Introduction
Qelbree (viloxazine extended-release) is a non-stimulant medication approved by the FDA in 2021 for the treatment of attention-deficit/hyperactivity disorder (ADHD) in pediatric patients ages 6-17 years. It represents a novel therapeutic option as the first non-stimulant approved for ADHD in over a decade, offering an alternative mechanism of action to traditional stimulant medications.
Mechanism of Action
Viloxazine, the active ingredient in Qelbree, is a selective norepinephrine reuptake inhibitor (NRI). Unlike traditional ADHD medications that primarily target dopamine neurotransmission, viloxazine preferentially inhibits the reuptake of norepinephrine in the prefrontal cortex. This action enhances norepinephrine signaling, which plays a crucial role in executive functions including attention, working memory, and behavioral inhibition. The extended-release formulation provides sustained plasma concentrations over 24 hours.
Indications
- Treatment of ADHD in pediatric patients 6-17 years of age
- May be considered as first-line therapy or when stimulants are not tolerated, ineffective, or contraindicated
Dosage and Administration
Initial dose: 100 mg once daily Titration: Increase by 100 mg weekly to optimal response Maximum dose: 400 mg daily for patients 6-17 years Administration: Swallow capsule whole with or without food. Do not crush, chew, or break. Special populations:- Renal impairment: Use caution in severe impairment
- Hepatic impairment: Not studied; use with caution
- Geriatric: Safety not established
- Pregnancy: Category C
Pharmacokinetics
Absorption: Peak plasma concentrations reached in approximately 5 hours Distribution: Extensive tissue distribution; protein binding ~80% Metabolism: Primarily via CYP2D6, CYP3A4, and UGT enzymes Elimination: Half-life ~5 hours; excreted primarily in urine (90%) as metabolites Special considerations: CYP2D6 poor metabolizers may have increased exposureContraindications
- Hypersensitivity to viloxazine or any component of the formulation
- Concomitant use with monoamine oxidase inhibitors (MAOIs) or within 14 days of MAOI use
- History of suicidal ideation or behavior (relative contraindication)
Warnings and Precautions
Suicidal thoughts and behaviors: Monitor for emergence or worsening of depression, suicidal thoughts, or unusual changes in behavior Heart rate and blood pressure increases: Regular monitoring recommended Sedation and fatigue: May impair ability to operate vehicles or machinery Manic episodes: Use cautiously in patients with bipolar disorder Angle-closure glaucoma: May precipitate attacks in susceptible individuals Sexual dysfunction: May occur in some patientsDrug Interactions
Strong CYP2D6 inhibitors: (e.g., fluoxetine, paroxetine) - May increase viloxazine exposure MAOIs: Contraindicated due to risk of serotonin syndrome Other serotonergic drugs: (e.g., SSRIs, SNRIs, triptans) - Increased risk of serotonin syndrome Drugs that prolong QTc: Potential additive effects Antihypertensive agents: May diminish effectivenessAdverse Effects
Common (>5%):- Somnolence (15%)
- Fatigue (10%)
- Decreased appetite (8%)
- Nausea (7%)
- Headache (6%)
- Suicidal ideation and behavior
- Increased heart rate and blood pressure
- Manic episodes
- Serotonin syndrome
- Angle-closure glaucoma
Monitoring Parameters
- Blood pressure and heart rate at baseline and periodically during treatment
- Height and weight in pediatric patients
- Mental status for emergence of suicidal thoughts, aggression, or manic symptoms
- ADHD symptom assessment using validated scales
- Sleep patterns and appetite
- Liver function tests in patients with hepatic impairment
Patient Education
- Take medication at the same time each day
- Do not stop abruptly; taper under medical supervision
- Report any new or worsening mental health symptoms immediately
- Be aware of potential sedation and avoid activities requiring alertness until effects are known
- Inform all healthcare providers about Qelbree use
- Store at room temperature away from moisture
- Use effective contraception if sexually active
References
1. FDA Prescribing Information: Qelbree (viloxazine) extended-release capsules. 2021 2. Nasser A, Liranso T, Adewole T, et al. A Phase III, Randomized, Placebo-Controlled Trial to Assess the Efficacy and Safety of Viloxazine Extended-Release Capsules in Adults with Attention-Deficit/Hyperactivity Disorder. CNS Drugs. 2022;36(8):897-915 3. Johnson J, Saylor K, Brittain ST, et al. A Phase 3, Placebo-Controlled Trial of Once-Daily Viloxazine Extended-Release Capsules in Adolescents with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2022;32(2):112-123 4. Childress AC, Berry SA. Pharmacotherapy of Attention-Deficit Hyperactivity Disorder in Adolescents. Drugs. 2022;82(11):1127-1145 5. ClinicalTrials.gov: Studies of viloxazine extended-release in pediatric ADHD populations (NCT03247530, NCT03247543)