Table 3. [The DPWG Recommendations for Tramadol Dosing based on CYP2D6 Phenotype (2017)]. - Medical Genetics Summaries

CYP2D6 phenotype	Dosing 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).

CYP2D6 phenotype

Dosing 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).

From: Tramadol Therapy and CYP2D6 Genotype

Medical Genetics Summaries [Internet].

Pratt VM, Scott SA, Pirmohamed M, et al., editors.

Bethesda (MD): National Center for Biotechnology Information (US); 2012-.

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