What are the most effective treatments for fungal toenails and what danger do they pose to the liver?

The short version: oral terbinafine is the most effective drug for common fungal toenail infections, but it carries real liver risks, and topical options are far safer though less effective.

The evidence here is a mixed bag of manufacturer-funded trials and small independent studies. The 1998 double-blind trial of 378 patients, funded by the drug maker, found terbinafine 250 mg daily for 12 weeks achieved mycologic cure in 73% of patients at 48 weeks, compared to 46% for itraconazole [3]. A 2002 systematic review confirmed terbinafine as the most effective oral option, with cure rates around 72% [1]. A 2022 Pakistani trial of 100 patients claimed pulse itraconazole beat continuous terbinafine (86% vs 64% effective cure), but that study had no blinding and reported no safety data at all [2]. The older, better-designed trial says the opposite.

The liver danger is real and dose-dependent. A 2014 safety review of oral ketoconazole found liver enzyme elevations in 17.5% of onychomycosis patients and overt hepatitis in 3% [6]. For terbinafine, the same review found a lower rate: about 16 liver injuries per 100,000 patients, compared to 36 for itraconazole and 49 for ketoconazole [6]. But "lower" is not "safe." A 2025 study of itraconazole in 103 patients found elevated liver enzymes in 2.9% and dyspeptic symptoms in 11.6% [7]. These are not rare events.

Topical efinaconazole 10% is the safer alternative. A 2025 pooled analysis of two phase 3 trials in older adults found complete cure in 13.6% of patients at 52 weeks, versus 3.6% with placebo [4]. That is a low cure rate, but the safety profile was essentially identical to placebo [4]. No liver toxicity. No systemic effects. The trade-off is clear: you trade efficacy for safety.

For mild to moderate infections, start with topical efinaconazole. It will not work for everyone, but it will not hurt your liver. For severe or resistant cases, terbinafine is the best oral option, but you need baseline liver function tests and monitoring during treatment. Do not take oral antifungals without a doctor checking your liver enzymes first.

My call: for most people, topical efinaconazole is the right first choice despite low cure rates, because the liver risk from oral drugs is not trivial. Reserve oral terbinafine for confirmed severe cases with liver monitoring. Confidence: moderate.