Oral SCH 39304 as primary, salvage, and maintenance therapy for cryptococcal meningitis in AIDS.
To determine the efficacy and toxicity of SCH 39304 in the treatment and suppression of cryptococcal meningitis, we conducted a prospective, noncomparative study in three groups of patients: patients with acute cryptococcal meningitis, patients with acute cryptococcal meningitis in whom other therapies have failed (salvage), and patients who required maintenance therapy. As primary therapy, the patients received up to 14 days or 1 g of amphotericin B followed by SCH 39304 200 mg once daily for 12 weeks. As maintenance therapy, the patients received SCH 39304 600 mg once weekly for 12 months. Of five salvage patients, none completed the study. Two patients died, two patients clinically deteriorated, and one patient was noncompliant. Two of three patients with acute cryptococcal meningitis completed the 12-week primary therapy, and one patient was discontinued from therapy because of a skin rash (95% confidence interval, 14-100%). All four patients who were receiving weekly maintenance therapy followed up to 27 weeks were clinically stable with no change in their serum cryptococcal antigen titer from baseline when the study was prematurely terminated. Elevation of liver function test results developed in three patients and skin rash developed in one patient. The unique pharmacologic and pharmacokinetic properties of SCH 39304 (low incidence of toxicity, long serum half-life, and good penetration into the cerebrospinal fluid) lend promise to pursue other triazole antifungals at higher doses as primary therapy and less frequent dosing for maintenance therapy.
Lee
B L
BL
Department of Medicine, University of California, San Francisco.
Padula
A M
AM
Täuber
M G
MG
Chambers
H F
HF
Sande
M A
MA
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000188:drug therapy; D000284:Administration, Oral; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D016919:Meningitis, Cryptococcal / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D011446:Prospective Studies; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015215:Zidovudine / Q000627:therapeutic use
D000935:Antifungal Agents; D014230:Triazoles; C056513:Sch 39304; D015215:Zidovudine