Methotrexate and Trimethoprim Sulfamethoxazole: Drug Interaction Guide

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

Interaction severity: Major — avoid combination

How Methotrexate interacts with Trimethoprim Sulfamethoxazole

Both drugs inhibit dihydrofolate reductase and trimethoprim-sulfamethoxazole additionally displaces methotrexate from protein binding and reduces renal tubular secretion, causing severe pancytopenia and mucositis.

What you should do

Avoid combination; if essential, use leucovorin rescue and monitor complete blood count and methotrexate levels; consider doxycycline alternative.

Key facts

Severity

Major — avoid combination

Mechanism

Both drugs inhibit dihydrofolate reductase and trimethoprim-sulfamethoxazole additionally displaces methotrexate from pr...

Action

Avoid combination; if essential, use leucovorin rescue and monitor complete blood count and methotrexate levels; conside...

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 Methotrexate and Trimethoprim Sulfamethoxazole together?

No — this combination should generally be avoided. Avoid combination; if essential, use leucovorin rescue and monitor complete blood count and methotrexate levels; consider doxycycline alternative.

What is the severity of this interaction?

The interaction between Methotrexate and Trimethoprim Sulfamethoxazole is classified as Major — avoid combination. Both drugs inhibit dihydrofolate reductase and trimethoprim-sulfamethoxazole additionally displaces methotrexate from protein binding and reduces renal tubular secretion, causing severe pancytopenia and mucositis.

What should I do if I'm prescribed both?

Avoid combination; if essential, use leucovorin rescue and monitor complete blood count and methotrexate levels; consider doxycycline alternative. Always consult your prescribing clinician — do not stop or change medications without medical guidance.

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