ITRACONAZOLE

ITRACONAZOLE (i-tra-con'a-zole) Sporanox Classifications: antibiotic; antifungal; Therapeutic:antifungal, antibiotic Prototype: Fluconazole Pregnancy Category: C

Availability

100 mg capsules; 10 mg/mL oral solution

Action

Interferes with formation of ergosterol, the principal sterol in the fungal cell membrane that, when depleted, interrupts fungal membrane functioning.

Therapeutic Effect

Antifungal properties affect the fungal cell membrane functioning. Fungistatic; may also be fungicidal depending on the concentration of drug.

Uses

Treatment of systemic fungal infections caused by blastomycosis, histoplasmosis, aspergillosis, onychomycosis due to dermatophytes of the toenail with or without fingernail involvement; oropharyngeal and esophageal candidiasis; orally to treat superficial mycoses (Candida, pityriasis versicolor).

Unlabeled Uses

Systemic and vaginal candidiasis.

Contraindications

Hypersensitivity to itraconazole; renal failure; systolic BP <90 mm of Hg (hypotension); pregnancy (category C), lactation.

Cautious Use

Hypersensitivity to other azole antifungal agents, achlorhydria; GERD; COPD, cystic fibrosis; dialysis; older adults, females of childbearing age; hepatic disease, hepatitis, HIV infection; hypochlorhydria; pulmonary disease; renal disease, renal impairment; valvular heart disease, ventricular dysfunction, angina, cardiac disease; children.

Route & Dosage

Blastomycosis, Nonmeningeal Histoplasmosis, Aspergillosis Adult: PO 200 mg once daily (increase to max: 200 mg b.i.d. if no apparent improvement). Continue for at least 3 mo; for life-threatening infections, start with 200 mg t.i.d. for 3 d, then 200–400 mg/d. Child: PO 3–5 mg/kg/d for 3–6 mo Oropharyngeal Candidiasis Adult: PO 200 mg daily for 1–2 wk Esophageal Candidiasis Adult: PO 100 mg daily for at least 3 wk (max: 200 mg/d) Vaginal Candidiasis Adult: PO 200 mg daily for 3 d Life-Threatening Infections Adult: PO 200 mg t.i.d. x 3 d Onychomycosis Adult: PO 200 mg daily x 3 mo

Administration

Oral

• Give capsules with a full meal.
• Give oral solution without food. Liquid should be vigorously swished for several seconds and swallowed.
• Do not interchange oral solution and capsules.
• Divide dosages greater than 200 mg/d into two doses.
• Store liquid at or below 25° C (77° F).

Adverse Effects (≥1%)

CV: Hypertension with higher doses. CNS: Headache, dizziness, fatigue, somnolence (euphoria, drowsiness <1%). Endocrine: Gynecomastia, hypokalemia (especially with higher doses), hypertriglyceridemia. GI: Nausea, vomiting, dyspepsia, abdominal pain, diarrhea, anorexia, flatulence, gastritis; elevations of serum transaminases, alkaline phosphatase, and bilirubin. Urogenital: Decreased libido, impotence. Skin: Rash, pruritus. Acute Poisoning: Severe toxicity (doses exceeding 400 mg daily have been associated with higher risk of hypokalemia, hypertension, adrenal insufficiency).

Interactions

Drug: Itraconazole may increase levels and toxicity of ergotamine, dihydroergotamine, oral hypoglycemic agents warfarin, ritonavir, indinavir, vinca alkaloids, busulfan, ergonovine, methylergonovine, midazolam, triazolam, diazepam, nifedipine, nicardipine, amlodipine, felodipine, lovastatin, simvastatin, cyclosporine, tacrolimus, methylprednisolone, digoxin. Combination with dofetilide, levomethadyl, oral midazolam, pimozide, quinidine, triazolam may cause severe cardiac events including cardiac arrest or sudden death. Itraconazole levels are decreased by carbamazepine, phenytoin, phenobarbital, isoniazid, rifabutin, rifampin. Herbal: St. John's wort and garlic may decrease itraconazole levels.

Pharmacokinetics

Absorption: Well absorbed from GI tract when taken with food. Onset: 2 wk–3 mo. Peak: Peak levels at 1.5–5 h. Steady-state concentrations reached in 10–14 d. Distribution: Highly protein bound, minimal concentrations in CSF. Higher concentrations in tissues than in plasma. Metabolism: Extensively in liver by CYP3A4, may undergo enterohepatic recirculation. Elimination: 35% in urine, 55% in feces. Half-Life: 34–42 h.

Nursing Implications

Assessment & Drug Effects

• Lab tests: C&S tests should be done before initiation of therapy. Drug may be started pending results. Monitor hepatic functions especially in those with preexisting hepatic abnormalities.
• Monitor for digoxin toxicity when given concurrently with digoxin.
• Monitor PT and INR carefully when given concurrently with warfarin.
• Monitor for S&S of hypersensitivity (see Appendix F); discontinue drug and notify physician if noted.

Patient & Family Education

• Take capsules, but NOT oral solution, with food.
• Notify physician promptly for S&S of liver dysfunction, including anorexia, nausea, and vomiting; weakness and fatigue; dark urine and clay-colored stool.
• Note: Risk of hypoglycemia may increase in diabetics on oral hypoglycemic agents.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug