The Basics
What is Buprenorphine?
Used to treat dependence/addiction to opioid and helps prevent withdrawal symptoms.
Brand names for Buprenorphine
Buprenex
How Buprenorphine is classified
Analgesics – Opioid, Narcotics, Narcotic Antagonists
Buprenorphine During Pregnancy
Buprenorphine pregnancy category
Category CNote that the FDA has deprecated the use of pregnancy categories, so for some medications, this information isn’t available. We still think it’s useful to list historical info, however, given what a common proxy this has been in the past.
What we know about taking Buprenorphine while pregnant
Recent evidence supports the use of buprenorphine for opioid use disorder treatment during pregnancy. Buprenorphine was not teratogenic in rats or rabbits after I.M. or S.C. doses up to 5 mg/kg/day (approximately 48 and 95 times the recommended human daily dose of 1.2 mg on a mg/m2 basis), I.V. doses up to 0.8 mg/kg/day (approximately 8 times and 15 times the recommended human daily dose of 1.2 mg on a mg/m2 basis), or oral doses up to 160 mg/kg/day in rats (approximately 1525 times the recommended human daily dose of 1.2 mg on a mg/m2 basis) and 25 mg/kg/day in rabbits (approximately 475 times the recommended human daily dose of 1.2 mg on a mg/m2 basis). Significant increases in skeletal abnormalities (e.g. extra thoracic vertebra or thoraco-lumbar ribs) were noted in rats after S.C. administration of 1 mg/kg/day and up (approximately 9.5 times the recommended human daily dose of 1.2 mg on a mg/m2 basis) and in rabbits after I.M. administration of 5 mg/kg/day (approximately 95 times the recommended human daily dose of 1.2 mg on a mg/m2 basis), but these increases were not statistically significant. Increases in skeletal abnormalities after oral administration were not observed in rats, and increases in rabbits (1-25 mg/kg/day) were not statistically significant. There are no adequate and well-controlled studies in pregnant women. Buprenex (buprenorphine) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Taking Buprenorphine While Breastfeeding
What are recommendations for lactation if you're taking Buprenorphine?
Because of the low levels of buprenorphine in breastmilk, its poor oral bioavailability in infants, and the low drug concentrations found in the serum and urine of breastfed infants, its use is acceptable in nursing mothers. Monitor the infant for drowsiness, respiratory depression, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants. Although unlikely, if the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately. Observe infants for withdrawal signs if breastfeeding is stopped abruptly. Women who received buprenorphine for opiate abuse during pregnancy and are stable should be encouraged to breastfeed their infants postpartum, unless there is another contraindication, such as use of street drugs.[1][2][3][4][5][6][7][8][9][10][11] The long-term outcome of infants breastfed during maternal buprenorphine therapy for opiate abuse has not been well studied.[12] The breastfeeding rate among mothers taking buprenorphine for opiate dependency may be lower than in other mothers.
Maternal / infant drug levels
Because of the low levels of buprenorphine in breastmilk, its poor oral bioavailability in infants, and the low drug concentrations found in the serum and urine of breastfed infants, its use is acceptable in nursing mothers. Monitor the infant for drowsiness, respiratory depression, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants. Although unlikely, if the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately. Observe infants for withdrawal signs if breastfeeding is stopped abruptly. Women who received buprenorphine for opiate abuse during pregnancy and are stable should be encouraged to breastfeed their infants postpartum, unless there is another contraindication, such as use of street drugs.[1][2][3][4][5][6][7][8][9][10][11] The long-term outcome of infants breastfed during maternal buprenorphine therapy for opiate abuse has not been well studied.[12] The breastfeeding rate among mothers taking buprenorphine for opiate dependency may be lower than in other mothers.
Possible effects of Buprenorphine on milk supply
Buprenorphine can increase serum prolactin.[34] However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.
