In 2020, viloxazine was reported to have significant affinity for the serotonin 5-HT2B and 5-HT2C receptors (Ki = 3,900 nM and 6,400 nM) and to act as an antagonist and agonist of these receptors, respectively. It also showed weak antagonistic activity at the serotonin 5-HT7 receptor and the α1B- and β2-adrenergic receptors. These actions, although relatively weak, might be involved in its effects and possibly its therapeutic effectiveness in the treatment of ADHD. Pharmacokinetics
Absorption
The bioavailability of extended-release viloxazine relative to an instant-release formulation was about 88%. Peak and AUC levels of extended-release viloxazine are proportional over a dosage range of 100 to 400 mg once daily. The time to peak levels is 5 hours with a range of 3 to 9 hours after a single 200 mg dose. A high-fat meal modestly decreases levels of viloxazine and delays the time to peak by about 2 hours. Steady-state levels of viloxazine are released after 2 days of once-daily administration and no accumulation occurs. Levels of viloxazine are approximately 40 to 50% higher in children age 6 to 11 years compared to children age 12 to 17 years. Distribution
The plasma protein binding of viloxazine is 76 to 82% over a concentration range of 0.5 to 10 μg/mL. Metabolism
The metabolism of viloxazine is primarily via the cytochrome P450 enzyme CYP2D6 and the UDP-glucuronosyltransferases UGT1A9 and UGT2B15. The major metabolite of viloxazine is 5-hydroxyviloxazine glucuronide. Viloxazine levels are slightly higher in CYP2D6 poor metabolizers relative to CYP2D6 extensive metabolizers. Elimination
The elimination of viloxazine is mainly renal.
Medical uses
Attention deficit hyperactivity disorder
Viloxazine is indicated to treat attention deficit hyperactivity disorder (ADHD) in children age 6 to 12 years, adolescents age 13 to 17 years, and adults.In a phase 3 regulatory randomized controlled trial of viloxazine for ADHD in adults, scores on the Attention-Deficit/Hyperactivity Disorder Investigator Symptom Rating Scale (AISRS) with viloxazine therapy decreased from 38.5 points at baseline to 23.0 points following treatment (–40%) and with placebo decreased from 37.6 points at baseline to 25.9 points (–31%). This gave a placebo-subtracted score difference (drug minus placebo), or improvement in scores attributable to the effects of viloxazine, of –3.7 points (–9%). Depression
Viloxazine was previously marketed as an antidepressant for the treatment of major depressive disorder. It was considered to be effective in mild to moderate as well as severe depression with or without co-morbid symptoms. The typical dose range for depression was 100 to 400 mg per day in divided doses administered generally two to three times per day. Available forms
Viloxazine is available for ADHD in the form of 100, 150, and 200 mg extended-release capsules. These capsules can be opened and sprinkled into food for easier administration.