Version May 2024
In clinical studies, higher rates of suicidal thoughts and behavior were reported in patients with attention-deficit hyperactivity disorder (ADHD) treated with viloxazine than in patients treated with placebo. Closely monitor all viloxazine-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors.
Attention-deficit/hyperactivity disorder: Oral: Initial: 200 mg once daily; may titrate by 200 mg increments at weekly intervals based on response and tolerability; maximum daily dose: 600 mg/day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function:
Mild to moderate impairment (eGFR 30 to 89 mL/minute/1.73 m 2 ): No dosage adjustment necessary.
Severe impairment (eGFR <30 mL/minute/1.73 m2): Oral: Initial dose: 100 mg once daily; may titrate by 50 to 100 mg increments at weekly intervals based on response and tolerability; maximum daily dose: 200 mg/day.
Mild to severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling.
(For additional information see "Viloxazine: Pediatric drug information")
Attention-deficit/hyperactivity disorder (ADHD):
Children 6 to 11 years: Oral: Initial: 100 mg once daily; may titrate in 100 mg increments at weekly intervals based on response and tolerability; maximum daily dose: 400 mg/day.
Children ≥12 years and Adolescents ≤17 years: Oral: Initial: 200 mg once daily; may increase to 400 mg after 1 week based on response and tolerability; maximum daily dose: 400 mg/day.
Adolescents ≥18 years: Oral: Initial: 200 mg once daily; may titrate in 200 mg increments at weekly intervals based on response and tolerability; maximum daily dose: 600 mg/day.
Altered kidney function: Children ≥6 years and Adolescents:
Mild to moderate impairment (eGFR 30 to 89 mL/minute/1.73 m2): No dosage adjustment necessary.
Severe impairment (eGFR <30 ml/minute/1.73 m2): Oral: Initial dose: 100 mg once daily; may titrate in 50 to 100 mg increments at weekly intervals based on response and tolerability; maximum daily dose: 200 mg/day.
Children ≥6 years and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling.
Viloxazine commonly causes increased heart rate and increased diastolic blood pressure. In children, adolescents, and adults, a ≥20 beat per minute increase in heart rate has been observed; tachycardia has also been reported. In adolescents and adults, a ≥15 mm Hg increase in diastolic blood pressure has been observed.
Mechanism: Has not been fully elucidated, but it has been suggested that viloxazine, due to its moderate inhibition of the reuptake of norepinephrine, may increase blood pressure by way of increased norepinephrine (Ref).
Risk factors:
• Preexisting cardiovascular disease (potential risk factor)
• Concomitant use with a monoamine oxidase inhibitor (MAOI), or administration within 14 days after MAOI discontinuation. Of note, concomitant use of MAOIs is contraindicated.
Suicidal ideation and suicidal tendencies have been observed. Other symptoms (eg, insomnia, irritability, depressed mood) may represent precursors to emerging suicidal ideation or behavior, although causality has not been established.
Mechanism: Unknown; although it has been suggested that the relationship between attention-deficit hyperactivity disorder (ADHD) and suicidal ideation (if one exists) may be related to underlying impulsivity and aggression and/or indirectly mediated by comorbidities such as depression rather than related to medication use (Ref).
Risk factors:
• Patients with ADHD, regardless of medication use, are often considered to be at higher risk for suicide compared to the general population and typically have an increased prevalence of many psychiatric comorbidities, such as depression, conduct disorder, substance abuse, which are associated with an increased risk of suicide, regardless of medication use (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in children, adolescents, and adults unless otherwise indicated.
