An Open-Label Comparative Pilot Study of Oral Voriconazole and Itraconazole for Long-Term Treatment of Paracoccidioidomycosis

• Published in: Clinical infectious diseases 2007-12, Vol.45 (11), p.1462-1469
• Main Authors: Telles, Flavio Queiroz, Goldani, Luciano Z., Schlamm, Haran T., Goodrich, James M., Ingroff, Ana Espinel, Yasuda, Maria A. Shikanai
• Format: Article
• Language: English
• Subjects: Administration, Oral; Adult; Aged; Aged, 80 and over; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antifungal Agents - administration & dosage; Antifungal Agents - therapeutic use; Articles and Commentaries; Biological and medical sciences; Blastomycoses and paracoccidioidomycosis; Central nervous system; Comparative analysis; Dosage; Drug Administration Schedule; Drug therapy; Exanthema; Female; Fungal infections; Headache; Human mycoses; Humans; Infections; Infectious diseases; Itraconazole - administration & dosage; Itraconazole - therapeutic use; Lesions; Male; Medical sciences; Middle Aged; Mycoses; Paracoccidioidomycosis; Paracoccidioidomycosis - drug therapy; Pharmacology. Drug treatments; Pilot Projects; Prescription drugs; Pyrimidines - administration & dosage; Pyrimidines - therapeutic use; Radiology; Studies; Symptoms; Triazoles - administration & dosage; Triazoles - therapeutic use; Tropical mycoses; Voriconazole
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/522973

Background. In previous studies, itraconazole was revealed to be an effective therapy and was considered to be the gold standard treatment for mild-to-moderate acute and chronic clinical forms of paracoccidioidomycosis. A pilot study was conducted to investigate the efficacy, safety, and tolerability of voriconazole for the long-term treatment of acute or chronic paracoccidioidomycosis, with itraconazole as the control treatment. Methods. A randomized, open-label study was conducted at 3 Brazilian tertiary care hospitals. Patients were randomized (at a 2 : 1 ratio) to receive oral therapy with voriconazole or itraconazole for 6 months. Patients receiving ⩾1 dose of study drug were evaluated for safety; patients with confirmed paracoccidioidomycosis who completed ⩾6 months of therapy (treatment-evaluable patients) were evaluated for treatment efficacy. Satisfactory global response was assessed at the end of treatment. Results. Fifty-three patients were evaluated for treatment safety (35 received voriconazole, and 18 received itraconazole). Both drugs were well tolerated. The most common treatment-related adverse events in the voriconazole group included abnormal vision, chromatopsia, rash, and headache; the most common treatment-related adverse events in the itraconazole group included bradycardia, diarrhea, and headache. Liver function test values were slightly higher in patients receiving voriconazole than in those receiving itraconazole; 2 patients in the voriconazole group were withdrawn from treatment because of increased liver function test values. In the intent-to-treat populations, the satisfactory response rate (i.e., complete or partial global response) was 88.6% among the voriconazole group and 94.4% among the itraconazole group. The response rate among treatment-evaluable patients was 100% for both treatment groups; no relapses were observed after 8 weeks of follow-up. Conclusions. This is, to our knowledge, the first study to demonstrate that voriconazole is as well tolerated and effective as itraconazole for the long-term treatment of paracoccidioidomycosis.