TABLE 4.

HYDROCODONE THERAPY RECOMMENDATIONS BASED ON CYP2D6 PHENOTYPE

Phenotype	Activity score	Implications	Recommendations	Classification of recommendationa
CYP2D6 ultrarapid metabolizer	> 2.25	Minimal evidence for pharmacokinetic or clinical effect.	No recommendation for hydrocodone therapy because of minimal evidence regarding adverse events or analgesia.	No recommendation
CYP2D6 normal metabolizer	1.25≤x≤2.25	Normal hydromorphone formation	Use hydrocodone label recommended age- or weight-specific dosing.	Strong
CYP2D6 intermediate metabolizer	0<x<1.25	Minimal evidence for pharmacokinetic or clinical effect.	Use hydrocodone label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine or non-tramadol opioid.	Optional
CYP2D6 poor metabolizer	0	Decreased metabolism of hydrocodone to active metabolite, hydromorphone, but there is insufficient evidence to determine if these effects on pharmacokinetics translate into decreased analgesia or side effects.	Use hydrocodone label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine and non-tramadol opioid.	Optional
CYP2D6 indeterminate	n/a	n/a	No recommendation	No recommendation

^aRating scheme described in the Supplement.