E104 The interaction between methotrexate and proton pump inhibitors: a systematic literature review
Abstract
Abstract Background/Aims Methotrexate is one of the most commonly used disease-modifying anti-rheumatic drugs, with a multitude of indications, spanning immune-mediated inflammatory diseases (IMID) and oncology. The British National Formulary (BNF) cites methotrexate’s interaction with proton pump inhibitors (PPIs) as an interaction; however, this is variably recognised in clinical practice. We performed a systematic review assess the clinical implications and significance of the interaction between methotrexate and PPIs. Methods We performed a Pubmed/MEDLINE and Embase literature search, utilising the search terms ‘methotrexate’, ‘proton pump inhibitor’, ‘omeprazole’, ‘lansoprazole’, ‘esomeprazole’, ‘pantoprazole’, ‘rabeprazole’, ‘dexlansoprazole’, from database inception to 25 August 2025. Studies reporting on serum methotrexate levels and methotrexate clearance with concomitant proton pump inhibitor use were eligible for inclusion. Baseline data were collected for age, methotrexate dosage, indication, proton pump inhibitor type, and reported adverse events. Additionally, studies registered on clinicaltrials.gov involving patients with rheumatoid arthritis (RA) receiving methotrexate as monotherapy or as combination DMARD therapy were screened to assess whether concomitant proton pump inhibitor use was an exclusion criterion for these trials. Results The search yielded 2,493 articles, which resulted in 12 articles being eligible for inclusion in the analysis after…
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