In a multicenter prospective study of 246 pregnant women receiving either methadone or buprenorphine for opiate dependency, 153 women were receiving high-dose buprenorphine. Twenty-two percent of women receiving buprenorphine breastfed their infants, which was the same percentage as those receiving methadone.[35]
A retrospective chart review of 276 opiate-dependent mothers who delivered in a Baby Friendly Hospital found that mothers taking buprenorphine or methadone for opiate dependency were unlikely to breastfeed their infants. Only 45% of the 20 mothers on buprenorphine maintenance initiated breastfeeding. Of all women in the study, 60% discontinued breastfeeding before discharge from the hospital.[36]
A retrospective case series reported on 85 opioid-dependent women maintained on buprenorphine during pregnancy and postpartum during the period of December 2007 to August 2012. Of these women, 65 were breastfeeding on discharge from the hospital and 66% of these were breastfeeding at their 6- to 8-week follow-up appointment (extent of nursing not stated).[37]
A retrospective cohort study in Australia compared breastfeeding rates on discharge of drug-using mothers who were taking either buprenorphine, other opiates or nonopiates (e.g., benzodiazepines, amphetamines, cocaine, alcohol, inhalants, cannabinoids, psychotropics). Breastfeeding rates at discharge from the hospital were as follows: buprenorphine 27%, other opiates 31%, and nonopiates 51%.[38]
A small retrospective study found that only 3 of 10 pregnant women treated with buprenorphine plus naloxone for opioid dependence were breastfeeding their infants at the time of hospital discharge.[39]
A retrospective cohort study of 150 women enrolled in a substance abuse treatment program found that women taking methadone had a higher prevalence of breastfeeding than women taking buprenorphine plus naloxone. However, this difference appeard to be related to the greater intention to breastfeed before delivery in the methadone group.[40]
A retrospective cohort study of 228 women enrolled in a perinatal substance abuse treatment program found that women taking buprenorphine had a higher prevalence of breastfeeding than women taking methadone. The intention to breastfeed before delivery was similar in both groups.[41] A systematic review of studies on the effect of breastfeeding on the outcomes of infants whose mothers were taking methadone during pregnancy and postpartum concluded that the association between newborn feeding method and neonatal abstinence syndrome among newborns exposed to buprenorphine in breastmilk was unclear.[42]
Possible alternatives to Buprenorphine
(Analgesia) Acetaminophen, Butorphanol, Fentanyl, Hydromorphone, Ibuprofen, Morphine; (Opiate Dependency) Methadone, Naltrexone.
List of References
Lactation sources: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501922/1. Kocherlakota P. Neonatal abstinence syndrome. Pediatrics. 2014;134:e547-e561. PMID: 25070299
2. Sutter MB, Leeman L, Hsi A. Neonatal opioid withdrawal syndrome. Obstet Gynecol Clin North Am. 2014;41:317-34. PMID: 24845493
3. Mozurkewich EL, Rayburn WF. Buprenorphine and methadone for opioid addiction during pregnancy. Obstet Gynecol Clin North Am. 2014;41:241-53. PMID: 24845488
4. Bagley SM, Wachman EM, Holland E, Brogly SB. Review of the assessment and management of neonatal abstinence syndrome. Addict Sci Clin Pract. 2014;9:19. PMID: 25199822
5. Lefevere J, Allegaert K. Question: Is breastfeeding useful in the management of neonatal abstinence syndrome? Arch Dis Child. 2015;100:414-5. PMID: 25784740
6. Reece-Stremtan S, Marinelli KA. ABM Clinical Protocol #21: Guidelines for Breastfeeding and Substance Use or Substance Use Disorder, Revised 2015. Breastfeed Med. 2015;10:135-41. PMID: 25836677
