anticonvulsants →

Fosphenytoin CYP2C9

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer CYP2C9	Normal fosphenytoin metabolism	No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to standard practice.	Strong
Intermediate Metabolizer CYP2C9	Slightly reduced fosphenytoin metabolism; however, this does not appear to translate into increased side effects.	No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to standard practice.	Moderate
Intermediate Metabolizer CYP2C9	Reduced fosphenytoin metabolism; higher plasma concentrations will increase probability of toxicities.	For first dose, use typical initial or loading dose. For subsequent doses, use ~25% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to standard practice.	Moderate
Poor Metabolizer CYP2C9	Reduced fosphenytoin metabolism; higher plasma concentrations will increase probability of toxicities.	For first dose, use typical initial or loading dose. For subsequent doses, use ~50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to standard practice.	Strong
Poor Metabolizer CYP2C9	Reduced fosphenytoin metabolism; higher plasma concentrations will increase probability of toxicities.	For first dose, use typical initial or loading dose. For subsequent doses, use ~50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to standard practice.	Strong

Phenytoin CYP2C9

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer CYP2C9	Normal phenytoin metabolism	No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to standard practice.	Strong
Intermediate Metabolizer CYP2C9	Slightly reduced phenytoin metabolism; however, this does not appear to translate into increased side effects.	No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to standard practice.	Moderate
Intermediate Metabolizer CYP2C9	Reduced phenytoin metabolism; higher plasma concentrations will increase probability of toxicities.	For first dose, use typical initial or loading dose. For subsequent doses, use ~25% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to standard practice.	Moderate
Poor Metabolizer CYP2C9	Reduced phenytoin metabolism; higher plasma concentrations will increase probability of toxicities.	For first dose, use typical initial or loading dose. For subsequent doses, use ~50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to standard practice.	Strong
Poor Metabolizer CYP2C9	Reduced phenytoin metabolism; higher plasma concentrations will increase probability of toxicities.	For first dose, use typical initial or loading dose. For subsequent doses, use ~50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to standard practice.	Strong

antidepressants - SNRI

Venlafaxine CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased metabolism of venlafaxine to the active metabolite O-desmethylvenlafaxine (desvenlafaxine) and increased O-desmethylvenlafaxine:venlafaxine ratio compared with normal metabolizers. There is insufficient evidence supporting the clinical impact of this increased ratio.	No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.	Optional
Normal Metabolizer CYP2D6	Normal metabolism of venlafaxine.	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Decreased metabolism of venlafaxine to the active metabolite O-desmethylvenlafaxine and decreased O-desmethylvenlafaxine:venlafaxine ratio compared with normal metabolizers. There is insufficient evidence supporting the clinical impact of this decreased ratio.	No action recommended based on genotype for venlafaxine because of minimal evidence regarding the impact on efficacy or side effects.	Optional
Poor Metabolizer CYP2D6	Decreased metabolism of venlafaxine to the active metabolite O-desmethylvenlafaxine and greatly decreased O-desmethylvenlafaxine:venlafaxine ratio compared with normal and intermediate metabolizers. Although the clinical impact is unclear, poor metabolizer status has been associated with adverse effects.	Consider a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2D6.	Optional

antidepressants - SSRI →

Citalopram CYP2C19

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2C19	Increased metabolism of citalopram and escitalopram to less active compounds when compared with CYP2C19 rapid and normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit.	Consider a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19. If citalopram or escitalopram are clinically appropriate, and adequate efficacy is not achieved at standard maintenance dosing, consider titrating to a higher maintenance dose.	Moderate
Rapid Metabolizer CYP2C19	Increased metabolism of citalopram and escitalopram to less active compounds when compared with CYP2C19 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit.	Initiate therapy with recommended starting dose. If patient does not adequately respond to recommended maintenance dosing, consider titrating to a higher maintenance dose or switching to a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19.	Moderate
Normal Metabolizer CYP2C19	Normal metabolism.	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2C19	Reduced metabolism when compared with CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.	Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than normal metabolizers.	Strong
Likely Intermediate Metabolizer CYP2C19	Reduced metabolism when compared with CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.	Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than normal metabolizers.	Strong
Likely Poor Metabolizer CYP2C19	Reduced metabolism of citalopram and escitalopram to less active compounds when compared with CYP2C19 normal and intermediate metabolizers. Higher plasma concentrations may increase the probability of side effects.	Consider a clinically appropriate antidepressant not predominantly metabolized by CYP2C19. If citalopram or escitalopram are clinically appropriate, consider a lower starting dose, slower titration schedule, and 50% reduction of the standard maintenance dose as compared with normal metabolizers.	Moderate
Poor Metabolizer CYP2C19	Reduced metabolism of citalopram and escitalopram to less active compounds when compared with CYP2C19 normal and intermediate metabolizers. Higher plasma concentrations may increase the probability of side effects.	Consider a clinically appropriate antidepressant not predominantly metabolized by CYP2C19. If citalopram or escitalopram are clinically appropriate, consider a lower starting dose, slower titration schedule, and 50% reduction of the standard maintenance dose as compared with normal metabolizers.	Moderate

Escitalopram CYP2C19

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2C19	Increased metabolism of citalopram and escitalopram to less active compounds when compared with CYP2C19 rapid and normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit.	Consider a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19. If citalopram or escitalopram are clinically appropriate, and adequate efficacy is not achieved at standard maintenance dosing, consider titrating to a higher maintenance dose.	Moderate
Rapid Metabolizer CYP2C19	Increased metabolism of citalopram and escitalopram to less active compounds when compared with CYP2C19 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit.	Initiate therapy with recommended starting dose. If patient does not adequately respond to recommended maintenance dosing, consider titrating to a higher maintenance dose or switching to a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19.	Moderate
Normal Metabolizer CYP2C19	Normal metabolism.	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2C19	Reduced metabolism when compared with CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.	Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than normal metabolizers.	Strong
Likely Intermediate Metabolizer CYP2C19	Reduced metabolism when compared with CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.	Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than normal metabolizers.	Strong
Likely Poor Metabolizer CYP2C19	Reduced metabolism of citalopram and escitalopram to less active compounds when compared with CYP2C19 normal and intermediate metabolizers. Higher plasma concentrations may increase the probability of side effects.	Consider a clinically appropriate antidepressant not predominantly metabolized by CYP2C19. If citalopram or escitalopram are clinically appropriate, consider a lower starting dose, slower titration schedule, and 50% reduction of the standard maintenance dose as compared with normal metabolizers.	Moderate
Poor Metabolizer CYP2C19	Reduced metabolism of citalopram and escitalopram to less active compounds when compared with CYP2C19 normal and intermediate metabolizers. Higher plasma concentrations may increase the probability of side effects.	Consider a clinically appropriate antidepressant not predominantly metabolized by CYP2C19. If citalopram or escitalopram are clinically appropriate, consider a lower starting dose, slower titration schedule, and 50% reduction of the standard maintenance dose as compared with normal metabolizers.	Moderate

Fluvoxamine CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	No data available for CYP2D6 ultrarapid metabolizers.	No recommendation due to lack of evidence.	Optional
Normal Metabolizer CYP2D6	Normal metabolism of fluvoxamine.	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Reduced metabolism of fluvoxamine to less active compounds compared with normal metabolizers. Higher plasma concentrations may increase the probability of side effects.	Initiate therapy with recommended starting dose.	Moderate
Poor Metabolizer CYP2D6	Greatly reduced metabolism of fluvoxamine to less active compounds compared with normal metabolizers. Higher plasma concentrations may increase the probability of side effects.	Consider a 25–50% lower starting dose and slower titration schedule as compared with normal metabolizers or consider a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2D6.	Optional

Paroxetine CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased metabolism of paroxetine to less active compounds compared with CYP2D6 normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit.	Select alternative drug not predominantly metabolized by CYP2D6.	Strong
Normal Metabolizer CYP2D6	Normal metabolism of paroxetine to less active compounds. Paroxetine-associated phenoconversion of normal metabolizers to intermediate or poor metabolizers due to CYP2D6 autoinhibition may occur and is dose-dependent.	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Reduced metabolism of paroxetine to less active compounds compared with CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.	Consider a lower starting dose and slower titration schedule as compared with normal metabolizers.	Strong
Poor Metabolizer CYP2D6	Greatly reduced metabolism compared with CYP2D6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.	Consider a 50% reduction in recommended starting dose, slower titration schedule, and a 50% lower maintenance dose as compared with normal metabolizers.	Strong

Sertraline CYP2B6 · CYP2C19

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2C19	Small increase in metabolism of sertraline to less active compounds when compared with CYP2C19 normal metabolizers.	Initiate therapy with recommended starting dose.	Optional
Rapid Metabolizer CYP2C19	Small increase in metabolism of sertraline to less active compounds when compared with normal metabolizers.	Initiate therapy with recommended starting dose.	Optional
Normal Metabolizer CYP2C19	Normal metabolism.	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2C19	Reduced metabolism of sertraline to less active compounds when compared with CYP2C19 normal metabolizers.	Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than CYP2C19 normal metabolizers.	Moderate
Likely Intermediate Metabolizer CYP2C19	Reduced metabolism of sertraline to less active compounds when compared with CYP2C19 normal metabolizers.	Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than CYP2C19 normal metabolizers.	Moderate
Poor Metabolizer CYP2C19	Greatly reduced metabolism of sertraline to less active compounds when compared with CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.	Consider a lower starting dose, slower titration schedule, and 50% reduction of standard maintenance dose as compared with CYP2C19 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19.	Moderate
Likely Poor Metabolizer CYP2C19	Greatly reduced metabolism of sertraline to less active compounds when compared with CYP2C19 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.	Consider a lower starting dose, slower titration schedule, and 50% reduction of standard maintenance dose as compared with CYP2C19 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2C19.	Moderate
Ultrarapid Metabolizer CYP2B6	Increase in metabolism of sertraline to less active compounds when compared with CYP2B6 normal metabolizers.	Initiate therapy with recommended starting dose.	Optional
Rapid Metabolizer CYP2B6	Small increase in metabolism of sertraline to less active compounds when compared with CYP2B6 normal metabolizers.	Initiate therapy with recommended starting dose.	Optional
Normal Metabolizer CYP2B6	Normal metabolism of sertraline to less active compounds.	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2B6	Reduced metabolism of sertraline to less active compounds when compared with CYP2B6 normal metabolizers.	Initiate therapy with recommended starting dose. Consider a slower titration schedule and lower maintenance dose than CYP2B6 normal metabolizers.	Moderate
Poor Metabolizer CYP2B6	Greatly reduced metabolism of sertraline to less active compounds when compared with CYP2B6 normal metabolizers. Higher plasma concentrations may increase the probability of side effects.	Consider a lower starting dose, slower titration schedule, and 25% reduction of standard maintenance dose as compared with CYP2B6 normal metabolizers or select a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2B6.	Moderate

