Pharmacokinetics of Viloxazine Extended-Release Capsules in Breastmilk of Healthy Lactating Women
Background:
Despite increasing ADHD treatment in women, ADHD medication safety in pregnancy and lactation is not well documented. Viloxazine ER is the first ADHD medication studied under the new FDA Guidance on Clinical Lactation Studies. We report pharmacokinetics of viloxazine and its major metabolite (5-HVLX-gluc) in breastmilk and estimate infant exposure.
Methods:
Healthy lactating women (Nf15; median weight 68.8kg) received viloxazine ER 600mg/day (maximum recommended adult dosage) for 3 days (NCT06259331). Calculated measures of potential infant exposure included: Daily Infant Dosage (DID): total daily drug present in breastmilk with potential to be consumed by infant; Estimated Daily Infant Dosage (EDID): milk-plasma ratio [ML/PL] x average steady-state maternal plasma concentration x estimated infant milk intake/kg/day; and Relative Infant Dose (RID): EDID/weight-adjusted maternal daily dosage x 100.
Results:
Viloxazine did not appear to affect daily milk production. At steady-state, median Tmax in breastmilk was 5.5h. Mean DID of viloxazine and 5-HVLX-gluc were 0.599±0.322 and 0.0393±0.0175 mg/day (~0.1% and 0.007% of the 600mg/day viloxazine ER dose). Mean viloxazine EDID-150 (milk intake of 150 mL/kg/day) was 0.141±0.0519 mg/kg/day; mean viloxazine EDID-200 (using early infancy milk intake of 200 mL/kg/day) was 0.189±0.0692 mg/kg/day. Mean RID-150 and RID-200 of viloxazine were 1.58±0.424% and 2.11±0.565%, respectively. Mild treatment-related AEs were reported by 80% of participants, most commonly somnolence (67%), nausea (20%), and dizziness (20%). No participants discontinued.
Conclusions:
The estimated daily viloxazine exposure in breast-fed-infants is ~2% of weight-adjusted maternal daily dose. Lactation specialists consider medications with RID < 10% generally acceptable for breast-feeding.
