Drug interactions
Acetylsalicylic acid + Methotrexate
Severity: Major
Acetylsalicylic acid 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
Salicylates can raise methotrexate concentrations and increase the risk of bone marrow suppression, mucositis, and hepatic and renal toxicity. The risk is greatest with high-dose methotrexate and with anti-inflammatory aspirin doses, but toxicity has also been described with low-dose methotrexate, particularly in renal impairment.
What this interaction means in plain words
Acetylsalicylic acid 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.
Acetylsalicylic acid belongs to Musculoskeletal; Methotrexate belongs to Oncology.
Why it happens
Salicylates reduce renal tubular secretion of methotrexate, can displace it from plasma proteins and impair renal function via prostaglandin inhibition.
What to do
Avoid aspirin at anti-inflammatory doses with high-dose methotrexate. With low-dose methotrexate, monitor blood counts, renal function and liver enzymes closely and consider an alternative analgesic.
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 Acetylsalicylic acid
- Acetylsalicylic acid + Ketorolac Contraindicated
- Acetylsalicylic acid + Ketorolac intranasal Contraindicated
- Abciximab + Acetylsalicylic acid Major
- Acemetacin + Acetylsalicylic acid Major
- Acetazolamide + Acetylsalicylic acid Major
- Acetylsalicylic acid + Alteplase Major
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
Frequently asked questions
Can I take Acetylsalicylic acid with Methotrexate?
MediHelp rates the interaction as major. Acetylsalicylic acid 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. Salicylates can raise methotrexate concentrations and increase the risk of bone marrow suppression, mucositis, and hepatic and renal toxicity. The risk is greatest with high-dose methotrexate and with anti-inflammatory aspirin doses, but toxicity has also been described with low-dose methotrexate, particularly in renal impairment.
How serious is the interaction between Acetylsalicylic acid 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 aspirin at anti-inflammatory doses with high-dose methotrexate. With low-dose methotrexate, monitor blood counts, renal function and liver enzymes closely and consider an alternative analgesic.
What other medicines interact with Acetylsalicylic acid?
MediHelp also lists interactions of Acetylsalicylic acid with, for example, Ketorolac, Ketorolac intranasal, Abciximab. The full list is on the Acetylsalicylic acid page.
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