title: Safety and efficacy of oral terbinafine in the treatment of onychomycosis: analysis of the elderly subgroup in Improving Results in ONychomycosis-Concomitant Lamisil and Debridement (IRON-CLAD), an open-label, randomized trial.
abstract: OBJECTIVE
  The primary objective of this subanalysis was to examine the safety, tolerability, and efficacy of terbinafine in the treatment of toenail onychomycosis in the patients aged > or = 65 years in the Improving Results in Onychomycosis Concomitant Lamisil And Debridement (IRON-CLAD) trial. (Lamisil and IRON-CLAD are trademarks of Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.) The secondary objective was to determine if toenail debridement would provide additional efficacy benefits in this subgroup.
  
  
  METHODS
  The IRON-CLAD trial was an open-label, randomized, multicenter study of adults who underwent 4 weeks of screening and received terbinafine 250 mg/d for 12 weeks with or without aggressive toenail debridement (at baseline and weeks 6, 12, and 24). Clinic visits occurred at weeks 6, 12, 24, and 48. Safety and tolerability were assessed by adverse event (AE) rates based on changes in laboratory values, patient-volunteered information, answers to investigator questions, and physical examinations. Efficacy was evaluated by mycologic cure (negative microscopy of potassium hydroxide samples and negative culture), clinical cure (> or = 87.5% nail clearing), and complete cure (mycologic cure and complete toenail clearing) at week 48. The present subanalysis of IRON-CLAD results assessed participants aged > or = 65 years (older subgroup).
  
  
  RESULTS
  A total of 504 patients were randomized, of whom 75 were aged > or = 65 years. In the older subgroup, the mean (SD) age was 68.9 (3.04), 86.7% (65/75) were white, and 66.7% (50/75) were male. Incidence of AEs reported during the treatment period or within 30 days after treatment discontinuation (treatment-emergent AEs [TEAEs]) was 28.0% in the older subgroup and 23.0% in the overall study population. Most TEAEs were mild (73.7%) to moderate (23.7%) in severity, and most (86.8%) were not suspected by the investigators to be related to study treatment. The most frequently occurring TEAEs in the older subgroup were nausea (4.0%), sinusitis (4.0%) arthralgia (2.7%), and hypercholesterolemia (2.7%). The proportion of participants who withdrew from the trial due to TEAEs was 4.0% (3/75) in the older group and 2.8% (14/504) in the overall population. Only 3 of 11 discontinuations in the older subgroup were due to a TEAE suspected by the investigator to be related to study treatment. Sixty-four percent of the older subgroup took antihypertensive medications, 25% took antidiabetics, and 47% took antilipemic medications. There were no clinical signs of drug interactions in the older subgroup. Clinical efficacy outcomes in the older subgroup were generally good and appeared to be comparable with those in the younger subgroup. At week 48, mycologic cure had occurred in 64.0% (95% CI, 53.1%-74.9%) of the older subgroup, clinical cure in 41.3% (95% CI, 30.2%-52.5%), and complete cure in 28.0% (95% CI, 17.8%-38.2%). Debridement did not appear to affect mycologic outcomes or clinical effectiveness, but rates of clinical and complete cure appeared to be higher among older patients who underwent adjuvant debridement.
  
  
  CONCLUSIONS
  The results of this subanalysis suggest that terbinafine was well tolerated and efficacious in these patients aged > or = 65 years with moderate to severe toenail onychomycosis, many of whom were taking antihypertensives, antidiabetics, or lipid-lowering agents concomitantly. There were no reported clinical signs of drug interactions.
authors.affiliation: US Clinical Development & Medical Affairs, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey 07936-1080, USA. amir.tavakkol@novartis.com
authors.forename: Amir
authors.initials: A
authors.lastname: Tavakkol
authors.forename: Stephanie
authors.initials: S
authors.lastname: Fellman
authors.forename: Farid
authors.initials: F
authors.lastname: Kianifard
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003646:Debridement; D005260:Female; D005533:Foot Dermatoses / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes / Q000009:adverse effects / Q000627:therapeutic use*; D014009:Onychomycosis / Q000188:drug therapy*; D000077291:Terbinafine
chemical_list: D000935:Antifungal Agents; D009281:Naphthalenes; D000077291:Terbinafine