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CYP2D6

Cytochrome P450 2D6

What it does

Metabolizes codeine, tramadol, tamoxifen, many antidepressants and antipsychotics. Phenotype ranges from poor to ultrarapid metabolizer.

Why this matters for Black patients

African-ancestry populations carry the *17 variant (intermediate metabolism) at much higher frequencies than European populations. This affects efficacy of codeine, tamoxifen, and several SSRIs.

Common variants

Variant Phenotype African European
*17 Intermediate metabolizer 0.200 0.005
*4 Poor metabolizer 0.050 0.200
*xN Ultrarapid metabolizer (duplications) 0.050 0.010

Medications affected by CYP2D6

Metoprolol CPIC B — moderate recommendation

No recommendation for metoprolol therapy due to insufficient evidence regarding diminished metoprolol effectiveness clinically Initiate standard dosing Initiate therapy with lowest recommended starting dose. Carefully titrate dose upward to clinical effect or guideline-recommended dose; monitor more closely for bradycardia. Alternatively, consider selecting another beta-blocker. No recommendation

CPIC guideline →

Paroxetine CPIC A — strong recommendation

Select alternative drug not predominantly metabolized by CYP2D6. Initiate therapy with recommended starting dose Consider a lower starting dose and slower titration schedule as compared to normal metabolizers. Consider a 50% reduction in recommended starting dose, slower titration schedule, and a 50% lower maintenance dose as compared to normal metabolizers. No recommendation

CPIC guideline →

Tramadol CPIC A — strong recommendation

Use tramadol label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine opioid. Use tramadol label recommended age- or weight-specific dosing. Avoid tramadol use because of possibility of diminished analgesia. If opioid use is warranted, consider a non-codeine opioid. Avoid tramadol use because of potential for toxicity. If opioid use is warranted, consider a non-codeine opioid. No recommendation

CPIC guideline →

Venlafaxine CPIC B — moderate recommendation

No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects. Initiate therapy with recommended starting dose. Consider a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2D6. No recommendation

CPIC guideline →

Note: This page is reference information, not medical advice. Pharmacogenomic differences are about ancestry, not race; race is an imperfect proxy. Discuss any medication changes with your prescriber.