Vortioxetine CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased metabolism of vortioxetine to inactive compounds compared with normal metabolizers. Lower plasma concentrations decrease the probability of clinical benefit.	Select alternative drug not predominantly metabolized by CYP2D6. If vortioxetine use is warranted, initiate therapy at standard starting dose and titrate to maintenance dose based on efficacy and side effects. Increasing the target maintenance dose by 50% or more may be needed for efficacy.	Optional
Normal Metabolizer CYP2D6	Normal metabolism of vortioxetine.	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Reduced metabolism of vortioxetine to less active compounds compared with normal metabolizers. Higher plasma concentrations may increase the probability of side effects.	Initiate therapy with recommended starting dose.	Moderate
Poor Metabolizer CYP2D6	Greatly reduced metabolism of vortioxetine to inactive compounds compared with normal metabolizers. Higher plasma concentrations may increase the probability of side effects.	Initiate 50% of starting dose (e.g., 5 mg) and titrate to the maximum recommended dose of 10 mg or consider a clinically appropriate alternative antidepressant not predominantly metabolized by CYP2D6.	Optional

antidepressants - TCA →

Amitriptyline CYP2C19 · CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure.	Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments.	Strong
Normal Metabolizer CYP2D6	Normal metabolism	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Reduced metabolism of TCAs to less active compounds when compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Consider 25% reduction of recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	Moderate
Poor Metabolizer CYP2D6	Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider 50% reduction of recommended starting dose.g Utilize therapeutic drug monitoring to guide dose adjustments.	Strong
Ultrarapid Metabolizer CYP2C19	Increased metabolism of tertiary amines compared to normal metabolizers. Greater conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Rapid Metabolizer CYP2C19	Increased metabolism of tertiary amines compared to normal metabolizers. Greater conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Normal Metabolizer CYP2C19	Normal metabolism	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2C19	Reduced metabolism of tertiary amines compared to normal metabolizers.	Initiate therapy with recommended starting dose.	Strong
Poor Metabolizer CYP2C19	Greatly reduced metabolism of tertiary amines compared to normal metabolizers. Decreased conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose.f Utilize therapeutic drug monitoring to guide dose adjustments.	Moderate
Likely Intermediate Metabolizer CYP2C19	Reduced metabolism of tertiary amines compared to normal metabolizers.	Initiate therapy with recommended starting dose.	Strong
Likely Poor Metabolizer CYP2C19	Greatly reduced metabolism of tertiary amines compared to normal metabolizers. Decreased conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose.f Utilize therapeutic drug monitoring to guide dose adjustments.	Moderate

Clomipramine CYP2C19 · CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure.	Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments.	Strong
Normal Metabolizer CYP2D6	Normal metabolism	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Reduced metabolism of TCAs to less active compounds when compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Consider 25% reduction of recommended starting dose.g Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Poor Metabolizer CYP2D6	Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider 50% reduction of recommended starting dose.g Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Ultrarapid Metabolizer CYP2C19	Increased metabolism of tertiary amines compared to normal metabolizers. Greater conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Rapid Metabolizer CYP2C19	Increased metabolism of tertiary amines compared to normal metabolizers. Greater conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Normal Metabolizer CYP2C19	Normal metabolism	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2C19	Reduced metabolism of tertiary amines compared to normal metabolizers.	Initiate therapy with recommended starting dose.	Optional
Poor Metabolizer CYP2C19	Greatly reduced metabolism of tertiary amines compared to normal metabolizers. Decreased conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose.f Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Likely Intermediate Metabolizer CYP2C19	Reduced metabolism of tertiary amines compared to normal metabolizers.	Initiate therapy with recommended starting dose.	Optional
Likely Poor Metabolizer CYP2C19	Greatly reduced metabolism of tertiary amines compared to normal metabolizers. Decreased conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose.f Utilize therapeutic drug monitoring to guide dose adjustments.	Optional

Desipramine CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure.	Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Normal Metabolizer CYP2D6	Normal metabolism	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Reduced metabolism of TCAs to less active compounds when compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Consider 25% reduction of recommended starting dose.g Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Poor Metabolizer CYP2D6	Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider 50% reduction of recommended starting dose.g Utilize therapeutic drug monitoring to guide dose adjustments.	Optional

Doxepin CYP2C19 · CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure.	Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Normal Metabolizer CYP2D6	Normal metabolism	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Reduced metabolism of TCAs to less active compounds when compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Consider 25% reduction of recommended starting dose.g Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Poor Metabolizer CYP2D6	Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider 50% reduction of recommended starting dose.g Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Ultrarapid Metabolizer CYP2C19	Increased metabolism of tertiary amines compared to normal metabolizers. Greater conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Rapid Metabolizer CYP2C19	Increased metabolism of tertiary amines compared to normal metabolizers. Greater conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Normal Metabolizer CYP2C19	Normal metabolism	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2C19	Reduced metabolism of tertiary amines compared to normal metabolizers.	Initiate therapy with recommended starting dose.	Optional
Poor Metabolizer CYP2C19	Greatly reduced metabolism of tertiary amines compared to normal metabolizers. Decreased conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose.f Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Likely Intermediate Metabolizer CYP2C19	Reduced metabolism of tertiary amines compared to normal metabolizers.	Initiate therapy with recommended starting dose.	Optional
Likely Poor Metabolizer CYP2C19	Greatly reduced metabolism of tertiary amines compared to normal metabolizers. Decreased conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose.f Utilize therapeutic drug monitoring to guide dose adjustments.	Optional

Imipramine CYP2C19 · CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure.	Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Normal Metabolizer CYP2D6	Normal metabolism	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Reduced metabolism of TCAs to less active compounds when compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Consider 25% reduction of recommended starting dose.g Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Poor Metabolizer CYP2D6	Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider 50% reduction of recommended starting dose.g Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Ultrarapid Metabolizer CYP2C19	Increased metabolism of tertiary amines compared to normal metabolizers. Greater conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Rapid Metabolizer CYP2C19	Increased metabolism of tertiary amines compared to normal metabolizers. Greater conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Normal Metabolizer CYP2C19	Normal metabolism	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2C19	Reduced metabolism of tertiary amines compared to normal metabolizers.	Initiate therapy with recommended starting dose.	Moderate
Poor Metabolizer CYP2C19	Greatly reduced metabolism of tertiary amines compared to normal metabolizers. Decreased conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	Strong
Likely Intermediate Metabolizer CYP2C19	Reduced metabolism of tertiary amines compared to normal metabolizers.	Initiate therapy with recommended starting dose.	Moderate
Likely Poor Metabolizer CYP2C19	Greatly reduced metabolism of tertiary amines compared to normal metabolizers. Decreased conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	Strong

Nortriptyline CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure.	Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments.	Strong
Normal Metabolizer CYP2D6	Normal metabolism	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Reduced metabolism of TCAs to less active compounds when compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Consider 25% reduction of recommended starting dose.g Utilize therapeutic drug monitoring to guide dose adjustments.	Moderate
Poor Metabolizer CYP2D6	Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider 50% reduction of recommended starting dose.g Utilize therapeutic drug monitoring to guide dose adjustments.	Strong

Trimipramine CYP2C19 · CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased metabolism of TCAs to less active compounds compared to normal metabolizers. Lower plasma concentrations of active drug will increase probability of pharmacotherapy failure.	Avoid tricyclic use due to potential lack of efficacy. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider titrating to a higher target dose (compared to normal metabolizers). Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Normal Metabolizer CYP2D6	Normal metabolism	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Reduced metabolism of TCAs to less active compounds when compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Consider 25% reduction of recommended starting dose.g Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Poor Metabolizer CYP2D6	Greatly reduced metabolism of TCAs to less active compounds compared to normal metabolizers. Higher plasma concentrations of active drug will increase the probability of side effects.	Avoid tricyclic use due to potential for side effects. Consider alternative drug not metabolized by CYP2D6. If a TCA is warranted, consider 50% reduction of recommended starting dose.g Utilize therapeutic drug monitoring to guide dose adjustments.	Optional
Ultrarapid Metabolizer CYP2C19	Increased metabolism of tertiary amines compared to normal metabolizers. Greater conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	Strong
Rapid Metabolizer CYP2C19	Increased metabolism of tertiary amines compared to normal metabolizers. Greater conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments.	Moderate
Normal Metabolizer CYP2C19	Normal metabolism	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2C19	Reduced metabolism of tertiary amines compared to normal metabolizers.	Initiate therapy with recommended starting dose.	Moderate
Poor Metabolizer CYP2C19	Greatly reduced metabolism of tertiary amines compared to normal metabolizers. Decreased conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	Strong
Likely Intermediate Metabolizer CYP2C19	Reduced metabolism of tertiary amines compared to normal metabolizers.	Initiate therapy with recommended starting dose.	Moderate
Likely Poor Metabolizer CYP2C19	Greatly reduced metabolism of tertiary amines compared to normal metabolizers. Decreased conversion of tertiary amines to secondary amines may affect response or side effects.	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of the recommended starting dose. Utilize therapeutic drug monitoring to guide dose adjustments.	Strong

antiemetics →

Ondansetron CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting).	Select and alternative drug not predominantly metabolized by CYP2D6 (i.e. granisetron).	Moderate
Normal Metabolizer CYP2D6	Normal metabolism	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Very limited data available for CYP2D6 intermediate metabolizers	Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose.	—
Poor Metabolizer CYP2D6	Very limited data available for CYP2D6 poor metabolizers	Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose.	—

