Internal validity gaps in repurposing olopatadine ophthalmic solution for intranasal use: A Regulatory and scientific feasibility appraisal for Thailand
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Keywords
olopatadine, Allergic rhinitis, repurposing, internal validity, nasal delivery
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.
References
2. Patcharanarumol S, Wachiruksasawakul T, Phadungvorasart W, Poachanukoon O. The beliefs about allergic rhinitis and its treatment options from people in Central Thailand. Asia Pac Allergy. 2022;12(1):e11. doi:10.5415/apallergy.2022.12.e11.
3. Sousa-Pinto B, Vieira RJ, Bognanni A, Gil-Mata S, Ferreira-da-Silva R, Ferreira A, Cardoso-Fernandes A, Ferreira-Cardoso H, Marques-Cruz M, Duarte VH, Castro-Teles J, Campos-Lopes M, Teixeira-Ferreira A, Lourenço-Silva N, Chérrez-Ojeda I, Bedbrook A, Klimek L, Nuñez JJY, Zuberbier T, Fonseca JA, Schünemann HJ, Bousquet J. Efficacy and safety of intranasal medications for allergic rhinitis: Network meta-analysis. Allergy. 2025;80(1):94-105. doi:10.1111/all.16384.
4. Roland PS, Ryan MW, Wall GM. Olopatadine nasal spray for the treatment of seasonal allergic rhinitis in patients aged 6 years and older. Expert Opin Pharmacother. 2010;11(9):1559-1567. doi:10.1517/14656566.2010.485609.
5. Krungkraipetch L, Tansavadi T, Krungkraipetch D. Ranking the efficacy of topical treatments for ocular allergy: A network meta-analysis of current evidence. Ocul Surf. 2025;37:273-282. doi:10.1016/j.jtos.2025.05.003.
6. Kaliner MA, Oppenheimer J, Farrar JR. Comprehensive review of olopatadine: the molecule and its clinical entities. Allergy Asthma Proc. 2010;31(2):112-119. doi:10.2500/aap.2010.31.3317.
7. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, Shamseer L, Tetzlaff JM, Akl EA, Brennan SE, Chou R, Glanville J, Grimshaw JM, Hróbjartsson A, Lalu MM, Li T, Loder EW, Mayo-Wilson E, McDonald S, McGuinness LA, Stewart LA, Thomas J, Tricco AC, Welch VA, Whiting P, Moher D. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi:10.1136/bmj.n71.
8. Nejadghaderi SA, Balibegloo M, Rezaei N. The Cochrane risk of bias assessment tool 2 (RoB 2) versus the original RoB: A perspective on the pros and cons. Health Sci Rep. 2024;7(6):e2165. doi:10.1002/hsr2.2165.
9. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, Henry D, Altman DG, Ansari MT, Boutron I, Carpenter JR, Chan AW, Churchill R, Deeks JJ, Hróbjartsson A, Kirkham J, Jüni P, Loke YK, Pigott TD, Ramsay CR, Regidor D, Rothstein HR, Sandhu L, Santaguida PL, Schünemann HJ, Shea B, Shrier I, Tugwell P, Turner L, Valentine JC, Waddington H, Waters E, Wells GA, Whiting PF, Higgins JP. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ. 2016;355:i4919. doi:10.1136/bmj.i4919.
10. National Toxicology Program. OHAT Risk of Bias Rating Tool for Human and Animal Studies. Research Triangle Park (NC): Office of Health Assessment and Translation, National Institute of Environmental Health Sciences; 2015.
11. Uchio E. Treatment of allergic conjunctivitis with olopatadine hydrochloride eye drops. Clin Ophthalmol. 2008;2(3):525-531. doi:10.2147/opth.s3294.
12. Abelson MB. Evaluation of olopatadine, a new ophthalmic antiallergic agent with dual activity, using the conjunctival allergen challenge model. Ann Allergy Asthma Immunol. 1998;81(3):211-218. doi:10.1016/S1081-1206(10)62814-1.
13. National Center for Biotechnology Information. PubChem Compound Summary for CID 5281071, Olopatadine. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Olopatadine
14. Morgan-Warren PJ, Morarji JB. Trends in licence approvals for ophthalmic medicines in the United Kingdom. Eye (Lond). 2020;34(10):1856-1865. doi:10.1038/s41433-019-0758-7.
15. Wise SK, Lin SY, Toskala E, Orlandi RR, Akdis CA, Alt JA, Azar A, Baroody FM, Bachert C, Canonica GW, Chacko T, Cingi C, Ciprandi G, Corey J, Cox LS, Creticos PS, Custovic A, Damask C, DeConde A, DelGaudio JM, Ebert CS, Eloy JA, Flanagan CE, Fokkens WJ, Franzese C, Gosepath J, Halderman A, Hamilton RG, Hoffman HJ, Hohlfeld JM, Houser SM, Hwang PH, Incorvaia C, Jarvis D, Khalid AN, Kilpeläinen M, Kingdom TT, Krouse H, Larenas-Linnemann D, Laury AM, Lee SE, Levy JM, Luong AU, Marple BF, McCoul ED, McMains KC, Melén E, Mims JW, Moscato G, Mullol J, Nelson HS, Patadia M, Pawankar R, Pfaar O, Platt MP, Reisacher W, Rondón C, Rudmik L, Ryan M, Sastre J, Schlosser RJ, Settipane RA, Sharma HP, Sheikh A, Smith TL, Tantilipikorn P, Tversky JR, Veling MC, Wang Y, Westman M, Wickman M, Zacharek M. International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis. Int Forum Allergy Rhinol. 2018;8(2):108-352. doi:10.1002/alr.22073.
