title: The safety of oral antifungal treatments for superficial dermatophytosis and onychomycosis: a meta-analysis.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Chia-Hsuin
authors.initials: CH
authors.lastname: Chang
authors.forename: Yinong
authors.initials: Y
authors.lastname: Young-Xu
authors.forename: Tobias
authors.initials: T
authors.lastname: Kurth
authors.forename: John E
authors.initials: JE
authors.lastname: Orav
authors.forename: Arnold K
authors.initials: AK
authors.lastname: Chan
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D003881:Dermatomycoses / Q000188:drug therapy*; D015725:Fluconazole / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage / Q000627:therapeutic use; D008111:Liver Function Tests; D015233:Models, Statistical; D009281:Naphthalenes / Q000008:administration & dosage / Q000627:therapeutic use; D014009:Onychomycosis / Q000188:drug therapy*; D020551:Pulse Therapy, Drug; D018570:Risk Assessment; D000077291:Terbinafine; D000637:Transaminases / Q000097:blood
chemical_list: D000935:Antifungal Agents; D009281:Naphthalenes; D017964:Itraconazole; D015725:Fluconazole; D000637:Transaminases; D000077291:Terbinafine