Which of the following is least likely to prevent NSAID-induced GI irritation?

• A. Take NSAID 30 minutes after a meal
• B. Add a proton pump inhibitor to the drug regimen
• C. Switch to a drug class without GI irritation
• D. Replace the drug with Rofecoxib, a selective COX-2 inhibitor

Answer: (D)

NSAID-induced GI irritation mainly comes from COX-1 inhibition, which removes protective gastric prostaglandins. A COX-2–selective inhibitor like rofecoxib reduces this problem by sparing COX-1, thus lowering the risk of gastric ulcers and GI bleeding compared with nonselective NSAIDs. Among the options, switching to a COX-2–selective inhibitor directly targets the mechanism behind GI injury, offering a stronger preventive effect than merely taking the NSAID after a meal, adding a proton pump inhibitor, or switching to a non-GI–irritating drug class. Keep in mind that COX-2 inhibitors carry other risks, but in terms of GI protection, they are the most effective option listed.