NutriStack
Ibuprofen and Methotrexate, a caution.
NSAIDs reduce renal clearance of methotrexate, potentially leading to toxic methotrexate accumulation. This can cause severe bone marrow suppression, hepatotoxicity, and nephrotoxicity.
One pair, every claim cited. The two substances, the type, the mechanism, the recommendation, and the primary literature.
Same shape as the other 1,729 pairs in the public database.
From the interaction database
What the row says.
Every entry follows the same shape: what is happening, the mechanism, the recommendation, and the primary literature.
At a glance
- Substances
- Ibuprofen and Methotrexate
- Pair type
- Caution
- Evidence (highest tier)
- Strong
- Source citations
- 3 sources
- Stack Score effect
- −5 to your Stack Score (per scored caution row).
- Scope
- Supplement × Prescription
- Last verified
- May 30, 2026
Caution · Strong evidence
Caution
What is happening. NSAIDs reduce renal clearance of methotrexate, potentially leading to toxic methotrexate accumulation. This can cause severe bone marrow suppression, hepatotoxicity, and nephrotoxicity.
Mechanism. NSAIDs reduce renal blood flow via prostaglandin inhibition and compete with methotrexate for renal tubular secretion, decreasing methotrexate clearance by 20-40%.
Recommendation. Avoid concurrent use, especially with high-dose methotrexate. If low-dose methotrexate (for RA) is combined with occasional NSAID use, monitor CBC and renal function closely.
Sources (3)
- Svanstrom H et al. Use of NSAIDs and risk of methotrexate toxicity. Arthritis Rheumatol. 2017. PMID 28499043
- Tan E, Braithwaite I, McKinlay CJD et al.. Comparison of Acetaminophen (Paracetamol) With Ibuprofen for Treatment of Fever or Pain in Children Younger Than 2 Years: A Systematic Review and Meta-analysis.. JAMA Network Open. 2020. PMID 33125495
- Miroshnychenko A, Ibrahim S, Azab M et al.. Acute Postoperative Pain Due to Dental Extraction in the Adult Population: A Systematic Review and Network Meta-analysis.. Journal of Dental Research. 2023. PMID 36631957
Stack Score
How this pair moves the number.
Effect on the composite score
If both Ibuprofen and Methotrexate are in the same stack, this pair applies −5 to your Stack Score (per scored caution row).
The full algorithm, the clamping rules, and four worked stacks are documented at /methodology/stack-score.
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