Methotrexate and Naproxen: Drug Interaction Guide
Quick answer: This is a major interaction — avoid combining Methotrexate and Naproxen unless specifically directed by your doctor.
How Methotrexate interacts with Naproxen
NSAIDs inhibit renal prostaglandin synthesis and compete for tubular secretion, reducing methotrexate clearance and increasing risk of mucositis, pancytopenia, and nephrotoxicity at oncology doses.
What you should do
Avoid NSAIDs around high-dose methotrexate (oncology); for low-dose weekly rheumatology methotrexate, use cautiously with stable renal function and monitor FBC.
Key facts
Severity
Major — avoid combination
Mechanism
NSAIDs inhibit renal prostaglandin synthesis and compete for tubular secretion, reducing methotrexate clearance and incr...
Action
Avoid NSAIDs around high-dose methotrexate (oncology); for low-dose weekly rheumatology methotrexate, use cautiously wit...
Frequently asked questions
Can I take Methotrexate and Naproxen together?
No — this combination should generally be avoided. Avoid NSAIDs around high-dose methotrexate (oncology); for low-dose weekly rheumatology methotrexate, use cautiously with stable renal function and monitor FBC.
What is the severity of this interaction?
The interaction between Methotrexate and Naproxen is classified as Major — avoid combination. NSAIDs inhibit renal prostaglandin synthesis and compete for tubular secretion, reducing methotrexate clearance and increasing risk of mucositis, pancytopenia, and nephrotoxicity at oncology doses.
What should I do if I'm prescribed both?
Avoid NSAIDs around high-dose methotrexate (oncology); for low-dose weekly rheumatology methotrexate, use cautiously with stable renal function and monitor FBC. Always consult your prescribing clinician — do not stop or change medications without medical guidance.
Last reviewed: by iMedic Medical Editorial Team. Our editorial process.