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

Abstract

Background and AimsPolyhexamethyl 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.MethodsA 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) 12× daily for 7 days, then 6× 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.Results5/90 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.ConclusionThese 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.Trial registration numberNCT02506257.

The Activity of PHMB and Other Guanidino Containing Compounds against Acanthamoeba and Other Ocular Pathogens

“…Weekly and monthly contact lens wearers are required to disinfect their lenses daily, and due to a variety of risk factors, including poor hand hygiene and the choice of MPS, are at risk of infection. AK which is caused by Acanthamoeba is of particular concern, as it is able to form a highly resistant cyst that is resistant to disinfection [ 12 ], and when a patient contracts AK, it requires a protracted treatment regime with a mean treatment time of many moths to effect a cure [ 10 ]. Therefore, there is an urgent need to identify alternative compounds for the inclusion into MPS for contact lens disinfection and for the treatment of AK.…”

“…Besides its use in commercial MPS, PHMB is also widely used topically in the treatment of Acanthamoeba keratitis (AK) [ 10 ]. Current first-line medical therapy for AK is unlicensed and usually involves a biguanide, which is either chlorhexidine or PHMB as a monotherapy at 0.02% ( v / v ) or in combination with 0.1% ( v / v ) propamidine or 0.1% hexamidine ( v / v ), all administered as eye drops several times per day [ 11 ].…”

“…Current first-line medical therapy for AK is unlicensed and usually involves a biguanide, which is either chlorhexidine or PHMB as a monotherapy at 0.02% ( v / v ) or in combination with 0.1% ( v / v ) propamidine or 0.1% hexamidine ( v / v ), all administered as eye drops several times per day [ 11 ]. Despite the in vitro sensitivity of Acanthamoeba to PHMB, the response to treatment is highly variable and requires a protracted treatment regime, which has an average cure time of 5 months, with individual patients varying from 1 to 26.24 months [ 10 ]. This demonstrates that there is an urgent need to identify alternative compounds for the treatment of AK.…”

Topical Antibiofilm Agents With Potential Utility in the Treatment of Chronic Rhinosinusitis: A Narrative Review

“…However, this has not prevented clinical use suggesting that these laboratory findings are less relevant in vivo. Polyhexanide drops have been used to treat ophthalmic infections, and one phase I trial has demonstrated no dose-limiting adverse effects when used at a concentration of 0.04% ( Papa et al, 2020 ). Nasal epithelial ciliary beating is markedly slowed on exposure to concentrations as low as 0.01%, however, with complete and relatively swift ciliostasis seen at higher concentrations within the clinical dosage range ( Birk et al, 2015 ).…”

Challenges in Acanthamoeba Keratitis: A Review

“…is susceptible to multiple therapies, the cystic form is highly drug resistant and may persist for months [8]. The principal initial treatment is the administration of a topical biguanide, such as polyhexamethylene biguanide (PHMB) 0.02-0.08% [37] or chlorhexidine 0.02-0.06% [38], along with or without a topical diamidine, such as propamidine isethionate 0.1% [2][3][4][6][7][8]11,12,20,21,27]. Initially, these medications should be administered every hour around the clock for the first 48-72 h and then tapered gradually.…”