New Nonstimulant Medication Is Approved for ADHD in Children

On April 2, 2021, the FDA approved viloxazine (Qelbree; Supernus Pharmaceuticals, Inc) for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children aged 6 to 17 years. Viloxazine is a selective norepinephrine reuptake inhibitor and is the first new nonstimulant medication for treatment of ADHD in children in more than 10 years. 

Efficacy

The FDA evaluated the safety of viloxazine in 3 randomized, placebo-controlled trials. Studies 1 and 2 included participants aged 6 to 11 years and lasted either 6 or 8 weeks that included a titration period to achieve maintenance dosing of 100 mg, 200mg, or placebo daily (study 1) and 200mg, 400mg, or placebo daily (study 2). Participants aged 12 to 17 years were titrated to either 200 mg or 400 mg or placebo in study 3. The primary end point in each study is a change in total score on the ADHD Rating Scale (AHD-RS-5), comparing baseline to the end of the maintenance period assessments. The change in Clinical Global Impression-Improvement (CGI-I) score from baseline served as a secondary end point in each study. In all 3 studies, patients administered viloxazine demonstrated statistically significant improvements in ADHD rating scale scores and in CGI-I scores compared with participants administered placebo. 

Safety

In trials, 826 participants were exposed to a dose of viloxazine that ranged from 100 mg to 400 mg. In this group, the most common adverse effects (AEs) included nausea, vomiting, insomnia, irritability, decreased appetite, and somnolence. The most common AEs leading to discontinuation of the medication included somnolence, nausea, fatigue, decreased appetite, headache, tachycardia, and irritability. Viloxazine carries a boxed warning regarding higher rates of suicidal thoughts and behaviors among participants administered viloxazine in clinical trials compared with participants administered placebo. Patients treated with viloxazine should be monitored for suicidal ideation or behaviors, particularly when initiating or increasing therapy. Patients experiencing these symptoms may require a discontinuation of viloxazine therapy. Viloxazine may activate mania in patients at risk for bipolar disorder. Patients should be screened prior to initiating therapy for a history of suicide, depression, or bipolar disorder. 

Viloxazine may also cause an increase in blood pressure and heart rate. A patient’s blood pressure and heart rate should be assessed at baseline when initiating therapy and periodically throughout treatment. Somnolence and fatigue associated with viloxazine administration may affect a patient’s mental alertness. Until a patient knows how viloxazine will affect them, they should avoid operating machinery or driving. Concomitant administration of viloxazine with monoamine oxidase inhibitors is contraindicated due to an increased risk of hypertensive crisis. Viloxazine strongly inhibits cytochrome P450 1A2 (CYP1A2) and will increase exposure to concomitant CYP1A4 substrates and increase the risk of AEs to those medications. In addition, viloxazine weakly inhibits CYP2D6 and CYP3A4. Patients should be monitored for AEs associated with any additional medications they take that may be impacted by this interaction.

Dosing and Administration

In patients aged 6 to 11 years, the recommended starting dosage of viloxazine is 100 mg once daily and may be titrated in 100-mg increments weekly to a maximum dosage of 400 mg once daily. The recommended starting dosage for patients aged 12 to 17 years is 200 mg once daily. In this age group, the dosage may be titrated up in 1 week to the maximum recommended dosage of 400 mg once daily. Capsules may be swallowed whole with or without food or may be opened and contents sprinkled on applesauce. The capsule or applesauce with sprinkled medication must not be chewed. Medication mixed with applesauce must be used within 2 hours of mixing and cannot be stored for later use.

Reference

1. Qelbree. Prescribing information. Supernus Pharmaceuticals Inc; 2021. Accessed May 11, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/211964s000lbl.pdf