Safety and tolerability of topical polyhexamethylene biguanide: a randomised clinical trial in healthy adult volunteers

Background and Aims Polyhexamethyl biguanide (PHMB), a widely used topical treatment for Acanthamoeba keratitis (AK), is unlicensed with no formal safety assessment. This study evaluated its safety and tolerability. Methods A prospective, randomised, double-masked controlled trial in 90 healthy volunteers. Subjects were treated with topical 0.04%, 0.06%, 0.08% PHMB or placebo (vehicle) 12x daily for 7 days, then 6x daily for 7 days. The rates of dose-limiting adverse events (DLAEs) leading to interruption of dosing, mild adverse events (AEs) (not dose limiting) and incidental AEs (unrelated to treatment) were compared. The primary outcome was the difference between treatments for DLAE rates. Results 5/90 subjects developed DLAE within <1-4 days of starting treatment; 2/5 using PHMB 0.06% and 3/5 PHMB 0.08%. These resolved within 1-15 days. There were no significant differences in DLAE between treatment groups. Mild AEs occurred in 48/90 subjects (including placebo). There was no trend for an increased incidence of any AE with increasing concentrations of PHMB, except for corneal punctate keratopathy with PHMB 0.08%, which fully resolved within 7-14 days. Conclusion These findings are reassuring for PHMB 0.02% users. They also suggest that higher PHMB concentrations may show acceptable levels of tolerance and toxicity in AK subjects, whose susceptibility to AE may be greater than for the normal eyes in this study. Given the potential benefits of higher PHMB concentrations for treating deep stromal invasion in AK, we think that the use of PHMB 0.08% is justified in treatment trials.

Automated summary

This study evaluated the safety and tolerability of Polyhexamethyl biguanide (PHMB) in the treatment of Acanthamoeba keratitis (AK). The results showed that DLAE occurred in the treatment process of 0.06% and 0.08% concentrations of PHMB, but these adverse events were resolved within a short period of time. There was no significant trend in the incidence of other adverse events associated with increasing concentrations of PHMB. These findings are reassuring for patients using 0.02% PHMB.