Onychomycosis, a common nail disease caused by fungi, poses significant challenges in terms of treatment failure and relapse, particularly in an aging population with increasing comorbidities and polydrug use. It adversely impacts patients health, psychosocial behavior and quality of life. Therefore, an ideal antifungal for onychomycosis should exhibit high mycological cure rates, pharmacokinetics favoring high concentrations in the nail plate and the subungual space, a mechanism of action mitigating the risk of resistance, minimal adverse events and recurrence.

Resistance to antifungal drugs and adverse drug interactions are major concerns that necessitate a shift to safer drugs, particularly topical antifungals, which are regarded as less toxic and minimally interact with other drugs. Treatment guidelines suggest that topical treatments are monotherapies for superficial white onychomycosis and early distal-lateral subungual onychomycosis when systemic antifungal drugs are contraindicated. The choice of appropriate topical treatment should consider the depth and location of the infection on the nail unit and the agents high affinity for keratin.

The evolution of new topical drugs for onychomycosis, like efinaconazole, tavaborole and luliconazole, has resulted from an unmet need for effective agents with prolonged post-treatment disease-free time which does not have a systemic impact on patients health. The researchers are currently focused on developing new products with appealing pharmacokinetic, efficacy and safety properties or reformulating old, well-known drugs using new excipients as penetration enhancers.

In conclusion, onychomycosis is a challenging disease that requires a more sophisticated therapeutic approach to achieve high efficacy, safety and prolonged post-treatment disease-free time. Developing new topical antifungals and optimizing their use based on pharmacokinetics would assist dermatologists in achieving better outcomes for patients with onychomycosis.

Source: Gregoriou S, Kyriazopoulou M, Tsiogka A, Rigopoulos D. Novel and investigational treatments for onychomycosis. J Fungi (Basel). 2022;8(10):1079.