Clinical Data Highlighting ADHD Treatment for Adults

 PRODUCT BULLETIN 

Do your adult patients (18 years and older) need a nonstimulant option to treat their Attention-Deficit/Hyperactivity Disorder (ADHD)? Read more about a nonstimulant ADHD medication approved for adults.

INDICATION

Qelbree is indicated for the treatment of ADHD in adults and pediatric patients 6 years and older.

Please see full Important Safety Information to the top left.
 

Qelbree (viloxazine extended-release capsules) is an FDA-approved, nonstimulant treatment option for adults and pediatric patients 6 years and older with Attention-Deficit/Hyperactivity Disorder (ADHD).^1,2 This is the first nonstimulant ADHD treatment option to be approved for adults (18 years and older) in 20 years.^1,2 Several clinical studies evaluated the efficacy and safety of Qelbree for ADHD treatment.¹ 

Qelbree contains the selective norepinephrine reuptake inhibitor, viloxazine, in the form of water-soluble viloxazine hydrochloride.¹ This white to off-white powder is formulated as extended-release capsules using 2-bead Microtrol® technology.^1,3  (Figure 1) The relative bioavailability of viloxazine extended-release is about 88% compared to an immediate-release formulation.¹ 
 

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

• Concomitant administration of a monoamine oxidase inhibitor (MAOI), or dosing within 14 days after discontinuing an MAOI, because of an increased risk of hypertensive crisis 
• Concomitant administration of sensitive CYP1A2 substrates or CYP1A2 substrates with a narrow therapeutic range 

Please see full Important Safety Information to the top left.
 

Qelbree (viloxazine extended-release capsules) is available in 3 dosage strengths of viloxazine free base: 100 mg, 150 mg, and 200 mg.¹ These are equivalent to 115 mg, 173 mg, and 231 mg of viloxazine hydrochloride salt, respectively.¹ The median time to reach peak plasma concentration for viloxazine is approximately 5 (range: 3 to 9) hours.¹ The half-life of viloxazine is around 7 hours, and a steady state is reached after 2 consecutive days of daily administration.¹ 

Pre-clinical studies demonstrated that viloxazine hydrochloride does not result in physical drug dependence in abuse liability models using rhesus monkeys.⁴ In these studies, five conditions of drug abuse liability were compared.⁴ Viloxazine hydrochloride showed minimal effects on gross behavior, demonstrating a low potential of physical dependence.⁴ Furthermore, no withdrawal symptoms or signs of dependence were reported as adverse events (AEs) by participants in the human clinical trials.³ 

Clinical Study

A phase III, multicenter, randomized, double-blind, flexible-dose, placebo-controlled, parallel-group, monotherapy trial was designed to assess the effectiveness and safety of Qelbree in adult ADHD patients 18 to 65 years of age.^1,5 

Study Design

In this trial, the first 2 weeks of treatment served as a titration period followed by a 4-week maintenance period, completing the 6-week trial.^1,5 Patients started at 200 mg in week one and titrated up to 400 mg at week two.^1,5  (Figure 2) The dose could then be titrated up by another 200 mg increment for a maximum daily dose of 600 mg.^1,5 All participants were randomized to receive a once-daily, single dose between 200 mg and 600 mg or placebo.^1,5 

The primary endpoint measured in this study was the change from baseline (CFB) to the end of study (EOS) on the total score of the Adult ADHD Investigator Symptom Rating Scale (AISRS).^1,5 This 18-item scale assesses common symptoms of ADHD. Higher scores on this scale represent more severe symptoms.¹ The key secondary endpoint measured in this study was the CFB in the Clinical Global Impression-Severity of Illness (CGI-S) score at the end of the trial.^1,5 
 

IMPORTANT SAFETY INFORMATION

• Suicidal thoughts and behaviors: Closely monitor all Qelbree-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes 

Please see full Important Safety Information to the top left.

Study Results

Adult patients treated with Qelbree (viloxazine extended-release capsules) experienced a statistically significantly greater reduction from baseline to EOS in the AISRS total scores compared to those who received placebo.^1,5  (Figure 3) The change from baseline (CFB) (LS mean ± SE) in AISRS total scores was -15.5 ± 0.91 for Qelbree as compared to -11.7 ± 0.90 for placebo.^1,5 As mentioned, Qelbree doses in the trial ranged from a 200 mg minimum to 600 mg maximum once daily.^1,5 The average dose taken by patients at the end of the trial was 504 mg once daily.^1,5 Furthermore, the total symptom score reductions were observed as early as week two during the trial.⁵ As for the secondary endpoint, a statistically significantly greater reduction in CGI-S scores was observed at the end of the study in patients taking Qelbree compared to those receiving placebo.^1,5 
 

IMPORTANT SAFETY INFORMATION

• Heart rate, blood pressure increases: Qelbree can cause an increase in diastolic blood pressure and heart rate. Assess these mea­sures prior to starting therapy, following increases in dosage, and periodically during therapy 

Please see full Important Safety Information to the top left.