Tropisetron CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased metabolism to less active compounds when compared to normal metabolizers and is associated with decreased response to ondansetron and tropisetron (i.e. vomiting).	Select and alternative drug not predominantly metabolized by CYP2D6 (i.e. granisetron).	Moderate
Normal Metabolizer CYP2D6	Normal metabolism	Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2D6	Very limited data available for CYP2D6 intermediate metabolizers	Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose.	No recommendation
Poor Metabolizer CYP2D6	Very limited data available for CYP2D6 poor metabolizers	Insufficient evidence demonstrating clinical impact based on CYP2D6 genotype. Initiate therapy with recommended starting dose.	No recommendation

antifungals

Voriconazole CYP2C19

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2C19	In patients for whom an ultrarapid metabolizer genotype is identified, the probability of attainment of therapeutic voriconazole concentrations is small with standard dosing.	Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole. Such agents include isavuconazole, liposomal amphotericin B, and posaconazole.	Strong
Rapid Metabolizer CYP2C19	In patients for whom a rapid metabolizer genotype is identified, the probability of attainment of therapeutic concentrations is modest with standard dosing.	Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole. Such agents include isavuconazole, liposomal amphotericin B, and posaconazole.	Strong
Normal Metabolizer CYP2C19	Normal metabolism	Initiate therapy with recommended standard of care dosing.	Strong
Intermediate Metabolizer CYP2C19	Higher dose-adjusted trough concentrations of voriconazole compared to normal metabolizers.	Initiate therapy with recommended standard of care dosing.	Moderate
Poor Metabolizer CYP2C19	Higher dose-adjusted trough concentrations of voriconazole and may increase probability of adverse events.	Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole. Such agents include isavuconazole, liposomal amphotericin B, and posaconazole. In the event that voriconazole is considered to be the most appropriate agent, based on clinical advice, for a patient with poor metabolizer genotype, voriconazole should be administered at a preferably lower than standard dosage with careful therapeutic drug monitoring.	Strong
Likely Intermediate Metabolizer CYP2C19	Higher dose-adjusted trough concentrations of voriconazole compared to normal metabolizers.	Initiate therapy with recommended standard of care dosing.	Moderate
Likely Poor Metabolizer CYP2C19	Higher dose-adjusted trough concentrations of voriconazole and may increase probability of adverse events.	Choose an alternative agent that is not dependent on CYP2C19 metabolism as primary therapy in lieu of voriconazole. Such agents include isavuconazole, liposomal amphotericin B, and posaconazole. In the event that voriconazole is considered to be the most appropriate agent, based on clinical advice, for a patient with poor metabolizer genotype, voriconazole should be administered at a preferably lower than standard dosage with careful therapeutic drug monitoring.	Strong

antiretrovirals

Atazanavir UGT1A1

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer UGT1A1	Reference UGT1A1 activity; very low likelihood of bilirubin-related discontinuation of atazanavir.	There is no need to avoid prescribing of atazanavir based on UGT1A1 genetic test result.	Strong
Intermediate Metabolizer UGT1A1	Somewhat decreased UGT1A1 activity; low likelihood of bilirubin-related discontinuation of atazanavir.	There is no need to avoid prescribing of atazanavir based on UGT1A1 genetic test result. Inform the patient that some patients stop atazanavir because of jaundice (yellow eyes and skin), but that this patient’s genotype makes this unlikely	Strong
Poor Metabolizer UGT1A1	Markedly decreased UGT1A1 activity; high likelihood of bilirubin-related discontinuation of atazanavir.	Consider an alternative agent particularly where jaundice would be of concern to the patient.	Strong

Efavirenz CYP2B6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2B6	Slightly lower dose-adjusted trough concentrations of efavirenz compared with normal metabolizers	Initiate efavirenz with standard dosing (600 mg/day)	Strong
Ultra Rapid Metabolizer CYP2B6	Slightly lower dose-adjusted trough concentrations of efavirenz compared with normal metabolizers	Initiate efavirenz with standard dosing (600 mg/day)	Strong
Rapid Metabolizer CYP2B6	Slightly lower dose-adjusted trough concentrations of efavirenz compared with normal metabolizers	Initiate efavirenz with standard dosing (600 mg/day)	Strong
Normal Metabolizer CYP2B6	Normal efavirenz metabolism	Initiate efavirenz with standard dosing (600 mg/day)	Strong
Intermediate Metabolizer CYP2B6	Higher dose-adjusted trough concentrations of efavirenz compared with normal metabolizers; increased risk of CNS adverse events.	Consider initiating efavirenz with decreased dose of 400 mg/day.	Moderate
Poor Metabolizer CYP2B6	Higher dose-adjusted trough concentrations of efavirenz compared with normal metabolizers; significantly increased risk of CNS adverse events and treatment discontinuation	Consider initiating efavirenz with decreased dose of 400 or 200 mg/day.	Moderate

antivirals →

Peginterferon Alfa 2A IFNL3

Metabolizer group	What it means	CPIC recommendation	Evidence
Favorable response genotype IFNL3	Approximately 70% chance for sustained virologic response (SVR) after 48 weeks of treatment. Consider implications before initiating PEG-IFN alpha and RBV containing regimens.	Approximately 90% chance for SVR after 24-48 weeks of treatment. Approximately 80-90% of patients are eligible for shortened therapy (24-28 weeks vs. 48 weeks)d. Weighs in favor of using PEG-IFN alpha and RBV containing regimens.	Strong
Unfavorable response genotype IFNL3	Approximately 30% chance for sustained virologic response (SVR) after 48 weeks of treatment. Consider implications before initiating PEG-IFN alpha and RBV containing regimens.	Approximately 60% chance for SVR after 24-48 weeks of treatment. Approximately 50% of patients are eligible for shortened therapy (24-28 weeks). Consider implications before initiating PEG-IFN and RBV containing regimens.	Strong

Peginterferon Alfa 2B IFNL3

Metabolizer group	What it means	CPIC recommendation	Evidence
Favorable response genotype IFNL3	Approximately 70% chance for sustained virologic response (SVR) after 48 weeks of treatment. Consider implications before initiating PEG-IFN alpha and RBV containing regimens.	Approximately 90% chance for SVR after 24-48 weeks of treatment. Approximately 80-90% of patients are eligible for shortened therapy (24-28 weeks vs. 48 weeks)d. Weighs in favor of using PEG-IFN alpha and RBV containing regimens.	Strong
Unfavorable response genotype IFNL3	Approximately 30% chance for sustained virologic response (SVR) after 48 weeks of treatment. Consider implications before initiating PEG-IFN alpha and RBV containing regimens.	Approximately 60% chance for SVR after 24-48 weeks of treatment. Approximately 50% of patients are eligible for shortened therapy (24-28 weeks). Consider implications before initiating PEG-IFN and RBV containing regimens.	Strong

Ribavirin IFNL3

Metabolizer group	What it means	CPIC recommendation	Evidence
Favorable response genotype IFNL3	Approximately 70% chance for sustained virologic response (SVR) after 48 weeks of treatment. Consider implications before initiating PEG-IFN alpha and RBV containing regimens.	Approximately 90% chance for SVR after 24-48 weeks of treatment. Approximately 80-90% of patients are eligible for shortened therapy (24-28 weeks vs. 48 weeks)d. Weighs in favor of using PEG-IFN alpha and RBV containing regimens.	Strong
Unfavorable response genotype IFNL3	Approximately 30% chance for sustained virologic response (SVR) after 48 weeks of treatment. Consider implications before initiating PEG-IFN alpha and RBV containing regimens.	Approximately 60% chance for SVR after 24-48 weeks of treatment. Approximately 50% of patients are eligible for shortened therapy (24-28 weeks). Consider implications before initiating PEG-IFN and RBV containing regimens.	Strong

beta blockers

Metoprolol CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased metabolism of metoprolol leading to decreased drug concentrations; however, it is unclear whether this results in clinically significant changes in heart rate, blood pressure, or clinical outcomes.	No recommendation for metoprolol therapy due to insufficient evidence regarding diminished metoprolol effectiveness clinically.	Optional
Normal Metabolizer CYP2D6	Normal metabolism of metoprolol.	Initiate standard dosing.	Strong
Normal Metabolizer CYP2D6	Normal metabolism of metoprolol.	Initiate standard dosing.	Strong
Normal Metabolizer CYP2D6	Normal metabolism of metoprolol.	Initiate standard dosing.	Strong
Normal Metabolizer CYP2D6	Normal metabolism of metoprolol.	Initiate standard dosing.	Strong
Intermediate Metabolizer CYP2D6	Decreased metabolism of metoprolol leading to increased drug concentrations; however, this does not appear to translate into clinically significant changes in heart rate, blood pressure, or clinical outcomes.	Initiate standard dosing.	Moderate
Intermediate Metabolizer CYP2D6	Decreased metabolism of metoprolol leading to increased drug concentrations; however, this does not appear to translate into clinically significant changes in heart rate, blood pressure, or clinical outcomes.	Initiate standard dosing.	Moderate
Intermediate Metabolizer CYP2D6	Decreased metabolism of metoprolol leading to increased drug concentrations; however, this does not appear to translate into clinically significant changes in heart rate, blood pressure, or clinical outcomes.	Initiate standard dosing.	Moderate
Intermediate Metabolizer CYP2D6	Decreased metabolism of metoprolol leading to increased drug concentrations; however, this does not appear to translate into clinically significant changes in heart rate, blood pressure, or clinical outcomes.	Initiate standard dosing.	Moderate
Poor Metabolizer CYP2D6	Decreased metabolism of metoprolol leading to markedly increased drug concentrations; this leads to greater heart rate and blood pressure reductions. The effect on clinical outcomes is unclear.	Initiate therapy with the 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.	Moderate

blood thinners

Clopidogrel CYP2C19

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2C19	Increased clopidogrel active metabolite formation; lower on-treatment platelet reactivity; no association with higher bleeding risk	If considering clopidogrel, use at standard dose (75 mg/day)	Strong
Rapid Metabolizer CYP2C19	Normal or increased clopidogrel active metabolite formation; normal or lower on-treatment platelet reactivity; no association with higher bleeding risk	If considering clopidogrel, use at standard dose (75 mg/day)	Strong
Normal Metabolizer CYP2C19	Normal clopidogrel active metabolite formation; normal on-treatment platelet reactivity	If considering clopidogrel, use at standard dose (75 mg/day)	Strong
Likely Intermediate Metabolizer CYP2C19	Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events	Avoid standard dose clopidogrel (75 mg) if possible. Use prasugrel or ticagrelor at standard dose if no contraindication	Moderate
Intermediate Metabolizer CYP2C19	Reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events	Avoid standard dose (75 mg) clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication	Strong
Likely Poor Metabolizer CYP2C19	Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events	Avoid clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication	Strong
Poor Metabolizer CYP2C19	Significantly reduced clopidogrel active metabolite formation; increased on-treatment platelet reactivity; increased risk for adverse cardiac and cerebrovascular events	Avoid clopidogrel if possible. Use prasugrel or ticagrelor at standard dose if no contraindication	Strong

