AlleleMedicationsTest results* and clinical implicationsComments
Pain
CYP2D6Codeine, hydrocodone, oxycodone, tramadol
  • Ultrarapid metabolizer: Avoid codeine because of potential for toxicity13,23

  • Poor metabolizer: Avoid codeine and possibly tramadol because of possible lack of effectiveness13,23

  • CPIC guidance limits genotype-guided dosing recommendations to codeine.13

  • Alternative analgesics not affected by CYP2D6 variability include morphine, oxymorphone, and nonopioid analgesics.13

  • Oxycodone may also have reduced effectiveness in poor CYP2D6 metabolizers.11,13,23

Cardiovascular (percutaneous coronary intervention)
CYP2C19Clopidogrel (Plavix)
  • Intermediate metabolizer: Use alternative antiplatelet therapy if no contraindications9

  • Poor metabolizer: Use alternative antiplatelet therapy if no contraindications9

  • Clopidogrel prescribing information states that CYP2C19 tests can be used as an aid to determine therapeutic strategy in patients with acute coronary syndromes who are undergoing percutaneous coronary intervention.24

  • CPIC guidance limits genotype-guided dosing recommendations to patients undergoing percutaneous coronary intervention for acute coronary syndromes (excluding medical management of acute coronary syndromes, stroke, and peripheral artery disease).9

  • ACCF/AHA guidelines state that genotyping may be considered in patients with unstable angina/non-ST segment elevation myocardial infarction (or after percutaneous coronary intervention for acute coronary syndromes) if test results could alter management.25

  • Alternative antiplatelet therapy not affected by CYP2C19 variability includes prasugrel (Effient) and ticagrelor (Brilinta).9

Depression/psychiatry
CYP2C19Amitriptyline
  • Poor metabolizer: Consider 50% reduction in recommended starting dose26

  • CPIC guidance is available for CYP2D6- and CYP2C19-genotype guided tricyclic antidepressant therapy.26

  • Although limited data exist for other tricyclic antidepressants, most supporting evidence of clinically relevant gene-drug effects is for amitriptyline and nortriptyline (Pamelor).26

CYP2C19Citalopram (Celexa), escitalopram (Lexapro)
  • Ultrarapid metabolizer: Consider alternative

  • Poor metabolizer: Consider 50% starting dose reduction and titrate to response, or use alternative27

  • CPIC guidance is available for CYP2C19-genotype guided citalopram and escitalopram therapy.27

  • FDA label for citalopram states that 20 mg per day is the maximum recommended dosage for patients older than 60 years, patients with hepatic impairment, and CYP2C19 poor metabolizers or patients taking cimetidine (Tagamet) or another CYP2C19 inhibitor.28

CYP2C19Sertraline (Zoloft)
  • Ultrarapid metabolizer: If patient does not respond to recommended dose, consider alternative

  • Poor metabolizer: Consider 50% dose reduction or alternative27

  • CPIC guidance is available for CYP2C19-genotype guided sertraline therapy.27

CYP2D6Amitriptyline, nortriptyline
  • Ultrarapid metabolizer: Avoid because of possible lack of effectiveness26

  • Poor metabolizer: Avoid because of possible adverse effects; if use is warranted, consider 50% reduction in recommended starting dose26

  • CPIC guidance is available for CYP2D6- and CYP2C19-genotype guided tricyclic antidepressant therapy. 26

  • Although limited data exist for other tricyclic antidepressants, most supporting evidence of clinically relevant gene-drug effects is for amitriptyline and nortriptyline.26

CYP2D6Aripiprazole (Abilify)
  • Poor metabolizer: Decrease dose29

  • Quality of supporting evidence is classified as low by PharmGKB.

  • FDA label for aripiprazole states that in poor metabolizers, the usual dose should initially be reduced to 50% and then adjusted to achieve a favorable clinical response; in poor metabolizers receiving a strong CYP3A4 inhibitor, the usual dose should be reduced to 25%.29

CYP2D6Atomoxetine (Strattera)
  • Poor metabolizer: Adjust dose30

  • Quality of supporting evidence is classified as moderate (Level 2a) by PharmGKB.

  • FDA label for atomoxetine states that in poor metabolizers, the initial dosage should be 0.5 mg per kg per day and then increased to the the usual target dosage of 1.2 mg per kg per day only if symptoms do not improve after 4 weeks and the initial dose is well tolerated.30

CYP2D6Paroxetine (Paxil)
  • Ultrarapid metabolizer: Select alternative because of possible lack of effectiveness.

  • Poor metabolizer: Select alternative or if use is warranted, consider 50% starting dose reduction27

  • CPIC guidance is available for CYP2D6-genotype guided paroxetine therapy.27