Qelbree Drug Information

Qelbree is indicated for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD) in adults and pediatric patients 6 years and older.

Important Considerations Prior to Initiating Treatment

Assess heart rate and blood pressure prior to initiating treatment with Qelbree, following increases in dosage, and periodically while on therapy. Prior to initiating treatment with Qelbree, screen patients for a personal or family history of suicide, bipolar disorder, and depression.

Recommended Dosage

Pediatric patients The recommended starting dosage for pediatric patients 6 to 11 years of age is 100 mg orally once daily. Dosage may be titrated in increments of 100 mg at weekly intervals to the maximum recommended dosage of 400 mg once daily, depending on response and tolerability. The recommended starting dosage for pediatric patients 12 to 17 years of age is 200 mg orally once daily.

After 1 week, dosage may be titrated by an increment of 200 mg to the maximum recommended dosage of 400 mg once daily, depending on response and tolerability. Adult patients The recommended starting dosage for adults is 200 mg orally once daily. Pharmacological treatment of ADHD may be needed for extended periods.

Periodically reevaluate the long-term use of Qelbree and adjust dosage as needed.

Administration Information Administer

Qelbree orally with or without food. Do not cut, crush, or chew the capsules. Swallow Qelbree capsules whole, or open the capsule and sprinkle the entire contents over a teaspoonful or tablespoonful of pudding or applesauce.

Consume the food mixture in its entirety, without chewing, within 15 minutes for pudding, or within 2 hours for applesauce; do not store for future use.

Dosage Recommendations in Patients with Renal Impairment

In patients with severe renal impairment (eGFR < 30 mL/min/1.73m 2 ), the recommended starting dosage is 100 mg once daily. Dosage may be titrated in weekly increments of 50 to 100 mg once daily, to a maximum recommended dosage of 200 mg once daily. No dosage adjustment is recommended in patients with mild to moderate (eGFR of 30 to 89 mL/min/1.73m 2 ) renal impairment.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of Qelbree has been evaluated in 189 adult patients (18 to 60 years of age) with ADHD exposed to one or more doses in a short-term (6 week), randomized, double-blind, placebo-controlled trial. A total of 277 adult patients with ADHD have been exposed to one or more doses of Qelbree.

Eighty-four adult patients were treated for at least 6 months, and 22 adult patients for at least 12 months. Adverse Reactions Leading to Discontinuation of Qelbree Treatment: Approximately 3% (n=27) of the 826 patients receiving Qelbree in clinical studies discontinued treatment due to an adverse reaction. The adverse reactions most commonly associated with discontinuation of Qelbree were somnolence (n=5), nausea (n=3), headache (n=2), irritability (n=2), tachycardia (n=2), fatigue (n=2), and decreased appetite (n=2).

Most Common Adverse Reactions (occurring at ≥5% and at least twice the placebo rate for any dose): somnolence, decreased appetite, fatigue, nausea, vomiting, insomnia, and irritability. Table 1 lists adverse reactions that occurred in at least 2% of patients treated with Qelbree and more frequently in Qelbree-treated patients than in placebo-treated patients. Table 1 data represents pooled data from pediatric patients 6 to 17 years of age who were enrolled in randomized, placebo-controlled trials of Qelbree.

Table 1. In a long-term open-label extension safety trial, 1097 patients received at least 1 dose of Qelbree. In the absence of a control group, it is unclear whether the weight change observed in the long-term open-label extension was attributable to the effect of Qelbree.

Adults The data described below reflect exposure to Qelbree in 189 adults with ADHD who participated in the flexible-dose, randomized, double-blind, placebo-controlled trial with doses ranging from 200 mg to 600 mg. The adverse reactions most commonly associated with discontinuation of Qelbree were fatigue (n=4), insomnia (n=3), constipation (n=3), and headache (n=2). Most Common Adverse Reactions (occurring at ≥5% and at least twice the placebo rate of Qelbree): insomnia, headache, somnolence, fatigue, nausea, decreased appetite, dry mouth, and constipation.

Table 2 represents data from adults with ADHD who were enrolled in a flexible-dose, randomized, placebo-controlled trial of Qelbree at doses of 200 mg to 600 mg. Table 2. Adverse Reactions Reported in ≥2% of Adults Treated with Qelbree and at a Rate Greater than Placebo-Treated Patients in a Flexible-Dose Placebo-Controlled ADHD Study 1 4

Drugs Having Clinically Important Interactions with Qelbree Table 3: Clinically Important Drug Interactions with Qelbree Monoamine Oxidase Inhibitors (MAOI) Clinical Impact Concomitant use of Qelbree with an MAOI may lead to a potentially life-threatening hypertensive crisis. Intervention Concomitant use of Qelbree with an MAOI or within 2 weeks after discontinuing an MAOI is contraindicated. Sensitive CYP1A2 Substrates or CYP1A2 Substrates with a Narrow Therapeutic Range Clinical Impact Viloxazine is a strong CYP1A2 inhibitor.