7. Cleveland LM. Breastfeeding recommendations for women who receive medication-assisted treatment for opioid use disorders: AWHONN Practice Brief Number 4. Nurs Womens Health. 2016;20:432-4. PMID: 27520608
8. McQueen K, Murphy-Oikonen J. Neonatal abstinence syndrome. N Engl J Med. 2016;375:2468-79. PMID: 28002715
9. Holmes AP, Schmidlin HN, Kurzum EN. Breastfeeding considerations for mothers of infants with neonatal abstinence syndrome. Pharmacotherapy. 2017;37:861-9. PMID: 28488805
10. Mascola MA, Borders AE, Terplan M. Committee Opinion No. 711: Opioid Use and Opioid Use Disorder in Pregnancy. Obstet Gynecol. 2017;130:e81-e94. PMID: 28742676
11. Bogen DL, Whalen BL. Breastmilk feeding for mothers and infants with opioid exposure: What is best? Semin Fetal Neonatal Med . 2019;24:95-104. PMID: 30922811
12. Wachman EM, Schiff DM, Silverstein M. Neonatal abstinence syndrome: Advances in diagnosis and treatment. JAMA. 2018;319:1362-74. PMID: 29614184
13. Marquet P, Chevrel J, Lavignasse P et al. Buprenorphine withdrawal syndrome in a newborn. Clin Pharmacol Ther. 1997;62:569-71. PMID: 9390114
14. Jernite M, Diemunsch P, Kintz P. Buprenorphine excretion in breast milk. Anesthesiology. 1999;91:A1095. Abstract.
15. Jernite M, Diemunsch P, Kintz P et al. [Passage of buprenorphine into mother’s milk]. Ann Fr Anesth Reanim. 1999;18 (Suppl 1):109S. Abstract.
16. Johnson RE, Jones HE, Jasinski DR et al. Buprenorphine treatment of pregnant opioid–dependent women: maternal and neonatal outcomes. Drug Alcohol Depend. 2001;63:97-103. PMID: 11297835
17. Grimm D, Pauly E, Poschl J et al. Buprenorphine and norbuprenorphine concentrations in human breast milk samples determined by liquid chromatography-tandem mass spectrometry. Ther Drug Monit. 2005;27:526-30. PMID: 16044112
18. Lindemalm S, Nydert P, Svensson JO et al. Transfer of buprenorphine into breast milk and calculation of infant drug dose. J Hum Lact. 2009;25:199-205. PMID: 19136395
19. Ilett KF, Hackett LP, Gower S et al. Estimated dose exposure of the neonate to buprenorphine and its metabolite norbuprenorphine via breastmilk during maternal buprenorphine substitution treatment. Breastfeed Med. 2012;7:269-74. PMID: 22011128
20. Swortwood MJ, Scheidweiler KB, Barnes AJ et al. Simultaneous quantification of buprenorphine, naloxone and phase I and II metabolites in plasma and breastmilk by liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2016;1446:70-7. PMID: 27083254
21. Jansson LM, Spencer N, McConnell K et al. Maternal buprenorphine maintenance and lactation. J Hum Lact. 2016;32:675-81. PMID: 27563013
22. Schindler SD, Eder H, Ortner R et al. Neonatal outcome following buprenorphine maintenance during conception and throughout pregnancy. Addiction. 2003;98:103-10. PMID: 12492761
23. Kayemba-Kay’s S, Laclyde JP. Buprenorphine withdrawal syndrome in newborns: a report of 13 cases. Addiction. 2003;98:1599-604. PMID: 14616186
24. Johnson RE, Jones HE, Fischer G. Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend. 2003;70 (2 Suppl):S87-S101. PMID: 12738353
25. Loustauneau A, Auriacombe M, Daulouede JP, Tignol J. [Is buprenorphine a potential alternative to methadone for treating pregnant drug users? Inventory of clinical data in the literature]. Ann Med Interne (Paris). 2002;153 (7 Suppl):2S31-6. PMID: 12518080
26. Hirose M, Hosokawa T, Tanaka Y. Extradural buprenorphine suppresses breast feeding after cesarean section. Br J Anaesth. 1997;79:120-1. PMID: 9301399
27. Elladki H, Thill P. Buprenorphine withdrawal in an infant after cessation of breastfeeding: A case report and review of the literature. Pharmacotherapy. 2011;31:435e. Abstract.
