When a patient on methotrexate is also taking an NSAID such as ibuprofen, which of the following is the most clinically significant risk to be aware of?

• A. Increased ibuprofen efficacy
• B. No interaction
• C. Increased risk of methotrexate toxicity
• D. Decreased methotrexate efficacy

Answer: (C)

When methotrexate is used with an NSAID, the biggest clinical concern is increased methotrexate exposure due to reduced renal clearance. NSAIDs can impair kidney function and compete for tubular secretion, so methotrexate stays in the blood longer and reaches higher levels. This raises the risk of toxicity, especially bone marrow suppression, mucositis, hepatotoxicity, and nephrotoxicity. The risk is heightened with high-dose methotrexate or in patients with existing kidney impairment or dehydration. So the most clinically significant risk is increased methotrexate toxicity. To manage, minimize NSAID use if possible, use alternatives like acetaminophen, ensure good hydration, monitor renal function, and consider methotrexate level checks if indicated, adjusting therapy accordingly.