phenytoin and omeprazole

Omeprazole inhibits CYP2C19, an enzyme involved in the metabolism of phenytoin. This inhibition reduces phenytoin clearance, leading to increased plasma concentrations. Conversely, phenytoin may induce CYP2C19, potentially lowering omeprazole levels, but the clinically relevant effect is on phenytoin.

Elevated phenytoin levels can cause toxicity, manifesting as nystagmus, ataxia, drowsiness, and confusion. The risk is higher in patients with pre-existing high phenytoin concentrations or those who are poor CYP2C19 metabolisers. This interaction is of particular concern because phenytoin has a narrow therapeutic index.

Monitor plasma phenytoin concentrations and observe for signs of toxicity when omeprazole is started, stopped, or the dose is changed. Consider reducing the phenytoin dose if levels rise. If clinically appropriate, an alternative proton pump inhibitor with less CYP2C19 inhibition, such as pantoprazole, could be substituted.

The interaction is well documented in case reports and clinical studies, and is recognised in standard drug interaction databases and prescribing information.