High-dose itraconazole in the treatment of severe mycoses

Eight patients with systemic mycoses and with prior treatment failures were treated with itraconazole (600 mg/day) for a mean duration of 5.5 months. All six patients without AIDS experienced improvement or stabilization of their fungal infections while receiving high-dose itraconazole, although two patients later experienced treatment failures, one by relapse and one by progression, on lower doses. Treatment failures also occurred in the two patients with AIDS and cryptococcal meningitis. The failures were associated with low serum itraconazole concentrations (less than 2.5 micrograms/ml) in both patients. All other patients had mean trough levels in serum above 5 micrograms/ml. One patient who was improving on 600 mg/day developed a progressive infection after reduction of the dose to 400 mg/day. Side effects included reversible adrenal insufficiency in one patient; severe hypokalemia, mild diastolic hypertension, and rhabdomyolysis in one patient; mild hypokalemia and hypertension in four other patients; and breast tenderness in one patient. The mean decrease in serum potassium during treatment was statistically significant (P = 0.05). Selected patients with severe systemic mycoses may benefit from prolonged high-dose itraconazole treatment. However, 600 mg/day may be approaching the upper limits of acceptable dosing for long-term treatment.