16. Ellis AK, Cook V, Keith PK, Mace SR, Moote W, O’Keefe A, Quirt J, Rosenfield L, Small P, Watson W. Focused allergic rhinitis practice parameter for Canada. Allergy Asthma Clin Immunol. 2024;20(1):45. doi:10.1186/s13223-024-00899-3.
17. Batool S, Burks CA, Bergmark RW. Healthcare disparities in otolaryngology. Curr Otorhinolaryngol Rep. 2023;11:1-14. doi:10.1007/s40136-023-00459-0.
18. Abdullah B, Abdul Latiff AH, Manuel AM, Mohamed Jamli F, Dalip Singh HS, Ismail IH, Jahendran J, Saniasiaya J, Keen Woo KC, Khoo PC, Singh K, Mohammad N, Mohamad S, Husain S, Mösges R. Pharmacological management of allergic rhinitis: A consensus statement from the Malaysian Society of Allergy and Immunology. J Asthma Allergy. 2022;15:983-1003. doi:10.2147/JAA.S374346.
19. Tantilipikorn P, Kirtsreesakul V, Bunnag C, Vangveeravong M, Thanaviratananich S, Chusakul S. The use of azelastine hydrochloride/fluticasone propionate in the management of allergic rhinitis in Asia: A review. J Asthma Allergy. 2024;17:667-679. doi:10.2147/JAA.S451733.
20. Meltzer EO, Hampel FC, Ratner PH, Bernstein DI, Larsen LV, Berger WE, Finn AF Jr, Marple BF, Roland PS, Wall GM, Brubaker MJ, Dimas C, Potts SL, Silver LH, Barnes JR. Safety and efficacy of olopatadine hydrochloride nasal spray for the treatment of seasonal allergic rhinitis. Ann Allergy Asthma Immunol. 2005;95(6):600-606. doi:10.1016/S1081-1206(10)61025-3.
21. Ratner PH, Hampel FC, Amar NJ, van Bavel JH, Mohar D, Marple BF, Roland PS, Wall GM, Brubaker MJ, Drake M, Turner D, Silver LH. Safety and efficacy of olopatadine hydrochloride nasal spray for the treatment of seasonal allergic rhinitis to mountain cedar. Ann Allergy Asthma Immunol. 2005;95(5):474-479. doi:10.1016/S1081-1206(10)61174-X.
22. Patel D, Garadi R, Brubaker M, Conroy JP, Kaji Y, Crenshaw K, Whitling A, Wall GM. Onset and duration of action of nasal sprays in seasonal allergic rhinitis patients: olopatadine hydrochloride versus mometasone furoate monohydrate. Allergy Asthma Proc. 2007;28(5):592-599. doi:10.2500/aap2007.28.3033.
23. Shah SR, Nayak A, Ratner P, Roland P, Wall GM. Effects of olopatadine hydrochloride nasal spray 0.6% in the treatment of seasonal allergic rhinitis: a phase III randomized controlled study. Clin Ther. 2009;31(1):99-107. doi:10.1016/j.clinthera.2009.01.016.
24. Lieberman P, Meltzer EO, LaForce CF, Darter AL, Tort MJ. Comparison of olopatadine hydrochloride nasal spray 0.6% versus azelastine hydrochloride nasal spray 0.1% in patients with vasomotor rhinitis. Allergy Asthma Proc. 2011;32(2):151-158. doi:10.2500/aap.2011.32.3439.
25. Meier E, Narvekar A, Iyer GR, DuBiner HB, Vutikullird A, Wirta D, Sall K. Pharmacokinetics and safety of olopatadine hydrochloride 0.77% in healthy subjects. Clin Ophthalmol. 2017;11:669-681. doi:10.2147/OPTH.S126690.
26. Ministry of Public Health, Thailand. Drug Act B.E. 2510 (1967) and amendments. Bangkok: Food and Drug Administration; 1967.
27. Thai Food and Drug Administration. Guideline on registration of new drug products (human use). Bangkok: Ministry of Public Health; 2020.
28. International Conference on Harmonisation (ICH). ICH Harmonised Tripartite Guideline: E5 – Ethnic factors in the acceptability of foreign clinical data. London: European Medicines Agency; 1998.
29. World Medical Association. Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191-2194.
30. Teresi JA, Yu X, Stewart AL, Hays RD. Guidelines for designing and evaluating feasibility pilot studies. Med Care. 2022;60(1):95-103. doi:10.1097/MLR.0000000000001664.
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