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Viloxazine Hydrochloride

FDA Drug Information • Also known as: Qelbree

Brand Names
Qelbree
Dosage Form
POWDER
Product Type
BULK INGREDIENT

⚠ Boxed Warning (Black Box)

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS In clinical studies, higher rates of suicidal thoughts and behavior were reported in patients with ADHD treated with Qelbree than in patients treated with placebo . Closely monitor all Qelbree-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors [see Warnings and Precautions (5.1) ] . WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. In clinical trials, higher rates of suicidal thoughts and behavior were reported in patients treated with Qelbree than in patients treated with placebo. Closely monitor for worsening and emergence of suicidal thoughts and behaviors ( 5.1 ).

Description

11 DESCRIPTION Qelbree contains viloxazine, a selective norepinephrine reuptake inhibitor, in the form of viloxazine hydrochloride which is (±)-2-[(2-ethoxyphenoxy)methyl]morpholine hydrochloride. The molecular formula is C 13 H 20 NO 3 Cl and its molecular weight is 273.8 (HCl salt) with the following structural formula: Viloxazine hydrochloride is a white to off-white powder. Viloxazine hydrochloride is soluble in water, 0.1N HCl and aqueous solutions of pH 9.5 and lower. Viloxazine hydrochloride is sparingly soluble in methanol, very slightly soluble in acetonitrile, acetic acid and isopropyl alcohol, and practically insoluble in ethyl acetate. Qelbree extended-release capsules are intended for oral administration. Each extended-release capsule contains 100 mg, 150 mg, and 200 mg of viloxazine free base equivalent to 115mg, 173mg, and 231mg, respectively, of viloxazine hydrochloride salt. The inactive ingredients are: Ammonium hydroxide, black iron oxide, butyl alcohol, corn starch, ethylcellulose, FD&C Blue #1, FD&C Red #28, FD&C Yellow #5, FD&C Yellow #6, FD&C Yellow #10, gelatin, hypromellose, isopropyl alcohol, lactose monohydrate, medium chain triglycerides, oleic acid, polyethylene glycol, potassium hydroxide, propylene glycol, shellac, strong ammonia solution, sucrose, talc, triacetin, titanium dioxide. Chemical Structure

What Is Viloxazine Hydrochloride Used For?

1 INDICATIONS AND USAGE Qelbree is indicated for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD) in adults and pediatric patients 6 years and older. Qelbree is a selective norepinephrine reuptake inhibitor indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in adults and pediatric patients 6 years and older ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Pediatric patients 6 to 11 years of age : Recommended starting dosage is 100 mg once daily. May titrate in increments of 100 mg weekly to the maximum recommended dosage of 400 mg once daily ( 2.2 ) Pediatric patients 12 to 17 years of age : Recommended starting dosage is 200 mg once daily. May titrate after 1 week, by an increment of 200mg, to the maximum recommended dosage of 400 mg once daily ( 2.2 ) Adult patients : Recommended starting dosage is 200 mg once daily. May titrate in increments of 200 mg weekly, to maximum recommended dosage of 600 mg once daily ( 2.2 ) Capsules may be swallowed whole or opened and the entire contents sprinkled onto applesauce or pudding ( 2.3 ) Severe Renal Impairment : Initial dosage is 100 mg once daily. Titrate in weekly increments of 50 mg to 100 mg to a maximum recommended dosage of 200 mg once daily ( 2.4 , 8.6 ) 2.1 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 [see Warnings and Precautions (5.2) ] . Prior to initiating treatment with Qelbree, screen patients for a personal or family history of suicide, bipolar disorder, and depression [see Warnings and Precautions (5.3) ]. 2.2 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. Dosage may be titrated in increments of 200 mg weekly to the maximum recommended dosage of 600 mg once daily, depending on response and tolerability. Pharmacological treatment of ADHD may be needed for extended periods. Periodically reevaluate the long-term use of Qelbree and adjust dosage as needed. 2.3 Administration Information Administer Qelbree orally with or without food [see Clinical Pharmacology (12.3) ] . 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. 2.4 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious adverse reactions are described in other sections of the labeling: Suicidal Thoughts and Behaviors [see Warnings and Precautions (5.1) ] Blood Pressure and Heart Rate Increases [see Warnings and Precautions (5.2) ] Activation of Mania or Hypomania [see Warnings and Precautions (5.3) ] Somnolence and Fatigue [see Warnings and Precautions (5.4) ] Most commonly observed adverse reactions (≥5% and at least twice the rate of placebo) were: Pediatric patients 6 to 17 years of age : somnolence, decreased appetite, fatigue, nausea, vomiting, insomnia, and irritability ( 6.1 ) Adult patients : insomnia, headache, somnolence, fatigue, nausea, decreased appetite, dry mouth and constipation ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Supernus Pharmaceuticals at 1-866-398-0833 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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 1118 pediatric patients (6 to 17 years of age) with ADHD exposed to one or more doses in short-term (6 to 8 week), randomized, double-blind, placebo-controlled trials. A total of 682 pediatric patients 6 to 17 years of age were treated for at least 6 months, and 347 pediatric patients 6 to 17 years of age for at least 12 months with Qelbree. 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. Pediatric Patients (6 to 17 Years of Age) The data described below reflect exposure to Qelbree in 826 pediatric patients (6 to 17 years) who participated in randomized, double-blind, placebo-controlled trials with doses ranging from 100 mg to 400 mg. The population (N=826) was 65% male, 35% female, 54% White, 41% Black, 4% multiracial, and 1% other races. 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. Adverse Reactions Reported in ≥2% of Pediatric Patients (6 to 17 Years of Age) Treated with Qelbree and at a Rate Greater than Placebo-Treated Patients in Placebo-Controlled ADHD Studies Qelbree Body System Adverse Reaction Placebo N=463 (%) 100mg N=154 (%) 200mg N=367 (%) 400mg N=305 (%) All Qelbree N=826 (%) Nervous system disorders Somnolence The following terms were combined: Somnolence: somnolence, lethargy, sedation Headache: headache, migraine, migraine with aura, tension headache Upper respiratory tract infection: nasopharyngitis, pharyngitis, sinusitis, upper respiratory tract infection, viral sinusitis, viral upper respiratory tract infection Abdominal pain: abdominal discomfort, abdominal pain, abdominal pain...

