Can you take Aleve (naproxen) with methotrexate?
Often, yes—many people are prescribed an NSAID like naproxen (Aleve) alongside low-dose methotrexate for conditions such as rheumatoid arthritis. But it is not a “no-questions-asked” combination because both drugs affect kidney function and methotrexate levels can rise if kidney clearance is reduced.
The safest approach is to confirm with your prescriber or pharmacist, especially if you:
- have kidney disease or reduced kidney function
- are older (risk goes up with age)
- take other medicines that can affect kidneys (for example, certain blood pressure drugs like ACE inhibitors/ARBs, diuretics, or other NSAIDs)
- take higher-dose methotrexate (used in some cancers), where interactions are more dangerous
Why is the Aleve–methotrexate interaction a concern?
NSAIDs such as naproxen can reduce blood flow to the kidneys. If kidney function drops, methotrexate can clear more slowly, which can increase methotrexate exposure and toxicity risk.
This is why clinicians are more cautious when patients have kidney impairment, are dehydrated, or take additional kidney-stressing medications.
What symptoms would mean you should stop and get medical help?
If you take methotrexate and then develop signs of methotrexate toxicity, seek urgent medical advice. Symptoms that can be concerning include:
- mouth sores or severe sore throat
- unusual bruising or bleeding
- fever or signs of infection
- severe nausea/vomiting, persistent diarrhea
- sudden unusual fatigue or weakness
Is it different for low-dose vs high-dose methotrexate?
Yes. Low-dose methotrexate (commonly for autoimmune diseases) is more commonly co-prescribed with NSAIDs under supervision. High-dose methotrexate (commonly for cancer regimens) is a different situation with much higher risk; NSAIDs are handled more carefully and are less likely to be used casually.
If you know your methotrexate dose and whether it’s for arthritis/autoimmune disease vs cancer, that matters for the answer.
What’s the safest way to take them if your clinician approves?
- Use the NSAID only as directed (dose and duration).
- Avoid adding other NSAIDs (for example, ibuprofen) at the same time.
- Stay well hydrated unless your doctor has limited fluids.
- Ask whether you need additional monitoring (commonly blood tests for blood counts and liver/kidney function while on methotrexate).
Alternatives if NSAIDs aren’t advised
If your clinician wants to avoid naproxen, they may suggest another pain/fever option that is easier to pair with methotrexate (often acetaminophen/paracetamol), but you should confirm based on your medical history and current medications.
Quick check: what I need to give you a more exact answer
If you share:
1) your methotrexate dose (mg) and how often you take it,
2) why you take methotrexate (arthritis/RA vs cancer), and
3) any kidney problems or other meds (blood pressure meds/diuretics),
I can tell you what risks matter most for your situation and what questions to ask your pharmacist.