The Safety of Oral Antifungal Treatments for Superficial Dermatophytosis and Onychomycosis: A Meta-Analysis

PURPOSE: We estimated the absolute risks of treatment termination and incidence of adverse liver outcomes among all commonly used oral antifungal treatments for superficial dermatophytosis and onychomycosis. METHODS: MEDLINE, EMBASE , and Cochrane Library were searched to identify randomized and nonrandomized controlled trials, case series, and cohort studies published before December 31, 2005. Two reviewers independently applied selection criteria, performed quality assessment, and extracted data. Treatment arms with the same regimen in terms of drug, type ( continuous or intermittent) , and dosage were combined to estimate the risk of an outcome of interest. RESULTS: We identified 122 studies with approximately 20,000 enrolled patients for planned comparison. The pooled risks (95% confidence intervals) of treatment discontinuation resulting from adverse reactions for continuous therapy were 3.44% (95% confidence interval [ CI], 2.28%-4.61%) for terbinafine 250 mg/ day; 1.96% (95% CI, 0 .35%-3.57%) for itraconazole 100 mg/ day; 4.21% (95% CI , 2.33%-6.09%) for itraconazole 200 mg/ day; and 1.51% (95% CI, 0%-4.01%) for fluconazole 50 mg/ day. For intermittent therapy, the pooled risks were as follows: pulse terbinafine : 2.09% (95% CI, 0%-4.42%); pulse itraconazole: 2.58% ( 95% CI, 1.15%-4.01%); intermittent fluconazole 150 mg/ week: 1. 98% (95% CI, 0.05%-3.92%); and intermittent fluconazole 300 to 450 mg/ week: 5.76% (95% CI, 2.42%-9.10%). The risk of liver injury requiring termination of treatment ranged from 0.11% (continuous itraconazole 100 mg/ day) to 1.22% ( continuous fluconazole 50 mg/ day). The risk of having asymptomatic elevation of serum transaminase but not requiring treatment discontinuation was less than 2.0% for all treatment regimens evaluated. CONCLUSION: Oral antifungal therapy against superficial dermatophytosis and onychomycosis, including intermittent and continuous terbinafine, itraconazole, and fluconazole, was associated with a low incidence of adverse events in an immunocompetent population. (C) 2007 Elsevier Inc. All rights reserved