Unintentional exposure to pregabalin in ≤6-year-old children: a nationwide French Poison Control Center study

Abstract

Introduction In France, pregabalin is widely prescribed in adults but still not approved for children. We aimed to investigate the incidence of pregabalin exposure in ≤6-year-old children, to describe the characteristics and outcome of ingestions involving pregabalin alone, and to estimate a clinically relevant toxic dose in this population. Methods Retrospective analysis of pregabalin exposures in ≤6-year-old children, collected by the French Poison Control Centers in 2004–2019. The incidence was estimated using pregabalin prescription data from the Health Improvement Network database (the French version of THIN). The poison severity score (PSS) was used to grade severity. Results We found 313 unintentional immediate-release pregabalin ingestions in ≤6-year-old children. The number of cases per 100,000 pregabalin-treated adults increased over time (p < 0.001). One hundred twenty-six cases involving pregabalin alone (age, 2 years [1.6–3.0] (median [25th–75th percentiles]); median ingested dose 6.4 mg/kg [3.6–10.9]) were analyzed. No child presented an underlying neurological/cardiac disease and/or took concomitant medications. Most of the children (77%) remained asymptomatic (PSS0) while 21% and 2% developed minor (PSS1) or moderate (PSS2) neurological symptoms, respectively. No severe complications/fatalities were reported. All symptomatic children recovered within 24 h. The ingested pregabalin dose was positively correlated with PSS (p < 0.0001). Using a ROC curve approach (area under the curve, 0.85; p < 0.001), ingestion of ≥19.4 mg/kg pregabalin was appropriate to recommend hospital referral (sensitivity, 39% [95% confidence interval (95% CI), 24–56], specificity, 100% [95% CI, 96–100], predictive positive value, 100% [95% CI, 64–100], and negative predictive value, 85% [95% CI, 82–89]). Symptomatic children who ingested <19.4 mg/kg pregabalin developed minor symptoms. Conclusion Despite increasing prescriptions in adults in France, unintentional pregabalin ingestions in ≤6-year-old children remain rare and cause minimal toxicity. Children with no underlying neurological/cardiac disease and concomitant medication ingesting <19.4 mg/kg immediate-release pregabalin alone can be safely observed at home.