Warfarin CYP2C9 · CYP4F2 · VKORC1

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer CYP2C9	Normal warfarin metabolism	Following clinical dosing guidelines for starting dose	Strong
Intermediate Metabolizer CYP2C9	Decreased warfarin metabolism compared to normal metabolizers	Follow pharmacogenomic dosing guidelines for optimal starting dose	Strong
Poor Metabolizer CYP2C9	Severely decreased warfarin metabolism compared to normal metabolizers	Follow pharmacogenomic dosing guidelines for optimal starting dose	Strong
Normal Metabolizer CYP4F2	Normal warfarin response	Following clinical dosing guidelines for starting dose	Moderate
Intermediate Metabolizer CYP4F2	Decreased vitamin K metabolism	Follow pharmacogenomic dosing guidelines for optimal starting dose	Moderate
Normal expression VKORC1	Normal VKORC1-warfarin binding	Following clinical dosing guidelines for starting dose	Strong
Decreased expression VKORC1	Increased warfarin sensitivity	Follow pharmacogenomic dosing guidelines for optimal starting dose	Strong
Low expression VKORC1	Increased warfarin sensitivity	Initiate therapy with recommended starting dose.	—

chemotherapies →

Capecitabine DPYD

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer DPYD	Normal DPD activity and “normal” risk for fluoropyrimidine toxicity	Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration	Strong
Intermediate Metabolizer DPYD	Decreased DPD activity (leukocyte DPD activity at 30% to 70% that of the normal population) and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs	Reduce starting dose by 50% followed by titration of dose based on toxicity or therapeutic drug monitoring (if available). Patients with the c.[2846A>T];[2846A>T] genotype may require >50% reduction in starting dose.	Moderate
Intermediate Metabolizer DPYD	Decreased DPD activity (leukocyte DPD activity at 30% to 70% that of the normal population) and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs	Reduce starting dose by 50% followed by titration of dose based on toxicity or therapeutic drug monitoring (if available). Patients with the c.[2846A>T];[2846A>T] genotype may require >50% reduction in starting dose.	Strong
Poor Metabolizer DPYD	Complete DPD deficiency and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs	Activity score 0.5: Avoid use of 5- fluorouracil or 5-fluorouracil prodrug-based regimens. In the event, based on clinical advice, alternative agents are not considered a suitable therapeutic option, 5-fluorouracil should be administered at a strongly reduced dose with early therapeutic drug monitoring.l Activity score 0: Avoid use of 5-fluorouracil or 5-fluorouracil prodrug-based regimens.	Strong
Poor Metabolizer DPYD	Complete DPD deficiency and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs	Activity score 0.5: Avoid use of 5- fluorouracil or 5-fluorouracil prodrug-based regimens. In the event, based on clinical advice, alternative agents are not considered a suitable therapeutic option, 5-fluorouracil should be administered at a strongly reduced dose with early therapeutic drug monitoring.l Activity score 0: Avoid use of 5-fluorouracil or 5-fluorouracil prodrug-based regimens.	Strong

Fluorouracil DPYD

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer DPYD	Normal DPD activity and “normal” risk for fluoropyrimidine toxicity	Based on genotype, there is no indication to change dose or therapy. Use label-recommended dosage and administration	Strong
Intermediate Metabolizer DPYD	Decreased DPD activity (leukocyte DPD activity at 30% to 70% that of the normal population) and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs	Reduce starting dose by 50% followed by titration of dose based on toxicity or therapeutic drug monitoring (if available). Patients with the c.[2846A>T];[2846A>T] genotype may require >50% reduction in starting dose.	Moderate
Intermediate Metabolizer DPYD	Decreased DPD activity (leukocyte DPD activity at 30% to 70% that of the normal population) and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs	Reduce starting dose by 50% followed by titration of dose based on toxicity or therapeutic drug monitoring (if available). Patients with the c.[2846A>T];[2846A>T] genotype may require >50% reduction in starting dose.	Strong
Poor Metabolizer DPYD	Complete DPD deficiency and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs	Activity score 0.5: Avoid use of 5- fluorouracil or 5-fluorouracil prodrug-based regimens. In the event, based on clinical advice, alternative agents are not considered a suitable therapeutic option, 5-fluorouracil should be administered at a strongly reduced dose with early therapeutic drug monitoring.l Activity score 0: Avoid use of 5-fluorouracil or 5-fluorouracil prodrug-based regimens.	Strong
Poor Metabolizer DPYD	Complete DPD deficiency and increased risk for severe or even fatal drug toxicity when treated with fluoropyrimidine drugs	Activity score 0.5: Avoid use of 5- fluorouracil or 5-fluorouracil prodrug-based regimens. In the event, based on clinical advice, alternative agents are not considered a suitable therapeutic option, 5-fluorouracil should be administered at a strongly reduced dose with early therapeutic drug monitoring.l Activity score 0: Avoid use of 5-fluorouracil or 5-fluorouracil prodrug-based regimens.	Strong

Mercaptopurine NUDT15 · TPMT

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer TPMT	TPMT NMs have lower erythrocyte concentrations of TGN metabolites and higher concentrations of MeMPNs compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern.	Initiate therapy with standard starting dose of mecaptopurine (e.g., 75 mg/m2/day for malignancy or 1.5 mg/kg/day for nonmalignancy). During therapy, adjust the doses of myelosuppressive agents, as per standard clinical practice. It usually takes at least 2 weeks of stable dosing to reach steady state after each dose adjustment.	Strong
Intermediate Metabolizer TPMT	TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs when receiving standard dose.	Initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.	Strong
Possible Intermediate Metabolizer TPMT	TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs when receiving standard dose.	Initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.	Strong
Poor Metabolizer TPMT	TPMT PMs have extremelly high erythrocyte concentrations of TGN metabolites and no MeMPN compared to TPMT NMs.	For malignancy: initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily (e.g. 10 mg/m2/day given 3 days/week). During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For nonmalignancy: consider alternative nonthiopurine immunosuppressant therapy.	Strong
Normal Metabolizer NUDT15	Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression.	Initiate therapy with standard starting dose of mecaptopurine (e.g., 75 mg/m2/day for malignancy or 1.5 mg/kg/day for nonmalignancy). During therapy, adjust the doses of myelosuppressive agents, as per standard clinical practice. It usually takes at least 2 weeks of stable dosing to reach steady state after each dose adjustment.	Strong
Intermediate Metabolizer NUDT15	Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression.	Initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.	Strong
Possible Intermediate Metabolizer NUDT15	Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression.	Initiate therapy with decreased starting doses (30-80% of standard starting dose) if starting dose is ≥75 mg/m2/day (for malignancy) or ≥1.5 mg/kg/day (for nonmalignancy). If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing mercaptopurine over other agents.	Strong
Poor Metabolizer NUDT15	Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease.	For malignancy: initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily (e.g. 10 mg/m2/day given 3 days/week). During therapy, adjust mercaptopurine doses based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing mercaptopurine over other agents. For nonmalignancy: consider alternative nonthiopurine immunosuppressant therapy.	Strong

Thioguanine NUDT15 · TPMT

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer TPMT	TPMT NMs have lower erythrocyte concentrations of TGN metabolites compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern.	Initiate therapy with standard starting dose of thioguanine (e.g., 40 mg/m2/day for malignancy). During therapy, adjust the doses of myelosuppressive agents, as per standard clinical practice. It usually takes at least 2 weeks of stable dosing to reach steady state after each dose adjustment.	Strong
Intermediate Metabolizer TPMT	TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.	Initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.	Moderate
Possible Intermediate Metabolizer TPMT	TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.	Initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.	Moderate
Poor Metabolizer TPMT	TPMT PMs have extremelly high erythrocyte concentrations of TGN metabolites compared to TPMT NMs.	Initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily. During therapy, adjust thioguanine doses based on degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents.	Strong
Normal Metabolizer NUDT15	Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression.	Initiate therapy with standard starting dose of thioguanine (e.g., 40 mg/m2/day for malignancy). During therapy, adjust the doses of myelosuppressive agents, as per standard clinical practice. It usually takes at least 2 weeks of stable dosing to reach steady state after each dose adjustment.	Strong
Intermediate Metabolizer NUDT15	Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression.	Initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.	Moderate
Possible Intermediate Metabolizer NUDT15	Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression.	Initiate therapy with decreased starting doses (30-80% of standard starting dose) if standard starting dose is ≥40 mg/m2/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of thioguanine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, and the patient is on combination therapy, emphasis should be on reducing thioguanine over other agents.	Moderate
Poor Metabolizer NUDT15	Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease.	Initiate therapy with drastically reduced starting doses. Reduce starting dose by 10-fold and reduce frequency to thrice weekly instead of daily. During therapy, adjust thioguanine doses based on degree of myelosuppression and disease-specific guidelines. It usually takes at least 4-6 weeks of stable dosing to reach steady state after each dose adjustment. If myelosuppression occurs, emphasis should be on reducing thioguanine over other agents.	Strong

