What is Quelbree (viloxazine)?

What is Qelbree (Viloxazine)?

Qelbree is a nonstimulant medication containing viloxazine extended-release that functions as a selective norepinephrine reuptake inhibitor, FDA-approved for treating ADHD in patients 6 years of age and older, including adults. 1

Mechanism of Action

• Viloxazine works primarily by inhibiting norepinephrine reuptake, though the exact mechanism for treating ADHD remains unclear 1
• The medication also exhibits serotonin-norepinephrine modulating properties, including partial agonist activity at the serotonin 5-HT2C receptor 2, 1
• Unlike stimulants, viloxazine produces minimal elevation in dopamine levels in the nucleus accumbens, resulting in lower abuse potential and no evidence of drug dependence 3, 4

Administration and Dosing

• Administer once daily in the morning for optimal ADHD symptom control throughout the day 5, 2, 6
• Available in extended-release capsules containing 100 mg, 150 mg, and 200 mg of viloxazine free base 1
• Capsules should be swallowed whole, or may be opened and sprinkled on applesauce or pudding if unable to swallow whole 1
• When mixed with food, consume within 15 minutes for pudding or within 2 hours for applesauce 1

Timeline for Therapeutic Effect

• Therapeutic effects may not be observed until 2-4 weeks after initiation, though some studies show benefits as early as week 2 2, 6
• This represents a faster onset compared to atomoxetine (which typically requires ~4 weeks), making viloxazine ER a potentially advantageous nonstimulant option 7

Common Adverse Effects

• Most frequently reported adverse events (≥5% incidence) include somnolence/sedation, fatigue, headache, decreased appetite, nasopharyngitis, and insomnia 1, 8, 9
• In pediatric long-term studies, nasopharyngitis (9.7%), somnolence (9.5%), headache (8.9%), decreased appetite (6.0%), and fatigue (5.7%) were most common 8
• In adult studies, insomnia (13.8%), nausea (13.8%), headache (10.7%), and fatigue (10.1%) predominated 9
• Most adverse events are mild to moderate in severity, with only 3.9% of pediatric participants reporting severe adverse events 8

Critical Safety Warnings

• Qelbree carries an FDA boxed warning for increased risk of suicidal thoughts or actions, particularly within the first few months of treatment or when the dose is changed 1
• Monitor blood pressure and heart rate, as increases can occur 1
• Patients should use caution when driving or operating machinery until they know how the medication affects them, due to potential somnolence and fatigue 1

Special Population Considerations

• Discontinue viloxazine when pregnancy is recognized due to limited safety data; alternative agents are preferred during pregnancy 6
• The medication passes into breast milk with a relative infant dose of approximately 1% of the maternal dose 1
• Dosage reduction is required in patients with severe renal impairment (eGFR < 30 mL/min/1.73m²) 1
• Limited data exists on efficacy for ADHD treatment in adults compared to pediatric populations 6

Contraindications and Drug Interactions

• Do not use in patients taking monoamine oxidase inhibitors (MAOIs) or within 14 days of stopping an MAOI 1
• Contraindicated with concurrent use of alosetron, duloxetine, ramelteon, tasimelteon, tizanidine, or theophylline 1
• Viloxazine is primarily metabolized by CYP2D6, UGT1A9, and UGT2B15 1

Clinical Efficacy Data

• Long-term pediatric studies (up to 72 months) demonstrated sustained improvement in ADHD-RS-IV/5 total scores, with mean changes of -24.3 at Month 3, -26.1 at Month 12, and -22.4 at last study visit from double-blind baseline 8
• Adult studies showed rapid improvement by week 2 (-11.4 points) with continued improvement at last on-study visit (-18.2 points) 9
• In pediatric trials, median modal doses were 300 mg/day for children and 400 mg/day for adolescents 8
• In adult maintenance treatment, 73% of participants used doses ≥400 mg/day, with 36% using 600 mg/day 9

Role in ADHD Treatment Algorithm

• Viloxazine represents a nonstimulant alternative when patients do not respond to first-line stimulants, cannot tolerate stimulant side effects, or have contraindications to stimulant use 3, 7
• Stimulant medications may be added to existing Qelbree therapy for residual ADHD symptoms, with careful monitoring for irritability, insomnia, feeding difficulty, and cardiovascular effects 5