Can you take methotrexate and Advil (ibuprofen) together?
Using methotrexate and Advil (ibuprofen) at the same time can increase the risk of methotrexate toxicity. This is because ibuprofen (an NSAID) can reduce the kidney’s ability to clear methotrexate, which may raise methotrexate levels and lead to side effects such as mouth sores, unusual bruising or bleeding, severe nausea/vomiting, or signs of infection. The risk is higher with higher methotrexate doses, kidney problems, dehydration, and in older adults.
What specific problems does the interaction raise?
When methotrexate levels rise, people may develop:
- Blood count suppression (low white cells, anemia, low platelets), which can cause infections, fatigue, or easy bruising/bleeding
- Gastrointestinal toxicity (significant nausea, vomiting, mouth sores)
- Liver toxicity
- Kidney-related worsening, especially if you’re dehydrated or have underlying kidney disease
What increases risk the most?
Higher-risk situations include:
- Reduced kidney function (chronic kidney disease or acute dehydration)
- Higher-dose methotrexate regimens (often used in oncology and sometimes in severe inflammatory disease)
- Frequent NSAID use or high ibuprofen doses
- Dehydration from illness, vomiting/diarrhea, or not drinking enough
- Concomitant medicines that also affect kidney function (for example, some blood pressure drugs like ACE inhibitors/ARBs and diuretics can compound kidney stress)
What should you do if you need pain relief or fever control?
Check with your prescriber before combining them. If you’ve been told methotrexate is part of your ongoing regimen, don’t rely on self-treatment with ibuprofen without medical advice, especially if you’re on higher doses or have kidney issues.
Clinicians often suggest using the safest option for that person, which may include an alternative pain/fever medicine and close monitoring, but the right choice depends on:
- Your methotrexate dose and schedule
- Your kidney function
- Other medications you take
- The reason you need ibuprofen (pain vs fever, and how often)
When is it urgent to get medical help?
Seek urgent care or contact your prescriber right away if you’re taking both and develop:
- Fever or signs of infection
- Severe mouth sores
- Uncontrolled nausea/vomiting or inability to keep fluids down
- Unusual bruising or bleeding
- Shortness of breath, rash, or swelling
- Marked decrease in urination or severe weakness
What information would help determine your risk?
If you share the following, I can give more tailored guidance based on typical interaction risk factors:
- Your methotrexate dose (mg) and how often you take it
- Your Advil dose and how many times per day you plan to take it
- Whether methotrexate is for rheumatoid arthritis/psoriasis (often weekly) or another condition
- Any kidney disease, age, and other medicines (especially blood pressure meds or diuretics)