Trade Names:Sporanox- Capsules 100 mg- Solution, oral 10 mg/mL
Inhibits the CYP-450–dependent synthesis of ergosterol, which is a vital component of fungal cell membranes.
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).
99.8% of itraconazole and 99.5% of hydroxyitraconazole are protein bound.
The active metabolite is hydroxyitraconazole. Metabolized predominantly by CYP-450 3A4 isoenzyme, resulting in several metabolites.
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.
Bioavailability is slightly reduced.Hepatic Function Impairment
Prolonged t ½ . Monitor closely. Reduced C max 147% (capsules).
Treatment of aspergillosis, blastomycosis, histoplasmosis, and onychomycosis (non-immunocompromised patients only).Solution
Treatment of oropharyngeal or esophageal candidiasis and empiric treatment of febrile neutropenic patients with suspected fungal infections.
Recommended as an alternative to fluconazole as secondary prevention of oropharyngeal, vaginal, or esophageal candidiasis in HIV-infected patients who have severe or frequent recurrences.Capsules
Alternative to fluconazole for prevention of Cryptococcus in adults with advanced HIV disease (CD4 counts less than 50 cell/mcL) and recommended as an alternative to fluconazole for lifelong secondary prevention of cryptococcal disease in HIV-infected adults; first-line agent in the primary prevention of histoplasmosis in adults with advanced HIV disease (CD4 counts less than 100 cells/mcL) and live in endemic areas (rate of at least 10 cases per 100 patient-years) and also as first-line agent for lifelong secondary prophylaxis; recommended as an alternate agent to fluconazole for lifelong secondary prevention of coccidioidomycosis in HIV-infected adults. Oral itraconazole is recommended also for secondary prevention of histoplasmosis, cryptococcal disease, and coccidioidomycosis in children with HIV; primary prevention of histoplasmosis (first-line agent) and cryptococcal disease (alternate therapy) in children with HIV, with severe immunosuppression, and who live in endemic areas (histoplasmosis).
Coadministration with cisapride, dofetilide, ergot derivatives (eg, ergotamine), nisoldipine, pimozide, quinidine, triazolam, levacetylmethadol (levomethadyl), oral midazolam, or HMG-CoA reductase inhibitors metabolized by the CYP-450 3A enzyme system (eg, lovastatin, simvastatin); not for treatment of onychomycosis in pregnant women or women contemplating pregnancy; ventricular dysfunction such as CHF or history of CHF; hypersensitivity to any component of the product.
PO 200 to 400 mg/day. Give doses higher than 200 mg in 2 divided doses. An inadequate treatment period may lead to recurrence.Esophageal CandidiasisAdults
PO 100 mg/day (10 mL) for a minimum of 3 wk. Continue treatment for 2 wk following resolution of symptoms. Doses up to 200 mg/day may be used based on medical judgment of the patient's response. Vigorously swish solution in mouth (10 mL at a time) for several seconds and swallow.Life-Threatening SituationsAdults
Loading dose of 200 mg 3 times daily for 3 days. Continue treatment for a minimum of 3 mo and until clinical parameters and laboratory tests indicate the active fungal infection has subsided.Onychomycosis, Fingernails OnlyAdults
PO 2 treatment pulses separated by a 3-wk period without itraconazole. Each pulse consisting of 200 mg twice daily for 1 wk.Onychomycosis, Toenails With or Without Fingernail InvolvementAdults
PO 200 mg/day for 12 wk.Oropharyngeal CandidiasisAdults
PO 200 mg (20 mL)/day of oral solution for 1 to 2 wk. Vigorously swish solution in mouth (10 mL at a time) for several seconds and swallow. For patients with oropharyngeal candidiasis unresponsive/refractory to treatment with fluconazole tablets, the recommended dose is 100 mg (10 mL) twice daily.
Store capsules at controlled room temperature (59° to 77°F). Protect from light and moisture.Oral solution
Store oral solution below 77°F. Protect from freezing.
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.
None well documented.
The incidence and type of adverse reaction vary depending on usage and route of administration.
Hypertension (3%); hypotension, orthostatic hypotension, tachycardia, vasculitis (1%); CHF (postmarketing).
Headache (4%); fatigue (3%); depression, dizziness (2%); decreased libido, malaise, somnolence, vertigo (1%); hypoesthesia, paresthesia, peripheral neuropathy (postmarketing).
Rash (9%); increased sweating (4%); pruritus (3%); skin disorder (2%); hypotension (1%); alopecia, erythema multiforme, exfoliative dermatitis, leukocytoclastic vasculitis, photosensitivity, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria (postmarketing).
Ophthalmic malformations, tinnitus, visual disturbances including blurred vision and diplopia (postmarketing).
Diarrhea, nausea (11%); vomiting (7%); abdominal pain (6%); GI disorders (4%); constipation (2%); anorexia (1%); dysgeusia, dyspepsia (postmarketing).
Abnormal renal function, albuminuria, impotence (1%); erectile dysfunction, menstrual disorder, pollakiuria, urinary incontinence (postmarketing).
Leukopenia, neutropenia, thrombocytopenia (postmarketing).
Bilirubinemia (6%); elevated liver enzymes (4%); abnormal hepatic function, ALT increased (3%); AST increased, jaundice (2%); hepatitis, hepatotoxicity (some fatal), reversible increases in hepatic enzymes (postmarketing).
Hypokalemia (9%); hypertriglyceridemia, increased serum creatinine (3%); hypomagnesemia, increased alkaline phosphatase, increased LDH (2%); fluid overload, hypocalcemia, increased BUN (1%).
Myalgia, rigors (1%); arthralgia (postmarketing).
Coughing (4%); increased sputum, dyspnea, pneumonia, sinusitis (2%); pulmonary edema (postmarketing).
Fever (7%); edema (4%); chest pain (3%); pain, Pneumocystis carinii infection (2%); anaphylactic, anaphylactoid, and allergic reactions, anaphylaxis, angioneurotic edema, chromosomal and multiple malformations, peripheral edema, serum sickness (postmarketing).
Not to be administered for treatment of onychomycosis in patients with evidence of ventricular dysfunction (eg, CHF) or history of CHF. Monitor for signs and symptoms of CHF; discontinue if they develop. Coadministration of cisapride, levacetylmethadol (levomethadyl), dofetilide, pimozide, or quinidine is contraindicated. Serious CV events, including arrhythmias and QT prolongation, may occur.
Monitor for signs and symptoms of CHF. Monitor patient for signs and symptoms of hepatic injury (fatigue, right upper quadrant abdominal pain, persistent appetite loss or nausea, vomiting, dark urine, yellowing of skin or eyes).
Category C .
Excreted in breast milk.
Safety and efficacy not established.
Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.
Use with caution because of limited available data.
Rare cases of serious hepatotoxicity, including liver failure and death, have been reported.
Absorption may be decreased in HIV-infected patients with hypochlorhydria.
Limited data available.
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