The oral azoles present an attractive alternative to amphotericin, even in the absence of an approved licensed indication for the disease. Their toxicity is much less, and response rates appear similar, though comparative trials have not been performed. The imidazole, ketoconazole, optimally used at 400 mg once daily (in adults) is effective for nonmeningeal disease and is the least expensive agent but may have more side effects, and relapse rates may be higher. The newer triazoles show promise. Itraconazole, at 200 mg twice a day with food, appears similarly effective, but absorption may be decreased in the presence of any gastroenteropathy, and drug-drug interactions may be a problem. Response rates with fluconazole are likewise excellent if doses of 400-600 mg/day are used, but it is the most expensive. The optimal duration of azole therapy has not been defined, but based an relapse data, therapy should probably continue for greater than or equal to 6 months after the disease has been rendered inactive. A current clinical trial is under way to compare the two triazoles as first therapy for nonmeningeal disease.The oral azoles also offer an attractive alternative for meningeal disease. Ketoconazole at doses of 800-1200 mg/day can produce responses but side effects at these doses makes this least desirable. Fluconazole and itraconazole, at the same doses as used for nonmeningeal disease, produce a similar high percent of responses. This has been described for primary therapy, for amphotericin failures, or to lessen the amount of intra-cerebrospinal fluid therapy usually needed to achieve remission. Unfortunately, data suggest very high relapse rates once azole therapy is stopped. Even if cure with azoles is unattainable and lifelong suppression may be needed, triazoles are generally well tolerated and amphotericin's toxicity and the need for intra- CSF therapy is avoided, In an otherwise fatal illness this represents an important advance.
Full conference title:
Coccidioidomycosis - Centennial Conference