An open-label comparison of oral voriconazole and itraconazole for long-term treatment of paracoccidioidomycosis

Abstract number: 1134_01_205

Queiroz-Telles F., Goldani L.Z., Shikanai-Yasuda M.A., Goodrich J.M., Schlamm H.T.

Objectives:  

Paracoccidioidomycosis, previously named South American Blastomycosis, is a subacute to chronic systemic mycosis caused by Paracoccidioides brasiliensis. The aim of this study was to investigate the efficacy, safety, and tolerability of voriconazole in the long-term treatment of acute or chronic paracoccidioidomycosis, with itraconazole as control treatment.

Methods:  

This was a randomized, multicentre, open-label, comparative study conducted in Brazil in 2000–2002. Subjects were randomized (2:1) to receive oral therapy with voriconazole or itraconazole for up to 12 months. Satisfactory global response (incorporating clinical, mycologic, radiologic, and serologic assessments) at end of treatment (EOT) was compared for the two treatment groups.

Results:  

Fifty-three subjects received at least one dose of study drug: 35 received voriconazole and 18 received itraconazole. All but 4 subjects with confirmed paracoccidioidomycosis (3 on voriconazole, 1 on itraconazole) received at least 6 months of continuous study treatment. The response rates in these treatment-evaluable patients were 100% for both treatment groups, and there were no relapses after 8 weeks of follow-up in either group. The majority of cases had lung involvement at baseline; one case with both lung and CNS involvement responded well to voriconazole. The most common treatment-related events included abnormal vision, chromatopsia, rash, and headache in the voriconazole group, and bradycardia, diarrhoea, and headache in the itraconazole group. Two voriconazole subjects were withdrawn prematurely, as required by the protocol, due to study drug related elevated alkaline phosphatase and hepatic enzymes (ALT, AST, and GGT). The frequency of liver function test abnormalities was slightly higher in subjects receiving voriconazole compared to itraconazole, but the median changes in these parameters from baseline values were similar between treatment groups. One voriconazole subject expired after 52 days because of a rupture of an aortic aneurysm: an autopsy was performed and was negative for paracoccidioidomycosis.

Conclusions:  

This is the first study to demonstrate that voriconazole is well tolerated and effective for the long-term treatment of paracoccidioidomycosis.