Indomethacin and Methotrexate: Drug Interaction Guide
Quick answer: This is a major interaction — avoid combining Indomethacin and Methotrexate unless specifically directed by your doctor.
How Indomethacin interacts with Methotrexate
NSAIDs reduce renal clearance of methotrexate and displace it from plasma protein binding, increasing systemic exposure and toxicity risk (myelosuppression, mucositis).
What you should do
Avoid NSAIDs with high-dose methotrexate. With low-dose weekly methotrexate, use cautiously with stable renal function and FBC monitoring.
Key facts
Severity
Major — avoid combination
Mechanism
NSAIDs reduce renal clearance of methotrexate and displace it from plasma protein binding, increasing systemic exposure ...
Action
Avoid NSAIDs with high-dose methotrexate. With low-dose weekly methotrexate, use cautiously with stable renal function a...
Frequently asked questions
Can I take Indomethacin and Methotrexate together?
No — this combination should generally be avoided. Avoid NSAIDs with high-dose methotrexate. With low-dose weekly methotrexate, use cautiously with stable renal function and FBC monitoring.
What is the severity of this interaction?
The interaction between Indomethacin and Methotrexate is classified as Major — avoid combination. NSAIDs reduce renal clearance of methotrexate and displace it from plasma protein binding, increasing systemic exposure and toxicity risk (myelosuppression, mucositis).
What should I do if I'm prescribed both?
Avoid NSAIDs with high-dose methotrexate. With low-dose weekly methotrexate, use cautiously with stable renal function and FBC monitoring. Always consult your prescribing clinician — do not stop or change medications without medical guidance.
Last reviewed: by iMedic Medical Editorial Team. Our editorial process.