Which statement best describes drug interactions involving phenytoin?

• A. Phenytoin has no significant drug interactions.
• B. Phenytoin inhibits CYP enzymes, decreasing metabolism of other drugs.
• C. Phenytoin is only excreted unchanged and has no interactions.
• D. Phenytoin induces CYP enzymes, increasing metabolism of other drugs, which can reduce effectiveness of concomitant medications.

Answer: (D)

Phenytoin acts as a hepatic enzyme inducer, speeding up the metabolism of other drugs. It stimulates cytochrome P450 enzymes, such as CYP3A4, CYP2C9, and CYP2C19, which increases the clearance of medications that are substrates of these enzymes. As a result, the plasma concentrations of coadministered drugs can drop, potentially reducing their effectiveness unless doses are adjusted. This induction can also affect phenytoin itself (autoinduction), meaning its own metabolism can increase over time and may require dose changes.

This explains why the statement describing phenytoin as increasing the metabolism of other drugs—and thereby potentially decreasing the effectiveness of concurrently used meds—is the best description. It also clarifies why explanations suggesting no interactions, enzyme inhibition, or excretion unchanged are not accurate.