Codeine

The analgesic effect of codeine is mainly attributed to its con- version to morphine mediated by CYP2D6. Morphine has a 200 times higher affinity and 50 times higher intrinsic activity at the m-opioid receptor than codeine itself. Codeine-related deaths have been reported in patients known to be CYP2D6 UMs, now a black-box warning [20–26]. Alternatively, CYP2D6 PMs will find codeine to be an ineffective analgesic given that they have no conversion of codeine to the more active morphine. CPIC guidelines strongly recommend that CYP2D6 UMs and PMs should avoid codeine because of the increased risk of toxicities and lack of analgesic effects, respectively.Without pharma- cogenomic testing, astute clinicians might avoid codeine if patients report inefficacy; however, the issue of codeine in CYP2D6 UMs is a real risk of harm without the benefit of formal pharmacogenomic testing.