A non-interventional retrospective cohort study of the interaction between methotrexate and proton pump inhibitors or aspirin

E Boerrigter, M Crul

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INTRODUCTION: Methotrexate (MTX) is an antifolate drug, which is frequently used in the treatment of cancer. Proton pump inhibitors (PPIs) could delay the elimination of plasma MTX in high-dose MTX therapy by inhibition of tubular secretion, which could lead to MTX toxicity. However, the evidence of the clinical relevance of this drug-drug interaction is inconsistent. No previous studies into the effect of low dose aspirin on the elimination of MTX in high-dose therapy have been performed. Therefore, we evaluated the interaction between MTX and PPIs or aspirin.

METHODS: We conducted a non-interventional retrospective cohort study in patients treated with high dose MTX (≥500mg/m2 or >1000mg), between 2009 and 2016 at the OLVG ("Onze Lieve Vrouwe Gasthuis, Oost") in Amsterdam, the Netherlands. Patients were included if MTX concentrations were determined at 24, 48 or 72hours after high dose MTX treatment. We categorised the cycles of high dose MTX therapy into delayed elimination or normal elimination. Differences in patient characteristics and MTX dosing regimen were compared between all groups by X2-test, Fisher's exact probability test or Mann-Whitney U-test.

RESULTS: In total, 89 high dose MTX cycles were included. Delayed MTX elimination was observed in 27 (30.3%) cycles. Co-administration of a PPI was significantly more frequent in the delayed elimination group than in the normal elimination group (P<0.001). There was no statistical effect observed by co-administration of aspirin.

CONCLUSION: The use of PPIs during high dose MTX treatment can lead to delayed MTX elimination. Discontinuation of PPIs during high dose MTX treatment is recommended. Co-administration of aspirin did not influence the elimination of MTX, but further research is needed.

Original languageEnglish
Pages (from-to)344-348
Number of pages5
JournalMolecular pharmaceutics
Issue number5
Publication statusPublished - Sept 2017


  • Aspirin
  • Drug Interactions
  • Humans
  • Methotrexate/chemistry
  • Proton Pump Inhibitors/chemistry
  • Retrospective Studies

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