Concomitant use of viloxazine significantly increases the total exposure, but not peak exposure, of sensitive CYP1A2 substrates, which may increase the risk of adverse reactions associated with these CYP1A2 substrates. Intervention Coadministration with Qelbree is contraindicated. Moderate Sensitive CYP1A2 Substrate Clinical Impact Viloxazine is a strong CYP1A2 inhibitor.

Intervention Not recommended for coadministration with Qelbree. CYP2D6 Substrates Clinical Impact Viloxazine is a weak inhibitor of CYP2D6, and increases the exposure of CYP2D6 substrates when coadministered. Intervention Monitor patients for adverse reactions and adjust dosages of CYP2D6 substrates, as clinically indicated.

CYP3A4 Substrates Clinical Impact Viloxazine is a weak inhibitor of CYP3A4 which increases the exposure of CYP3A4 substrates when coadministered.

Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed Qelbree during pregnancy. Healthcare 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. Risk Summary Based on findings from animal reproduction studies, viloxazine may cause maternal harm when used during pregnancy.

Discontinue Qelbree when pregnancy is recognized unless the benefits of therapy outweigh the potential risk to the mother. Available data from case series with viloxazine use in pregnant women are insufficient to determine a drug-associated risk of major birth defects, miscarriage or adverse maternal outcomes. In animal reproduction studies, oral administration of viloxazine during the period of organogenesis caused fetal toxicities and delayed fetal development in the rat and maternal toxicities in the rabbit at doses approximately equal to the maximum recommended human dose (MRHD) of 600 mg in adults, based on mg/m 2.Oral administration of viloxazine to pregnant rats and mice during pregnancy and lactation caused maternal toxicities and deaths and fetal toxicities at doses equal to or less than the MRHD of 600 mg in adults, based on mg/m 2, respectively (see Data ).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.

Data Animal Data Viloxazine was administered orally to pregnant rats during the period of organogenesis at doses of 13, 33, and 82 mg/kg/day. The high dose is approximately equal to the MRHD of 600 mg in adults, based on mg/m 2. Viloxazine did not cause maternal toxicity up to the high dose.

Viloxazine at the high dose increased early and late resorption, delayed fetal development, and possibly caused low incidences of fetal malformations or anomalies (craniorachischisis, missing cervical vertebrae, and morphological changes associated with hydranencephaly). The NOAEL for fetal toxicity and malformation is 33 mg/kg/day, which is less than the MRHD of 600 mg in adults, based on mg/m 2. Viloxazine decreased maternal body weight, weight gain, or food consumption at doses ≥ 87 mg/kg/day but did not cause fetal toxicity at doses up to 130 mg/kg/day.

Viloxazine caused maternal toxicity of decreased body weight, weight gain, and food consumption at doses ≥ 87 mg/kg/day and maternal deaths near term at 217 mg/kg/day. At these maternally toxic doses, viloxazine caused lower live birth, decreased viability, and delayed growth and sexual maturation without affecting learning and memory in the offspring. The NOAEL for maternal and developmental toxicity is 43 mg/kg/day, which is less than the MRHD of 600 mg in adults, based on mg/m 2.

Viloxazine treatment at 82 mg/kg/day during the gestation period caused maternal deaths and decreased body weight in the offspring.

Pediatric Use The safety and effectiveness of Qelbree in pediatric patients 6 to 17 years of age with ADHD have been established based on randomized, placebo-controlled studies in pediatric patients. The safety and effectiveness of Qelbree have not been established in pediatric patients younger than 6 years old. Patients treated with Qelbree should be monitored for suicidal thoughts and behavior, and for changes in weight.

Viloxazine decreased body weight, weight gain, and food consumption in both sexes at 217 mg/kg/day. Sexual maturation, reproductive capacity, and learning and memory were not affected.

Qelbree is contraindicated in patients: receiving concomitant treatment with monoamine oxidase inhibitors (MAOI), or within 14 days following discontinuing an MAOI, because of an increased risk of hypertensive crisis. receiving concomitant administration of sensitive CYP1A2 substrates or CYP1A2 substrates with a narrow therapeutic range.

Human Experience The pre-market clinical trials with Qelbree do not provide information regarding symptoms of overdose. The most reported symptom was drowsiness. Impaired consciousness, diminished reflexes, and increased heart rate have also been reported.

Treatment and Management There is no specific antidote for Qelbree overdose. Administer symptomatic and supportive treatment as appropriate. In case of overdose, consult a Certified Poison Control Center (1-800-222-1222 or www.poison.org ).