Drug Interactions

7 DRUG INTERACTIONS Moderate sensitive CYP1A2 substrates : Not recommended for coadministration with Qelbree. Dose reduction may be warranted ( 7.1 ) 7.1 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 [see Contraindications (4) ] . 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 [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions associated with these CYP1A2 substrates. Intervention Coadministration with Qelbree is contraindicated [see Contraindications (4) ] . Moderate Sensitive CYP1A2 Substrate Clinical Impact Viloxazine is a strong CYP1A2 inhibitor. Concomitant use of viloxazine significantly increases the total, but not peak, exposure of sensitive CYP1A2 substrates [see Clinical Pharmacology (12.3) ] , which may increase the risk of adverse reactions associated with these CYP1A2 substrates. Intervention Not recommended for coadministration with Qelbree. Dose reduction may be warranted if coadministered. CYP2D6 Substrates Clinical Impact Viloxazine is a weak inhibitor of CYP2D6, and increases the exposure of CYP2D6 substrates when coadministered [see Clinical Pharmacology (12.3) ] . 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 [see Clinical Pharmacology (12.3) ]. Intervention Monitor patients for adverse reactions and adjust dosages of CYP3A4 substrates, as clinically indicated.

Contraindications

4 CONTRAINDICATIONS 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 [see Drug Interactions (7.1) ] . receiving concomitant administration of sensitive CYP1A2 substrates or CYP1A2 substrates with a narrow therapeutic range [see Drug Interactions (7.1) ]. Concomitant administration of monoamine oxidase inhibitors (MAOI), or dosing within 14 days after discontinuing an MAOI ( 4 , 7.1 ) Concomitant administration of sensitive CYP1A2 substrates or CYP1A2 substrates with a narrow therapeutic range ( 4 , 7.1 )

Pregnancy and Breastfeeding

8.1 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 2 to 4% and 15 to 20%, 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...

Overdosage

10 OVERDOSAGE Human Experience The pre-market clinical trials with Qelbree do not provide information regarding symptoms of overdose. Literature reports from post marketing experience with immediate-release viloxazine include cases of overdosage from 1000 mg to 6500 mg (1.7 to 10.8 times the maximum recommended daily dose). 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 ).

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Qelbree (viloxazine extended-release capsules) are available in the following strengths and colors: 100mg (yellow capsule printed with "SPN" on capsule cap and "100" on capsule body with edible black ink). Bottles of 100 capsules………………..…….NDC 17772-131-01 Bottles of 90 capsules……………………….NDC 17772-131-90 Bottles of 60 capsules……………………….NDC 17772-131-60 Bottles of 30 capsules……………………….NDC 17772-131-30 150mg (lavender capsule printed with "SPN" on capsule cap and "150" on capsule body with edible black ink). Bottles of 100 capsules………………………NDC 17772-132-01 Bottles of 90 capsules………………………..NDC 17772-132-90 Bottles of 60 capsules………………………..NDC 17772-132-60 Bottles of 30 capsules………………………..NDC 17772-132-30 200mg (light green capsule printed with "SPN" on capsule cap and "200" on capsule body with edible black ink). Bottles of 100 capsules…………………..…NDC 17772-133-01 Bottles of 90 capsules………………………NDC 17772-133-90 Bottles of 60 capsules………………………NDC 17772-133-60 Bottles of 30 capsules………………………NDC 17772-133-30 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F).

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.