Buprenorphine substitution therapy in pregnancy
- Vincenzo Berghella, MD
Vincenzo Berghella, MD
- Section Editor — Obstetrics
- Director, Maternal-Fetal Medicine
- Professor, Obstetrics and Gynecology
- Thomas Jefferson University
- Neil S Seligman, MD
Neil S Seligman, MD
- Assistant Professor
- Department of Obstetrics & Gynecology
- Division of Maternal-Fetal Medicine
- University of Rochester Medical Center
- Brian J Cleary, PhD
Brian J Cleary, PhD
- Chief Pharmacist, Rotunda Hospital
- Honorary Clinical Associate Professor, School of Pharmacy
- Royal College of Surgeons in Ireland
- Section Editors
- Susan M Ramin, MD
Susan M Ramin, MD
- Section Editor — Obstetrics
- The American Board of Obstetrics and Gynecology (ABOG)
- Andrew J Saxon, MD
Andrew J Saxon, MD
- Section Editor — Substance Use Disorders
- Professor and Director, Addiction Psychiatry Residency Program, Department of Psychiatry & Behavioral Sciences
- University of Washington
Illicit opioid use during pregnancy is associated with substantial maternal, fetal, and neonatal risks. (See "Substance misuse in pregnant women", section on 'Opiates'.) Some of these risks are related to repeated opioid exposure and withdrawal, while others are related to factors associated with substance abuse (eg, smoking, poor nutrition, needle sharing). The rationale for opioid-substitution therapy during pregnancy is to reduce these risks by preventing complications associated with illicit opioid use and narcotic withdrawal, facilitating prenatal care and drug treatment, reducing drug-related criminal activity, and helping the patient avoid the myriad of other risks associated with the drug culture [1,2].
Comprehensive opioid-substitution therapy that includes prenatal care reduces the risk of obstetric and neonatal complications [1,2]. While methadone remains the standard choice for opioid agonist therapy during pregnancy, there is increasing interest in the use of buprenorphine because neonatal withdrawal appears to be less frequent and less severe .
This topic will discuss the use of buprenorphine for opioid substitution during pregnancy. General issues related to prevalence, screening, complications, and care of the pregnant opioid user and methadone maintenance therapy in pregnancy are reviewed separately. (See "Substance misuse in pregnant women", section on 'Opiates' and "Methadone substitution treatment of opioid use disorder during pregnancy".)
CANDIDATES FOR OPIOID-SUBSTITUTION THERAPY
Pregnant women with substance dependence (table 1) are candidates for opioid-substitution therapy, regardless of the duration of dependence if a return to dependence is likely during pregnancy. (See "Clinical assessment of substance use disorders" and "Pharmacotherapy for opioid use disorder".)
Candidates for treatment should be referred to a local physician and/or substance use disorders treatment program that specializes in opioid substitution therapy. Treatment programs that are oriented to abstinence only and do not utilize or understand opioid substitution therapy should be avoided. In addition, prenatal care should be arranged.
- ACOG Committee on Health Care for Underserved Women, American Society of Addiction Medicine. ACOG Committee Opinion No. 524: Opioid abuse, dependence, and addiction in pregnancy. Obstet Gynecol 2012; 119:1070.
- Center for Substance Abuse Treatment. Medication-Assisted Treatment for Opioid Addiction in Opioid Treatment Programs. Treatment Improvement Protocol (TIP) Series 43. DHHS Publication No. (SMA) 05-4048. Rockville, MD: Substance Abuse and Mental Health Services Administration, 2005.
- Kakko J, Heilig M, Sarman I. Buprenorphine and methadone treatment of opiate dependence during pregnancy: comparison of fetal growth and neonatal outcomes in two consecutive case series. Drug Alcohol Depend 2008; 96:69.
- Nanda S, Brant R, Regier M, Yossuck P. Buprenorphine: a new player in neonatal withdrawal syndrome. W V Med J 2015; 111:16.
- Krans EE, Bogen D, Richardson G, et al. Factors associated with buprenorphine versus methadone use in pregnancy. Subst Abus 2016; 37:550.
- Bell JR, Butler B, Lawrance A, et al. Comparing overdose mortality associated with methadone and buprenorphine treatment. Drug Alcohol Depend 2009; 104:73.
- Auriacombe M, Franques P, Tignol J. Deaths attributable to methadone vs buprenorphine in France. JAMA 2001; 285:45.
- Zedler BK, Mann AL, Kim MM, et al. Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus and child. Addiction 2016; 111:2115.
- Young JL, Martin PR. Treatment of opioid dependence in the setting of pregnancy. Psychiatr Clin North Am 2012; 35:441.
