Mt-Isa Shahrul, Tomlin Stephen, Sutcliffe Alastair, Underwood Martin, Williamson Paula, Croft Nicholas M, Ashby Deborah
*Imperial Clinical Trials Unit, School of Public Health, Imperial College London †Evelina Children's Hospital, Pharmacy Department, King's Health Partners, Guy's and St Thomas' NHS Foundation Trust ‡General and Adolescent Paediatrics Unit, Institute of Child Health, University College London, London §Warwick Medical School, University of Warwick, Coventry ||Centre for Medical Statistics and Health Evaluation, University of Liverpool, Liverpool ¶Centre for Digestive Diseases, Blizard Institute, Barts and the London School of Medicine, Queen Mary University of London, London, UK.
J Pediatr Gastroenterol Nutr. 2015 Apr;60(4):508-14. doi: 10.1097/MPG.0000000000000657.
Domperidone and metoclopramide are prokinetics commonly prescribed off-label to infants and younger children in an attempt to treat gastro-oesophageal reflux symptoms. Another prokinetic drug, cisapride, was used but withdrawn in 2000 in the United Kingdom because of serious arrhythmic adverse events. Medicines and Healthcare Products Regulatory Agency issued safety warnings for domperidone in May 2012 and restricted its indications. We report here national primary care prescribing trends and safety signals of these drugs in children.
We used data from the General Practice Research Database between 1990 and 2006 for children <18 years. Descriptive statistics and Poisson regressions were performed to characterise prescribing trends. We examined safety signals in nested case-control studies.
The proportion of children <2 years old being prescribed one of the medications doubled during the study period. Prescriptions of domperidone increased 10-fold, mainly following the withdrawal of cisapride in 2000. Prescriptions of metoclopramide did not change significantly. Despite the increase in prescriptions of domperidone, no new safety signals were identified.
These data showed dramatic changes in prescribing of cisapride and domperidone despite the lack of good-quality supporting evidence. It is possible that these prescribing trends were influenced by published guidelines. Even if produced without robust efficacy and safety evidence, published guidelines can influence clinicians and consequently affect prescribing. Therefore, improving the evidence base on prokinetics to inform future guidelines is vital. The lack of new safety signals during this period would support the development of suitable powered clinical studies.
多潘立酮和甲氧氯普胺是常用于婴儿和年幼儿童的促动力药，通常为非适应证用药，旨在治疗胃食管反流症状。另一种促动力药物西沙必利也曾被使用，但因严重心律失常不良事件于2000年在英国退市。药品和医疗产品监管局于2012年5月发布了多潘立酮的安全警告并限制了其适应证。我们在此报告这些药物在儿童中的全国基层医疗处方趋势和安全信号。
我们使用了1990年至2006年来自全科医疗研究数据库中18岁以下儿童的数据。进行描述性统计和泊松回归以描述处方趋势。我们在巢式病例对照研究中检查安全信号。
在研究期间，2岁以下儿童中开具其中一种药物的比例增加了一倍。多潘立酮的处方量增加了10倍，主要是在2000年西沙必利退市之后。甲氧氯普胺的处方量没有显著变化。尽管多潘立酮的处方量增加，但未发现新的安全信号。
这些数据显示，尽管缺乏高质量的支持证据，但西沙必利和多潘立酮的处方情况发生了显著变化。这些处方趋势可能受到已发表指南的影响。即使没有强有力的疗效和安全性证据，已发表的指南也可能影响临床医生，从而影响处方。因此，改善促动力药的证据基础以指导未来的指南至关重要。在此期间缺乏新的安全信号将支持开展有足够样本量的临床研究。
