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NSAID Methotrexate Interaction — SCE Rheumatology MCQ

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ModerateRheumatology PharmacologyNSAID Methotrexate InteractionSCE Rheumatology

A 72-year-old woman with rheumatoid arthritis takes methotrexate 20 mg once weekly. Her estimated glomerular filtration rate is 42 mL/min/1.73 m². She is considering taking regular ibuprofen for persistent joint pain. Which pharmacological interaction is most important?

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Reveal the answer and explanation

Correct answer: C — Decreased renal tubular secretion of methotrexate, increasing its exposure and toxicity

Explanation lettering: D = shown as A · E = shown as B · A = shown as C · C = shown as D · B = shown as E

NSAIDs, including ibuprofen, can inhibit the renal tubular secretion of methotrexate and may also impair renal function. This can reduce methotrexate clearance, increasing systemic exposure and the risk of gastrointestinal, haematological and renal toxicity. The interaction is particularly important here because the patient has impaired renal function and is taking 20 mg weekly rather than a very low methotrexate dose. NSAIDs and low-dose methotrexate are sometimes co-prescribed, but the interaction must still be considered and renal function and routine methotrexate safety tests monitored. NSAIDs do not induce methotrexate metabolism or excretion, and they do not characteristically reduce its intestinal absorption or directly antagonise its anti-inflammatory action; therefore B–E do not describe the relevant interaction.

Reference: Electronic Medicines Compendium. Ibuprofen 200 mg film-coated tablets (POM), Summary of Product Characteristics, section 4.5: Interaction with other medicinal products. Updated 1 July 2026. https://www.medicines.org.uk/emc/product/11166/smpc