There is weak evidence to suggest that oral itraconazole is less effective than oral terbinafine for dermatophyte onychomycosis. Six randomized controlled trials (RCTs) found mixed results, but on balance the evidence favours terbinafine over itraconazole. Methodological weaknesses were common in the studies.

Systematic reviews (search date: up to June 2006) found four RCTs that compared oral itraconazole and oral terbinafine to treat fungal toenail infection [Crawford et al, 2002; Crawford and Ferrari, 2007].

• Data for meta-analysis could be pooled for two of the RCTs (n = 501).
• At the 1-year follow-up point, cure rates after 12 weeks of treatment were significantly lower with itraconazole 200 mg daily than with terbinafine 250 mg daily.
• Cure rates: 48% compared with 69%, absolute risk reduction 21% (95% CI 13% to 29%).
  These results are from a later review [Crawford and Ferrari, 2007] and are slightly different from those in the original [Crawford et al, 2002].
• A small open-label RCT (21 participants in each arm) assessed the effectiveness of three treatments for fungal nail infection [Tosti et al, 1996].
• Six months after completing treatment, that lasted 4 months for toenail infection and 2 months for fingernail infection, mycological cure rates in the different groups were:
• Pulsed itraconazole 400 mg daily for 1 week in every month: 15 of 21 (76%).
• Continuous terbinafine 250 mg daily: 18 of 19 (95%).
• Pulsed terbinafine 500 mg daily for 1 week in every month: 16 of 20 (80%).
• Cure rates were significantly lower for pulsed itraconazole 400 mg daily for 1 week per month compared with continuous terbinafine 250 mg daily (p = 0.013).
• When results for the three people with exclusive fingernail infection were excluded, there was no significant difference in cure rates between pulsed itraconazole and continuous terbinafine: 75% compared with 84%; absolute risk difference 9% (95% CI –34% to +16%).
• A double-blind RCT (n = 496) compared pulsed itraconazole (400 mg daily for 1 week in every 4 weeks) with continuous terbinafine (250 mg daily) for treatment courses of 12 weeks and 16 weeks. Cure rates for pulsed itraconazole were significantly lower than those for continuous terbinafine, for both 12-week and 16-week treatments.
• Cure rates at 72 weeks after 12 weeks of treatment, comparing itraconazole with terbinafine:
• 33% compared with 65%; absolute risk difference 33% (95% CI 21% to 44%).
• Cure rates at 72 weeks after 16 weeks of treatment, comparing itraconazole with terbinafine:
• 42% compared with 67%; absolute risk difference 25% (95% CI 13% to 37%).
• Long-term outcomes after treatment for dermatophyte toenail onychomycosis were assessed in a subgroup of 151 people [Sigurgeirsson et al, 2002]. People who had not achieved clinical cure at 18 months, or who relapsed or were reinfected, were offered an additional course of terbinafine. At final follow up (median 54 months), itraconazole was less effective than terbinafine in terms of rates of:
• Mycological cure without a second course of treatment: 13% compared with 46% (p < 0.001).
• Clinical cure without a second course of treatment: 18% compared with 42% (p < 0.002).
• Cure rates in people who had a second course of treatment were:
• Mycological cure: 88%.
• Clinical cure after a second course of treatment: 76%.
• The quality of evidence from these four trials was assessed as very low because of the possibility of publication bias, inconsistent definitions of cure, and inconsistency in the results [Crawford and Ferrari, 2007].

CKS found two further RCTs published subsequent to the systematic reviews; their results were mixed.

• One RCT (n = 63) found pulsed itraconazole and continuous terbinafine to be similarly effective for treating dermatophyte distal and lateral subungual onychomycosis of the toenails in people with diabetes mellitus [Gupta et al, 2006].
• Participants were treated either with pulsed itraconazole 200 mg twice daily (1 week on, 3 weeks off) for 12 weeks, or with continuous terbinafine (250 mg once daily for 12 weeks).
• At week 48:
• Mycological cure rates in the itraconazole and terbinafine groups were 88% and 79% (no statistically significant difference).
• Complete cure (mycological cure with up to 10% of nail plate involvement) in the itraconazole and terbinafine groups were 53% and 52% (no statistically significant difference).
• One open-label RCT (n = 30) found pulsed itraconazole and pulsed terbinafine to be similarly effective for treating onychomycosis [Sikder et al, 2006].
• Participants were treated, for 1 week in each 4-week cycle, for 16 weeks with either itraconazole 200 mg daily or terbinafine 250 mg daily.
• At week 36:
• Clinical cure rates (no residual deformity or some deformity) in the itraconazole and terbinafine groups were 87% and 100% (p = 0.864).
• Mycological cure rates were the same as the clinical cure rates.