Drug Interactions between atomoxetine and methotrimeprazine

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 2D6 may significantly increase the plasma concentrations of atomoxetine, which is primarily metabolized by the isoenzyme. In patients who are extensive metabolizers of CYP450 2D6 (approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent), potent inhibitors of the isoenzyme such as fluoxetine and paroxetine have been shown to increase atomoxetine systemic exposure (AUC) by 6- to 8-fold and peak plasma concentration (Cmax) by 3- to 4-fold. These higher concentrations are similar to those observed in CYP450 2D6 poor metabolizers given the drug alone. In vitro studies suggest that coadministration of CYP450 2D6 inhibitors to poor metabolizers will not further increase atomoxetine plasma concentrations.

MANAGEMENT: Pharmacologic response to atomoxetine should be monitored more closely whenever a potent CYP450 2D6 inhibitor such as fluoxetine, paroxetine, or quinidine is added to or withdrawn from therapy, as dosage adjustment of atomoxetine may be necessary in extensive metabolizers. The initial recommended dose should only be increased up to the usual target dose if symptoms fail to improve after 4 weeks and the initial dose is well tolerated. During coadministration, patients should be advised to contact their physician if they experience excessive adverse effects of atomoxetine such as dizziness, dry mouth, anorexia, sleep disturbances, and palpitations.