Table 3.

The DPWG Recommendations for Tramadol Dosing based on CYP2D6 Phenotype (2017)

CYP2D6 phenotypeDosing recommendations
Poor metabolizer
(gene dose 0, absent enzyme activity)		It is not possible to provide a recommendation for dose adjustment, because the total analgesic effect changes when the ratio between the mother compound and the active metabolite changes.
1.

be alert to a reduced effectiveness

2.

in the case of inadequate effectiveness:

  • try a dose increase.
  • if this does not work, choose an alternative*
3.

if no alternative is selected: advise the individual to report inadequate analgesia

Intermediate metabolizer
(gene dose 0.5-1, decreased enzyme activity)
Ultrarapid metabolizer
(gene dose ≥ 3)
(enhanced enzyme activity)		As the total analgesic effect changes when the ratio between the mother compound and the active metabolite changes, the effect of a dose reduction cannot be predicted with certainty.
1.

select an alternative*

2.

if an alternative is not possible:

  • use 40% of the standard dose
  • advise the individual to report side effects (such as drowsiness, confusion, constipation, nausea and vomiting, respiratory depression or urine retention).
*

Do not select codeine, as this is also metabolized by CYP2D6. Morphine is not metabolized by CYP2D6. Oxycodone is metabolized by CYP2D6 to a limited extent, but this does not result in differences in analgesia and side effects in clinical practice.

This table is adapted from (3).

From: Tramadol Therapy and CYP2D6 Genotype

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