Kotb Magd Ahmed, Mosallam Dalia, Basanti Christine William Shaker, El Sorogy Sally Talaat Mostafa, Badr Ahmed M, Abd El Baky Hend El Hosainy, Draz Iman Hassan
Pediatrics Department, Faculty of Medicine, Kasr Alainy, Cairo University.
Public Mounira Hospital, Cairo, Egypt.
Medicine (Baltimore). 2020 Feb;99(7):e18730. doi: 10.1097/MD.0000000000018730.
The off-label use of medications is a "right" for pediatricians, owing to lack of enough safety and effectiveness drug trials in pediatric age group. Pediatricians have to rely on their personal judicial use of medications in children.We studied off-label use of ursodeoxycholic acid (UDCA) retrospectively during 2005 to 2015 among those who attended the Pediatic Hepatology Unit, Cairo University.We analyzed data of 779 neonates and infants with cholestasis. 15% dropped out. Males comprised 374 (56.5%). Cholestasis was due to surgical causes in 129 (19.5%), neonatal hepatitis in 445 (67.2%), and paucity of intrahepatic bile ducts in 88 (13.3%). Three hundred sixty (54.4%) received UDCA (15-30 mg/kg/d), and 302 (45.6%) did not. Both groups were matched as regards causes and severity of cholestasis. Those who received UDCA had worse outcome (P < .001), and more complications (P < .001). A total of 73.1% (221) achieved cure without UDCA compared to only 45.8% (165) of those on UDCA (P < .001).UDCA is not effective and not safe in Egyptian neonates and infants with cholestasis. UDCA use compromises chance of cure, and is associated with serious morbidity, progression of disease, and death. UDCA off-label use mortality was absolutely preventable. Off- label use of UDCA in neonates and children should be utterly prohibited. Information of use of off-label medications, effectiveness, and safety, should be recorded, analyzed, and made available within context of Off-label Use Registry Studies with informed consent of parents.
由于儿科年龄组缺乏足够的药物安全性和有效性试验,药物的非标签使用是儿科医生的一项“权利”。儿科医生必须依靠自己对儿童用药的合理判断。我们回顾性研究了2005年至2015年期间在开罗大学儿科肝病科就诊的患者中熊去氧胆酸(UDCA)的非标签使用情况。我们分析了779例胆汁淤积新生儿和婴儿的数据。15%的患者退出研究。男性有374例(56.5%)。胆汁淤积的原因包括手术原因129例(19.5%)、新生儿肝炎445例(67.2%)、肝内胆管稀少88例(13.3%)。360例(54.4%)接受了UDCA(15 - 30mg/kg/天),302例(45.6%)未接受。两组在胆汁淤积的原因和严重程度方面相匹配。接受UDCA治疗的患者预后更差(P < 0.001),并发症更多(P < 0.001)。未使用UDCA的患者中共有73.1%(221例)治愈,而使用UDCA的患者中只有45.8%(165例)治愈(P < 0.001)。在埃及患有胆汁淤积的新生儿和婴儿中,UDCA既无效也不安全。使用UDCA会降低治愈的机会,并与严重的发病率、疾病进展和死亡相关。UDCA的非标签使用导致的死亡是完全可以预防的。应绝对禁止在新生儿和儿童中对UDCA进行非标签使用。在获得家长知情同意的情况下,应在非标签使用登记研究的背景下记录、分析并提供有关非标签药物使用、有效性和安全性的信息。