Aspirin and Methotrexate: Drug Interaction Guide

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

Interaction severity: Major — avoid combination

How Aspirin interacts with Methotrexate

Aspirin and other NSAIDs reduce renal clearance of methotrexate by inhibiting tubular secretion and displace methotrexate from plasma protein binding, increasing systemic exposure and toxicity.

What you should do

Avoid concurrent use, particularly with high-dose methotrexate. With low-dose weekly methotrexate, monitor full blood count, renal function, and liver enzymes closely.

Key facts

Severity

Major — avoid combination

Mechanism

Aspirin and other NSAIDs reduce renal clearance of methotrexate by inhibiting tubular secretion and displace methotrexat...

Action

Avoid concurrent use, particularly with high-dose methotrexate. With low-dose weekly methotrexate, monitor full blood co...

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 Aspirin and Methotrexate together?

No — this combination should generally be avoided. Avoid concurrent use, particularly with high-dose methotrexate. With low-dose weekly methotrexate, monitor full blood count, renal function, and liver enzymes closely.

What is the severity of this interaction?

The interaction between Aspirin and Methotrexate is classified as Major — avoid combination. Aspirin and other NSAIDs reduce renal clearance of methotrexate by inhibiting tubular secretion and displace methotrexate from plasma protein binding, increasing systemic exposure and toxicity.

What should I do if I'm prescribed both?

Avoid concurrent use, particularly with high-dose methotrexate. With low-dose weekly methotrexate, monitor full blood count, renal function, and liver enzymes closely. Always consult your prescribing clinician — do not stop or change medications without medical guidance.

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