>10%:
Cardiovascular: Increased diastolic blood pressure (13% to 25%) (table 1), increased heart rate (22% to 34%; tachycardia: 4% [adults]) (table 2)
|
Drug (Viloxazine) |
Placebo |
Population |
Dose |
Number of Patients (Viloxazine) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|
|
25% |
13% |
Adolescents |
400 mg daily |
205 |
201 |
≥15 mmHg increase |
|
13% |
9% |
Adults |
200 mg to 600 mg daily |
178 |
181 |
≥15 mmHg increase |
|
Drug (Viloxazine) |
Placebo |
Population |
Dose |
Number of Patients (Viloxazine) |
Number of Patients (Placebo) |
Comments |
|---|---|---|---|---|---|---|
|
31% |
15% |
Children |
200 mg daily |
268 |
262 |
≥20 beat per minute increase in heart rate at any time point in the clinical trial |
|
28% |
23% |
Children |
400 mg daily |
100 |
103 |
≥20 beat per minute increase in heart rate at any time point in the clinical trial |
|
22% |
9% |
Children |
100 mg daily |
154 |
159 |
≥20 beat per minute increase in heart rate at any time point in the clinical trial |
|
34% |
17% |
Adolescents |
400 mg daily |
205 |
201 |
≥20 beat per minute increase in heart rate at any time point in the clinical trial |
|
22% |
14% |
Adolescents |
200 mg daily |
99 |
104 |
≥20 beat per minute increase in heart rate at any time point in the clinical trial |
|
29% |
13% |
Adults |
200 mg to 600 mg daily |
178 |
181 |
≥20 beat per minute increase in heart rate at any time point in the clinical trial |
Gastrointestinal: Nausea (4% to 12%)
Nervous system: Drowsiness (including lethargy and sedated state; 6% to 19%), fatigue (4% to 12%), headache (including migraine; 10% to 17%), insomnia (children and adolescents: 2% to 5%; adults: 23%)
1% to 10%:
Gastrointestinal: Abdominal pain (children and adolescents: 6% to 7%), constipation (adults: 6%), decreased appetite (5% to 10%), gastroesophageal reflux disease (adults: 2%), vomiting (3% to 6%), xerostomia (adults: 10%)
Nervous system: Dizziness (adults: 4%), irritability (2% to 5%), suicidal ideation (≤2%)
Respiratory: Upper respiratory tract infection (including nasopharyngitis, pharyngitis, sinusitis; children and adolescents: 7% to 8%)
Miscellaneous: Fever (children and adolescents: 1% to 3%)
<1%: Nervous system: Suicidal tendencies
Frequency not defined: Endocrine & metabolic: Weight loss (adolescents)
Concomitant use with or within 14 days of monoamine oxidase inhibitors (MAOI); concomitant use of sensitive CYP1A2 substrates or CYP1A2 substrates with a narrow therapeutic range.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• CNS effects: May cause fatigue, lethargy, and sedation, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, driving, operating machinery).
Disease-related concerns:
• Mania/hypomania: Use with caution in patients with bipolar disorder; may induce mixed or manic episode. Patients should be screened for bipolar disorder and risk factors for developing a manic episode prior to treatment (eg, comorbid or history of depressive symptoms; family history of suicide, bipolar disorder, or depression).
Viloxazine can increase heart rate and blood pressure. Prior to treatment with medications for attention-deficit hyperactivity disorder (ADHD), the American Heart Association and the American Academy of Pediatrics recommend that all children and adolescents diagnosed with ADHD have a thorough cardiovascular assessment, including patient and family health histories, determination of all medications used (prescribed and over-the-counter), and a physical examination focused on cardiovascular disease risk factors. An ECG is not mandatory but is reasonable to consider prior to stimulant medication therapy. Prompt evaluation and appropriate referral and testing, if warranted, should occur if any cardiac symptoms present (AAP [Wolraich 2019]; AHA [Vetter 2008]).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Capsule Extended Release 24 Hour, Oral, as hydrochloride:
Qelbree: 100 mg, 150 mg, 200 mg [contains corn starch, fd&c blue #1 (brilliant blue), fd&c yellow #5 (tartrazine), fd&c yellow #6 (sunset yellow), quinoline yellow (d&c yellow #10)]
No
Capsule ER 24 Hour Therapy Pack (Qelbree Oral)
100 mg (per each): $14.24
150 mg (per each): $14.24
200 mg (per each): $14.24
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Oral: Administer without regard to food; do not cut, chew, or crush capsule. Swallow capsules whole or open and sprinkle entire contents on teaspoonful of applesauce or pudding; consume entire mixture without chewing within 15 minutes for pudding or 2 hours for applesauce; do not store for future use.
Oral: Administer without regard to food; do not cut, chew, or crush capsule. Swallow capsules whole or open and sprinkle entire contents on teaspoonful of pudding or applesauce; consume entire mixture without chewing within 15 minutes for pudding or within 2 hours for applesauce; do not store for future use.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Viloxazine may cause teratogenicity and reproductive toxicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/211964s003lbl.pdf#page=21, must be dispensed with this medication.
Attention-deficit hyperactivity disorder: Treatment of attention-deficit hyperactivity disorder (ADHD) in adults and pediatric patients ≥6 years of age.