- Jones HE, Heil SH, Baewert A, et al. Buprenorphine treatment of opioid-dependent pregnant women: a comprehensive review. Addiction 2012; 107 Suppl 1:5.
- O'Connor AB, O'Brien L, Alto WA. Maternal Buprenorphine Dose at Delivery and Its Relationship to Neonatal Outcomes. Eur Addict Res 2016; 22:127.
- Brogly SB, Saia KA, Walley AY, et al. Prenatal buprenorphine versus methadone exposure and neonatal outcomes: systematic review and meta-analysis. Am J Epidemiol 2014; 180:673.
- Jones HE, Kaltenbach K, Heil SH, et al. Neonatal abstinence syndrome after methadone or buprenorphine exposure. N Engl J Med 2010; 363:2320.
- Newman RG, Gevertz SG. Efficacy versus effectiveness of buprenorphine and methadone maintenance in pregnancy. J Addict Dis 2011; 30:318.
- Kacinko SL, Jones HE, Johnson RE, et al. Correlations of maternal buprenorphine dose, buprenorphine, and metabolite concentrations in meconium with neonatal outcomes. Clin Pharmacol Ther 2008; 84:604.
- Hytinantti T, Kahila H, Renlund M, et al. Neonatal outcome of 58 infants exposed to maternal buprenorphine in utero. Acta Paediatr 2008; 97:1040.
- Kahila H, Saisto T, Kivitie-Kallio S, et al. A prospective study on buprenorphine use during pregnancy: effects on maternal and neonatal outcome. Acta Obstet Gynecol Scand 2007; 86:185.
- Lejeune C, Simmat-Durand L, Gourarier L, et al. Prospective multicenter observational study of 260 infants born to 259 opiate-dependent mothers on methadone or high-dose buprenophine substitution. Drug Alcohol Depend 2006; 82:250.
- Whitham J, Prenatal exposure to buprenorphine or methadone 2012.
- Salo S, Kivisto K, Korja R, et al. Emotional Availability, Parental Self-Efficacy Beliefs, and Child Development in Caregiver-Child Relationships with Buprenorphine-Exposed 3-year-olds. Parent Sci Pract 2009; 9:244.
- Kahila H, Kivitie-Kallio S, Halmesmäki E, et al. Brain magnetic resonance imaging of infants exposed prenatally to buprenorphine. Acta Radiol 2007; 48:228.
- Kayemba-Kay's S, Laclyde JP. Buprenorphine withdrawal syndrome in newborns: a report of 13 cases. Addiction 2003; 98:1599.
- Bier JB, Finger AS, Bier BA, et al. Growth and developmental outcome of infants with in-utero exposure to methadone vs buprenorphine. J Perinatol 2015; 35:656.
- Humbarger O, Galanto D, Saia K, et al. Childhood health and development in cohort of Infants exposed prenatally to methadone or buprenorphine. J Addict Res Ther 2016; 7:1.
- Kivistö K, Tupola S, Kivitie-Kallio S. Prenatally buprenorphine-exposed children: health to 3 years of age. Eur J Pediatr 2015; 174:1525.
- Whitham JN, Spurrier NJ, Baghurst PA, et al. Visual evoked potential latencies of three-year-old children prenatally exposed to buprenorphine or methadone compared with non-opioid exposed children: The results of a longitudinal study. Neurotoxicol Teratol 2015; 52:17.
- Jones HE, Johnson RE, Jasinski DR, et al. Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome. Drug Alcohol Depend 2005; 79:1.
- Fischer G, Ortner R, Rohrmeister K, et al. Methadone versus buprenorphine in pregnant addicts: a double-blind, double-dummy comparison study. Addiction 2006; 101:275.
- Mattick RP, Kimber J, Breen C, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev 2008; :CD002207.
- Jones HE, Martin PR, Heil SH, et al. Treatment of opioid-dependent pregnant women: clinical and research issues. J Subst Abuse Treat 2008; 35:245.
- Jones HE, Johnson RE, Jasinski DR, Milio L. Randomized controlled study transitioning opioid-dependent pregnant women from short-acting morphine to buprenorphine or methadone. Drug Alcohol Depend 2005; 78:33.
- World Health Organization. Guidelines for the Psychosocially Assisted Pharmacological Treatment of Opioid Dependence 2009.
- Walsh SL, Preston KL, Stitzer ML, et al. Clinical pharmacology of buprenorphine: ceiling effects at high doses. Clin Pharmacol Ther 1994; 55:569.
- Bullingham RE, McQuay HJ, Porter EJ, et al. Sublingual buprenorphine used postoperatively: ten hour plasma drug concentration analysis. Br J Clin Pharmacol 1982; 13:665.
