The Case for Expanding the FDA Box Warning on Clopidogrel to CYP2C19 Intermediate Metabolizers

In 2010, concern over the diminished antiplatelet effects of clopidogrel led the US Food and Drug Administration (FDA) to update the product label to include a black box warning (BBW) on the use of clopidogrel in cytochrome P450 2C19 (CYP2C19) poor metabolizers (PMs).(1) However, there is no mention of CYP2C19 intermediate metabolizers (IMs) in the BBW; over the last decade, additional evidence has accumulated showing CYP2C19 IMs are also at risk of diminished antiplatelet effects.

Automated summary

Concerns about diminished antiplatelet effects of clopidogrel in CYP2C19 poor metabolizers led the FDA to update the product label with a black box warning, but there is no mention of CYP2C19 intermediate metabolizers in the warning. Accumulating evidence over the past decade suggests that CYP2C19 IMs are also at risk of diminished antiplatelet effects.