Low risk of ocular toxicity following topical ocular administration of epinephrine nasal spray: implications for unintentional exposure

Abstract Introduction Unintentional ocular exposure to epinephrine nasal spray (10 mg/mL epinephrine) is a potential safety concern. Although epinephrine is used in multiple ocular formulations, unintentional ocular administration of epinephrine nasal spray was assessed to determine tolerability and support the overall safety profile. Methods A non-GLP ocular tolerability study was conducted using six naïve New Zealand White rabbits (3 males, 3 females). Vehicle control or epinephrine nasal spray (1 mg) was applied to the right or left eye, respectively, once on Day 1. Animals were monitored over seven days for mortality, clinical signs, body weight changes, ophthalmic findings, ocular irritation (using the Modified Hackett-McDonald Scoring System), and gross necropsy findings. Results Epinephrine nasal spray was well tolerated with no mortality, clinical abnormalities, or changes in body weight. Ophthalmic examinations via indirect ophthalmoscopy and slit-lamp biomicroscopy revealed no signs of irritation or ocular toxicity. No gross pathological changes were noted at necropsy. Conclusion A single topical administration of epinephrine nasal spray (10 mg/mL) in rabbit eyes was not associated with any adverse effects, indicating a low risk of ocular toxicity. These results support the safety of epinephrine nasal spray in the event of unintentional ocular exposure and taken together with epinephrine’s use in other ocular formulations, suggest that no further nonclinical ocular studies are necessary.