cholesterol medications →

Atorvastatin SLCO1B1

Metabolizer group	What it means	CPIC recommendation	Evidence
Increased Function SLCO1B1	Normal myopathy risk	Prescribe desired starting dose and adjust doses of atorvastatin based on disease-specific guidelines.	Strong
Normal Function SLCO1B1	Normal myopathy risk	Prescribe desired starting dose and adjust doses of atorvastatin based on disease-specific guidelines.	Strong
Decreased Function SLCO1B1	Increased atorvastatin exposure as compared with normal function, which may translate to increased myopathy risk.	Prescribe ≤40 mg as a starting dose and adjust doses of atorvastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially for the 40-mg dose. If dose >40 mg is needed for desired efficacy, consider combination therapy (i.e., atorvastatin plus nonstatin guideline-directed medical therapy).	Strong
Possible Decreased Function SLCO1B1	Increased atorvastatin exposure as compared with normal function, which may translate to increased myopathy risk.	Prescribe ≤40 mg as a starting dose and adjust doses of atorvastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially for the 40-mg dose. If dose >40 mg is needed for desired efficacy, consider combination therapy (i.e., atorvastatin plus nonstatin guideline-directed medical therapy).	Strong
Poor Function SLCO1B1	Increased atorvastatin exposure as compared with normal and decreased function, which may translate to increased myopathy risk.	Prescribe ≤20 mg as a starting dose and adjust doses of atorvastatin based on disease-specific guidelines. If dose >20 mg is needed for desired efficacy, consider rosuvastatin or combination therapy (i.e., atorvastatin plus nonstatin guideline-directed medical therapy).	Strong
Possible Poor Function SLCO1B1	Increased atorvastatin exposure as compared with normal and decreased function, which may translate to increased myopathy risk.	Prescribe ≤20 mg as a starting dose and adjust doses of atorvastatin based on disease-specific guidelines. If dose >20 mg is needed for desired efficacy, consider rosuvastatin or combination therapy (i.e., atorvastatin plus nonstatin guideline-directed medical therapy).	Strong

Fluvastatin CYP2C9 · SLCO1B1

Metabolizer group	What it means	CPIC recommendation	Evidence
Increased Function SLCO1B1	Normal myopathy risk	Prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines.	Strong
Normal Function SLCO1B1	Normal myopathy risk	Prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines.	Strong
Decreased Function SLCO1B1	Increased fluvastatin exposure as compared with normal function; typical myopathy risk with doses ≤40 mg	Prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >40 mg per day.	Strong
Possible Decreased Function SLCO1B1	Increased fluvastatin exposure as compared with normal function; typical myopathy risk with doses ≤40 mg	Prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >40 mg per day.	Strong
Poor Function SLCO1B1	Increased fluvastatin exposure as compared with normal and decreased function; typical myopathy risk with doses ≤40 mg	Prescribe ≤40 mg per day as a starting dose and adjust doses based on disease-specific guidelines. If the patient tolerates 40 mg but higher potency is needed, consider switching to an alternative lower-risk statin such as atorvastatin (10–20 mg), pravastatin (40 mg), or rosuvastatin (5–10 mg), or adding combination therapy (e.g., fluvastatin plus nonstatin guideline-directed medical therapy). Prescriber should be aware of increased risk for myopathy especially with fluvastatin doses >40 mg per day.	Strong
Possible Poor Function SLCO1B1	Increased fluvastatin exposure as compared with normal and decreased function; typical myopathy risk with doses ≤40 mg	Prescribe ≤40 mg per day as a starting dose and adjust doses based on disease-specific guidelines. If the patient tolerates 40 mg but higher potency is needed, consider switching to an alternative lower-risk statin such as atorvastatin (10–20 mg), pravastatin (40 mg), or rosuvastatin (5–10 mg), or adding combination therapy (e.g., fluvastatin plus nonstatin guideline-directed medical therapy). Prescriber should be aware of increased risk for myopathy especially with fluvastatin doses >40 mg per day.	Strong
Normal Metabolizer CYP2C9	Normal fluvastatin exposure.	Prescribe desired starting dose and adjust doses of fluvastatin based on disease-specific guidelines.	Strong
Intermediate Metabolizer CYP2C9	Increased fluvastatin exposure compared with normal metabolizer, which may increase myopathy risk.	Prescribe ≤40 mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If dose >40 mg is needed for desired efficacy, consider an alternative statin or combination therapy (i.e., fluvastatin plus nonstatin guideline-directed medical therapy).	Strong
Intermediate Metabolizer CYP2C9	Increased fluvastatin exposure compared with normal metabolizer, which may increase myopathy risk.	Prescribe ≤40 mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If dose >40 mg is needed for desired efficacy, consider an alternative statin or combination therapy (i.e., fluvastatin plus nonstatin guideline-directed medical therapy).	Strong
Poor Metabolizer CYP2C9	Increased fluvastatin exposure compared with normal and intermediate metabolizers, which may increase myopathy risk.	Prescribe ≤20 mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If dose >20 mg is needed for desired efficacy, consider an alternative statin or combination therapy (i.e., fluvastatin plus nonstatin guideline-directed medical therapy).	Strong
Poor Metabolizer CYP2C9	Increased fluvastatin exposure compared with normal and intermediate metabolizers, which may increase myopathy risk.	Prescribe ≤20 mg per day as a starting dose and adjust doses of fluvastatin based on disease-specific guidelines. If dose >20 mg is needed for desired efficacy, consider an alternative statin or combination therapy (i.e., fluvastatin plus nonstatin guideline-directed medical therapy).	Strong

Lovastatin SLCO1B1

Metabolizer group	What it means	CPIC recommendation	Evidence
Increased Function SLCO1B1	Normal myopathy risk	Prescribe desired starting dose and adjust doses of lovastatin based on disease-specific guidelines.	Strong
Normal Function SLCO1B1	Normal myopathy risk	Prescribe desired starting dose and adjust doses of lovastatin based on disease-specific guidelines.	Strong
Decreased Function SLCO1B1	Increased lovastatin acid exposure as compared with normal function, which may translate to increased myopathy risk	Consider prescribing a lower-risk alternative such as atorvastatin (10–20 mg), pravastatin (40 mg), or rosuvastatin (5–10 mg). If lovastatin is warranted, limit the dose to ≤20 mg/day to reduce the risk of muscle-related side effects.	Strong
Possible Decreased Function SLCO1B1	Increased lovastatin acid exposure as compared with normal function, which may translate to increased myopathy risk	Consider prescribing a lower-risk alternative such as atorvastatin (10–20 mg), pravastatin (40 mg), or rosuvastatin (5–10 mg). If lovastatin is warranted, limit the dose to ≤20 mg/day to reduce the risk of muscle-related side effects.	Strong
Poor Function SLCO1B1	Increased lovastatin acid exposure as compared with normal and decreased function, which may translate to increased myopathy risk	Consider prescribing a lower-risk alternative such as atorvastatin (10–20 mg), pravastatin (40 mg), or rosuvastatin (5–10 mg) instead of lovastatin to reduce the risk of muscle-related side effects.	Strong
Possible Poor Function SLCO1B1	Increased lovastatin acid exposure as compared with normal and decreased function, which may translate to increased myopathy risk	Consider prescribing a lower-risk alternative such as atorvastatin (10–20 mg), pravastatin (40 mg), or rosuvastatin (5–10 mg) instead of lovastatin to reduce the risk of muscle-related side effects.	Strong

Pitavastatin SLCO1B1

Metabolizer group	What it means	CPIC recommendation	Evidence
Increased Function SLCO1B1	Normal myopathy risk	Prescribe desired starting dose and adjust doses of pitavastatin based on disease-specific guidelines.	Strong
Normal Function SLCO1B1	Normal myopathy risk	Prescribe desired starting dose and adjust doses of pitavastatin based on disease-specific guidelines.	Strong
Decreased Function SLCO1B1	Increased pitavastatin exposure as compared with normal function, which may translate to increased myopathy risk	Prescribe ≤2 mg as a starting dose and adjust doses of pitavastatin based on disease-specific guidelines. Be aware of possible increased risk for muscle-related side effects, especially for doses >1 mg. If dose >2 mg is needed for desired efficacy, consider switching to a lower-risk alternative such as atorvastatin (10–20 mg), pravastatin (40 mg), or rosuvastatin (5–10 mg), or using combination therapy (e.g., pitavastatin plus nonstatin guideline-directed medical therapy).	Strong
Possible Decreased Function SLCO1B1	Increased pitavastatin exposure as compared with normal function, which may translate to increased myopathy risk	Prescribe ≤2 mg as a starting dose and adjust doses of pitavastatin based on disease-specific guidelines. Be aware of possible increased risk for muscle-related side effects, especially for doses >1 mg. If dose >2 mg is needed for desired efficacy, consider switching to a lower-risk alternative such as atorvastatin (10–20 mg), pravastatin (40 mg), or rosuvastatin (5–10 mg), or using combination therapy (e.g., pitavastatin plus nonstatin guideline-directed medical therapy).	Strong
Poor Function SLCO1B1	Increased pitavastatin exposure as compared with normal and decreased function, which may translate to increased myopathy risk	Prescribe ≤1 mg as a starting dose and adjust doses of pitavastatin based on disease-specific guidelines. If dose >1 mg is needed for desired efficacy, consider switching to a lower-risk alternative such as atorvastatin (10–20 mg), pravastatin (40 mg), or rosuvastatin (5–10 mg), or using combination therapy (e.g., pitavastatin plus nonstatin guideline-directed medical therapy).	Strong
Possible Poor Function SLCO1B1	Increased pitavastatin exposure as compared with normal and decreased function, which may translate to increased myopathy risk	Prescribe ≤1 mg as a starting dose and adjust doses of pitavastatin based on disease-specific guidelines. If dose >1 mg is needed for desired efficacy, consider switching to a lower-risk alternative such as atorvastatin (10–20 mg), pravastatin (40 mg), or rosuvastatin (5–10 mg), or using combination therapy (e.g., pitavastatin plus nonstatin guideline-directed medical therapy).	Strong

