(228) Beta-blocker-associated Hypoglycemia in Pediatric Patients: Findings from the FDA Adverse Event Reporting System, National Poison Data System, Medical Literature, and Sentinel Distributed Database

Background: Hypoglycemia is a known risk with all beta-blockers (BB). Little is known about BB-associated hypoglycemia in pediatric patients in the post-market setting.

Objectives: To describe pediatric hypoglycemia cases associated with BB in the FDA Adverse Event Reporting System (FAERS), National Poison Data System (NPDS), and medical literature, and to characterize this adverse event in the population-based Sentinel Distributed Database (SDD)

Methods: We queried FAERS and medical literature (through Jan 25, 2022) and NPDS (from Jan 2000 to Dec 2021) for all reports of BB-associated hypoglycemia in pediatric patients. We identified pediatric patients (0-17 years) in the SDD who initiated BBs from Jan 2008 to Feb 2023. We followed patients for the occurrence of hypoglycemia from BB initiation until censoring events of interest. BB initiation was defined as no dispensing in the prior 6 months or no dispensing since birth for infants under 6 months of age.

Results: We identified 116 cases of hypoglycemia associated with propranolol (n=78), nadolol (n=20), carvedilol (n=8), sotalol (n=7), timolol (n=2), and atenolol (n=1) in FAERS and medical literature. Most cases were reported in children 0-1 year (n=61) and 2-5 years (n=41). The median time-to-onset was 152 days. Cardiovascular conditions (n=70) and hemangioma (n=35) were the most reported indications. Most cases (n=80) occurred in settings of poor appetite and fasting for surgery or illness. Serious outcomes included hospitalization (n=80), neurological damage (n=4), and death (n=2). In NPDS, single BB exposure and hypoglycemia was most frequently reported in pediatric patients ( < 20 years; n=183) with propranolol (n=82), metoprolol (n=34), and nadolol (n=11). Most cases involved children ≤5 years (n=138). Hypoglycemia occurred after acute BB exposure (n=119) followed by acute-on-chronic exposures (n=38), and chronic exposures (n=23). In the SDD, hypoglycemia developed in 1,178 treatment episodes (1.3%; incidence rate [IR]: 1.35 per 100 person-years [PYs]). The median time-to-onset was 34 days (IQR: 8 to 117 days), with most events occurring within 90 days of BB initiation (n=832) Younger children were more prone to develop hypoglycemia (IR per 100 PYs: 2.64 [0-1 year]; 2.64 [2-5 years]; 0.72 [6-11] years; 1.09 [12-17 years]). The crude incidence of hypoglycemia varied across BBs (IR per 100 PYs: 3.03 [labetalol]; 1.92 [carvedilol]; 1.40 [metoprolol]; 1.40 [propranolol]; 0.90 [atenolol]; 0.80 [nadolol]).

Conclusions: In FAERS, NPDS, medical literature, and the SDD, hypoglycemia was associated with BBs that are approved or unapproved in pediatrics. Younger children appear to be more prone to BB associated hypoglycemia especially during periods of decreased caloric intake, fasting for surgery, or illness.