Health Base Foundation, Houten, The Netherlands.
Department of Pharmacy, Unit of Pharmacotherapy, -Epidemiology & -Economics, University of Groningen, Groningen, The Netherlands.
Br J Clin Pharmacol. 2018 Aug;84(8):1806-1820. doi: 10.1111/bcp.13615. Epub 2018 Jun 7.
Proton pump inhibitors (PPIs) belong to the most frequently used drugs, also in patients with cirrhosis. PPIs are extensively metabolized by the liver, but practice guidance on prescribing in cirrhosis is lacking. We aim to develop practical guidance on the safe use of PPIs in patients with cirrhosis.
A systematic literature search identified studies on the safety (i.e. adverse events) and pharmacokinetics of PPIs in cirrhotic patients. This evidence and data from the product information was reviewed by an expert panel who classified drugs as safe; no additional risks known; additional risks known; unsafe; or unknown. Guidance was aimed at the oral use of PPIs and categorized by the severity of cirrhosis, using the Child-Turcotte-Pugh (CTP) classification.
A total of 69 studies were included. Esomeprazole, omeprazole and rabeprazole were classified as having 'no additional risks known'. A reduction in maximum dose of omeprazole and rabeprazole is recommended for CTP A and B patients. For patients with CTP C cirrhosis, the only PPI advised is esomeprazole at a maximum dosage of 20 mg per day. Pantoprazole and lansoprazole were classified as unsafe because of 4- to 8-fold increased exposure. The use of PPIs in cirrhotic patients has been associated with the development of infections and hepatic encephalopathy and should be carefully considered.
We suggest using esomeprazole, omeprazole or rabeprazole in patients with CTP A or B cirrhosis and only esomeprazole in patients with CTP C. Pharmacokinetic changes are also important to consider when prescribing PPIs to vulnerable, cirrhotic patients.
质子泵抑制剂（PPIs）属于最常使用的药物之一，也用于肝硬化患者。PPIs 主要在肝脏中代谢，但针对肝硬化患者的处方实践指南尚缺乏。我们旨在制定有关肝硬化患者安全使用 PPIs 的实用指南。
系统文献检索确定了关于肝硬化患者中 PPI 的安全性（即不良事件）和药代动力学的研究。该证据和产品信息中的数据由一个专家小组进行了审查，专家小组将药物分类为安全；已知有额外风险；已知有额外风险；不安全；或未知。该指南旨在针对肝硬化的严重程度，使用 Child-Turcotte-Pugh（CTP）分类，指导口服使用 PPI。
共纳入 69 项研究。埃索美拉唑、奥美拉唑和雷贝拉唑被归类为“已知无额外风险”。对于 CTP A 和 B 患者，建议减少奥美拉唑和雷贝拉唑的最大剂量。对于 CTP C 肝硬化患者，唯一建议使用的 PPI 是埃索美拉唑，最大剂量为每天 20 毫克。泮托拉唑和兰索拉唑被归类为不安全，因为其暴露量增加了 4 至 8 倍。在肝硬化患者中使用 PPIs 与感染和肝性脑病的发生有关，应谨慎考虑。
我们建议在 CTP A 或 B 肝硬化患者中使用埃索美拉唑、奥美拉唑或雷贝拉唑，在 CTP C 肝硬化患者中仅使用埃索美拉唑。在为易受影响的肝硬化患者开处方时，药代动力学变化也很重要。