Pravastatin SLCO1B1

Metabolizer group	What it means	CPIC recommendation	Evidence
Increased Function SLCO1B1	Typical myopathy risk and pravastatin exposure	Prescribe desired starting dose and adjust doses of pravastatin based on disease-specific guidelines.	Strong
Normal Function SLCO1B1	Typical myopathy risk and pravastatin exposure	Prescribe desired starting dose and adjust doses of pravastatin based on disease-specific guidelines.	Strong
Decreased Function SLCO1B1	Increased pravastatin exposure compared with normal function; typical myopathy risk with doses ≤40 mg	Prescribe desired starting dose and adjust doses of pravastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially with doses >40 mg per day.	Strong
Possible Decreased Function SLCO1B1	Increased pravastatin exposure compared with normal function; typical myopathy risk with doses ≤40 mg	Prescribe desired starting dose and adjust doses of pravastatin based on disease-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially with doses >40 mg per day.	Strong
Poor Function SLCO1B1	Increased pravastatin exposure compared with normal and decreased function; typical myopathy risk with doses ≤40 mg	Prescribe ≤40 mg as a starting dose and adjust doses of pravastatin based on disease-specific guidelines. If patient is tolerating 40-mg dose but higher potency is needed, a higher dose (>40 mg) or an alternative statin or combination therapy (pravastatin plus nonstatin guideline-directed medical therapy) could be considered. Prescriber should be aware of possible increased risk for myopathy especially with pravastatin doses >40 mg.	Strong
Possible Poor Function SLCO1B1	Increased pravastatin exposure compared with normal and decreased function; typical myopathy risk with doses ≤40 mg	Prescribe ≤40 mg as a starting dose and adjust doses of pravastatin based on disease-specific guidelines. If patient is tolerating 40-mg dose but higher potency is needed, a higher dose (>40 mg) or an alternative statin or combination therapy (pravastatin plus nonstatin guideline-directed medical therapy) could be considered. Prescriber should be aware of possible increased risk for myopathy especially with pravastatin doses >40 mg.	Strong

Rosuvastatin ABCG2 · SLCO1B1

Metabolizer group	What it means	CPIC recommendation	Evidence
Increased Function SLCO1B1	Typical myopathy risk and statin exposure	Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and population-specific guidelines.	Strong
Normal Function SLCO1B1	Typical myopathy risk and statin exposure	Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and population-specific guidelines.	Strong
Decreased Function SLCO1B1	Increased rosuvastatin exposure as compared with normal function; typical myopathy risk with doses ≤20 mg	Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and population-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >20 mg.	Strong
Possible Decreased Function SLCO1B1	Increased rosuvastatin exposure as compared with normal function; typical myopathy risk with doses ≤20 mg	Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and population-specific guidelines. Prescriber should be aware of possible increased risk for myopathy especially for doses >20 mg.	Strong
Poor Function SLCO1B1	Increased rosuvastatin exposure as compared with normal and decreased function; typical myopathy risk with doses ≤20 mg	Prescribe ≤20 mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and population-specific guidelines. If dose >20 mg is needed for desired efficacy, consider combination therapy (i.e., rosuvastatin plus nonstatin guideline-directed medical therapy).	Strong
Possible Poor Function SLCO1B1	Increased rosuvastatin exposure as compared with normal and decreased function; typical myopathy risk with doses ≤20 mg	Prescribe ≤20 mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and population-specific guidelines. If dose >20 mg is needed for desired efficacy, consider combination therapy (i.e., rosuvastatin plus nonstatin guideline-directed medical therapy).	Strong
Normal Function ABCG2	Typical myopathy risk and rosuvastatin exposure.	Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and population-specific guidelines.	Strong
Decreased Function ABCG2	Increased rosuvastatin exposure as compared with normal function; unknown risk for myopathy; increased lipid-lowering effects.	Prescribe desired starting dose and adjust doses of rosuvastatin based on disease-specific and population-specific guidelines.	Strong
Poor Function ABCG2	Increased rosuvastatin exposure compared with normal and decreased function; unknown myopathy risk; increased lipid-lowering effects.	Prescribe ≤20 mg as a starting dose and adjust doses of rosuvastatin based on disease-specific and population-specific guidelines. If dose >20 mg is needed for desired efficacy, consider an alternative statin or combination therapy (i.e., rosuvastatin plus nonstatin guideline-directed medical therapy).	Strong

Simvastatin SLCO1B1

Metabolizer group	What it means	CPIC recommendation	Evidence
Increased Function SLCO1B1	Typical myopathy risk and statin exposure	Prescribe desired starting dose and adjust doses based on disease-specific guidelines.	Strong
Normal Function SLCO1B1	Typical myopathy risk and statin exposure	Prescribe desired starting dose and adjust doses based on disease-specific guidelines.	Strong
Decreased Function SLCO1B1	Increased simvastatin acid exposure compared with normal function; increased risk of muscle side effects (myopathy)	Prescribe an alternative statin depending on desired potency. Low-risk options: atorvastatin 10–20 mg, pitavastatin 1 mg, pravastatin 40 mg, rosuvastatin 5–10 mg. Moderate-risk options: fluvastatin 80 mg, pitavastatin 2 mg, pravastatin 80 mg. High-risk options (use with caution): lovastatin 40–80 mg, pitavastatin 4 mg, simvastatin 20–40 mg. If simvastatin is used, limit dose to <20 mg/day.	Strong
Possible Decreased Function SLCO1B1	Increased simvastatin acid exposure compared with normal function; increased risk of muscle side effects (myopathy)	Prescribe an alternative statin depending on desired potency. Low-risk options: atorvastatin 10–20 mg, pitavastatin 1 mg, pravastatin 40 mg, rosuvastatin 5–10 mg. Moderate-risk options: fluvastatin 80 mg, pitavastatin 2 mg, pravastatin 80 mg. High-risk options (use with caution): lovastatin 40–80 mg, pitavastatin 4 mg, simvastatin 20–40 mg. If simvastatin is used, limit dose to <20 mg/day.	Strong
Poor Function SLCO1B1	Increased simvastatin acid exposure compared with normal and decreased function; highly increased myopathy risk	Prescribe an alternative statin depending on desired potency. Low-risk options: atorvastatin 10–20 mg, pitavastatin 1 mg, pravastatin 40 mg, rosuvastatin 5–10 mg. Moderate-risk options: fluvastatin 80 mg, pravastatin 80 mg. High-risk options (use with caution): lovastatin 40–80 mg, pitavastatin 2–4 mg, simvastatin 20–40 mg.	Strong
Possible Poor Function SLCO1B1	Increased simvastatin acid exposure compared with normal and decreased function; highly increased myopathy risk	Prescribe an alternative statin depending on desired potency. Low-risk options: atorvastatin 10–20 mg, pitavastatin 1 mg, pravastatin 40 mg, rosuvastatin 5–10 mg. Moderate-risk options: fluvastatin 80 mg, pravastatin 80 mg. High-risk options (use with caution): lovastatin 40–80 mg, pitavastatin 2–4 mg, simvastatin 20–40 mg.	Strong

cystic fibrosis treatment

Ivacaftor CFTR

Metabolizer group	What it means	CPIC recommendation	Evidence
ivacaftor responsive CFTR	Significant improvement in lung function, weight, risk of pulmonary exacerbation, patient reported outcomes, and reduction in sweat chloride concentrations through enhanced CFTR channel activity (increase probability of open channel).	Use ivacaftor according to the product label	Strong
ivacaftor non-responsive CFTR	No significant reduction in sweat chloride concentrations; no changes in other clinical measurements including spirometric measurements, pulmonary exacerbations, or body weight. Unlikely to respond to treatment.	Ivacaftor is not recommended	Moderate
ivacaftor irrelevant CFTR	Genotype does not affect the treatment of CFTR with ivacaftor	Initiate therapy with recommended starting dose.	—

estrogen modulators

Tamoxifen CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Therapeutic endoxifen concentrations	Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).	Strong
Normal Metabolizer CYP2D6	Therapeutic endoxifen concentrations	Avoid moderate and strong CYP2D6 inhibitors. Initiate therapy with recommended standard of care dosing (tamoxifen 20 mg/day).	Strong
Intermediate Metabolizer CYP2D6	Lower endoxifen concentrations compared to normal metabolizers; higher risk of breast cancer recurrence, event-free and recurrence-free survival compared to normal metabolizers.	Consider hormonal therapy such as an aromatase inhibitor for postmenopausal women or aromatase inhibitor along with ovarian function suppression in premenopausal women, given that these approaches are superior to tamoxifen regardless of CYP2D6 genotype. If aromatase inhibitor use is contraindicated, consideration should be given to use a higher but FDA approved tamoxifen dose (40 mg/day). Avoid CYP2D6 strong to weak inhibitors.	Moderate
Poor Metabolizer CYP2D6	Lower endoxifen concentrations compared to normal metabolizers; higher risk of breast cancer recurrence, event-free and recurrence-free survival compared to normal metabolizers.	Recommend alternative hormonal therapy such as an aromatase inhibitor for postmenopausal women or aromatase inhibitor along with ovarian function suppression in premenopausal women given that these approaches are superior to tamoxifen regardless of CYP2D6 genotype and based on knowledge that CYP2D6 poor metabolizers switched from tamoxifen to anastrozole do not have an increased risk of recurrence. Note, higher dose tamoxifen (40 mg/day) increases but does not normalize endoxifen concentrations and can be considered if there are contraindications to aromatase inhibitor therapy.	Strong

immunosuppressants →

Azathioprine NUDT15 · TPMT

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer TPMT	TPMT NMs have lower erythrocyte concentrations of TGN metabolites and higher concentrations of MeMPNs compared to TPMT IMs and TPMT PMs. This is the 'normal' pattern.	Initiate therapy with standard starting dose (e.g., 2 mg/kg/day for autoimmune diseases). During therapy, adjust doses of azathioprine based on disease-specific guidelines. It usually takes at least 2 weeks to reach steady state after each dose adjustment.	Strong
Intermediate Metabolizer TPMT	TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.	Initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.	Strong
Possible Intermediate Metabolizer TPMT	TPMT IMs have moderate to high erythrocyte concentrations of TGN metabolites and low concentrations of MeMPNs compared to TPMT NMs.	Initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.	Strong
Poor Metabolizer TPMT	TPMT PMs have extremely high erythrocyte concentrations of TGN metabolites and no MeMPN compared to TPMT NMs.	Consider alternative nonthiopurine immunosuppressant therapy.	Strong
Normal Metabolizer NUDT15	Normal risk of thiopurine-related leukopenia, neutropenia and myelosuppression.	Initiate therapy with standard starting dose (e.g., 2 mg/kg/day for autoimmune diseases). During therapy, adjust doses of azathioprine based on disease-specific guidelines. It usually takes at least 2 weeks to reach steady state after each dose adjustment.	Strong
Intermediate Metabolizer NUDT15	Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression.	Initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.	Strong
Possible Intermediate Metabolizer NUDT15	Increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression.	Initiate therapy with reduced starting doses (30-80% of standard starting dose) if standard starting dose is ≥2 mg/kg/day. If starting dose is already below standard starting dose, dose reduction might not be necessary. During therapy, adjust the doses of azathioprine based on the degree of myelosuppression and disease-specific guidelines. It usually takes at least 2-4 weeks of stable dosing to reach steady state after each dose adjustment.	Strong
Poor Metabolizer NUDT15	Greatly increased risk of thiopurine-related leukopenia, neutropenia and myelosuppression. Fatal toxicity possible without dose decrease.	Consider alternative nonthiopurine immunosuppressant therapy.	Strong

