High-dose methotrexate is cleared by the kidneys, and delayed clearance causes mucositis, myelosuppression, hepatotoxicity and further kidney injury. Safe delivery rests on vigorous hydration, urine alkalinisation, timed folinic acid rescue guided by methotrexate levels, and avoiding drugs that slow its excretion.
The common interacting drugs are proton pump inhibitors, NSAIDs, trimethoprim-sulfamethoxazole and penicillins. Third-space fluid such as pleural effusion or ascites acts as a reservoir and prolongs exposure.
- Check creatinine before each cycle and keep urine pH above about 7 during infusion.
- Stop or avoid proton pump inhibitors, NSAIDs, co-trimoxazole and penicillins around the infusion.
- Give folinic acid rescue on time and adjust it to methotrexate levels.
- Look for effusions or ascites before starting; drain or reconsider if present.
- Know where glucarpidase is available if levels stay high with kidney injury.
Why it matters
Most serious high-dose methotrexate toxicity comes from delayed clearance that the pre-infusion checklist can anticipate.
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