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Qelbree Tapering Guide

viloxazine

NRIFDA 2021
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Boxed Warning

Increased risk of suicidal thoughts and behavior in pediatric and young adult patients. Monitor closely during initial therapy and dose changes.

Overview

Viloxazine ER (Qelbree) is a non-stimulant medication approved in 2021 for the treatment of attention-deficit/hyperactivity disorder (ADHD) in patients aged 6 and older. Originally developed as an antidepressant in Europe in the 1970s, it was reformulated and re-approved as an extended-release ADHD treatment.

Common Doses

100mg, 150mg, 200mg ER

Formulations

Extended-release capsules: 100mg, 150mg, 200mg

Pregnancy

Insufficient data — discuss with prescriber

Mechanism of Action

Selective norepinephrine reuptake inhibitor with serotonergic activity (5-HT2C receptor agonist, 5-HT2B receptor antagonist). The combined noradrenergic and serotonergic modulation is thought to underlie its efficacy in ADHD.

Taper Notes

Viloxazine ER is once-daily and generally tolerated on discontinuation, but rebound ADHD and mild dysphoria can emerge. Step down by available capsule strengths over 2–4 weeks. Strong CYP1A2 inhibition warrants review of co-medications during dose changes.

Maudsley Deprescribing Guidance

Limited published deprescribing data given recent approval (2021). Stepwise reductions by available capsule strengths over 2–4 weeks are reasonable for most patients; slow further in those with prior antidepressant withdrawal sensitivity.

Tapering Protocol

Evidence-based phased reduction schedule. Always taper under medical supervision.

PhaseDurationNotes
Initial reductions1-2 weeksStep down by 100 mg increments using available capsule strengths (200 → 100 mg).
Final reductions1-2 weeksHold at 100 mg for several days, then discontinue. Slow further in patients with prior antidepressant withdrawal sensitivity.

Withdrawal Timeline

Onset

1-3 days after dose reduction

📈Peak Severity

3-7 days

📉Resolution

Typically within 1-2 weeks

⚠️Protracted Risk

Rebound ADHD symptoms and irritability may persist 2-3 weeks; uncommon beyond that

Clinical Pearls

Practical considerations for clinicians supervising Qelbree tapers.

  • 1Viloxazine is too new for a robust evidence base on deprescribing; clinical experience and patient observation should be documented carefully during the taper.
  • 2Capsules may be opened and sprinkled on applesauce for patients with swallowing difficulty — do not chew or crush, which compromises ER kinetics.
  • 3Strong CYP1A2 inhibition by viloxazine elevates levels of co-administered CYP1A2 substrates (caffeine, theophylline, tizanidine, duloxetine); expect these to fall on discontinuation and dose-adjust accordingly.
  • 4Patients commonly report rebound ADHD symptoms as the predominant post-discontinuation issue; plan a successor strategy (alternative agent, behavioral support) before tapering.

Common Withdrawal Symptoms

rebound ADHD symptomsirritabilityfatiguelow moodinsomniaheadache

Interactions & Safety

Drug Interactions

  • MAOIs — contraindicated within 14 days
  • Sensitive CYP1A2 substrates (theophylline, tizanidine, duloxetine) — viloxazine is a strong CYP1A2 inhibitor; avoid or reduce dose
  • CYP2D6 substrates may have modest exposure increases

Food Interactions

  • May be taken with or without food
  • Capsules may be opened and sprinkled on applesauce; do not chew

Contraindications

  • Concurrent or recent (within 14 days) MAOI use
  • Concomitant use with sensitive CYP1A2 substrates with narrow therapeutic index
  • Known hypersensitivity to viloxazine

Toxicity

Suicidal ideation in pediatric and young adult patients. Increased blood pressure and heart rate. Mild somnolence and decreased appetite are common.

Pharmacokinetics

ADME Profile

Absorption

Tmax ~5 hours after oral ER administration. Bioavailability ~88%. High-fat meal reduces Cmax by ~9% and AUC by ~8%; can be taken with or without food.

Distribution

~80 L

Metabolism

Extensively metabolized via CYP2D6 (minor) and UGT1A9/UGT2B15 to inactive 5-hydroxy-viloxazine glucuronide.

Elimination

Renal (~90% as metabolites), <1% unchanged.

Protein Binding

~76–82%

Clearance

~13 L/h

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