Atomoxetine, a Novel Treatment for Attention-Deficit-Hyperactivity Disorder

Alisa K. Christman, Pharm.D.; Joli D. Fermo, Pharm.D.; John S. Markowitz, Pharm.D.

Disclosures

Pharmacotherapy. 2004;24(8) 

In This Article

Drug Interactions

Atomoxetine is metabolized primarily to an active metabolite, 4-hydroxyatomoxetine, by CYP2D6. Genetically poor metabolizers of this isoenzyme (5-10% of the United States population) may have an extended elimination (half-life approaching 20 hrs) that may necessitate dosage adjustments. In vitro studies have shown that atomoxetine is an inhibitor of both the CYP2D6 and CYP3A4 enzymes, but not CYP1A2 or CYP2C9.[35] Yet, studies performed in vivo in a population of extensive metabolizers demonstrate that atomoxetine administered at the maximum recommended dosage will not inhibit the clearance of drugs metabolized by CYP2D6.[35] In addition, studies performed to evaluate atomoxetine in poor metabolizers demonstrate that atomoxetine administered at the maximum recommended dosage will not likely inhibit the clearance of or induce the metabolism of CYP3A4 substrates.[35] However, one study demonstrated an increase in the steady-state plasma concentrations of atomoxetine with a prolonged half-life after exposure to a potent CYP2D6 inhibitor (e.g., fluoxetine, paroxetine) that was similar to atomoxetine plasma concentrations observed in poor metabolizers.[36] Note that combination therapy with ADHD drugs is common because of the high rate of comorbid psychiatric conditions. Combining pharmacotherapy is commonplace, although conventional psychostimulants (e.g., methylphenidate) pose little interaction liability; however, caution should be exercised when using amphetamine compounds with other sympathomimetic agents.[37] Atomoxetine should not be used in patients who receive therapy with a monoamine oxidase inhibitor or within the first 14 days after discontinuation of therapy.

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