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PPI Methotrexate Interaction — SCE Rheumatology MCQ

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ModerateRheumatology PharmacologyPPI Methotrexate InteractionSCE Rheumatology

A 45-year-old woman with rheumatoid arthritis takes oral methotrexate 20 mg once weekly. Her renal function and routine monitoring results are normal. Omeprazole is prescribed for dyspepsia. Which statement best describes the potential interaction between proton pump inhibitors and methotrexate?

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Correct answer: A — PPIs may delay renal methotrexate elimination; the risk is greatest with high-dose methotrexate or renal impairment

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

D is correct. Proton pump inhibitors, including omeprazole, can delay renal elimination of methotrexate and thereby increase exposure to methotrexate or its 7-hydroxymethotrexate metabolite. The evidence and regulatory concern are strongest for high-dose oncology regimens and in patients with impaired renal function. A PPI is not absolutely contraindicated with stable low-dose weekly methotrexate used for rheumatoid arthritis; clinically meaningful toxicity appears uncommon, but renal function, routine methotrexate monitoring and symptoms such as mucositis, gastrointestinal disturbance or marrow suppression remain relevant. PPIs do not predictably increase gastrointestinal absorption (A), render methotrexate ineffective (C), or require universal avoidance (B). Option E is incorrect because a recognised pharmacokinetic interaction exists even though its clinical significance at rheumatological doses is usually limited.

Reference: Electronic Medicines Compendium, Methotrexate 100 mg/ml Injection, Summary of Product Characteristics, section 4.5 Interactions, updated 13 July 2026. https://www.medicines.org.uk/emc/product/6756/smpc