Safe use of proton pump inhibitors in patients with cirrhosis

• Published in: British journal of clinical pharmacology 2018-08, Vol.84 (8), p.1806-1820
• Main Authors: Weersink, Rianne A., Bouma, Margriet, Burger, David M., Drenth, Joost P.H., Harkes‐Idzinga, S. Froukje, Hunfeld, Nicole G.M., Metselaar, Herold J., Monster‐Simons, Margje H., Putten, Sandra A.W., Taxis, Katja, Borgsteede, Sander D.
• Format: Article
• Language: English
• Subjects: Administration, Oral; Dose-Response Relationship, Drug; drug safety; evidence‐based medicine; Female; Hepatic Encephalopathy - epidemiology; Hepatic Encephalopathy - etiology; Hepatic Encephalopathy - prevention & control; hepatology; Humans; liver; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver Cirrhosis - complications; Liver Cirrhosis - diagnosis; Liver Cirrhosis - pathology; Male; Original; Practice Guidelines as Topic; Proton Pump Inhibitors - administration & dosage; Proton Pump Inhibitors - adverse effects; Proton Pump Inhibitors - pharmacokinetics; Proton Pump Inhibitors - standards; Severity of Illness Index
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.13615

Aims 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. Methods 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. Results 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. Conclusions 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.