- Kuhlman JJ Jr, Lalani S, Magluilo J Jr, et al. Human pharmacokinetics of intravenous, sublingual, and buccal buprenorphine. J Anal Toxicol 1996; 20:369.
- Concheiro M, Jones HE, Johnson RE, et al. Preliminary buprenorphine sublingual tablet pharmacokinetic data in plasma, oral fluid, and sweat during treatment of opioid-dependent pregnant women. Ther Drug Monit 2011; 33:619.
- Kacinko SL, Jones HE, Johnson RE, et al. Urinary excretion of buprenorphine, norbuprenorphine, buprenorphine-glucuronide, and norbuprenorphine-glucuronide in pregnant women receiving buprenorphine maintenance treatment. Clin Chem 2009; 55:1177.
- Nanovskaya T, Deshmukh S, Brooks M, Ahmed MS. Transplacental transfer and metabolism of buprenorphine. J Pharmacol Exp Ther 2002; 300:26.
- Bartu AE, Ilett KF, Hackett LP, et al. Buprenorphine exposure in infants of opioid-dependent mothers at birth. Aust N Z J Obstet Gynaecol 2012; 52:342.
- Fokina VM, Patrikeeva SL, Zharikova OL, et al. Transplacental transfer and metabolism of buprenorphine in preterm human placenta. Am J Perinatol 2011; 28:25.
- RB Pharmaceuticals Limited. Summary of Product Characteristics- Subutex 0.4 mg, 2 mg and 8 mg Sublingual Tablets. www.medicines.ie. (Accessed on January 07, 2013).
- Martindale: The Complete Drug Reference. [Online] London: Pharmaceutical Press. http://www.medicinescomplete.com.proxy.library.rcsi.ie/ (Accessed on December 11, 2012).
- Reckitt Benckiser Pharmaceuticals Inc. Prescription Drug Label- BUPRENEX (buprenorphine hydrochloride): Daily Med. http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=b086772e-d15a-4d13-b1a2-38bfbde1f18c. (Accessed on February 23, 2013).
- Nørgaard M, Nielsson MS, Heide-Jørgensen U. Birth and Neonatal Outcomes Following Opioid Use in Pregnancy: A Danish Population-Based Study. Subst Abuse 2015; 9:5.
- Bastian JR, Chen H, Zhang H, et al. Dose-adjusted plasma concentrations of sublingual buprenorphine are lower during than after pregnancy. Am J Obstet Gynecol 2017; 216:64.e1.
- Bryson EO, Lipson S, Gevirtz C. Anesthesia for patients on buprenorphine. Anesthesiol Clin 2010; 28:611.
- Gevirtz C, Frost EA, Bryson EO. Perioperative implications of buprenorphine maintenance treatment for opioid addiction. Int Anesthesiol Clin 2011; 49:147.
- UK data sheet. http://www.medicines.org.uk/emcmobile/medicine/26614/spc#POSOLOGY. (Accessed on March 04, 2013).
- Irish data sheet. http://www.medicines.ie/document.aspx?documentId=1658#POSOLOGY. (Accessed on March 04, 2013).
- Newman RG, Gevertz SG. Comment on "a comparison of buprenorphine + naloxone to buprenorphine and methadone in the treatment of opioid dependence during pregnancy: maternal and neonatal outcomes". Subst Abuse 2013; 7:107.
- Gawronski KM, Prasad MR, Backes CR, et al. Neonatal outcomes following in utero exposure to buprenorphine/naloxone or methadone. SAGE Open Med 2014.
- Wiegand S, Stringer E, Seashore C, et al. Buprenorphine/naloxone (B/N) and methadone (M) maintenance during pregnancy: a chart review and comparison of maternal and neonatal outcomes. Am J Obstet Gynecol 2014; 210 (Suppl 1):S368.
- Lund IO, Fischer G, Welle-Strand GK, et al. A Comparison of Buprenorphine + Naloxone to Buprenorphine and Methadone in the Treatment of Opioid Dependence during Pregnancy: Maternal and Neonatal Outcomes. Subst Abuse 2013; 7:61.
- Wiegand SL, Stringer EM, Stuebe AM, et al. Buprenorphine and naloxone compared with methadone treatment in pregnancy. Obstet Gynecol 2015; 125:363.
- Alto WA, O'Connor AB. Management of women treated with buprenorphine during pregnancy. Am J Obstet Gynecol 2011; 205:302.
- Mehta V, Langford RM. Acute pain management for opioid dependent patients. Anaesthesia 2006; 61:269.
