Table 3. [CPIC Dosing Recommendations for Atomoxetine based on CYP2D6 Genotype for Children (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 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days If no clinical response and in the absence of adverse events 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	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 0.5 mg/kg and increase to 1.2 mg/kg/day after 3 days If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered) If <200 ng/ml, consider a proportional ^b,c increase in dose to approach 400 ng/ml	Moderate
Intermediate	>0–<1.25	Decreased metabolism of atomoxetine and 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 0.5 mg/kg/day and if no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a plasma concentration 2-4 h after dosing. If response is inadequate and 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 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 0.5 mg/kg/day and if no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a plasma concentration 4 hours after dosing If response is inadequate and 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	Strong

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 0.5 mg/kg/day and increase to 1.2 mg/kg/day after 3 days
If no clinical response and in the absence of adverse events 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

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 0.5 mg/kg and increase to 1.2 mg/kg/day after 3 days
If no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a peak plasma concentration (1 to 2 hours after dose administered)
If <200 ng/ml, consider a proportional ^b,c increase in dose to approach 400 ng/ml

Moderate

Intermediate

>0–<1.25

Decreased metabolism of atomoxetine and 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 0.5 mg/kg/day and if no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a plasma concentration 2-4 h after dosing. If response is inadequate and 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 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 0.5 mg/kg/day and if no clinical response and in the absence of adverse events after 2 weeks, consider obtaining a plasma concentration 4 hours after dosing
If response is inadequate and 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

Strong

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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