PPIs with methotrexate can lead to methotrexate toxicity

You'll see warnings that using PPIs with methotrexate can lead to methotrexate toxicity.

PPIs seem to decrease the renal clearance of methotrexate and its active metabolites...and increase their serum levels.

The greatest risk is with high-dose methotrexate infusions for cancer...but problems might also occur with lower doses.

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