Assessment of Infant Dose Through Milk in a Lactating Woman Taking Amisulpride and Desvenlafaxine for Treatment-Resistant Depression

Abstract

This study presents the case of a 35-year-old breastfeeding mother who delivered her fourth child 5 months previously and was prescribed 100 mg amisulpride twice daily and 250 mg desvenlafaxine in the morning for treatment-resistant depression. Arriving at this regimen took approximately 2 months postbirth. Because she was keen to continue breastfeeding her infant, and published data on the use of amisulpride and desvenlafaxine were very limited, the clinical team sought assistance from the therapeutic drug monitoring laboratory to quantify infant dose-exposure to guide consideration of continuing breastfeeding. A sampling schedule for milk and plasma from mother and plasma from her infant was agreed and drug concentrations were measured by high-performance liquid chromatography. Absolute (theoretic) infant dose (μg/kg/d) was calculated as the product of the average concentration in milk and an assumed milk intake of 0.15 L/kg/day (294 mg/kg/day for desvenlafaxine and 183 mg/kg/day for amisulpride), and relative infant dose was estimated as absolute infant dose expressed as a percentage of the maternal dose in μg/kg/day (7.8% for desvenlafaxine and 6.1% for amisulpride). Consistent with the infant being partially breastfed, the ratio of drug in the infant's plasma to that in mother's plasma was lower at 1.7% for desvenlafaxine and 3.9% for amisulpride. A pediatric assessment of the infant found achievement of expected developmental progress for age and no detectable drug-related adverse effects. Assessing the safety of breastfeeding was difficult because it involved simultaneous use of two drugs for which there was limited previous experience. However, after discussion of the infant dose-exposure data and lack of adverse effects, the mother elected to continue partial breastfeeding for the next few months. The clinical team plans a reassessment of the infant's progress in 3 months.

Breastfed Infants Exposed to Combined Antipsychotics: Two Case Reports

“…1 The available 2 case reports did not suggest any adverse events in the breastfed infants exposed to amisulpride at 250-400 mg/d, despite high RID values of 10.7%-19.5%. 5,6 Although it may be expected adverse events, especially extrapyramidal symptoms in an infant exposed to haloperidol + amisulpride, this expectation did not occur in the current case. Usage at low to moderate doses of these antipsychotics may explain this consequence.…”

“…1,3 Reports regarding haloperidol and amisulpride have been less frequently published in the literature. 1,[4][5][6] Almost all of the available reports examining effects of antipsychotics on breastfed infants included usage of only 1 antipsychotic drug, although some authors reported results in the infants exposed to a combination between antidepressants, benzodiazepines, and antipsychotics. [5][6][7] It is unclear whether combined antipsychotics have negative effects on the breastfed infants.…”

The Direct Factor Xa Inhibitor Rivaroxaban Passes Into Human Breast Milk

“…Results must be interpreted with caution as the relative infant dose only estimates the infant's exposure to the drug in milk and does not take the bioavailability of rivaroxaban in the infant into consideration. 7 Moreover, different developmental stages of breastfed infants may influence a drug's pharmacokinetics and thus the exposure to an ingested drug, 8 and potential age-related differences in the pharmacodynamic effects of rivaroxaban in neonates need to be considered. 9 To characterize the infant's exposure precisely, an assay of a drug in blood or urine samples of the breastfed infant would be required.…”

Amisulpride: A New Drug for Management of Postoperative Nausea and Vomiting

“…8 Based on case reports involving the oral formulation, amisulpride is excreted in breast milk. 8,[21][22][23] In women receiving 200 to 400 mg daily, exposure to the infant was estimated at 5% to 11% of the dose, and no adverse or developmental effects were discovered. According to the manufacturer, breastfeeding can be interrupted, and breast milk can be discarded 48 hours after infusion to prevent exposure to the infant.…”