Viloxazine may be confused with vilazodone.
Substrate of CYP2D6 (minor), UGT1A9, UGT2B15; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP1A2 (strong), CYP2D6 (weak), CYP3A4 (weak)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Agomelatine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Agomelatine. Risk X: Avoid combination
Alosetron: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Alosetron. Risk X: Avoid combination
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Anagrelide: CYP1A2 Inhibitors (Strong) may increase serum concentrations of the active metabolite(s) of Anagrelide. CYP1A2 Inhibitors (Strong) may increase the serum concentration of Anagrelide. Risk C: Monitor therapy
Asenapine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Asenapine. Risk C: Monitor therapy
Bendamustine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Bendamustine. Concentrations of the active metabolites of bendamustine may be decreased. Management: Consider alternatives to strong CYP1A2 inhibitors during therapy with bendamustine due to the potential for increased bendamustine plasma concentrations and increased bendamustine toxicity. Risk D: Consider therapy modification
Bromazepam: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Bromazepam. Risk C: Monitor therapy
Caffeine and Caffeine Containing Products: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Caffeine and Caffeine Containing Products. Risk C: Monitor therapy
CarBAMazepine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of CarBAMazepine. Risk C: Monitor therapy
ClomiPRAMINE: CYP1A2 Inhibitors (Strong) may increase the serum concentration of ClomiPRAMINE. Risk C: Monitor therapy
CloZAPine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of CloZAPine. Management: Reduce the dose of clozapine to one-third of the original dose when adding a strong CYP1A2 inhibitor and monitor patient response closely. Return to the original clozapine dose when the strong CYP1A2 inhibitor is discontinued. Risk D: Consider therapy modification
CycloSPORINE (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
DULoxetine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of DULoxetine. Risk X: Avoid combination
Fenfluramine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Fenfluramine. Management: Limit fenfluramine dose to 20 mg/day without concurrent stiripentol or to 17 mg/day with concomitant stiripentol and clobazam when used with a strong CYP1A2 inhibitor. Risk D: Consider therapy modification
Fezolinetant: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy
Fosphenytoin-Phenytoin: Viloxazine may increase the serum concentration of Fosphenytoin-Phenytoin. Risk C: Monitor therapy
Iobenguane Radiopharmaceutical Products: Selective Norepinephrine Reuptake Inhibitors may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid combination
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Risk D: Consider therapy modification
Levobupivacaine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Levobupivacaine. Risk C: Monitor therapy
Lidocaine (Systemic): CYP1A2 Inhibitors (Strong) may increase the serum concentration of Lidocaine (Systemic). Risk C: Monitor therapy
Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Risk D: Consider therapy modification
Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification
Melatonin: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Melatonin. Risk X: Avoid combination
Mexiletine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Mexiletine. Risk C: Monitor therapy
Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors: Viloxazine may enhance the hypertensive effect of Monoamine Oxidase Inhibitors. Risk X: Avoid combination
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
OLANZapine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of OLANZapine. Risk C: Monitor therapy
Ozanimod: May enhance the hypertensive effect of Selective Norepinephrine Reuptake Inhibitors. Risk C: Monitor therapy
Pentoxifylline: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pentoxifylline. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Pirfenidone: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pirfenidone. Management: Avoid concomitant use of pirfenidone and strong CYP1A2 inhibitors whenever possible. If combined, decrease the pirfenidone dose to 801 mg per day (267 mg three times daily) and monitor for increased pirfenidone toxicities. Risk D: Consider therapy modification
Pomalidomide: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Pomalidomide. Management: Avoid when possible. If coadministration is necessary, reduce the pomalidomide dose to 2 mg and monitor for increased pomalidomide effects/toxicities. Risk D: Consider therapy modification
Propranolol: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Propranolol. Management: Use a lower initial propranolol dose and be more cautious during propranolol dose titration when combined with strong CYP1A2 inhibitors. Risk D: Consider therapy modification
Ramelteon: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Ramelteon. Risk X: Avoid combination
