Transfer of Buprenorphine Into Breast Milk and Calculation of Infant Drug Dose

Abstract

Little is known about the safety of buprenorphine (BUP) in breastfeeding. The aim of this work was to investigate the transfer of buprenorphine and its main active metabolite, norbuprenorphine (n-BUP), into human milk and to determine the drug dose and effects in exposed infants. Seven lactating women, who were maintained on BUP treatment because of previous opiate addiction, were studied in an open observational study. All mothers had a strong wish to breastfeed their newborn infants. Buprenorphine samples for analysis were collected from the urine of 6 infants together with breast milk, blood, and urine from their mothers during a 24-hour period in the week after birth. One mother-infant pair was studied at 9 months of age. Buprenorphine and n-BUP were analyzed by a liquid chromatography/mass spectrometry method suitable for handling different matrices. Buprenorphine and n-BUP were found in low levels in the infants' urine. Breastfed infants were exposed to a calculated BUP dose per kg bodyweight less than 1%, with an average milk/plasma area under the curve of 1.7 (range, 1.1-2.8) for BUP and 0.7 (range, 0.4-1.2) for n-BUP. These data support the use of BUP during breastfeeding. However, the authors recommend that infants be monitored closely.

Observational Study of Buprenorphine Treatment of Opioid-Dependent Pregnant Women in a Family Medicine Residency: Reports on Maternal and Infant Outcomes

“…27 These recommendations seem to be supported by the results of a small study of 7 breastfeeding women maintained on buprenorphine, which showed that the relative dose per kilogram of body weight in the infant was Ͻ1% of the dose per body weight of the mother. 28 Similarly, the range of nor-buprenorphine (a metabolite of buprenorphine) in the mothers' urine ranged from 175 to 933 nmol/L compared with 1 to 4.8 nmol/L in the infants. 28 The infants in this case series were at least if not more likely to be breastfed (70% at hospital discharge and 50% at 6-to 8-week follow-up visit) than those in previous studies (50%, 45%, and 21% as measured during hospitalization).…”

“…28 Similarly, the range of nor-buprenorphine (a metabolite of buprenorphine) in the mothers' urine ranged from 175 to 933 nmol/L compared with 1 to 4.8 nmol/L in the infants. 28 The infants in this case series were at least if not more likely to be breastfed (70% at hospital discharge and 50% at 6-to 8-week follow-up visit) than those in previous studies (50%, 45%, and 21% as measured during hospitalization). 14,18,29 In addition, other authors have reported that, of the minority of opioid-dependent women who elected to breastfeed, more than half stopped within 1 week, whereas a much larger percentage of the women in this case series elected to breastfeed until at least their 6-to 8-week follow-up visit.…”

Opioid Use in Pregnancy, Neonatal Abstinence Syndrome, and Childhood Outcomes

“…(99) The American Academy of Pediatrics recommends breastfeeding for women taking methadone or buprenorphine, regardless of maternal dose as very little methadone (1–3% of the maternal weigh-adjusted dose) and minimal buprenorphine (<1% of the maternal weight-adjusted dose) is present in breastmilk. (99–101, 106–108)…”

The Transfer of Drugs and Therapeutics Into Human Breast Milk: An Update on Selected Topics

“…57 Infant exposure appears to be up to 2.4% of the maternal weight-adjusted dose. 55,56,58 However, buprenorphine can be abused, and although the significance in humans is unknown, labeling for buprenorphine and buprenorphine/naloxone combinations states that use is not advised by lactating women, because animal lactation studies have shown decreased milk production and viability of the offspring. FDA labeling also advises caution for use of naltrexone in nursing infants of opioiddependent women.…”