28. Gower S, Bartu A, Ilett KF et al. The wellbeing of infants exposed to buprenorphine via breast milk at 4 weeks of age. J Hum Lact. 2014;30:217-23. PMID: 24399105
29. Welle-Strand GK, Skurtveit S, Jansson LM et al. Breastfeeding reduces the need for withdrawal treatment in opioid-exposed infants. Acta Paediatr. 2014;102:1060-6. PMID: 23909865
30. Metz VE, Comer SD, Pribasnig A et al. Observational study in an outpatient clinic specializing in treating opioid-dependent pregnant women: Neonatal abstinence syndrome in infants exposed to methadone-, buprenorphine- and slow-release oral morphine. Heroin Addict Relat Clin Probl. 2015;17:5-15.
31. Short VL, Gannon M, Abatemarco DJ. The association between breastfeeding and length of hospital stay among infants diagnosed with neonatal abstinence syndrome: A population-based study of in-hospital births . Breastfeed Med. 2016;11:343-9. PMID: 27529500
32. Wachman EM , Hayes MJ, Sherva R et al. Association of maternal and infant variants in PNOC and COMT genes with neonatal abstinence syndrome severity. Am J Addict. 2017;26:42-9. PMID: 27983768
33. Wong J, Saver B, Scanlan JM et al. Does maternal buprenorphine dose affect severity or incidence of neonatal abstinence syndrome. J Addict Med. 2018. PMID: 29905586
34. Saarialho-Kere U, Mattila MJ, Paloheimo M, Seppala T. Psychomotor, respiratory and neuroendocrinological effects of buprenorphine and amitriptyline in healthy volunteers. Eur J Clin Pharmacol. 1987;33:139-46. PMID: 3691607
35. Lejeune C, Aubisson S, Simmat-Durand L et al. [Withdrawal syndromes of newborns of pregnant drug abusers maintained under methadone or high-dose buprenorphine: 246 cases]. Ann Med Interne (Paris). 2001;152 (Suppl 7):21-7. PMID: 11965095
36. Wachman EM, Byun J, Philipp BL. Breastfeeding rates among mothers of infants with neonatal abstinence syndrome. Breastfeed Med. 2010;5:159-64. PMID: 20658895
37. O’Connor AB, Collett A, Alto WA, O’Brien LM. Breastfeeding rates and the relationship between breastfeeding and neonatal abstinence syndrome in women maintained on buprenorphine during pregnancy. J Midwifery Womens Health. 2013;58:383-8. PMID: 23931660
38. Patel P, Abdel-Latif ME, Hazelton B et al. Perinatal outcomes of Australian buprenorphine-exposed mothers and their newborn infants. J Paediatr Child Health. 2013;49:746-53. PMID: 23745982
39. Debelak K, Morrone WR, O’Grady KE, Jones HE. Buprenorphine + naloxone in the treatment of opioid dependence during pregnancy-initial patient care and outcome data. Am J Addict. 2013;22:252-4. PMID: 23617867
40. Gawronski KM, Prasad MR, Backes CR et al. Neonatal outcomes following in utero exposure to buprenorphine/naloxone or methadone. SAGE Open Med. 2014;2:2050312114530282. PMID: 26770721
41. Yonke N, Maston R, Weitzen S et al. Breastfeeding intention compared with breastfeeding postpartum among women receiving medication-assisted treatment. J Hum Lact. 2019;35:71-9. PMID: 29723483
42. McQueen K, Taylor C, Murphy-Oikonen J. Systematic review of newborn feeding method and outcomes related to neonatal abstinence syndrome. J Obstet Gynecol Neonatal Nurs 2019;48:398-407. PMID: 31034790
Disclaimer: This material is provided for educational purposes only and is not intended for medical advice, diagnosis, or treatment. Consult your healthcare provider with any questions.
