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

E Boerrigter1, M Crul1

  • 1Division of Clinical Pharmacy, OLVG, Oosterpark 9, 1090HM Amsterdam, Netherlands.

Annales Pharmaceutiques Francaises
|July 15, 2017
PubMed
Abstract

Insights

Proton pump inhibitors (PPIs) significantly delay high-dose methotrexate (MTX) elimination, increasing toxicity risk. Aspirin showed no effect on MTX clearance, but further research is recommended for this drug interaction.

Area of Science:

  • Oncology
  • Clinical Pharmacology
  • Drug Interactions

Background:

  • Methotrexate (MTX) is a crucial antifolate chemotherapy agent.
  • Proton pump inhibitors (PPIs) may impede MTX elimination via tubular secretion, potentially causing toxicity.
  • Clinical data on the MTX-PPI interaction and the effect of aspirin on MTX elimination are limited and inconsistent.

Purpose of the Study:

  • To investigate the interaction between high-dose methotrexate (MTX) and proton pump inhibitors (PPIs) or aspirin.
  • To assess the clinical relevance of PPIs and aspirin co-administration on MTX elimination and toxicity.

Main Methods:

  • A retrospective cohort study of 89 high-dose MTX cycles (≥500mg/m² or >1000mg) was conducted between 2009-2016.
  • Patients were categorized based on MTX elimination at 24, 48, or 72 hours post-administration.
  • Statistical analyses (X2-test, Fisher's exact, Mann-Whitney U) compared patient characteristics and MTX dosing between groups.

Main Results:

  • Delayed MTX elimination occurred in 30.3% of cycles.
  • Co-administration of PPIs was significantly associated with delayed MTX elimination (P<0.001).
  • Aspirin co-administration did not demonstrate a statistically significant effect on MTX elimination.

Conclusions:

  • Proton pump inhibitor use during high-dose methotrexate therapy is linked to delayed MTX elimination.
  • Discontinuation of PPIs during high-dose MTX treatment is advisable to mitigate toxicity risks.
  • While aspirin did not impact MTX elimination in this study, further investigation is warranted.
Keywords:
AspirinAspirineDrug–drug interactionsInhibiteur de la pompe à protonsInteractionMethotrexateMéthotrexateProton pump inhibitor

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