Tacrolimus CYP3A5

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer CYP3A5	Lower dose-adjusted trough concentrations of tacrolimus and decreased chance of achieving target tacrolimus concentrations	Increase starting dose 1.5 to 2 times recommended starting dose. Total starting dose should not exceed 0.3mg/kg/day. Use therapeutic drug monitoring to guide dose adjustments	Strong
Intermediate Metabolizer CYP3A5	Lower dose-adjusted trough concentrations of tacrolimus and decreased chance of achieving target tacrolimus concentrations	Increase starting dose 1.5 to 2 times recommended starting dose. Total starting dose should not exceed 0.3mg/kg/day. Use therapeutic drug monitoring to guide dose adjustments	Strong
Poor Metabolizer CYP3A5	Higher (“normal”) dose-adjusted trough concentrations of tacrolimus and increased chance of achieving target tacrolimus concentrations	Initiate therapy with standard recommended dose. Use therapeutic drug monitoring to guide dose adjustments	Strong

pain management →

Celecoxib CYP2C9

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer CYP2C9	Normal metabolism	Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.	Strong
Intermediate Metabolizer CYP2C9	Mildly reduced metabolism	Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.	Moderate
Intermediate Metabolizer CYP2C9	Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities	Initiate therapy with lowest recommended starting dose. Titrate dose upward to clinical effect or maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Carefully monitor adverse events, such as blood pressure and kidney function, during course of therapy.	Moderate
Poor Metabolizer CYP2C9	Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities	Initiate therapy with 25–50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25–50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady-state is reached (at least 8 days for celecoxib and 5 days for ibuprofen, flurbiprofen, and lornoxicam after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.	Moderate
Poor Metabolizer CYP2C9	Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities	Initiate therapy with 25–50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25–50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady-state is reached (at least 8 days for celecoxib and 5 days for ibuprofen, flurbiprofen, and lornoxicam after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.	Moderate

Codeine CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased formation of morphine leading to higher risk of toxicity	Avoid codeine use because of potential for serious toxicity. If opioid use is warranted, consider a non-tramadol opioid.	Strong
Normal Metabolizer CYP2D6	Expected morphine formation	Use codeine label recommended age- or weight-specific dosing.	Strong
Intermediate Metabolizer CYP2D6	Reduced morphine formation	Use codeine label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider a non-tramadol opioid.	Moderate
Poor Metabolizer CYP2D6	Greatly reduced morphine formation leading to diminished analgesia.	Avoid codeine use because of possibility of diminished analgesia. If opioid use is warranted, consider a non-tramadol opioid.	Strong

Flurbiprofen CYP2C9

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer CYP2C9	Normal metabolism	Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.	Strong
Intermediate Metabolizer AS of 1.5 CYP2C9	Mildly reduced metabolism	Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.	Moderate
Intermediate Metabolizer AS of 1 CYP2C9	Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities	Initiate therapy with lowest recommended starting dose. Titrate dose upward to clinical effect or maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Carefully monitor adverse events, such as blood pressure and kidney function, during course of therapy.	Moderate
Poor Metabolizer CYP2C9	Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities	Initiate therapy with 25–50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25–50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady-state is reached (at least 8 days for celecoxib and 5 days for ibuprofen, flurbiprofen, and lornoxicam after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.	Moderate
Poor Metabolizer CYP2C9	Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities	Initiate therapy with 25–50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25–50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady-state is reached (at least 8 days for celecoxib and 5 days for ibuprofen, flurbiprofen, and lornoxicam after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.	Moderate

Ibuprofen CYP2C9

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer CYP2C9	Normal metabolism	Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.	Strong
Intermediate Metabolizer CYP2C9	Mildly reduced metabolism	Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.	Moderate
Intermediate Metabolizer CYP2C9	Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities	Initiate therapy with lowest recommended starting dose. Titrate dose upward to clinical effect or maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Carefully monitor adverse events, such as blood pressure and kidney function, during course of therapy.	Moderate
Poor Metabolizer CYP2C9	Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities	Initiate therapy with 25–50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25–50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady-state is reached (at least 8 days for celecoxib and 5 days for ibuprofen, flurbiprofen, and lornoxicam after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.	Moderate
Poor Metabolizer CYP2C9	Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities	Initiate therapy with 25–50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25–50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady-state is reached (at least 8 days for celecoxib and 5 days for ibuprofen, flurbiprofen, and lornoxicam after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.	Moderate

Lornoxicam CYP2C9

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer CYP2C9	Normal metabolism	Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.	Strong
Intermediate Metabolizer AS of 1.5 CYP2C9	Mildly reduced metabolism	Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.	Moderate
Intermediate Metabolizer AS of 1 CYP2C9	Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities	Initiate therapy with lowest recommended starting dose. Titrate dose upward to clinical effect or maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Carefully monitor adverse events, such as blood pressure and kidney function, during course of therapy.	Moderate
Poor Metabolizer CYP2C9	Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities	Initiate therapy with 25–50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25–50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady-state is reached (at least 8 days for celecoxib and 5 days for ibuprofen, flurbiprofen, and lornoxicam after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.	Moderate
Poor Metabolizer CYP2C9	Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities	Initiate therapy with 25–50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 25–50% of the maximum recommended dose with caution. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady-state is reached (at least 8 days for celecoxib and 5 days for ibuprofen, flurbiprofen, and lornoxicam after first dose in PMs). Carefully monitor adverse events such as blood pressure and kidney function during course of therapy. Alternatively, consider an alternate therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo.	Moderate

Meloxicam CYP2C9

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer CYP2C9	Normal metabolism	Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.	Strong
Intermediate Metabolizer CYP2C9	Mildly reduced metabolism	Initiate therapy with recommended starting dose. In accordance with the meloxicam prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.	Moderate
Intermediate Metabolizer CYP2C9	Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities	Initiate therapy with 50% of the lowest recommended starting dose. Titrate dose upward to clinical effect or 50% of the maximum recommended dose with caution. In accordance with the meloxicam prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals. Upward dose titration should not occur until after steady-state is reached (at least 7 days). Carefully monitor adverse events, such as blood pressure and kidney function, during course of therapy. Alternatively, consider alternative therapy. Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo, or choose an NSAID metabolized by CYP2C9 but with a shorter half-life.	Moderate
Poor Metabolizer CYP2C9	Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities	Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo, or choose an NSAID metabolized by CYP2C9 but with a shorter half-life.	Moderate
Poor Metabolizer CYP2C9	Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities	Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo, or choose an NSAID metabolized by CYP2C9 but with a shorter half-life.	Moderate

Piroxicam CYP2C9

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer CYP2C9	Normal metabolism	Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.	Strong
Intermediate Metabolizer CYP2C9	Mildly reduced metabolism	Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.	Moderate
Intermediate Metabolizer CYP2C9	Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities	Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo, or choose an NSAID metabolized by CYP2C9 but with a shorter half-life.	Moderate
Poor Metabolizer CYP2C9	Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities	Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo, or choose an NSAID metabolized by CYP2C9 but with a shorter half-life.	Moderate
Poor Metabolizer CYP2C9	Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities	Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo, or choose an NSAID metabolized by CYP2C9 but with a shorter half-life.	Moderate

Tenoxicam CYP2C9

Metabolizer group	What it means	CPIC recommendation	Evidence
Normal Metabolizer CYP2C9	Normal metabolism	Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.	Strong
Intermediate Metabolizer CYP2C9	Mildly reduced metabolism	Initiate therapy with recommended starting dose. In accordance with the prescribing information, use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals.	Moderate
Intermediate Metabolizer CYP2C9	Moderately reduced metabolism; higher plasma concentrations may increase probability of toxicities	Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo, or choose an NSAID metabolized by CYP2C9 but with a shorter half-life.	Moderate
Poor Metabolizer CYP2C9	Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities	Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo, or choose an NSAID metabolized by CYP2C9 but with a shorter half-life.	Moderate
Poor Metabolizer CYP2C9	Significantly reduced metabolism and prolonged half-life; higher plasma concentrations may increase probability and/or severity of toxicities	Choose an alternative therapy not metabolized by CYP2C9 or not significantly impacted by CYP2C9 genetic variants in vivo, or choose an NSAID metabolized by CYP2C9 but with a shorter half-life.	Moderate

