Acetylsalicylic Acid and Methotrexate: Drug Interaction Guide

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

Interaction severity: Major — avoid combination

How Acetylsalicylic Acid interacts with Methotrexate

Salicylates can reduce renal tubular secretion of methotrexate and displace it from plasma proteins, increasing exposure and the risk of marrow suppression, mucositis, and nephrotoxicity.

What you should do

Avoid analgesic or anti-inflammatory doses, particularly with high-dose methotrexate. If low-dose antiplatelet therapy is essential, monitor blood counts, renal function, and signs of methotrexate toxicity.

Key facts

Severity

Major — avoid combination

Mechanism

Salicylates can reduce renal tubular secretion of methotrexate and displace it from plasma proteins, increasing exposure...

Action

Avoid analgesic or anti-inflammatory doses, particularly with high-dose methotrexate. If low-dose antiplatelet therapy i...

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 Acetylsalicylic Acid and Methotrexate together?

No — this combination should generally be avoided. Avoid analgesic or anti-inflammatory doses, particularly with high-dose methotrexate. If low-dose antiplatelet therapy is essential, monitor blood counts, renal function, and signs of methotrexate toxicity.

What is the severity of this interaction?

The interaction between Acetylsalicylic Acid and Methotrexate is classified as Major — avoid combination. Salicylates can reduce renal tubular secretion of methotrexate and displace it from plasma proteins, increasing exposure and the risk of marrow suppression, mucositis, and nephrotoxicity.

What should I do if I'm prescribed both?

Avoid analgesic or anti-inflammatory doses, particularly with high-dose methotrexate. If low-dose antiplatelet therapy is essential, monitor blood counts, renal function, and signs of methotrexate toxicity. Always consult your prescribing clinician — do not stop or change medications without medical guidance.

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