A patient on diazepam develops obtundation after starting an OTC heartburn medication. Which interaction is most likely responsible?

• A. Cimetidine inhibits hepatic metabolism of diazepam, increasing CNS depression
• B. Cimetidine inhibits absorption of diazepam in the gut
• C. Cimetidine induces CYP450 leading to diazepam clearance
• D. Cimetidine has no interaction with diazepam

Answer: (C)

Drug interactions that affect how a drug is cleared by the liver can amplify its effects. Diazepam is metabolized in the liver by cytochrome P450 enzymes, especially CYP3A4. Cimetidine inhibits several of these enzymes, slowing diazepam’s clearance. With slower metabolism, diazepam builds up in the blood and enhances central nervous system depression, producing obtundation. This is why starting a cimetidine-containing heartburn medication can cause heightened diazepam effects. It wouldn’t be due to blocked absorption, and cimetidine doesn’t induce enzymes to increase clearance; it tends to inhibit metabolism instead.