Methadone distribution and excretion into breast milk of clients in a methadone maintenance programme

Abstract

Aims Methadone is widely used in maintenance programs for opioid-dependent subjects. The aims of the study were to quantify the distribution and excretion of methadone in human milk during the early postnatal period and to investigate exposure of breast fed infants to the drug. Methods Blood and milk samples were obtained from 12 breast feeding women who were taking methadone in daily doses ranging from 20-80 mg (0.3-1.14 mg kg −1 ). Blood was also obtained from eight of their infants. Methadone concentration in these samples was quantified by h.p.l.c. The infants were observed for withdrawal symptoms.Results The mean (95% CI) milk/plasma ratio was 0.44 (0.24-0.64). Exposure of the infants, calculated assuming an average milk intake of 0.15 l kg −1 day −1 and a bioavailability of 100% was 17.4 (10.8-24) mg kg. The mean infant dose expressed as a percentage of the maternal dose was 2.79 (2.07-3.51)%. Methadone concentrations in seven infants were below the limit of detection for the h.p.l.c. assay procedure, while one infant had a plasma methadone concentration of 6.5 mg l −1 . Infant exposure to methadone via human milk was insufficient to prevent the development of a neonatal abstinence syndrome which was seen in seven (64%) infants. No adverse effects attributable to methadone in milk were seen. Conclusions We conclude that exposure of breast fed infants to methadone taken by their mothers is minimal and that women in methadone maintenance programs should not be discouraged from breast feeding because of this exposure.

O uso de opióides no tratamento da dor crônica não oncológica: o papel da metadona

“…Metadona não é removida pela hemodiálise. Também está presente no leite materno em concentrações que teoricamente não impedem a amamentação, porém cruza a barreira placentária em concentração que pode causar síndrome de abstinência no recém-nascido de mães que usam metadona 22,23,25,27,28,[31][32][33] . A metadona produz menos náusea, constipação e sedação do que a morfina.…”

“…Methadone is removed by hemodialysis. It is also present in maternal milk in concentrations which, in theory, do not prevent breast-feeding, but crosses blood-brain barrier in concentrations able to cause withdrawal syndrome in neonates of mothers under methadone 22,23,25,27,28,[31][32][33] . Methadone causes less nausea, constipation and sedation than morphine.…”

Concentrations of Methadone in Breast Milk and Plasma in the Immediate Perinatal Period

“…39 Another important factor is the lipophilic nature of methadone. 28 Similarly, fat content in human milk increases over the first 28 days of lactation, 40 which may explain the lower mean increase in methadone concentration in breast milk in the first 4 days as compared to breast milk of women with older infants. A comparison of average (preand postfeed) trough to average (preand postfeed) peak methadone concentrations in breast milk yielded increasing concentrations of methadone in breast milk: by 50.6% on day 2, 48.6% on day 3, and 68.8% on day 4.…”

“…Despite small sample sizes (numbers of participants ranging from 1 to 12) and widely variable sample collection protocols and analysis techniques, in general, the mean concentration of methadone in human milk has been reported as ranging from 50 to 270 ng/mL; methadone exposure for the infant ranges from 0.01 to 0.09 mg/day. [23][24][25][26][27][28][29] Postfeed breast milk methadone concentrations are approximately 33% higher than prefeed concentrations; this is most likely due to the increase in lipid content in breast milk that occurs during the course of a feeding. 28 This study evaluates methadone content in breast milk in the immediate postnatal period, its relationship to maternal dose and plasma concentrations, and the variability in breast milk methadone concentrations in foreand hindmilk.…”

Maternal and neonatal factors impacting response to methadone therapy in infants treated for neonatal abstinence syndrome

“…[4][5][6] The onset, duration and severity of NAS may be impacted by the types and degree of fetal drug exposure and by neonatal treatment strategies, [7][8][9][10][11][12][13] use of tobacco during pregnancy, 14 gestational age 15,16 and use of maternal breast milk (MBM) as the primary source of nutrition. [17][18][19][20] The interactions of these factors and the composite impact on response to pharmacologic therapy for NAS have not been adequately elucidated in a large cohort of infants.…”