Can I take Methotrexate and Ibuprofen together?
Drug interaction guide
Originally published 25 Jan 2026
Meets Patient’s editorial guidelines
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Taking ibuprofen while on methotrexate can cause the levels of methotrexate in your blood to rise to dangerous levels. This significantly increases the risk of serious side effects, including damage to your bone marrow (which helps fight infection), kidney problems, and severe stomach or mouth ulcers.
Why this happens
Methotrexate is cleared from your body through the kidneys. Ibuprofen interferes with this process in two ways: it reduces blood flow to the kidneys and blocks the specific 'pumps' the kidneys use to flush methotrexate out. This causes the methotrexate to build up in your system.
What you should do
Do not take ibuprofen (or other similar anti-inflammatory drugs like naproxen or aspirin) while taking methotrexate unless your specialist doctor has specifically told you to do so and is monitoring your blood tests closely. For pain relief, paracetamol is usually a safer alternative. If you have already taken both and feel unwell, or develop a sore throat, fever, or unusual bruising, contact your doctor immediately.
Important precautions
Drug Interaction (Kidney/Blood)
Do not take ibuprofen while taking methotrexate unless specifically directed by your specialist. Ibuprofen can stop methotrexate from leaving your body, leading to a dangerous build-up and severe toxicity.
Pregnancy and Conception
Methotrexate causes severe birth defects and miscarriage. You must use effective contraception during treatment and for at least 6 months after stopping. This applies to both men and women.
Infection and Blood Disorders
Methotrexate can suppress your immune system and bone marrow. You must seek immediate medical help if you develop a sore throat, fever, mouth ulcers, or unexplained bruising/bleeding.
Stomach ulcers or bleeding
Avoid ibuprofen if you have ever had a stomach ulcer, perforation, or bleeding, as it can cause serious damage to the stomach lining.
Pregnancy (third trimester)
Do not take ibuprofen if you are more than 6 months pregnant, as it can cause serious heart and kidney problems in the unborn baby and complications during birth.
Asthma
Do not take ibuprofen if you have asthma and have ever experienced wheezing, shortness of breath, or a runny nose after taking aspirin or other NSAIDs, as it can trigger a life-threatening asthma attack.
Food and drink warnings
Alcohol
You should strictly limit or avoid alcohol while taking methotrexate. Both alcohol and methotrexate can cause liver damage; using them together significantly increases the risk of serious liver toxicity. Your doctor will advise if a very small amount is permissible based on your blood tests.
It is best to avoid or strictly limit alcohol while taking ibuprofen. Combining alcohol with non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen increases the risk of irritation to your stomach lining and can lead to stomach ulcers or bleeding.
Caffeine (Coffee, Tea, Cola)
High intake of caffeine may reduce the effectiveness of methotrexate for some conditions like rheumatoid arthritis. If you notice your symptoms worsening, try to keep your caffeine intake consistent and moderate.
Dairy products
Milk and other dairy products contain an enzyme called xanthine oxidase which can break down methotrexate before it is absorbed. If you are taking methotrexate tablets, it is best to avoid consuming large amounts of dairy at the same time as your dose to ensure you get the full benefit of the medicine.
Food (General)
It is best to take ibuprofen with food or a glass of milk. This helps to protect your stomach lining and reduces the chance of indigestion or stomach upset.
Using other medicines
Taking multiple medicines? Our Medicines Interaction Checker helps you check whether your prescriptions, over-the-counter medicines, and supplements are safe to take together. Simply search for your medicines to see potential interactions and what to do about them.
Disclaimer
This information is for general educational purposes only and should not be relied upon as a substitute for professional medical advice. Always consult your GP, pharmacist, or another qualified healthcare professional before making decisions about your medications. Individual circumstances may vary, and only a healthcare professional who knows your medical history can provide personalised guidance.
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Article history
The information on this page is written and peer reviewed by qualified clinicians.
Article also available in English, German, Spanish, French, Italian, Portuguese, Hindi, Hebrew, Arabic, and Swedish.
25 Jan 2026 | Originally published
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