Impact of Paroxetine, a Strong CYP2D6 Inhibitor, on SPN‐812 (Viloxazine Extended‐Release) Pharmacokinetics in Healthy Adults

SPN‐812 (viloxazine extended‐release) is a novel nonstimulant recently approved as a treatment for attention‐deficit/hyperactivity disorder in children and adolescents. Given that SPN‐812 is metabolized by CYP2D6 and may be coadministered with CYP2D6 inhibitors, this trial investigated the pharmacokinetics and safety of SPN‐812 coadministered with the potent CYP2D6 inhibitor paroxetine. In this single‐sequence, 3‐treatment period study in healthy volunteers, subjects received a single oral dose of 700 mg SPN‐812 alone (period 1), 20 mg daily paroxetine (10 days, period 2), followed by concurrent administration of SPN‐812 and paroxetine (period 3). Blood samples were collected for 72 hours post‐SPN‐812 dosing and analyzed for viloxazine and its primary metabolite, 5‐HVLX‐gluc. Twenty‐two healthy adults were enrolled; all completed the trial. The potential for drug interaction between SPN‐812 and paroxetine was assessed using analysis of variance on the log‐transformed pharmacokinetic parameters C(max), AUC(0‐t), and AUC(inf). The least‐squares geometric mean ratios for viloxazine were (reported as the ratio of combination/SPN‐812 alone) C(max), 116.04%; 90%CI, 109.49%‐122.99%; AUC(0‐t), 134.65%; 90%CI, 127.65‐142.03; and AUC(inf), 134.80%; 90%CI, 127.94%‐142.03%. CYP2D6 inhibition resulted in a modest change (<35%) on viloxazine AUCs with no change in C(max). All adverse events were mild in severity.