Which agent is particularly associated with methemoglobinemia risk and should be used with caution in patients with G6PD deficiency?

• A. Benzocaine topical
• B. Articaine
• C. Lidocaine
• D. Prilocaine

Answer: (D)

Methemoglobinemia risk with local anesthetics relates to how some drugs are metabolized into oxidizing compounds that push iron in hemoglobin from Fe2+ to Fe3+, reducing oxygen delivery. Prilocaine stands out because its metabolism produces o-toluidine, a potent oxidizer that increases methemoglobin formation. In someone with G6PD deficiency, the ability to regenerate NADPH and support methemoglobin reduction is impaired, so oxidative challenges are less well managed. That combination makes prilocaine particularly risky in G6PD-deficient patients, so it should be used with caution or avoided in favor of safer alternatives. For context, other agents like lidocaine or articaine have a much lower methemoglobinemia risk, though benzocaine topical can also cause this issue, especially in high doses or susceptible individuals.