Itraconazole
Itraconazole (Sporanox)
Itraconazole
( ih-trah- KON-ah-zohl)
Pregnancy Category: C Sporanox (Rx)

Classification: Antifungal

Action/Kinetics: Believed to inhibit cytochrome P-450-dependent synthesis of ergosterol, a necessary component of fungal cell membranes. Absorption appears to increase when taken with a cola beverage. Concentrates in fatty tissues, omentum, liver, kidney, and skin. t½, at steady-state: 30-40 hr. Extensively metabolized by the liver; the major metabolite is hydroxyitraconazole, which also has antifungal activity. The drug and major metabolite are extensively bound (over 99%) to plasma proteins. Metabolites are excreted in both the urine and feces.

Uses: Capsules/Injection: Treatment of blastomycosis (pulmonary and extrapulmonary) and histoplasmosis (including chronic cavitary pulmonary disease and disseminated, nonmeningeal histoplasmosis) in both immunocompromised and nonimmunocompromised clients. To treat aspergillus infections (pulmonary and extrapulmonary) in clients intolerant or refractory to amphotericin B.
Capsules: Onychomycosis of the fingernail due to tinea unguium; onychomycosis, due to tinea unguium, of the toenail with or without fingernail involvement.
Oral Solution: Oropharyngeal and esophageal candidiasis.
Investigational: (1) Superficial mycoses including dermatophytoses (tinea capitis, tinea corporis, tinea cruris, tinea pedis, and tinea manuum), pityriasis versicolor, candidiasis (vaginal, oral, chronic mucocutaneous), and sebopsoriasis. (2) Systemic mycoses including dimorphic infections (paracoccidioidomycosis, coccidioidomycosis), cryptococcal infections (meningitis, disseminated), and candidiasis. (3) Miscellaneous mycoses including fungal keratitis, alternariosis, leishmaniasis (cutaneous), subcutaneous mycoses (chromomycosis, sporotrichosis, visceral, lymphocutaneous), and zygomycosis.

Contraindications: Concomitant use of cisapride, triazolam, or oral midazolam. Hypersensitivity to the drug or its excipients. Lactation. Use for the treatment of onychomycosis in pregnant women or in women wishing to become pregnant. Use with severe renal dysfunction (C _CR less than 30 mL/min).

Special Concerns: Use with caution in clients with hypersensitivity to other azoles. Safety and efficacy have not been determined in children although pediatric clients have been treated for systemic fungal infections.

Side Effects: GI: N&V;, diarrhea, abdominal pain, anorexia, taste perversion, flatulence, general GI disorders, constipation, dyspepsia, gingivitis, ulcerative stomatitis, gastritis, gastroenteritis, increased appetite, dyspepsia, dysphagia, hemorrhoids. CNS: Headache, anxiety, depression, vertigo, dizziness, somnolence, decreased libido, abnormal dreaming, insomnia. CV: Hypertension, orthostatic hypotension, vasculitis. Respiratory: URTI, rhinitis, sinusitis, pharyngitis, coughing, dyspnea, pneumonia, increased sputum. Dermatologic: Increased sweating, skin disorders, hot flushes. GU: UTI, impotence, cystitis, menstrual disorders, abnormal renal function, gynecomastia, hematuria. Allergic: Rash, pruritus, urticaria, angioedema, anaphylaxis Body as a whole: Edema, fatigue, pain, fever, malaise, myalgia, asthenia, tremor, dehydration, infection. Miscellaneous: Bursitis, injury, herpes zoster, chest pain, Pneumocystis carinii infection, vein disorder, reaction at injection site, adrenal insufficiency, back pain, male breast pain, rigors, tinnitus, abnormal vision, weight loss.

Laboratory Test Alterations: ALT, AST, alkaline phosphatase, BUN. Hypertriglyceridemia, hypokalemia, hypomagnesemia, albuminuria, bilirubinemia.

Overdose Management: Symptoms: Extension of side effects. Treatment: Use supportive measures, including gastric lavage and sodium bicarbonate. Dialysis will not remove itraconazole.

Drug Interactions: Buspirone / Plasma buspirone levels Calcium blockers (especially amlodipine and nifedipine) / Development of edema Cisapride / Cisapride levels serious CV toxicity including VT, torsades de pointes, and death. Cyclosporine and HMG-CoA reductase inhibitors / Possible development of rhabdomyolysis. Cyclosporine levels (dose of cyclosporine should be by 50% if itraconazole doses are much greater than 100 mg/day) Didanosine / Effects of itraconazole Digoxin / Digoxin levels Grapefruit juice / Itraconazole bioavailability R/T inhibition of absorption H ₂ Antagonists / Plasma levels of itraconazole Lovastatin / Plasma lovastatin levels possible rhabdomyolysis Midazolam, oral / Levels of oral midazolam potentiation of sedative and hypnotic effects Ison iazid / Plasma levels of itraconazole Phenytoin / Plasma levels of itraconazole; also, drug metabolism may be altered Pimozide / Pimozide levels serious CV toxicity including VT, torsades de pointes, and death. Quinidine / Quinidine levels serious CV toxicity including VT, torsades de pointes, and death. Tinnitus and hearing. Rifampin, Rifabutin, Rifapentine / Plasma levels of itraconazole Simvastatin / Plasma simvastatin levels possible rhabdomyolysis Sulfonylureas / Risk of hypoglycemia Tacrolimus / Tacrolimus levels Triazolam / Drug levels potentiation of sedative and hypnotic effects Warfa rin / Anticoagulant drug effect

How Supplied: Capsule: 100 mg; Injection: 10 mg/mL; Oral Solution: 10 mg/mL

Dosage
? Capsules Blastomycosis or histoplasmosis.
Adults: 200 mg once daily. If there is no improvement or the disease is progressive, the dose may be increased in 100-mg increments to a maximum of 400 mg/day.
Aspergilliosis.
200-400 mg daily.
Life-threatening infections.
Adults: Give a loading dose of 200 mg t.i.d. for the first 3 days. Continue treatment for a minimum of 3 months and until tests indicate infection has decreased.
Onychomycosis.
200 mg once a day for 12 consecutive weeks for toenails with or without fingernail involvement. Alternatively, for fingernail fungus only, 200 mg b.i.d. for 1 week, followed by a 3-week rest and then a second 1-week pulse of 200 mg b.i.d.
Unlabeled uses.
Adults: 50-400 mg/day for 1 day to more than 6 months, depending on the condition and the response.
? Oral Solution Oropharyngeal candidiasis.
200 mg/day (20 mL) for 1-2 weeks.
Esophageal candidiasis.
100 mg/day (10 mL) for a minimum of 3 weeks.
? IV Blastomycosis, histoplasmosis, aspergillosis.
200 mg IV b.i.d. for 4 doses, followed by 200 mg/day. Infuse each IV dose over 1 hr.