title: Intermittent versus continuous terbinafine in the treatment of toenail onychomycosis: a randomized, double-blind comparison.
abstract: BACKGROUND
  Terbinafine is an established drug for the treatment of toenail onychomycosis. Minimizing the total dose of terbinafine and giving it intermittently could improve tolerability as well as compliance, provided efficacy is not compromised.
  
  
  OBJECTIVE
  Two identical trials were conducted to compare the efficacy, safety and tolerability of the current standard regimen of terbinafine 250 mg daily with a new formulation of terbinafine given intermittently for three cycles of 2 weeks of treatment (350 mg daily) followed by 2 weeks off treatment.
  
  
  METHODS
  A total of 2005 patients with a clinical diagnosis of subungual onychomycosis of the large toenail confirmed by microscopy and culture for a dermatophyte were recruited into the two trials and treated for 12 weeks.
  
  
  RESULTS
  Patients with onychomycosis of prolonged duration (mean 9 years) and a median nail involvement of 63% with or without spikes, lateral involvement and white superficial onychomycosis (WSO) were included in the trial. The studies found a significant difference (p<0.05) in favour of standard daily dosing with terbinafine. Response rates for the primary variable complete cure (mycological and clinical cure) were lower with the new formulation in both Trial I (-5.8%; 95% CI -11.8, 0.07) and Trial II (difference -5.9%; 95% CI -12, 0.1). Both treatments were equally well tolerated, with approximately 11% of patients in both groups reporting at least one treatment-related adverse event.
  
  
  CONCLUSIONS
  Pulsed dosing with terbinafine did not provide any clear safety advantages and was significantly less effective. Consequently, continuous treatment with terbinafine tablets remains the optimal therapy for onychomycosis.
authors.affiliation: Department of Dermatology, University of Iceland, Reykjavik, Iceland. bsig@hudlaeknastodin.is
authors.forename: Bardur
authors.initials: B
authors.lastname: Sigurgeirsson
authors.forename: Boni E
authors.initials: BE
authors.lastname: Elewski
authors.forename: Phoebe A
authors.initials: PA
authors.lastname: Rich
authors.forename: Carol
authors.initials: C
authors.lastname: Opper
authors.forename: Bin
authors.initials: B
authors.lastname: Cai
authors.forename: Judit
authors.initials: J
authors.lastname: Nyirady
authors.forename: Rajesh
authors.initials: R
authors.lastname: Bakshi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005533:Foot Dermatoses / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000008:administration & dosage*; D014009:Onychomycosis / Q000188:drug therapy*; D000077291:Terbinafine; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D009281:Naphthalenes; D000077291:Terbinafine