Table 4. [CPIC Dosing Recommendations for Atomoxetine based on CYP2D6 Genotype for Adults (2019)]. - Medical Genetics Summaries

CYP2D6 metabolizer phenotype	Activity score	Implication	Therapeutic recommendation	Classification of Recommendation^a
Ultrarapid	>2.25	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^b,c Dosages greater than 100 mg/day may be needed to achieve target concentrations^d	Moderate
Normal	1.25–2.25	Normal metabolizers of atomoxetine have a lower likelihood of response as compared with poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared with 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^b,c Dosages greater than 100 mg/day may be needed to achieve target concentrations^d	Moderate
Intermediate	>0–<1.25	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^b,c If unacceptable side effects are present at any time, consider a reduction in dose	Moderate
Poor	0	Significantly decreased metabolism of atomoxetine may result in higher concentrations as compared with 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 with 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^b,c If unacceptable side effects are present at any time, consider a reduction in dose	Moderate

CYP2D6 metabolizer phenotype

Activity score

Implication

Therapeutic recommendation

Classification of Recommendation^a

Ultrarapid

>2.25

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^b,c
Dosages greater than 100 mg/day may be needed to achieve target concentrations^d

Moderate

Normal

1.25–2.25

Normal metabolizers of atomoxetine have a lower likelihood of response as compared with poor metabolizers. This is associated with increased discontinuation due to lack of efficacy as compared with poor metabolizers

Moderate

Intermediate

>0–<1.25

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^b,c
If unacceptable side effects are present at any time, consider a reduction in dose

Moderate

Poor

Significantly decreased metabolism of atomoxetine may result in higher concentrations as compared with 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 with 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^b,c
If unacceptable side effects are present at any time, consider a reduction in dose

Moderate

From: Atomoxetine Therapy and CYP2D6 Genotype

Medical Genetics Summaries [Internet].

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

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

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