Ramosetron: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Ramosetron. Risk C: Monitor therapy
Riluzole: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Riluzole. Risk C: Monitor therapy
Roflumilast-Containing Products: Viloxazine may increase serum concentrations of the active metabolite(s) of Roflumilast-Containing Products. Viloxazine may increase the serum concentration of Roflumilast-Containing Products. Risk C: Monitor therapy
ROPINIRole: CYP1A2 Inhibitors (Strong) may increase the serum concentration of ROPINIRole. Risk C: Monitor therapy
ROPivacaine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of ROPivacaine. Risk C: Monitor therapy
Simvastatin: CYP3A4 Inhibitors (Weak) may increase serum concentrations of the active metabolite(s) of Simvastatin. CYP3A4 Inhibitors (Weak) may increase the serum concentration of Simvastatin. Risk C: Monitor therapy
Sirolimus (Conventional): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Conventional). Risk C: Monitor therapy
Sirolimus (Protein Bound): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Sirolimus (Protein Bound). Management: Reduce the dose of protein bound sirolimus to 56 mg/m2 when used concomitantly with a weak CYP3A4 inhibitor. Risk D: Consider therapy modification
Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tasimelteon: CYP1A2 Inhibitors (Strong) may increase the serum concentration of Tasimelteon. Risk X: Avoid combination
Theophylline Derivatives: Viloxazine may increase the serum concentration of Theophylline Derivatives. Risk X: Avoid combination
Thioridazine: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Thioridazine. Management: Consider avoiding concomitant use of thioridazine and weak CYP2D6 inhibitors. If combined, monitor closely for QTc interval prolongation and arrhythmias. Some weak CYP2D6 inhibitors list use with thioridazine as a contraindication. Risk D: Consider therapy modification
TiZANidine: CYP1A2 Inhibitors (Strong) may increase the serum concentration of TiZANidine. Risk X: Avoid combination
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Risk D: Consider therapy modification
High fat meal may increase time to peak concentration by 2 hours.
Based on data from animal reproduction studies, in utero exposure to viloxazine may cause fetal harm. According to the manufacturer, consider discontinuing viloxazine if pregnancy occurs during treatment.
Data collection to monitor pregnancy and infant outcomes following exposure to viloxazine is ongoing. Health care providers are encouraged to enroll patients exposed to viloxazine during pregnancy in the National Pregnancy Registry for Psychiatric Medications (1-866-961-2388 or https://www.womensmentalhealth.org/preg ).
It is not known if viloxazine is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Prior to initiating viloxazine, conduct a thorough physical exam to assess for cardiac disease and assessment of medical history and family history of sudden death or ventricular arrhythmia; patients should receive further evaluation if findings suggest cardiac disease, such as ECG and echocardiogram; promptly conduct cardiac evaluation in patients who develop exertional chest pain, unexplained syncope, or any other symptoms of cardiac disease during treatment (AAP [Wolraich 2019]; AHA [Vetter 2008]).
Patients should be screened for a personal or family history of suicide, bipolar disorder, and depression prior to initiating viloxazine. Family members and caregivers need to observe pediatric patients daily, especially during the initial few months of therapy or at times of dose changes, for clinical worsening and emergence of suicidal ideation, depression, irritability, agitation, unusual changes in behavior, anxiety, panic attacks, insomnia, impulsivity, aggressiveness, hostility, akathisia, psychosis, hypomania, and mania. Appearance of such symptoms needs to be immediately reported to health care provider.
Monitor blood pressure and pulse (baseline, following dose increases, and periodically during treatment); monitor liver enzymes, serum creatinine, GFR. Periodically re-evaluate the long-term usefulness of viloxazine.
Viloxazine blocks the reuptake of norepinephrine. The exact mechanism underlying the beneficial effects of viloxazine for the treatment of attention-deficit hyperactivity disorder (ADHD) has not been fully elucidated. Some data (in vitro) suggest that it appears to inhibit 5-HT2B receptor and activate 5-HT2C receptor (Yu 2020).
Absorption: Administration with a high-fat meal (800 to 1,000 calories) may decrease absorption.
Protein binding: 76% to 82%.
Metabolism: Metabolized by CYP2D6, UGT1A9, and UGT2B15.
Bioavailability: ~88%.
Half-life elimination: 7.02 ± (4.74 hours).
Time to peak: ~5 hours (range 3 to 9 hours).
Excretion: Primarily renal. Urine: 90%; feces: <1%.
Pediatric: After administration of 200 to 400 mg doses, Cmax and AUC concentrations were ~130% to 250% and 60% to 140% higher in pediatric patients 6 to 11 years of age and 12 to 17 years of age, respectively, compared to adults.
Altered kidney function: Exposure increases can be expected in patients with renal impairment.
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