoxicity

May increase amlodipine, benzodiazepine, buspirone, corticosteroids, and oral hypoglycemic levels; use with caution in patients prescribed medications eliminated by CYP3A4 metabolism

Dilute with 0.9% sodium chloride only; do not dilute in dextrose or lactated Ringer's; may be stored refrigerated or at room temperature for 48 hours; use dedicated infusion line; do not mix with any other medication

Interferes with cytochrome P-450 activity, decreasing ergosterol synthesis (principal sterol in fungal cell membrane) and inhibiting cell membrane formation

Absorption: Requires gastric acidity; capsule better absorbed with food, solution better absorbed on empty stomach

Distribution: Apparent volume averaged 796±185 L or 10 L/kg; highly lipophilic and tissue concentrations are higher than plasma concentrations. The highest itraconazole concentrations are achieved in adipose, omentum, endometrium, cervical and vaginal mucus, and skin/nails. Aqueous fluids, such as cerebrospinal fluid and urine, contain negligible amounts of itraconazole; steady-state concentrations are achieved in 13 days with multiple administration of itraconazole 100-400 mg/day.

Protein binding: 99.9% bound to plasma proteins; metabolite hydroxy-itraconazole is 99.5% bound to plasma proteins

Metabolism: Extensive by the liver into >30 metabolites including hydroxy-itraconazole which is the major metabolite and appears to have in vitro antifungal activity. The main metabolic pathway is oxidation; may undergo saturation metabolism with multiple dosing

Bioavailability: Increased from 40% fasting to 100% postprandial; absolute oral bioavailability: 55%; hypochlorhydria has been reported in HIV-infected patients; therefore, oral absorption in these patients may be decreased

Half-life: Oral: After single 200 mg dose: 21±5 hours; 64 hours at steady-state; I.V.: steady-state: 35 hours

Elimination: ~3% to 18% excreted in feces; ~0.03% of parent drug excreted renally and 40% of dose excreted as inactive metabolites in urine

Oral: Capsule: Absorption is best if taken with food, therefore, it is best to administer itraconazole after meals; Solution: Should be taken on an empty stomach. Absorption of both products is significantly increased when taken with a cola beverage.

Adults:

Oral:

Blastomycosis/histoplasmosis: 200 mg once daily, if no obvious improvement or there is evidence of progressive fungal disease, increase the dose in 100 mg increments to a maximum of 400 mg/day; doses >200 mg/day are given in 2 divided doses; length of therapy varies from 1 day to >6 months depending on the condition and mycological response

Aspergillosis: 200-400 mg/day

Onychomycosis: 200 mg once daily for 12 consecutive weeks

Life-threatening infections: Loading dose: 200 mg 3 times/day (600 mg/day) should be given for the first 3 days of therapy

Oropharyngeal and esophageal candidiasis: Oral solution: 100-200 mg once daily

I.V.: 200 mg twice daily for 4 doses, followed by 200 mg daily

Dosing adjustment in renal impairment: Not necessary; itraconazole injection is not recommended in patients with Cl_cr <30 mL/minute

Hemodialysis: Not dialyzable

Dosing adjustment in hepatic impairment: May be necessary, but specific guidelines are not available

Food increases absorption of capsule and decreases absorption of the solution

May cause sedation

None reported

No information available to require special precautions

No effects or complications reported

Take as directed, around-the-clock, with food. Take full course of medication; do not discontinue without notifying prescriber. Practice good hygiene measures to prevent reinfection. If diabetic, test serum glucose regularly (can cause hypoglycemia when given with sulfonylureas). Frequent blood tests may be required with prolonged therapy. You may experience dizziness or drowsiness (use caution when driving or engaging in tasks that require alertness until response to drug is known); nausea, vomiting, or diarrhea (small frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). Report skin rash or other persistent adverse reactions. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Do not administer with antacids; doses >200 mg/day are administered in 2 divided doses

Capsule: 100 mg

Injection kit: 10 mg/mL - 25 mL ampul, one 50 mL (100 mL capacity) bag 0.9% sodium chloride, one filtered infusion set

Solution, oral: 100 mg/10 mL (150 mL)

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