CYP2C8 interactions

CYP2C8 has a short substrate list and, clinically, one inhibitor that dominates it: gemfibrozil.

Repaglinide is the drug that demonstrates the problem. Gemfibrozil inhibits both CYP2C8 and hepatic OATP uptake, so repaglinide exposure rises far enough to cause serious hypoglycemia, and the combination is contraindicated rather than merely monitored.

The other substrates are the glitazones pioglitazone and rosiglitazone, montelukast, paclitaxel, selexipag, resmetirom and enzalutamide. Clopidogrel is the second inhibitor, and rifampin is the only inducer shown.

For most prescribers 2C8 reduces to a single habit: before adding gemfibrozil, look for repaglinide or a glitazone already on the list.