- Huxtable CA, Roberts LJ, Somogyi AA, MacIntyre PE. Acute pain management in opioid-tolerant patients: a growing challenge. Anaesth Intensive Care 2011; 39:804.
- American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 106: Intrapartum fetal heart rate monitoring: nomenclature, interpretation, and general management principles. Obstet Gynecol 2009; 114:192. Reaffirmed 2017.
- Archie CL, Lee MI, Sokol RJ, Norman G. The effects of methadone treatment on the reactivity of the nonstress test. Obstet Gynecol 1989; 74:254.
- Cejtin HE, Mills A, Swift EL. Effect of methadone on the biophysical profile. J Reprod Med 1996; 41:819.
- Levine AB, Rebarber A. Methadone maintenance treatment and the nonstress test. J Perinatol 1995; 15:229.
- Salisbury AL, Coyle MG, O'Grady KE, et al. Fetal assessment before and after dosing with buprenorphine or methadone. Addiction 2012; 107 Suppl 1:36.
- Jansson LM, Dipietro JA, Velez M, et al. Fetal neurobehavioral effects of exposure to methadone or buprenorphine. Neurotoxicol Teratol 2011; 33:240.
- Jansson LM, Velez M, McConnell K, et al. Maternal buprenorphine treatment and fetal neurobehavioral development. Am J Obstet Gynecol 2017; 216:529.e1.
- Carroll IR, Angst MS, Clark JD. Management of perioperative pain in patients chronically consuming opioids. Reg Anesth Pain Med 2004; 29:576.
- Alford DP, Compton P, Samet JH. Acute pain management for patients receiving maintenance methadone or buprenorphine therapy. Ann Intern Med 2006; 144:127.
- Creekmore FM, Lugo RA, Weiland KJ. Postoperative opiate analgesia requirements of smokers and nonsmokers. Ann Pharmacother 2004; 38:949.
- Mitra S, Sinatra RS. Perioperative management of acute pain in the opioid-dependent patient. Anesthesiology 2004; 101:212.
- Höflich AS, Langer M, Jagsch R, et al. Peripartum pain management in opioid dependent women. Eur J Pain 2012; 16:574.
- Kornfeld H, Manfredi L. Effectiveness of full agonist opioids in patients stabilized on buprenorphine undergoing major surgery: a case series. Am J Ther 2010; 17:523.
- Meyer M, Wagner K, Benvenuto A, et al. Intrapartum and postpartum analgesia for women maintained on methadone during pregnancy. Obstet Gynecol 2007; 110:261.
- Jones HE, Johnson RE, Milio L. Post-cesarean pain management of patients maintained on methadone or buprenorphine. Am J Addict 2006; 15:258.
- Jones HE, O'Grady K, Dahne J, et al. Management of acute postpartum pain in patients maintained on methadone or buprenorphine during pregnancy. Am J Drug Alcohol Abuse 2009; 35:151.
- Meyer M, Paranya G, Keefer Norris A, Howard D. Intrapartum and postpartum analgesia for women maintained on buprenorphine during pregnancy. Eur J Pain 2010; 14:939.
- Wong S, Ordean A, Kahan M, Society of Obstetricians and Gynecologists of Canada. SOGC clinical practice guidelines: Substance use in pregnancy: no. 256, April 2011. Int J Gynaecol Obstet 2011; 114:190.
- Center for Substance Abuse Treatment (CSAT). Clinical Guidelines for the Use of Buprenorphine in the Treatment of Opioid Addiction. DHHS Publication No. (SMA) 04-3939. Rockville (MD): Substance Abuse and Mental Health Services Administration (SAMHSA), 2004.
- Lactmed. Buprenorphine: National Library of Medicine. http://toxnet.nlm.nih.gov (Accessed on January 23, 2013).
- Sachs HC, Committee On Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics 2013; 132:e796.
- 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.
- 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.
- CANDIDATES FOR OPIOID-SUBSTITUTION THERAPY
- BUPRENORPHINE OR METHADONE?
- Comparative outcome data
- - Neonatal abstinence syndrome
- - Other neonatal outcomes
- - Maternal treatment retention
- Switching from methadone therapy
- Switching to methadone therapy
- Safety, side effects, drug interactions
- - Risk of congenital anomalies
- Initiation of buprenorphine and subsequent management
- - Patients with hepatic or renal insufficiency
- Missed doses
- Buprenorphine versus buprenorphine plus naloxone
- PREGNANCY MANAGEMENT
- Antenatal fetal surveillance
- - Effect on fetal heart rate
- Management of pain during labor, delivery, and postpartum
- - Labor and delivery
- - Postpartum
- Management of buprenorphine postpartum
- SUMMARY AND RECOMMENDATIONS