Important Considerations Prior to Starting Treatment for ADHD

Qelbree (viloxazine extended-release capsules) has demonstrated safety and efficacy through clinical trials – two pediatric (6 to 11 years) trials, one adolescent (12 to 17 years) trial, and one adult (18 years and older) trial. However, there are factors to consider prior to initiating treatment for Attention Deficit/Hyperactivity Disorder (ADHD) with Qelbree in adult and pediatric patients 6 years and older.

INDICATION

Qelbree® (viloxazine extended-release capsules) 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.

Heart Rate and Blood Pressure

Qelbree can cause an increase in heart rate and diastolic blood pressure.¹ In a clinical study, 22% of pediatric patients between 6 and 11 years of age receiving 100 mg of Qelbree daily showed an increase of ≥20 beats per minute (bpm) at any point during the study.¹ Comparatively, 9% of placebo patients in this age group experienced a similar increase in heart rate.¹ Thirty-one percent of pediatric patients receiving 200 mg of Qelbree daily showed similarly increased heart rates compared to 15% receiving placebo.¹ Twenty-eight percent of pediatric patients receiving 400 mg daily showed a similar increase in heart rate compared to 23% of those receiving placebo.¹

In adolescents (12 to 17 years of age), 22% of patients treated with Qelbree 200 mg daily showed a ≥20 bpm increase in heart rate during the trial at any time point compared to 14% on placebo.¹ Of the patients in this age group receiving Qelbree 400 mg daily, 34% showed an increased heart rate compared to 17% on placebo.¹ Furthermore, 25% of adolescent patients treated with Qelbree 400 mg daily showed a ≥15 mmHg increase in diastolic blood pressure at any time during the trial as compared to 13% in the placebo group.¹

In adults (18 to 60 years of age), 29% of patients treated with 200 mg to 600 mg of Qelbree daily showed a ≥20 bpm increase in heart rate at any time point during a clinical trial compared to 13% on placebo.¹ Of this same age group, 13% had a ≥15 mmHg increase in diastolic blood pressure at any time during the trial as compared to 9% of patients receiving placebo.¹

Therefore, heart rate and blood pressure should be assessed for all patients prior to initiating treatment with Qelbree, following any dosage increases, and periodically throughout the duration of treatment.¹

Screening for Suicide, Bipolar Disorder, and Depression 

Qelbree, a noradrenergic drug, may induce a manic or mixed episode in patients with bipolar disorder.¹ Prior to starting on Qelbree, patients should be screened for any risk of developing bipolar disorder.¹ This screening can include a detailed psychiatric history, including a personal or family history of suicide, bipolar disorder, and depression.¹ 

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Higher rates of suicidal thoughts and behaviors were reported in pediatric and adult patients treated with Qelbree compared to patients treated with placebo. For pediatric patients (ages 6 to 11 years), 0.9% reported suicidal ideation, behavior, or both.¹ None of the patients treated with placebo reported suicidal behavior. Within the adult studies, 1.6% of Qelbree-treated patients reported suicidal ideation compared to zero patients on placebo.¹

Patients treated with Qelbree had higher rates of insomnia and irritability.¹ A causal link between insomnia and irritability and the emergence of suicidal impulses has not been identified.¹ However, these and other symptoms such as depressed mood, anxiety, agitation, akathisia, mania, hypomania, panic attacks, impulsive behavior, and aggression may all represent precursors to emerging suicidal ideation or behavior.¹ As a result, patients taking Qelbree should be observed for the emergence of such precursor symptoms.¹

All patients must be closely monitored for clinical worsening and emergence of suicidal thoughts and behaviors, particularly during the first few months of treatment and at times of dosage changes.¹ If patients experience emergent suicidal ideation behavior or precursor symptoms, consider changing regimens or possibly discontinuing Qelbree.¹ Family members and/or caregivers should be advised to monitor these patients for the emergence of these symptoms, ideations, or behaviors.¹ Any such signs should be immediately reported to the health care provider.¹ 

Somnolence and Fatigue 

Qelbree can cause somnolence and fatigue. In pediatric and adolescent clinical trials for patients 6 to 17 years of age with ADHD, somnolence was observed in 16% of patients taking Qelbree compared to 4% of patients taking placebo. Fatigue was noted in 6% of patients taking Qelbree compared to 2% of patients taking placebo.

