Viloxazine

Breast Feeding; Lactation; Milk, Human; Adrenergic Uptake Inhibitors

Pharmaceuticals

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

In four placebo-controlled trials of viloxazine in children with ADHD, minor serum aminotransferase elevations occurred in 5% to 10% of recipients but were more than 2 times the upper limit of normal in less than 1%. In the preregistration trials, there were no instances of clinically apparent liver injury or serum aminotransferase elevations with jaundice attributable to viloxazine. Since its approval as therapy for depression in Europe more than 30 years ago and as therapy of ADHD in the United States in 2021, there have been no publications describing clinically apparent liver injury due to viloxazine. Furthermore, summaries of the efficacy and safety of viloxazine do not mention hepatic adverse events. Nevertheless, long term clinical experience with viloxazine in children is limited, and other SNRIs (such as atomoxetine) have been linked to rare instances of clinically apparent liver injury.

Viloxazine is considered a relatively safe drug. A case study demonstrated that overdoses of viloxazine ranging from 100 mg to 4 g resulted in fewer severe adverse effects, particularly related to arrhythmias and QT prolongations, than tricyclic antidepressants or MAO inhibitor overdoses. The most significant adverse effect observed in viloxazine overdose was convulsing seizures, with one case reporting extrapyramidal symptoms, loss of consciousness, and CNS depression.

N - Nervous system

QN - Nervous system

Viloxazine is a serotonin-norepinephrine modulating agent that has been used as a treatment for depression and Attention Deficit Hyperactivity Disorder (ADHD). Although it is not a stimulant agent, viloxazine produces amphetamine-like CNS stimulant effects without a risk for drug abuse or dependence. Viloxazine does not produce sedative anticholinergic or adrenergic effects.

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in children characterized by inattention and hyperactivity. In current literature, the pathophysiology of ADHD is understood to involve the imbalance of neurotransmitters, especially dopamine (DA) and norepinephrine (NE). The mechanism of action of viloxazine has not been fully elucidated; however, viloxazine is believed to work by modulating the monoaminergic neurotransmitter systems. Viloxazine is a selective and moderate norepinephrine reuptake inhibitor that binds to the norepinephrine transporter and inhibits the reuptake of norepinephrine. It thereby increases extracellular norepinephrine levels across several brain regions. Viloxazine potentiates serotonergic effects: it was shown to enhance neuronal sensitivity to serotonin and increase serotonin levels in the brain. _In vitro_, viloxazine is an antagonist at 5-HT_2B receptors and an agonist 5-HT_2C receptors. 5-HT_2B receptors expressed on GABAergic interneurons are involved in tonic inhibitory control of serotonin neurons that innervate the medial prefrontal context; thus, antagonism of 5-HT_2B receptors may result in disinhibition and enhanced serotonin release in the brain region. There is conflicting evidence in the literature that viloxazine increases dopamine levels in the brain via direct or indirect effects. For example, the norepinephrine transporter is also involved in the reuptake of dopamine in the prefrontal cortex and stimulation of 5-HT_2C receptors facilitates DA release and enhances dopaminergic transmission in the brain. As dopamine dysregulation in the prefrontal cortex and amygdala is implicated in ADHD pathophysiology, the impact of viloxazine on dopamine levels may contribute to its mechanism of action. However, there is insufficient evidence to conclude this. Viloxazine has a negligible impact on dopamine in the nucleus accumbens and is not associated with an abuse risk.