Centre Antipoison de Paris - Fédération de Toxicologie (FeTox), Hôpital Fernand-Widal, APHP, Paris, France.
INSERM, UMRS-1144, Faculté de pharmacie, Paris, France.
Clin Toxicol (Phila). 2021 May;59(5):433-439. doi: 10.1080/15563650.2020.1822530. Epub 2020 Oct 2.
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.
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.
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 ( < 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 ( < 0.0001). Using a ROC curve approach (area under the curve, 0.85; < 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.
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.
在法国，普瑞巴林被广泛用于治疗成年人，但尚未获得儿童使用的批准。我们旨在调查≤6 岁儿童中普瑞巴林暴露的发生率，描述单独使用普瑞巴林的摄入情况和结果，并估计该人群中临床相关的中毒剂量。
回顾性分析了 2004 年至 2019 年法国中毒控制中心收集的≤6 岁儿童的普瑞巴林暴露情况。使用健康改善网络数据库（法国版 THIN）中的普瑞巴林处方数据估计发生率。使用中毒严重程度评分（PSS）对严重程度进行分级。
我们发现 313 例≤6 岁儿童意外摄入即释型普瑞巴林。每 10 万接受普瑞巴林治疗的成年人中，病例数随时间增加（ < 0.001）。分析了 126 例单独使用普瑞巴林的病例（年龄 2 岁 [1.6-3.0]（中位数[25 百分位-75 百分位]）；中位数摄入剂量 6.4mg/kg [3.6-10.9]）。没有儿童患有潜在的神经/心脏疾病和/或同时服用其他药物。大多数儿童（77%）无症状（PSS0），21%和 2%分别出现轻度（PSS1）和中度（PSS2）神经系统症状。没有严重并发症/死亡报告。所有有症状的儿童在 24 小时内恢复。摄入的普瑞巴林剂量与 PSS 呈正相关（ < 0.0001）。使用 ROC 曲线方法（曲线下面积，0.85； < 0.001），摄入≥19.4mg/kg 普瑞巴林时建议住院治疗（灵敏度，39%[95%置信区间（95%CI），24-56]；特异性，100%[95%CI，96-100]；阳性预测值，100%[95%CI，64-100]；阴性预测值，85%[95%CI，82-89]）。摄入＜19.4mg/kg 普瑞巴林的有症状儿童出现轻度症状。
尽管法国成年人的处方量不断增加，但≤6 岁儿童意外摄入普瑞巴林仍很少见，且毒性很小。无潜在神经/心脏疾病且同时服用其他药物的儿童单独摄入＜19.4mg/kg 即释型普瑞巴林时，可在家中安全观察。
