Ibuprofen can cause dangerous increases in methotrexate blood levels, leading to severe toxicity. Methotrexate toxicity can cause life-threatening bone marrow suppression, kidney failure, liver damage, and fatal infections. This interaction is especially dangerous at higher methotrexate doses used in cancer treatment.
How This Interaction Works (Mechanism)
Ibuprofen reduces renal blood flow by inhibiting prostaglandin synthesis in the kidneys, which decreases the glomerular filtration rate. Since methotrexate is primarily eliminated by the kidneys, reduced renal clearance causes methotrexate to accumulate in the body. Ibuprofen may also compete with methotrexate for tubular secretion in the kidneys. Additionally, ibuprofen can displace methotrexate from plasma protein binding sites, increasing the free (active) fraction.
Source: National Comprehensive Cancer Network Drug Interactions, 2025
Avoid ibuprofen and all NSAIDs while taking methotrexate unless specifically approved by your oncologist or rheumatologist. For pain management, use acetaminophen at recommended doses. If NSAIDs are deemed necessary, your doctor should monitor methotrexate levels and kidney function closely. Report any mouth sores, unusual fatigue, easy bruising, or fever immediately, as these may indicate methotrexate toxicity.
Check More Drug Interactions
Use our free interaction checker to search thousands of drug, supplement, and food combinations.
Open Interaction CheckerFrequently Asked Questions
Methotrexate and Ibuprofen have a severe interaction and should generally not be taken together without close medical supervision. The combination can cause serious, potentially life-threatening side effects. Contact your doctor immediately if you are currently taking both medications.
Ibuprofen can cause dangerous increases in methotrexate blood levels, leading to severe toxicity. Methotrexate toxicity can cause life-threatening bone marrow suppression, kidney failure, liver damage, and fatal infections. This interaction is especially dangerous at higher methotrexate doses used in cancer treatment.
Yes. Anytime you are taking multiple medications, supplements, or substances, you should inform your doctor and pharmacist. They can evaluate your specific risk factors (age, kidney function, other medications, medical conditions) and determine whether the Methotrexate and Ibuprofen combination is safe for you, or whether adjustments are needed.
Related Resources
- Supplement interactions with Methotrexate on Health Britannica
- Supplement interactions with Ibuprofen on Health Britannica
- Methotrexate prices and pharmacy comparison on RxGrab
- Ibuprofen prices and pharmacy comparison on RxGrab
- Full drug interaction checker tool
Get Drug Safety Alerts
Subscribe to receive updates on FDA warnings, new drug interactions, and patient safety information.