Tramadol CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Increased formation of O-desmethyltramadol (active metabolite) leading to higher risk of toxicity	Avoid tramadol use because of potential for toxicity. If opioid use is warranted, consider a non-codeine opioid.	Strong
Normal Metabolizer CYP2D6	Expected O-desmethyltramadol (active metabolite) formation	Use tramadol label recommended age- or weight-specific dosing.	Strong
Intermediate Metabolizer CYP2D6	Reduced O-desmethyltramadol (active metabolite) formation	Use tramadol label recommended age- or weight-specific dosing. If no response and opioid use is warranted, consider non-codeine opioid.	Optional
Poor Metabolizer CYP2D6	Greatly reduced O-desmethyltramadol (active metabolite) formation leading to diminished analgesia.	Avoid tramadol use because of possibility of diminished analgesia. If opioid use is warranted, consider a non-codeine opioid.	Strong

proton pump inhibitors →

Dexlansoprazole CYP2C19

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2C19	Decreased plasma concentrations of PPIs compared with CYP2C19 normal metabolizers; increased risk of therapeutic failure	Increase starting daily dose by 100%. Daily dose may be given in divided doses. Monitor for efficacy.	Strong
Rapid Metabolizer CYP2C19	Decreased plasma concentrations of PPIs compared with CYP2C19 normal metabolizers; increased risk of therapeutic failure	Initiate standard starting daily dose. Consider increasing dose by 50–100% for the treatment of Helicobacter pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.	Moderate
Normal Metabolizer CYP2C19	Normal PPI metabolism; may be at increased risk of therapeutic failure compared with CYP2C19 intermediate and poor metabolizers	Initiate standard starting daily dose. Consider increasing dose by 50–100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.	Moderate
Likely Intermediate Metabolizer CYP2C19	Likely increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; likely increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Optional
Intermediate Metabolizer CYP2C19	Increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Optional
Likely Poor Metabolizer CYP2C19	Likely increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; likely increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Moderate
Poor Metabolizer CYP2C19	Increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Moderate

Lansoprazole CYP2C19

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2C19	Decreased plasma concentrations of PPIs compared with CYP2C19 normal metabolizers; increased risk of therapeutic failure	Increase starting daily dose by 100%. Daily dose may be given in divided doses. Monitor for efficacy.	Strong
Rapid Metabolizer CYP2C19	Decreased plasma concentrations of PPIs compared with CYP2C19 normal metabolizers; increased risk of therapeutic failure	Initiate standard starting daily dose. Consider increasing dose by 50–100% for the treatment of Helicobacter pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.	Moderate
Normal Metabolizer CYP2C19	Normal PPI metabolism; may be at increased risk of therapeutic failure compared with CYP2C19 intermediate and poor metabolizers	Initiate standard starting daily dose. Consider increasing dose by 50–100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.	Moderate
Likely Intermediate Metabolizer CYP2C19	Likely increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; likely increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Optional
Intermediate Metabolizer CYP2C19	Increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Optional
Likely Poor Metabolizer CYP2C19	Likely increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; likely increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Moderate
Poor Metabolizer CYP2C19	Increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Moderate

Omeprazole CYP2C19

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2C19	Decreased plasma concentrations of PPIs compared with CYP2C19 normal metabolizers; increased risk of therapeutic failure	Increase starting daily dose by 100%. Daily dose may be given in divided doses. Monitor for efficacy.	Strong
Rapid Metabolizer CYP2C19	Decreased plasma concentrations of PPIs compared with CYP2C19 normal metabolizers; increased risk of therapeutic failure	Initiate standard starting daily dose. Consider increasing dose by 50–100% for the treatment of Helicobacter pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.	Moderate
Normal Metabolizer CYP2C19	Normal PPI metabolism; may be at increased risk of therapeutic failure compared with CYP2C19 intermediate and poor metabolizers	Initiate standard starting daily dose. Consider increasing dose by 50–100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.	Moderate
Likely Intermediate Metabolizer CYP2C19	Likely increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; likely increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Optional
Intermediate Metabolizer CYP2C19	Increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Optional
Likely Poor Metabolizer CYP2C19	Likely increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; likely increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Moderate
Poor Metabolizer CYP2C19	Increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Moderate

Pantoprazole CYP2C19

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2C19	Decreased plasma concentrations of PPIs compared with CYP2C19 normal metabolizers; increased risk of therapeutic failure	Increase starting daily dose by 100%. Daily dose may be given in divided doses. Monitor for efficacy.	Strong
Rapid Metabolizer CYP2C19	Decreased plasma concentrations of PPIs compared with CYP2C19 normal metabolizers; increased risk of therapeutic failure	Initiate standard starting daily dose. Consider increasing dose by 50–100% for the treatment of Helicobacter pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.	Moderate
Normal Metabolizer CYP2C19	Normal PPI metabolism; may be at increased risk of therapeutic failure compared with CYP2C19 intermediate and poor metabolizers	Initiate standard starting daily dose. Consider increasing dose by 50–100% for the treatment of H. pylori infection and erosive esophagitis. Daily dose may be given in divided doses. Monitor for efficacy.	Moderate
Likely Intermediate Metabolizer CYP2C19	Likely increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; likely increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Optional
Intermediate Metabolizer CYP2C19	Increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Optional
Likely Poor Metabolizer CYP2C19	Likely increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; likely increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Moderate
Poor Metabolizer CYP2C19	Increased plasma concentration of PPI compared with CYP2C19 normal metabolizers; increased chance of efficacy and potentially toxicity	Initiate standard starting daily dose. For chronic therapy (>12 weeks) and efficacy achieved, consider 50% reduction in daily dose and monitor for continued efficacy.	Moderate

psychostimulants

Atomoxetine CYP2D6

Metabolizer group	What it means	CPIC recommendation	Evidence
Ultrarapid Metabolizer CYP2D6	Based on very limited data available for CYP2D6 ultrarapid metabolizers taking atomoxetine, it is unlikely ultrarapid metabolizers would achieve adequate serum concentrations for the intended effect at standard dosing.	Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/ml, consider a proportional increase in dose to approach 400 ng/ml.e,f Dosages greater than 100 mg/day may be needed to achieve target concentrations.	Moderate
Normal Metabolizer CYP2D6	Normal metabolizers of atomoxetine have a lower likelihood of response as compared to poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared to poor metabolizers.	Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/ml, consider a proportional increase in dose to approach 400 ng/ml.e,f Dosages greater than 100 mg/day may be needed to achieve target concentrations.	Moderate
Normal Metabolizer CYP2D6	Normal metabolizers of atomoxetine have a lower likelihood of response as compared to poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared to poor metabolizers.	Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/ml, consider a proportional increase in dose to approach 400 ng/ml.e,f Dosages greater than 100 mg/day may be needed to achieve target concentrations.	Moderate
Normal Metabolizer CYP2D6	Normal metabolizers of atomoxetine have a lower likelihood of response as compared to poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared to poor metabolizers.	Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/ml, consider a proportional increase in dose to approach 400 ng/ml.e,f Dosages greater than 100 mg/day may be needed to achieve target concentrations.	Moderate
Normal Metabolizer CYP2D6	Normal metabolizers of atomoxetine have a lower likelihood of response as compared to poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared to poor metabolizers.	Initiate with a dose of 40 mg/day and increase to 80 mg/day after 3 days. If no clinical response and in the absence of adverse events after 2 weeks, consider increasing dose to 100 mg/day. If no clinical response observed after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered). If <200 ng/ml, consider a proportional increase in dose to approach 400 ng/ml.e,f Dosages greater than 100 mg/day may be needed to achieve target concentrations.	Moderate
Intermediate Metabolizer CYP2D6	Possibly higher atomoxetine concentrations as compared with normal metabolizers but questionable clinical significance. Intermediate metabolizers may be at an increased risk of increased discontinuation as compared with poor metabolizers.	Initiate with a dose of 40 mg/day and if no clinical response and in the absence of adverse events after 2 weeks increase dose to 80 mg/day. If response is inadequate after 2 weeks consider obtaining a plasma concentration 2-4 h after dosing. If concentration is <200 ng/ml, consider a proportional dose increase to achieve a concentration to approach 400 ng/ml.e,f If unacceptable side effects are present at any time, consider a reduction in dose.	Moderate
Intermediate Metabolizer CYP2D6	Decreased metabolism of atomoxetine higher atomoxetine concentrations as compared with normal metabolizers. Intermediate metabolizers may be at an increased risk of discontinuation as compared with poor metabolizers.	Initiate with a dose of 40 mg/day and if no clinical response and in the absence of adverse events after 2 weeks increase dose to 80 mg/day. If response is inadequate after 2 weeks consider obtaining a plasma concentration 2-4 h after dosing. If concentration is <200 ng/ml, consider a proportional dose increase to achieve a concentration to approach 400 ng/ml.e,f If unacceptable side effects are present at any time, consider a reduction in dose.	Moderate
Intermediate Metabolizer CYP2D6	Decreased metabolism of atomoxetine higher atomoxetine concentrations as compared with normal metabolizers. Intermediate metabolizers may be at an increased risk of discontinuation as compared with poor metabolizers.	Initiate with a dose of 40 mg/day and if no clinical response and in the absence of adverse events after 2 weeks increase dose to 80 mg/day. If response is inadequate after 2 weeks consider obtaining a plasma concentration 2-4 h after dosing. If concentration is <200 ng/ml, consider a proportional dose increase to achieve a concentration to approach 400 ng/ml.e,f If unacceptable side effects are present at any time, consider a reduction in dose.	Moderate
Intermediate Metabolizer CYP2D6	Decreased metabolism of atomoxetine higher atomoxetine concentrations as compared with normal metabolizers. Intermediate metabolizers may be at an increased risk of discontinuation as compared with poor metabolizers.	Initiate with a dose of 40 mg/day and if no clinical response and in the absence of adverse events after 2 weeks increase dose to 80 mg/day. If response is inadequate after 2 weeks consider obtaining a plasma concentration 2-4 h after dosing. If concentration is <200 ng/ml, consider a proportional dose increase to achieve a concentration to approach 400 ng/ml.e,f If unacceptable side effects are present at any time, consider a reduction in dose.	Moderate
Poor Metabolizer CYP2D6	Significantly decreased metabolism of atomoxetine may result in higher concentrations as compared to non- poor metabolizers. This may increase the occurrence of treatment-emergent side effects, but also a greater improvement of ADHD symptoms as compared with non- poor metabolizers in those who tolerate treatment. Poor metabolizer status is associated with lower final dose requirements as compared to non- poor metabolizers.	Initiate with a dose of 40 mg/day and if no clinical response and in the absence of adverse events after 2 weeks increase dose to 80 mg/day. If response is inadequate after 2 weeks consider obtaining a plasma concentration 2-4 h after dosing. If concentration is <200 ng/ml, consider a proportional dose increase to achieve a concentration to approach 400 ng/ml.e,f If unacceptable side effects are present at any time, consider a reduction in dose.	Moderate

Clinical Pharmacogenetics Implementation Consortium

About CPIC

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Drugs with CPIC guidance