Viloxazine Does Not Alter Amphetamine Blood Levels
Viloxazine does not alter the blood levels of amphetamines in patients with ADHD or depression, and the combination can be safely used together with appropriate monitoring. 1, 2
Pharmacokinetic Evidence
The FDA drug label for viloxazine (Qelbree) does not list amphetamines or other psychostimulants as having clinically significant drug interactions with viloxazine. 1 The drug interaction section specifically addresses:
- CYP1A2 substrates (viloxazine is a strong CYP1A2 inhibitor) 1
- CYP2D6 substrates (viloxazine is a weak CYP2D6 inhibitor) 1
- CYP3A4 substrates (viloxazine is a weak CYP3A4 inhibitor) 1
Amphetamines are not metabolized through these pathways that viloxazine affects, meaning there is no pharmacokinetic interaction between the two medications. 1
Clinical Trial Evidence Supporting Combination Use
A recent 2025 phase 4 open-label trial directly evaluated the safety and efficacy of viloxazine extended-release administered concomitantly with psychostimulants (including amphetamines) in 56 children and adolescents with ADHD. 2 Key findings include:
- Combination therapy was well tolerated, with only 3.6% of participants withdrawing due to adverse events 2
- No drug-drug interactions were reported between viloxazine and psychostimulants 2
- ADHD symptoms improved significantly when viloxazine was added to inadequate psychostimulant response, with mean ADHD-RS-5 scores improving by 18.2 points at week 8 (p < 0.0001) 2
- 85.7% of participants completed the full 8-week study, demonstrating good tolerability of the combination 2
Safety Monitoring Recommendations
When combining viloxazine with amphetamines, monitor for:
- Additive cardiovascular effects: Both medications can affect blood pressure and heart rate, though viloxazine has less pronounced cardiovascular effects than stimulants 3
- Common side effects: Headache (17.9%), decreased appetite (12.5%), and upper respiratory tract infection (10.7%) were most frequently reported in the combination therapy trial 2
- Sleep disturbances and morning/evening ADHD behaviors: The combination trial showed improvement in these parameters regardless of whether viloxazine was dosed in the morning or evening 2
Contraindications to Note
The only absolute contraindication relevant to this combination is concurrent use with MAO inhibitors, which applies to both viloxazine and amphetamines separately. 1 Viloxazine must not be used with an MAOI or within 2 weeks after discontinuing an MAOI due to risk of potentially life-threatening hypertensive crisis. 1
Clinical Context
Viloxazine is often added to psychostimulant therapy when stimulant monotherapy provides inadequate response, which is a common clinical scenario. 2 The mechanism of action differs between the two medications—amphetamines increase dopamine and norepinephrine release, while viloxazine selectively inhibits norepinephrine reuptake—allowing for complementary therapeutic effects without pharmacokinetic interference. 1, 4