A patient with rheumatoid arthritis on weekly methotrexate asks which of her current medications has a severe interaction with methotrexate.

• A. Omeprazole
• B. Paracetamol
• C. Ibuprofen
• D. Amoxicillin

Answer: (C)

The main idea is that some drugs can raise methotrexate levels by affecting how it is cleared by the kidneys, increasing the risk of toxicity. Ibuprofen, an NSAID, can reduce renal elimination of methotrexate by altering kidney function and perfusion, which leads to higher methotrexate exposure. This increases the risk of adverse effects such as bone marrow suppression and mucosal toxicity, especially when methotrexate is used weekly for rheumatoid arthritis.

Paracetamol does not significantly affect methotrexate clearance, so it’s not associated with the same level of interaction. Omeprazole can sometimes modestly influence methotrexate excretion in certain patients, but the effect is not as severe. Amoxicillin can interact with methotrexate in some circumstances, but the interaction is not as clearly severe as with NSAIDs like ibuprofen. In practice, if an NSAID is needed, use the lowest effective dose for the shortest duration and monitor kidney function and blood counts.