Drug Interaction Report

MONITOR: Coadministration with drugs that are inhibitors of CYP450 2D6 may 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. The risk of QT prolongation may be increased with concomitant use of CYP450 2D6 inhibitors that also prolong the QT interval (e.g., abiraterone, osilodrostat, primaquine, propoxyphene, ranolazine). Additionally, the risk of serotonin syndrome may increase with concomitant use of CYP450 2D6 inhibitors that possess serotonergic activity (e.g., duloxetine, dexfenfluramine, fenfluramine).

MANAGEMENT: Pharmacologic response to atomoxetine should be monitored more closely whenever a CYP450 2D6 inhibitor is added to or withdrawn from therapy, as dosage adjustment of atomoxetine may be necessary in extensive metabolizers. If the CYP450 2D6 inhibitor also prolongs the QT interval, and/or has serotonergic activity, then obtaining more frequent electrocardiograms (ECGs) to monitor the QT interval as well as closer monitoring for signs and symptoms of serotonin syndrome is advised. Patients should be counseled to seek immediate medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes (e.g., dizziness, lightheadedness, syncope, palpitations, irregular heartbeat, and/or shortness of breath) and/or symptoms of serotonin syndrome (e.g., altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, tremor). During coadministration, patients should also be advised to contact their doctor if they experience excessive adverse effects of atomoxetine such as dizziness, dry mouth, anorexia, sleep disturbances, and palpitations.

The recommended maximum number of medicines in the 'norepinephrine reuptake inhibitors' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'norepinephrine reuptake inhibitors' category:

• Strattera (atomoxetine)
• viloxazine

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.