Systemic Toxicity With Use of Apraclonidine Ophthalmic Drops in Pediatric Patients.

Importance: Apraclonidine, a topical α-2 adrenergic agonist, reverses anisocoria in patients with Horner syndrome, a disruption of the sympathetic chain to 1 eye and side of the face. In pediatric patients with anisocoria, apraclonidine is used off-label to exclude Horner syndrome. Objective: To identify and characterize postmarketing case reports reported to the US Food and Drug Administration and reported in the medical literature of systemic toxicity in pediatric patients administered apraclonidine ophthalmic drops. Design, Setting, and Participants: A search of the US Food and Drug Administration's Adverse Event Reporting System and the medical literature was conducted from approval to September 18, 2024, for reports describing adverse events in pediatric patients who received apraclonidine ophthalmic drops. Participants included 21 children who developed systemic adverse events associated with use of apraclonidine ophthalmic drops. These data were analyzed from September 2024 to March 2025. Exposure: Apraclonidine ophthalmic drops. Main outcomes and measures: Reports describing nonsystemic adverse events, accidental oral ingestion, or duplicate reports for the same patient, and reports whose causal association with apraclonidine was unassessable, unclassifiable, or unlikely based on the World Health Organization-Uppsala Monitoring Center system were excluded. The assessment included demographic information, reason for use, concomitant medications, dose, latency, medical intervention, and outcome information. Results: This case series included 21 patients (aged 12 days to 6 years; median age, 6 months) who developed systemic adverse events associated with use of apraclonidine ophthalmic drops. The most commonly reported adverse event was prolonged lethargy and unresponsiveness (17 of 21 [81%]) followed by clinically significant cardiorespiratory events (eg, apnea, hypoxia, bradycardia, blood pressure changes, or respiratory failure) (8 of 21 [38%]). Three cases required intubation. Most cases (16 of 21 [76%]) described patients younger than 1 year. The reason for use in most (12 of 16 [75%]) patients younger than 1 year was for diagnostic purposes. Conclusions and Relevance: This case series suggests use of apraclonidine in pediatric patients poses a risk of central α-2 adrenergic agonist-induced central nervous system and respiratory depression. Clinicians who use apraclonidine in the pediatric population should be aware of potential serious systemic effects from ophthalmic use of the drug and be prepared to manage these.