A systematic review of 122 published studies found that oral antifungal drugs were associated with low incidences of serious adverse events in immunocompetent people. None of the treatment regimens had an incidence of serious adverse events substantially higher than the rates in people treated with placebo.

A systematic review and meta-analysis assessed the safety of oral antifungal treatments for superficial dermatophytosis and onychomycosis [Chang et al, 2007].

• The review included data from 122 studies with approximately 20,000 participants. Only studies published in English were included. Data from randomized controlled trials (RCTs) were used in the primary analysis. An auxiliary analysis included data from observational studies (cohort studies and case series).
• The most commonly used continuous regimens in the published randomized controlled trials were:
• Placebo (15 arms, 891 participants).
• Terbinafine 250 mg/day (41 arms, 3135 participants).
• Terbinafine 500 mg/day for 1 week and then repeated every month (5 arms, 359 participants).
• Itraconazole 100 mg/day (19 arms, 1002 participants).
• Itraconazole 200 mg/day (12 arms, 2145 participants).
• Itraconazole 400 mg/day for 1 week and then repeated every month (15 arms, 766 participants).
• Fluconazole 50 mg/day (3 arms, 235 participants).
• Fluconazole 150 mg once weekly (7 arms, 514 participants).
• Fluconazole 300 mg to 450 mg once weekly (3 arms, 468 participants).
• Risk of discontinuing treatment because of adverse reactions:
• Placebo 3.25% (95% CI 1.48 to 5.02).
• Terbinafine:
• Continuous terbinafine 250 mg/day: 3.44% (95% CI 2.28% to 4.61%).
• Pulse treatment: 2.09% (95% CI 0% to 4.42%).
• Itraconazole:
• Continuous itraconazole 100 mg/day: 1.96% (95% CI 0.35% to 3.57%).
• Continuous itraconazole 200 mg/day: 4.21% (95% CI 2.33% to 6.09%).
• Pulse treatment: 2.58% (95% CI 1.15% to 4.01%).
• Fluconazole:
• Continuous fluconazole 50 mg/day: 1.51% (95% CI 0% to 4.01%).
• Intermittent fluconazole 150 mg/week: 1.98% (95% CI 0.05% to 3.92%).
• Intermittent fluconazole 300 mg/week to 450 mg/week: 5.76% (95% CI 2.42% to 9.10%).
• Risk of having elevated serum transaminase levels that required treatment termination:
• Placebo 1.01% (95% CI 0% to 2.19%).
• Itraconazole 100 mg/day: 0.11% (minimum observed risk for continuous therapy).
• Fluconazole 50 mg/day: 1.22% (maximum observed risk for continuous therapy).
• Itraconazole 400 mg/day: 0.39% (minimum observed risk for pulse therapy).
• Fluconazole 150 mg/week: 0.39% (minimum observed risk for intermittent therapy).
• Fluconazole 300 mg/week to 450 mg/week: 0.85% (maximum observed risk for intermittent therapy).
• Risk of having elevated serum transaminase levels that did not require treatment termination:
• Placebo 1.15% (95% CI 0% to 3.46%).
• About 1.5% for all continuous treatment regimens.
• About 1% for all pulse or intermittent treatment regimens.
• An auxiliary analysis using data from 10 non-randomized controlled trials and 35 observational studies found similar results, although most of the risk estimates were lower and their confidence intervals were narrower. The authors suggested that this could be due to less rigorous monitoring in these trials compared with RCTs.