Internal validity gaps in repurposing olopatadine ophthalmic solution for intranasal use: A Regulatory and scientific feasibility appraisal for Thailand

Abstract

Background: Allergic rhinitis is a prevalent condition that often requires local treatment to minimize systemic side effects. While intranasal antihistamines are effective, access in some settings is limited. Olopatadine hydrochloride, currently approved for ophthalmic use, has pharmacological properties that may be suitable for intranasal administration. Objective: To evaluate the feasibility of repurposing olopatadine hydrochloride ophthalmic solution for intranasal use in treating allergic rhinitis by assessing pharmacologic rationale, formulation characteristics, safety, and regulatory considerations. Methods: A systematic review was conducted in accordance with the PRISMA 2020 guidelines. Eligible studies included randomized controlled trials (RCTs), pharmacokinetic investigations, mucosal safety assessments, and regulatory evaluations relevant to the intranasal administration of olopatadine. Risk of bias was appraised using the Cochrane RoB 2.0 tool for RCTs and the OHAT tool for non-randomized or preclinical studies. Findings were synthesized narratively, with meta-analysis performed where appropriate. Results: No studies were identified directly evaluated the intranasal use of olopatadine ophthalmic formulation. However, high-quality RCTs on olopatadine nasal spray (0.6%) demonstrated statistically significant improvements in allergic rhinitis symptoms, with an absolute risk reduction of 11.7%, a number needed to treat (NNT) of approximately 8.3, and low heterogeneity (I² = 19.5%). Despite these findings, they are not directly generalizable to the ophthalmic product due to formulation differences—including concentration, excipients, and pharmacokinetic properties—as well as the absence of population-bridging data for Thai patients. Additionally, no mucosal safety data or physiologically based pharmacokinetic (PBPK) models were identified to support intranasal safety or predict systemic exposure using ophthalmic preparation. Conclusions: Findings suggest pharmacologic and pharmaceutical feasibility for intranasal repurposing of olopatadine hydrochloride ophthalmic solution. While preclinical and clinical studies are needed to confirm efficacy and safety in nasal administration, the data provide a preliminary foundation for further development.