Ibuprofen and Methotrexate: Drug Interaction Guide

Quick answer: This is a major interaction — avoid combining Ibuprofen and Methotrexate unless specifically directed by your doctor.

Interaction severity: Major — avoid combination

How Ibuprofen interacts with Methotrexate

NSAIDs reduce renal clearance of methotrexate by inhibiting prostaglandin-mediated renal blood flow and competing for tubular secretion, raising methotrexate concentrations to potentially toxic levels.

What you should do

Avoid NSAIDs around high-dose methotrexate (oncology); for low-dose weekly methotrexate (rheumatology) the risk is lower but monitor full blood count, liver enzymes, and renal function.

Key facts

Severity

Major — avoid combination

Mechanism

NSAIDs reduce renal clearance of methotrexate by inhibiting prostaglandin-mediated renal blood flow and competing for tu...

Action

Avoid NSAIDs around high-dose methotrexate (oncology); for low-dose weekly methotrexate (rheumatology) the risk is lower...

Important medical disclaimer: This page provides educational information about drug interactions for general reference. It is not a substitute for professional medical advice, diagnosis, or treatment. Always discuss your specific medications with a qualified healthcare provider before starting, stopping, or changing any treatment. About our editorial team.

Frequently asked questions

Can I take Ibuprofen and Methotrexate together?

No — this combination should generally be avoided. Avoid NSAIDs around high-dose methotrexate (oncology); for low-dose weekly methotrexate (rheumatology) the risk is lower but monitor full blood count, liver enzymes, and renal function.

What is the severity of this interaction?

The interaction between Ibuprofen and Methotrexate is classified as Major — avoid combination. NSAIDs reduce renal clearance of methotrexate by inhibiting prostaglandin-mediated renal blood flow and competing for tubular secretion, raising methotrexate concentrations to potentially toxic levels.

What should I do if I'm prescribed both?

Avoid NSAIDs around high-dose methotrexate (oncology); for low-dose weekly methotrexate (rheumatology) the risk is lower but monitor full blood count, liver enzymes, and renal function. Always consult your prescribing clinician — do not stop or change medications without medical guidance.

Last reviewed: by iMedic Medical Editorial Team. Our editorial process.