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Methotrexate and proton pump inhibitors (PPIs)

Authoring team

Methotrexate toxicity

 

  • proton pump inhibitors (for example, lansoprazole, omeprazole or pantoprazole) reduce the clearance of methotrexate via the kidneys and therefore increase the risk of methotrexate toxicity
    • evidence to support a clinically significant interaction is limited (1)
    • risks of this interaction are greater at high doses of methotrexate and in those with renal impairment (1)

Suggested management options (1):

 

  • no additional action is required
  • routine monitoring of methotrexate should detect any signs of methotrexate toxicity
  • counsel the person to report signs of methotrexate toxicity, for example sore throat, mouth ulcers, unexplained bruising or bleeding
  • consider use of H2-receptor antagonists as an alternative if required

Reference:

  1. NHS Specialist Pharmacy Service (June 30th 2025). Managing interactions with methotrexate

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