Estimated Infant Exposure to Enantiomer-Specific Methadone Levels in Breastmilk

Abstract

Background and Objectives: Breastfeeding, a public health priority, improves outcomes for infants. Methadone is dispensed as a racemic mixture; R-methadone is the active enantiomer. Pharmacologic data for R-methadone in breastmilk could improve risk-benefit decision-making for treatment of lactating women. This study estimated infant exposure to R-and S-methadone via breastmilk by theoretic infant dose (TID) and relative infant dose (RID) and reported the milk-to-maternal plasma (M/P) ratio. Methods: Women treated with methadone doses of 40-200 mg/day (mean, 102 mg/day) provided concomitantly collected plasma and breastmilk samples 1-6 days after delivery. Most (16 of 20) samples were taken at the time of peak maternal plasma levels; thus infant exposure estimates are for maximum possible exposure. Concentrations of R-and S-methadone were measured in maternal plasma and breastmilk; M/P ratio, TID, and RID were calculated for each enantiomer and total methadone. Results: The 20 participants were 18-38 years old and publicly insured; a quarter did not complete high school, and only one was not white. R-Methadone concentration was 1.3-3.0 times that of S-methadone in all breastmilk samples. The mean (SD) R-, S-, and total methadone M/P ratios were 0.52 (0.28), 0.28 (0.15), and 0.40 (0.21), respectively. Mean (range) R-, S-, and total methadone TID were 0.02 mg/kg/day (0.004-0.099), 0.013 mg/kg/ day (0.002-0.071), and 0.033 mg/kg/day (0.006-0.170), respectively. Mean (range) RID of R-, S-, and total methadone were 2.7% (0.7-10.1%), 1.6% (0.3-7.2%), and 2.1% (0.52-8.8%), respectively. Conclusions: R-Methadone is found in higher concentrations than S-methadone in breastmilk. Even at high methadone doses, breastmilk methadone concentrations were relatively low and support American Academy of Pediatrics recommendations that dose should not be a factor in determining whether women on methadone breastfeed.

Neonatal Abstinence Syndrome

“…161,162 Subsequent to these recommendations, some improvements in breastfeeding practices have been noted. 127,163 The amount of methadone or buprenorphine in breast milk is too small to treat NAS, and the sudden discontinuation of breast milk is not associated with the worsening of NAS 164,165 ; however, gradual weaning from breastfeeding is advised. 166 Because of the high concentrations of hydrocodone and oxycodone in breast milk as well as the reduced clearance of some of these medications in some neonates, mothers taking these prescription opioids should be alerted to the problem of sedation among infants when breastfeeding.…”

Can kangaroo care help newborns with neonatal abstinence syndrome? Case report

“…methadone, buprenorphine, etc) to which the mother has been exposed and which may calm the newborn, too. Though the amount of opiate being transferred in breast milk is very slight, [43] the possibility of breast milk opiate reducing severity of NAS has been suggested by studies showing that breast milk-fed infants have lower NAS scores than formula-fed infants. [44] …”

Breastfeeding and Methadone Therapy: The Maternal Experience

“…21 While pregnant and postpartum women should be counseled in ways to reduce or quit smoking due to the association of tobacco with decreased breast milk volume and adverse fetal and neonatal outcomes (e.g., sudden infant death syndrome), they should also understand that the potential health benefits of breastfeeding likely outweigh the risks of tobacco products passing into breast milk. 9,22 Clinicians should also seek to dispel women's fears that infants can "OD" on methadone-emphasizing the proportionately small transfer of methadone through milk, 10 the poor correlation between maternal methadone dose and severity of NAS symptoms, 5,[11][12][13][23][24][25] and the mechanisms through which breastfeeding can potentially protect against NAS development (e.g., skin-to-skin contact; small transfer of methadone through breast milk). [26][27][28] It is equally imperative that clinicians communicate to women the infant health risks of unprotected sex (and HIV contraction), alcohol use, and illicit drugs while breastfeeding, as these substances pass readily into breast milk.…”

“…8,9 Recent work has suggested that transfer of methadone through breast milk is small (1-3% of the maternal weight-adjusted dose; equating to significantly less than the dose typically given to infants to treat NAS) 10 and remains relatively negligible even at higher maternal doses. 5,[11][12][13] Still, breastfeeding initiation among women in methadone treatment programs (who are adherent to treatment and with no contraindications to breastfeeding) is low, with reports ranging from ~24-46%, 14,15 compared to the national initiation rate of 77%. 16 Women taking methadone may face additional barriers to successful breastfeeding over and above that experienced in the general population.…”