Division of Clinical Pharmacology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
Pediatric & Maternal Health Policy, Global Drug Regulatory Affairs, Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.
Br J Clin Pharmacol. 2018 Feb;84(2):215-222. doi: 10.1111/bcp.13438. Epub 2017 Oct 22.
Pregnant and breastfeeding women have been rendered therapeutic orphans as they have been historically excluded from clinical trials. Labelling for most approved drugs does not provide information about safety and efficacy during pregnancy. This lack of data is mainly due to ethico-legal challenges that have remained entrenched in the post-diethylstilbestrol and thalidomide era, and that have led to pregnancy being viewed in the clinical trial setting primarily through a pharmacovigilance lens. Policy considerations that encourage and/or require the inclusion of pregnant or lactating women in clinical trials may address the current lack of available information. However, there are additional pragmatic strategies, such the employment of pharmacometric tools and the introduction of innovative clinical trial designs, which could improve knowledge about the safety and efficacy of medication use during pregnancy and lactation. This paper provides a broad overview of the pharmacoepidemiology of drugs used during pregnancy and lactation, and offers recommendations for regulators and researchers in academia and industry to increase the available pharmacokinetic and -dynamic understanding of medication use in pregnancy.
孕妇和哺乳期妇女一直被视为治疗孤儿,因为她们在历史上被排除在临床试验之外。大多数已批准药物的标签并未提供有关怀孕期间安全性和疗效的信息。这种数据的缺乏主要是由于在后己烯雌酚和沙利度胺时代仍然存在的伦理法律挑战,这些挑战导致在临床试验中主要通过药物警戒的角度来看待怀孕。鼓励和/或要求将孕妇或哺乳期妇女纳入临床试验的政策考虑因素可能会解决当前信息不足的问题。然而,还有其他实用策略,例如使用药物计量学工具和引入创新的临床试验设计,这可以提高对怀孕期间和哺乳期药物使用安全性和疗效的认识。本文广泛概述了怀孕期间和哺乳期使用的药物的药物流行病学,并为学术界和工业界的监管机构和研究人员提供了建议,以增加对怀孕期间药物使用的药代动力学和药效学的理解。