In adult patients (18 to 60 years of age), somnolence was recorded in 6% of patients taking Qelbree compared to 2% of those taking placebo. Fatigue was reported in 12% of adult Qelbree patients compared to 3% of placebo patients.

As a result, patients taking Qelbree should always use caution when driving or operating hazardous machinery due to potential somnolence (including sedation and lethargy) and fatigue.¹

Special Populations 

Pregnancy

A pregnancy exposure registry is available to monitor pregnancy outcomes in women exposed to Qelbree during pregnancy. Health care providers are encouraged to register patients by calling the National Pregnancy Registry for Psychiatric Medications at 1-866-961-2388 or visiting online at www.womensmentalhealth.org/preg.

Animal reproduction studies have shown that viloxazine may cause maternal harm when used during pregnancy. Qelbree should be discontinued when pregnancy is recognized unless the benefits of therapy outweigh the potential risk to the mother. There is insufficient case series data of viloxazine use in pregnant women to determine the drug-associated risk of major birth defects, miscarriage, or adverse maternal outcomes.

During animal reproduction studies, oral administration of viloxazine in rats and rabbits during organogenesis at doses approximately equal to the maximum recommended human dose (MRHD) of 600 mg in adults caused fetal toxicities and delayed fetal development in the rats and maternal toxicities in the rabbits. Oral administration of viloxazine in pregnant rats and mice during pregnancy and lactation caused maternal toxicities and deaths as well as fetal toxicities at doses equal to or less than the MRHD of 600 mg in adults. An estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

Lactation

There are no data on the presence of viloxazine in human milk, the effects on a breastfed infant, or effects on milk production. Viloxazine is likely present in rat milk. When a drug is present in animal milk, it is likely that it will also appear in human milk. The health benefits as well as developmental benefits of breastfeeding should be considered along with the mother’s clinical need for Qelbree treatment and any potential adverse effects on the breastfed child from Qelbree or the underlying maternal condition.

Renal Impairment

In patients with severe renal impairment (eGFR<30 mL/min/1.73m²), the recommended starting dose is 100 mg once daily. This dose may be titrated weekly in increments of 50 to 100 mg once daily, up to a maximum recommended dose of 200 mg once daily. No dosage adjustment is recommended in patients with mild to moderate (eGFR of 30 to 89 mL/min/1.73m²) renal impairment. The exposure of viloxazine increases in patients with renal impairment because renal excretion is its primary route of excretion. During pharmacokinetic studies, 90% of the dose was recovered in urine within the first 24 hours post-dose while less than 1% was excreted in the feces.  

Contraindications and Drug Interactions

Some drugs have clinically important drug interactions with Qelbree, and these need to be understood prior to initiating treatment.

Concomitant use of Qelbree with a monoamine oxidase inhibitor (MAOI) can lead to a potentially life-threatening hypertensive crisis. Therefore, concomitant use of Qelbree with an MAOI or within 2 weeks after discontinuing an MAOI is contraindicated.

The active ingredient in Qelbree, viloxazine, is a strong CYP1A2 inhibitor. Therefore, concomitant use of viloxazine significantly increases the total exposure, but not peak exposure, of sensitive CYP1A2 substrates. This can increase the risk of adverse reactions associated with these CYP1A2 substrates. For this reason, concurrent administration of Qelbree and sensitive CYP1A2 substrates or CYP1A2 substrates with a narrow therapeutic range is contraindicated. It is not recommended to coadminister moderate sensitive CYP1A2 substrates with Qelbree. If coadministered, dose reduction may be necessary.

Viloxazine is also a weak inhibitor of CYP2D6 substrates and therefore increases the exposure of CYP2D6 substrates when the two drugs are taken together. Patients must be monitored for adverse reactions when taking these two drugs. Adjusted dosages of CYP2D6 substrates may be necessary.

Viloxazine also weakly inhibits CYP3A4. Therefore, coadministration of Qelbree and CYP3A4 substrates can increase the exposure of CYP3A4 substrates. Patients must be monitored for adverse reactions. Dosage adjustments for CYP3A4 substrates may be necessary as clinically indicated.

All these factors should be considered before initiating treatment with Qelbree.

Please see full Prescribing Information, including Boxed Warning.

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

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