Drug interactions
Diflunisal + Methotrexate
Severity: Major
Diflunisal and Methotrexate: major interaction.
Last updated Sources: US FDA label
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
NSAIDs can raise and prolong methotrexate levels, especially with high doses or reduced kidney function, causing serious hematologic and gastrointestinal toxicity. Diflunisal in particular has been associated with raised methotrexate concentrations.
What this interaction means in plain words
Diflunisal and Methotrexate can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Diflunisal belongs to Musculoskeletal; Methotrexate belongs to Oncology.
Why it happens
Reduced renal tubular secretion of methotrexate and NSAID-induced reduction in renal perfusion.
What to do
Avoid with high-dose methotrexate and prefer another analgesic. If used with low-dose methotrexate, monitor renal function and blood counts.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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References
Other interactions of Methotrexate
- Acitretin + Methotrexate Contraindicated
- Adenovirus types 4 and 7 live + Methotrexate Contraindicated
- Influenza virus vaccine quadrivalent intranasal + Methotrexate Contraindicated
- Ketorolac + Methotrexate Contraindicated
- Measles mumps and rubella vaccine live + Methotrexate Contraindicated
- Measles mumps and rubella vaccine + Methotrexate Contraindicated
Other interactions of Diflunisal
- Diflunisal + Ketorolac Contraindicated
- Diflunisal + Ketorolac intranasal Contraindicated
- Acemetacin + Diflunisal Major
- Acetazolamide + Diflunisal Major
- Alteplase + Diflunisal Major
- Amiloride + Diflunisal Major
Frequently asked questions
Can I take Diflunisal with Methotrexate?
MediHelp rates the interaction as major. Diflunisal and Methotrexate can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. NSAIDs can raise and prolong methotrexate levels, especially with high doses or reduced kidney function, causing serious hematologic and gastrointestinal toxicity. Diflunisal in particular has been associated with raised methotrexate concentrations.
How serious is the interaction between Diflunisal and Methotrexate?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Avoid with high-dose methotrexate and prefer another analgesic. If used with low-dose methotrexate, monitor renal function and blood counts.
What other medicines interact with Methotrexate?
MediHelp also lists interactions of Methotrexate with, for example, Acitretin, Adenovirus types 4 and 7 live, Influenza virus vaccine quadrivalent intranasal. The full list is on the Methotrexate page.
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