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NSAID, SSRI and aspirin bleeding risk — GPhC CRA MCQ

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HardDrug InteractionsNSAID, SSRI and aspirin bleeding riskGPhC CRA

A patient taking methotrexate 15 mg once weekly develops mouth ulcers and rising creatinine after naproxen is started. Which pharmacokinetic change best explains the increased methotrexate toxicity?

Educational content. Not a substitute for clinical judgement or local policy.

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Correct answer: D — Naproxen reduces renal tubular secretion of methotrexate and raises exposure

Naproxen and other NSAIDs can reduce the renal tubular secretion of methotrexate, increasing methotrexate exposure and toxicity. New mouth ulceration plus worsening renal function is therefore a clinically important toxicity signal requiring prompt clinical assessment, full blood count and renal review. The mechanism is impaired renal elimination, not CYP induction, enhanced absorption or increased faecal clearance.

Reference: Naprosyn SmPC: https://www.medicines.org.uk/emc/product/13238/smpc