Viloxazine Extended-Release Capsules (Qelbree®) for Adults with Attention-Deficit/Hyperactivity Disorder: Evaluating the Potential Impact of Caffeine Exposure on Safety Profile

Abstract: Viloxazine ER (viloxazine extended-release capsules, Qelbree®) is a novel, nonstimulant, FDA-approved treatment for adults and children (≥6 yrs) with ADHD. Viloxazine ER inhibits cytochrome P450-1A2, which is responsible for caffeine metabolism. To evaluate the potential impact of caffeine consumption with viloxazine ER on safety, we analyzed data from a Phase 3 double-blind (DB), placebo-controlled trial and ongoing open-label extension (OLE) in adults with ADHD where caffeine use was reported at each study visit. Adverse event (AE) preferred and combined terms with known association to caffeine consumption were evaluated. For AEs occurring in ≥5% of viloxazine ER-treated subjects (200-600 mg/day) who experienced a potentially caffeine-related AE, the probability that the AE occurred as a function of viloxazine ER dose and caffeine consumption was estimated using a logistic regression model. Of 372 subjects, ~85% reported caffeine use during the DB trial; mean caffeine use was 859 and 1034 mg/week for viloxazine ER- and placebo-treated subjects respectively. There was no correlation between viloxazine ER dose and caffeine consumption. A total of 44 (DB placebo), 79 (DB viloxazine ER), and 33 (OLE viloxazine ER) subjects reported any caffeine-associated AEs, with insomnia-related, fatigue, nausea, headache-related, decreased appetite, and somnolence-related terms occurring in ≥5% of viloxazine ER-treated subjects. Caffeine consumption significantly increased the probability of experiencing insomnia-related AEs only (p=0.02). This analysis suggests using caffeine with viloxazine ER did not increase the likelihood of experiencing caffeine-related AEs, except for insomnia. Providers and patients should be aware of the potential for viloxazine ER to augment caffeine exposure.Short Description: As viloxazine ER is known to inhibit cytochrome P450-1A2, which is responsible for caffeine metabolism, we evaluated the potential impact of caffeine consumption with viloxazine ER on safety by analyzing data from a Phase 3 double-blind, placebo-controlled trial and ongoing open-label extension in adults with ADHD where caffeine use was reported at each study visit. This analysis suggests using caffeine with viloxazine ER did not increase the likelihood of experiencing caffeine-related AEs, except for insomniaName of Sponsoring Organization(s): Supernus Pharmaceuticals Inc.