Frequently Asked Questions

Viloxazine transfer into breast milk was low in this phase 4 lactation study of 15 healthy lactating women receiving viloxazine extended-release 600 mg daily for 3 days. At steady state on Day 3, the geometric mean breast milk exposure was AUCtau,milk 21.4 b5gh/mL, the geometric mean peak milk concentration was 1.41 b5g/mL, and the median time to peak milk concentration was 5.53 hours. The geometric mean breast milk-to-plasma exposure ratio was 0.338, indicating substantially lower exposure in milk than in maternal plasma.

Estimated infant exposure was low. The geometric mean estimated daily infant dose (EDID) for viloxazine was 0.134 mg/kg/day using an infant milk intake of 150 mL/kg/day and 0.178 mg/kg/day using 200 mL/kg/day for early infancy. The geometric mean daily infant dose based on measured milk output in the study was 0.511 mg/day, which was approximately 0.09% of the maternal 600 mg/day dose.

The weight-adjusted relative infant dose (RID) of viloxazine was 1.53% using an estimated infant milk intake of 150 mL/kg/day and 2.04% using 200 mL/kg/day for early infancy. The authors state that this is well below the less-than-10% RID threshold that lactation specialists and updated American College of Obstetricians and Gynecologists guidance generally consider acceptable for breastfeeding.

No. The study reports that concentrations of the major metabolite 5-HVLX-gluc in breast milk were negligible, with a relative infant dose of approximately 0.1%. The article also describes 5-HVLX-gluc as the major inactive metabolite of viloxazine.

Yes. Viloxazine extended-release was well tolerated in the women studied. Twelve of 15 participants (80%) reported 28 adverse events, all of which were mild and had resolved by the end of the study. No serious adverse events occurred, and no participant discontinued because of an adverse event.

• Most common adverse event: somnolence (n = 10)
• Other events reported in 2 or more participants: dizziness (n = 3), nausea (n = 3), breast tenderness (n = 3), headache (n = 2), and dry mouth (n = 2)

No clinically relevant changes were noted in vital signs, laboratory results, ECGs, physical examinations, or suicidality assessments.

No. The study did not collect infant safety or outcome data because infants did not participate. The study was designed to measure viloxazine and 5-HVLX-gluc concentrations in maternal breast milk and plasma and to estimate potential infant exposure rather than to assess adverse effects in breastfed infants.

This was a phase 4, open-label, single-arm lactation study in 15 healthy lactating women. Participants were 1845 years old, 12 weeks to 2 years postpartum, and received viloxazine extended-release 600 mg once daily for 3 consecutive days, which is the maximum recommended adult dose. Breast milk and plasma samples were collected predose on Days 1 and 3 and across 24 hours after the Day 3 dose to characterize steady-state pharmacokinetics and estimate infant exposure.

The main limitation is that the study estimated infant exposure but did not measure infant outcomes, because infants were not enrolled. The study also included only 15 healthy lactating women under controlled inpatient conditions, and milk production varied widely, with a median Day 3 milk volume of 543 mL and a range of 182 to 1,259 mL. The authors note that milk volumes collected in the inpatient setting may differ from real-world breastfeeding conditions.

In the comparisons cited by the article, viloxazine had a low relative infant dose of 1.53% to 2.04%. The article notes that reported RIDs for amphetamine have ranged from 2% to 13.8%, case reports for methylphenidate have reported RIDs less than 1%, and reported estimates for clonidine have ranged from 4.1% to 8.4%. The authors also cite a recently published observational study suggesting atomoxetine had an estimated RID less than 1%, although they note that study used unsupervised at-home sample collection.