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Drug interactions

Methotrexate + Salsalate

Severity: Major

Methotrexate and Salsalate: 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

Salsalate, a salicylate, can reduce methotrexate clearance and raise its levels. This increases the risk of bone marrow suppression, mucositis and renal toxicity, particularly with high doses or poor renal function.

What this interaction means in plain words

Methotrexate and Salsalate 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.

Evidence level: Moderate

Why it happens

Salicylates reduce renal tubular secretion of methotrexate and displace it from plasma protein binding.

What to do

Avoid with high-dose methotrexate. With low-dose methotrexate, monitor blood counts and renal function closely.

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?

Bring a full list of your medicines, including over-the-counter products, supplements and herbal remedies, to every pharmacy visit.

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References

Frequently asked questions

Can I take Methotrexate with Salsalate?

MediHelp rates the interaction as major. Methotrexate and Salsalate 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. Salsalate, a salicylate, can reduce methotrexate clearance and raise its levels. This increases the risk of bone marrow suppression, mucositis and renal toxicity, particularly with high doses or poor renal function.

How serious is the interaction between Methotrexate and Salsalate?

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. With low-dose methotrexate, monitor blood counts and renal function closely.

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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