Oxycodone and Hydrocodone
Although the drugs oxycodone and hydrocodone have some analgesic activity, they are metabolized by CYP2D6 to the much more potent metabolites of oxymorphone and hydromor- phone, respectively. A study of 450 patients with cancer receiv- ing oxycodone demonstrated that plasma concentrations of the more active oxymorphone were up to 11 times higher in patients with rapid metabolism than in those with poor metab- olism at CYP2D6 (p< .0001) [28]. In another study, depending on CYP2D6 metabolism, patients required either 16 (UMs) or 25 (PMs) mg of oxycodone to achieve equal analgesic effect (p5 .005) [29]. Studies have shown that a similar phenomenon occurs when patients are given hydrocodone. CYP2D6 UMs had
Figure 2. Pharmacogenetic-driven treatment pathway for pain management. CYP2D6 UMs and PMs should avoid tramadol, codeine, hydrocodone, and oxycodone. PMs may be at risk for treatment failure because of their inability to convert the parent drug into its more active metabolite. UMs may be at risk for treatment-related side effects because of supratherapeutic con- centrations of active metabolites. Patients with GG genotypes for COMT and/or OPRM1 may require higher morphine equivalents for analgesia. Oxycodone and hydrocodone are also inactivated via CYP3A4; therefore, drugs that inhibit or induce the CYP3A4 pathway should be avoided, when possible. 1, If patient is on a strong CYP2D6 inhibitor, then classify as a
poor metabolizer.
