Clinical Summary
Clinical Summary: Pharmacokinetics of Viloxazine ER (Viloxazine Extended-Release Capsules) in Breast Milk of Healthy Lactating Women
Postpartum women with attention-deficit/hyperactivity disorder increasingly need treatment decisions that account for breastfeeding, but lactation data for ADHD medications remain sparse. This study addresses a practical question clinicians face: how much viloxazine extended-release reaches breast milk at the maximum recommended adult dose, and what infant exposure that translates to.
Design
This was a phase 4, open-label, lactation study evaluating the pharmacokinetics of viloxazine and its 5-HVLX-gluc metabolite following multiple doses of viloxazine ER (600 mg) in 15 healthy lactating women
N
15 healthy lactating women
Population
healthy lactating women, 18–45 years of age, who were at least 12 weeks and not more than 2 years postpartum of a healthy-term newborn infant
Duration
The study duration was up to 32 days, consisting of a screening period (up to 28 days) and inpatient treatment period.
Key Findings
- At steady state on Day 3, geometric mean breast milk exposure to viloxazine was AUCtau,milk 21.4 µg•h/mL, with Cmax,milk 1.41 μcg/mL at a median Tmax of 5.53 h.
- Viloxazine exposure in breast milk was substantially lower than maternal plasma exposure, with a geometric mean breast milk to plasma ratio of 0.338; geometric mean plasma AUCtau,ss was 63.4 µg•h/mL and Cmax was 3.92 ug/mL.
- Estimated infant exposure to viloxazine was low: geometric mean DID was 0.511 mg/d (~0.09% of the administered 600 mg/d viloxazine ER dosage), EDID was 0.134 mg/kg/d based on 150 mL/kg/d infant milk intake and 0.178 mg/kg/d based on 200 mL/kg/d infant milk intake.
- Weight-adjusted RID for viloxazine was 1.53% based on 150 mL/kg/d infant milk intake and 2.04% based on 200 mL/kg/d infant milk intake.
- Viloxazine was well tolerated in lactating participants: 12 (80%) participants reported 28 AEs, all of which were mild in severity; no serious AEs were reported, no participants discontinued due to any AE, and the most commonly reported AE was somnolence (n = 10).
Clinical Bottom Line
Viloxazine extended-release 600 mg/d produced low transfer into breast milk, with relative infant dose of 1.53%–2.04%, well below the <10% threshold commonly accepted as compatible with breastfeeding. For lactating women who need viloxazine for attention-deficit/hyperactivity disorder, these data support low expected infant exposure through breast milk.
Practice Implications
- When counseling breastfeeding patients who need viloxazine extended-release, discuss that measured infant exposure estimates were 0.134 mg/kg/d to 0.178 mg/kg/d and the RID was 1.53% to 2.04% at the maximum recommended adult dose of 600 mg/d.
- If viloxazine extended-release is started postpartum, monitor the mother for tolerability, especially somnolence, which occurred in 10 participants; dizziness, nausea, and breast tenderness each occurred in 3 participants.
- Use these lactation data as part of a risk-benefit discussion rather than as infant safety outcome data, because infants did not participate in the study and no direct infant adverse effect data were collected.
- Remember that milk production varied widely in the study, with a median total milk volume of 543 mL and a range of 182–1,259 mL on Day 3, so individual infant exposure can differ even when average RID estimates are low.