Adverse Reactions

The most common AEs (≥2% and twice the rate of placebo) reported by patients in the adult study included: insomnia, headache, fatigue, nausea, decreased appetite, dry mouth, somnolence, and constipation (Table 1).^1,5 The discontinuation rate due to AEs among adult Qelbree (viloxazine extended-release capsules) recipients was 9% compared to 5% for placebo.^1,3 
 

In the clinical studies conducted in both children (6 to 11 years) and adult (18 to 65 years) patients, those treated with Qelbree reported higher rates of suicidal thoughts and behaviors.¹ As a result, patients who are prescribed Qelbree must be closely monitored for clinical worsening and the emergence of suicidal thoughts and behaviors.¹ Heart rate and diastolic blood pressure must also be assessed before and during treatment with Qelbree because increased levels of each were measured during the trials.¹ 

Before starting treatment with Qelbree, patients should be screened for bipolar disorder risk because Qelbree can also cause manic or mixed episodes in such patients.¹ Patients should also be advised to not perform activities requiring mental alertness when initiating treatment because Qelbree can cause somnolence and fatigue.¹ 

Dosage

The recommended starting dose of Qelbree for adult patients is 200 mg once daily.¹ The dose can then be increased weekly by 200 mg increments, based on treatment response and tolerability.¹ The maximum daily dose for adult patients is 600 mg.¹ 

IMPORTANT SAFETY INFORMATION

• Activation of mania or hypomania: Noradrenergic drugs may induce a manic or mixed episode in patients with bipolar disorder. Prior to initiating treatment with Qelbree, screen patients to determine if they are at risk for bipolar disorder. Screening should include a detailed psychiatric history, including a personal or family history of suicide, bipolar disorder, and depression 

Please see full Important Safety Information to the top left.

Administration

Qelbree (viloxazine extended-release capsules) is available in 3 dosage strengths and colors.¹ The 100 mg capsule has a yellow opaque body and cap with “SPN” printed on the cap and “100” printed on the body.¹ The 150 mg capsule has a lavender opaque body and cap with “SPN” printed on the cap and “150” printed on the body.¹ The 200 mg capsule has a light green opaque body and cap with “SPN” printed on the cap and “200” printed on the body.¹ Capsules can be swallowed whole each day, with or without food.¹ Capsules should never be cut, crushed, or chewed.¹ Alternatively, capsules can be opened, and the entire contents can be sprinkled over a spoonful of pudding or applesauce.¹  (Figure 4) This mixture should then be consumed, without chewing, in its entirety, within 15 minutes for pudding and within 2 hours for applesauce.¹ Do not store the mixture for future use.¹ 
 

Warnings and Precautions

Qelbree is contraindicated in patients who are simultaneously taking monoamine oxidase inhibitors (MAOIs), or within 14 days after discontinuation of an MAOI, because of an increased risk of hypertensive crisis.¹ Qelbree is also contraindicated in patients taking sensitive CYP1A2 substrates or CYP1A2 substrates with a narrow therapeutic range.¹ These patients should not take Qelbree to avoid negative drug-drug interactions.¹ Patients with severe renal impairment (EGFR <30 mL/min/1.73m²) should start at a once-daily dose of 100 mg.¹ This dose can then be titrated weekly in increments of 50 to 100 mg once daily up to a maximum daily dose of 200 mg. 

Summary

Qelbree is the first nonstimulant ADHD treatment option approved for adults in the past two decades.^1,2 Qelbree contains viloxazine hydrochloride, a selective norepinephrine reuptake inhibitor, formulated into extended-release oral capsules using 2-bead Microtrol® technology.¹ Several clinical studies have evaluated the safety and efficacy of Qelbree in ADHD patients ranging in age from 6 years to 65 years.¹ Patients taking Qelbree have demonstrated statistically significant reductions in ADHD symptoms compared to patients receiving placebo.^1,5 Importantly, Qelbree has also exhibited a safety and tolerability profile lacking any evidence of withdrawal symptoms or signs of dependence in both human clinical trials and animal models.^3-5 

IMPORTANT SAFETY INFORMATION

• Severe renal impairment: Initiate Qelbree at 100 mg once daily and increase by 50 mg to 100 mg at weekly intervals to a maximum recommended dosage of 200 mg once daily 

Please see full Important Safety Information to the top left.

Learn more about Qelbree, an extended-release, nonstimulant medication for ADHD: https://www.QelbreeHCP.com/ 
 

References

1. Qelbree [package insert]. Rockville, MD: Supernus Pharmaceuticals, Inc.
2. Food and Drug Administration. Novel drug approvals for 2021. May 13, 2022. Accessed June 13, 2022. https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2021
3. Data on file, Supernus Pharmaceuticals.
4. Yanagita T, Wakasa Y, Kiyohara H. Drug dependence potential of viloxazine hydrochloride tested in rhesus monkeys. Pharmacol Biochem Behav. 1980;12(1):155-161. doi:10.1016/0091-3057(80)90430-x
5. Nasser A, Hull JT, Chaturvedi SA, et al. A phase III, randomized, double-blind, placebo-controlled trial assessing the efficacy and safety of viloxazine extended-release capsules in adults with attention-deficit/hyperactivity disorder. CNS Drugs. 2022;36(8):897-915.doi:10.1007/s40263-022-00938-w
    

QBE.2022-0372