Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Drugline nr 19104

Publicerat 2002-04-04

Question

Is buprenorphine compatible with breast-feeding?

Answer

Buprenorphine is excreted into human breast milk at low concentrations (1). However, buprenorphine has poor oral bioavailability, due to extensive first pass metabolism, suggesting a low systemic exposure of buprenorphine to breast-fed infants (2).

A literature search has revealed three case reports concerning breast-fed infants to buprenorphine treated mothers (2-4). In these cases, breast milk concentrations of buprenorphine were comparable to maternal plasma concentrations, but no negative effects were obeserved in the children. One of the reports describes a 24-year-old woman, who had buprenorphine maintenance therapy (4 mg/day) during both pregnancy and nursing. When the child was 4 weeks old, milk concentrations of buprenorphine and the metabolite norbuprenorphine were determined. The total estimated doses of drug and metabolite ingested by the infant over a 24-hour period was 3.28 and 0.33 mikrogram, respectively. Breast-feeding was abruptly interrupted after 8 weeks (because of a respiratory infection in the mother), without any noticable withdrawal symptoms in the child (3). In the other two cases, the mothers had also been treated with buprenorphine (1.5 and 8-12 mg per day) during pregnancy.

Unpublished data, including six mothers with nursing children, have shown that milk buprenorphine levels are approximately equal to maternal plasma levels, whereas urine levels of the metabolite norbuprenorphine in the children are less than 1% of the levels in the mothers' urine. The investigators conclude that the exposure of a breast-fed infant to buprenorphine, when the mother is treated with the drug, is very small. Furthermore, clinical observation of the children suggests that this low exposure dose not induce any side effects (5).

Animal studies have shown that high doses of buprenorphine may reduce the production of breast milk (1,6). The effect of bupivacaine and buprenorphine on milk production was studied in 20 mother-infant pairs. The mothers received continuous epidural bupivacaine, with or without an addition of buprenorphine, for 3 days following caesarean section. In the bupivacaine plus buprenorphine group, both the amount of mother's milk and the weight gain of the baby (for eleven days) were significantly lower. There were no reported signs or symptoms in the breast-fed children (7). However, the extent of breast-feeding has been shown to be lower after caesarean section (due to post operative pain) compared with vaginal delivery (8). Bupivacaine has previously been reported to improve breast-feeding and in the study cited above (7), postoperative epidural bupivacaine together with buprenorphine suppressed the amount of breast milk to the same level as that without extradural analgesia after caesarean section.

Conclusion

Buprenorphine is excreted into human breast milk, but no negative effects have been observed in nine breast-fed infants whose mothers were treated with buprenorphine. Buprenorphine has poor oral bioavailability, which further suggests that the amount of buprenorphine absorbed after breast-feeding is low. However, it should be noted that buprenorphine might reduce breast milk production.

Annas A
Elwin CE

References

  1. Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999
  2. Johnson RE, Jones HE, Jasinski DR, Svikis DS, Haug NA, Jansson LM et al. Buprenorphine treatment of pregnant opioid-dependent women: maternal and neonatal outcomes. Drug Alcohol Depend 2001;63:97-103.
  3. Marquet P, Chevrel J, Lavignasse P, Merle L, Lachatre G. Buprenorphine withdrawal syndrome in a newborn. Clin Pharmacol Ther 1997;62:569-71.
  4. Reisinger M. Use of buprenorphine during pregnancy. Res Clin Forums 1997;19:43-5.
  5. Sahrman I, Svensson J-O, Ståhle L. (unpublished data, personal communication)
  6. Tomas Fokter, Schering-Plough. Personal communication
  7. Hirose M, Hosokawa T, Tanaka Y. Extradural buprenorphine suppresses breast feeding after Caesarean section. Br J Anaesth 1997;79:120-1.
  8. Hirose M, Ohmori M, Matsumoto Y, Amaya F, Hosokawa T, Tanaka Y. Effect of pain management on breast feeding after cesarean section and normal vaginal delivery. (Abstract) Anesth Resusc 1996;32:227-9.

Senast ändrad 2018-09-20