Division of Gastroenterology and Hepatology, Department of Medicine, Georgetown University Medical Center, Washington, DC 20007, USA.
Aliment Pharmacol Ther. 2013 Jun;37(12):1132-56. doi: 10.1111/apt.12324. Epub 2013 May 3.
Most drugs have not been well studied in cirrhosis; recommendations on safe use are based largely on experience and/or expert opinion, with dosing recommendations often based on pharmacokinetic (PK) changes.
To provide a practical approach to prescribing medications for cirrhotic patients.
An indexed MEDLINE search was conducted using keywords cirrhosis, drug-induced liver injury, pharmacodynamics (PDs), PKs, drug disposition and adverse drug reactions. Unpublished information from the Food and Drug Administration and industry was also reviewed.
Most medications have not been adequately studied in cirrhosis, and specific prescribing information is often lacking. Lower doses are generally recommended based on PK changes, but data are limited in terms of correlating PD effects with the degree of liver impairment. Very few drugs have been documented to have their hepatotoxicity potential enhanced by cirrhosis; most of these involve antituberculosis or antiretroviral agents used for HIV or viral hepatitis. Paracetamol can be used safely when prescribed in relatively small doses (2-3 g or less/day) for short durations, and is recommended as first-line treatment of pain. In contrast, NSAIDs should be used cautiously (or not at all) in advanced cirrhosis. Proton pump inhibitors have been linked to an increased risk of spontaneous bacterial peritonitis (SBP) in cirrhosis and should be used with care.
Most drugs can be used safely in cirrhosis, including those that are potentially hepatotoxic, but lower doses or reduced dosing frequency is often recommended, due to altered PKs. Drugs that can precipitate renal failure, gastrointestinal bleeding, SBP and encephalopathy should be identified and avoided.
大多数药物在肝硬化患者中研究不足;安全使用的建议主要基于经验和/或专家意见,剂量建议通常基于药代动力学(PK)变化。
为肝硬化患者开处方提供实用方法。
使用关键字肝硬化、药物性肝损伤、药效学(PDs)、药代动力学(PKs)、药物处置和药物不良反应对 MEDLINE 进行索引搜索。还审查了食品和药物管理局和行业的未发表信息。
大多数药物在肝硬化患者中未得到充分研究,具体的处方信息通常缺乏。通常根据 PK 变化推荐较低剂量,但将 PD 效应与肝损伤程度相关联的数据有限。极少数药物被证明其肝毒性潜力因肝硬化而增强;其中大多数涉及抗结核药或用于 HIV 或病毒性肝炎的抗逆转录病毒药物。扑热息痛在相对较小剂量(每天 2-3 克或更少)短期使用时可以安全使用,建议作为疼痛的一线治疗药物。相比之下,在晚期肝硬化中应谨慎使用(或根本不使用)非甾体抗炎药。质子泵抑制剂与肝硬化自发性细菌性腹膜炎(SBP)的风险增加有关,应谨慎使用。
大多数药物在肝硬化患者中可以安全使用,包括那些潜在的肝毒性药物,但由于 PK 改变,通常建议使用较低剂量或减少剂量频率。应识别并避免可能导致肾衰竭、胃肠道出血、SBP 和肝性脑病的药物。