Drug synergies and the potential for combination therapy in onychomycosis

Synergy between antifungal drugs is well recognized. However, combinations of antifungals are yet to be widely adopted to treat onychomycosis. The rationale for the combination of topical and oral therapy in the treatment of onychomycosis is that the systemic antifungal reaches the infection area via the nail bed and the topical agent is absorbed through the nail surface. The combination of antifungals used should ideally be synergistic in their mode of action. Synergy between amorolfine and other antifungals has been demonstrated in vitro. This is presumably due to differences in the precise point of action of the drugs on the fungal cell membrane, where they inhibit the synthesis of ergosterol. Thus, combinations can result in increased antifungal activity at lower concentrations of both drugs. The potential exists therefore for combinations of antifungals to achieve higher cure rates in onychomycosis, in a shorter time than is currently possible. This approach warrants further investigation.