title: A randomized trial of amorolfine 5% solution nail lacquer in association with itraconazole pulse therapy compared with itraconazole alone in the treatment of Candida fingernail onychomycosis.
abstract: BACKGROUND
  Treatment failures and relapses are not uncommon in onychomycosis. Therefore, it is worthwhile to consider the combination of systemic and topical antifungals to improve the cure rates further and to reduce the duration of systemic treatment.
  
  
  OBJECTIVE
  To evaluate and compare itraconazole pulse therapy combined with amorolfine with itraconazole alone in the treatment of Candida fingernail onychomycosis.
  
  
  METHODS
  Ninety patients with moderate to severe Candida fingernail onychomycosis were randomized into two treatment groups of 45 subjects each. Group 1 received itraconazole pulse therapy for 2 months and applied amorolfine 5% solution nail lacquer for 6 months, while group 2 received monotherapy with three pulses of itraconazole. The primary efficacy criterion was the result of mycological examination at 3 months. The secondary criterion was the combined mycological and clinical response at 9 months. A pharmacoeconomic analysis was also performed to compare the cost-effectiveness of combined therapy vs. monotherapy.
  
  
  RESULTS
  Eighty-five patients were analysed (73 women and 12 men, mean +/- SD age 44.2 +/- 12.9 years). Patients had a mean +/- SD of 3.64 +/- 2.0 nails involved and 228.6 +/- 148.0 mm2 of their nail surface diseased. The mean duration of onychomycosis was 11 months. Paronychial involvement was evident in 71 patients. C. albicans was isolated in 85 cases, C. parapsilosis in three and other Candida species in two cases. Side-effects were uncommon and in only one case led to withdrawal. At the 3-month visit, mycological cure was seen in 32 (74%) of 43 patients in group 1 and in 25 (60%) of 42 patients in group 2. At the 9-month visit, a global cure was seen in 40 patients (93%) in group 1 and in 34 patients (81%) in group 2. Statistical analysis showed no statistically significant difference (P > 0.1) between the two treatment groups. The cost per cure ratio was 1.63 and 1.70euro for groups 1 and 2, respectively.
  
  
  CONCLUSIONS
  The combination of amorolfine and oral itraconazole, which interfere with different steps of ergosterol synthesis, exhibited substantial synergy. Compared with oral itraconazole alone, the combination achieved greater mycological cure and increased total cure rate. However, no statistically significant difference was documented for this number of observations. Combination treatment with amorolfine and two pulses of itraconazole is at least as safe and effective as three pulses of itraconazole, with a lower cost per patient. In our opinion, the addition of amorolfine to oral itraconazole pulse therapy is of value in the treatment of moderate to severe Candida fingernail onychomycosis.
authors.affiliation: National and Kapodistrian University of Athens, Department of Dermatology and Venereology, A.Sygros Hospital, 5 Dragoumi Str., Athens 16121, Greece. eykat@panafonet.gr
authors.forename: D
authors.initials: D
authors.lastname: Rigopoulos
authors.forename: A C
authors.initials: AC
authors.lastname: Katoulis
authors.forename: D
authors.initials: D
authors.lastname: Ioannides
authors.forename: S
authors.initials: S
authors.lastname: Georgala
authors.forename: D
authors.initials: D
authors.lastname: Kalogeromitros
authors.forename: I
authors.initials: I
authors.lastname: Bolbasis
authors.forename: A
authors.initials: A
authors.lastname: Karistinou
authors.forename: E
authors.initials: E
authors.lastname: Christofidou
authors.forename: D
authors.initials: D
authors.lastname: Polydorou
authors.forename: P
authors.initials: P
authors.lastname: Balkou
authors.forename: E
authors.initials: E
authors.lastname: Fragouli
authors.forename: A D
authors.initials: AD
authors.lastname: Katsambas
mesh_terms: D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use*; D002177:Candidiasis / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006229:Hand Dermatoses / Q000188:drug therapy; D006801:Humans; D017964:Itraconazole / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use*; D014009:Onychomycosis / Q000188:drug therapy*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D009025:Morpholines; D017964:Itraconazole; C038974:amorolfine