Removal of preservative from Ganfort improves intraocular pressure (IOP) lowering in patients – A timolol dose‐response phenomenon

Purpose A benzalkonium chloride (BAK)‐free fixed‐combination formulation of bimatoprost and timolol (Ganfort) has been developed for patients who are sensitive to preservatives. A randomized controlled study in 561 patients compared the IOP‐lowering efficacy of the BAK‐free formulation versus the preserved Ganfort. At all timepoints, IOP lowering, numerically, consistently favoured the BAK‐free formulation. This finding contradicted expectations that the removal of BAK would result in lower ocular bioavailability of both bimatoprost and timolol, resulting in less efficacy. Research was conducted to explore possible explanation for the clinical observation. Methods Literature search on timolol dose response was performed, focusing on IOP lowering following topical dosing of 0.1%, 0.25%, and 0.5% timolol ophthalmic solutions. Results A U‐shaped dose‐response curve exists for timolol, and available data suggest that the dose that elicits maximal IOP lowering lies between 0.25% and 0.5%. Conclusion Removal of BAK from the fixed combination product Ganfort, which contains 0.5% timolol, may have resulted in a lower, but optimal, ocular concentration of timolol, leading to improved IOP‐lowering efficacy with the preservative‐free formulation. Commercial interest