title: Long-term visual safety of voriconazole in adult patients with paracoccidioidomycosis.
abstract: BACKGROUND
  Voriconazole is an antifungal agent with in vitro activity and clinical efficacy against yeasts, molds, and dimorphic fungi (eg, Paracoccidioides brasiliensis). The safety profile of voriconazole includes transient visual adverse events (VAEs) that resolve while undergoing treatment or after its discontinuation.
  
  
  OBJECTIVE
  The goal of this study was to assess the long-term (ie, 6-12 months) visual safety of voriconazole in adult patients with paracoccidioidomycosis.
  
  
  METHODS
  Ophthalmic data were prospectively collected as part of a multicenter, open-label, comparative study. Patients aged ≥18 years with paracoccidioidomycosis were randomized in a 2:1 ratio to receive either voriconazole (200 mg BID orally, after the loading dose of 400 mg BID on day 1) or itraconazole (100 mg BID orally, with no loading dose). Patients were expected to receive treatment for a minimum of 6 months, or longer if needed as determined by the investigator (maximum duration, 1 year). Visual function tests and safety assessments were performed at baseline, week 12, week 24, end of treatment (EOT), and 8 weeks post-EOT. Ophthalmic examinations included visual acuity, color vision, contrast sensitivity, visual field, funduscopy, and slit lamp biomicroscopy. Treatment compliance was monitored via pill counts at each study visit.
  
  
  RESULTS
  Thirty-five patients (mean age, 48 years; 96.2% male; 83.0% white) were randomized to receive voriconazole and 18 to receive itraconazole. Fourteen voriconazole-treated patients received >6 months of treatment (median, 169 days). Efficacy and overall safety results have been published previously. Sixteen voriconazole-treated patients and 2 itraconazole-treated patients experienced drug-related VAEs; none was considered serious or severe or led to dose reductions or resulted in discontinuation. Overall, visual examination results were not clinically significantly different between patients treated with voriconazole or itraconazole. There was no apparent relationship between changes in visual function test results and the occurrence of VAEs in either treatment group.
  
  
  CONCLUSIONS
  Clinical assessment in this study found no evidence of an effect of voriconazole on long-term visual function in these adult patients with paracoccidioidomycosis.
authors.affiliation: Department of Ophthalmology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Alan M
authors.initials: AM
authors.lastname: Laties
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Fraunfelder
authors.forename: Konrad
authors.initials: K
authors.lastname: Tomaszewski
authors.forename: James
authors.initials: J
authors.lastname: Goodrich
authors.forename: Ana Tereza
authors.initials: AT
authors.lastname: Moreira
authors.forename: Mario T
authors.initials: MT
authors.lastname: Sato
authors.forename: Flâvio
authors.initials: F
authors.lastname: de Queiroz-Telles
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D001938:Brazil; D004334:Drug Administration Schedule; D005123:Eye / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D019721:Ophthalmoscopes; D010229:Paracoccidioidomycosis / Q000188:drug therapy*; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D014785:Vision, Ocular / Q000187:drug effects*; D014792:Visual Acuity / Q000187:drug effects; D058609:Visual Field Tests; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole