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Pharmacy World & Science

, Volume 30, Issue 3, pp 227–234 | Cite as

Hospital morphine preparation for abstinence syndrome in newborns exposed to buprenorphine or methadone

  • Nathalie ColombiniEmail author
  • Riad Elias
  • Muriel Busuttil
  • Myriam Dubuc
  • Marie-Ange Einaudi
  • Martine Bues-Charbit
Research Article

Abstract

Objective This study was undertaken to evaluate the adequacy of a hospital formulated oral morphine preparation for management of neonatal abstinence syndrome (NAS) and to compare clinical features in infants exposed to methadone or buprenorphine in utero. Method Between October 1998 and October 2004 all infants born to mothers treated with buprenorphine or methadone during pregnancy were enrolled into this prospective study. Morphine hydrochloride solution (0.2 mg/ml) was prepared without preservatives under a flow laminar air box (class 100). Mean outcome measure Morphine solution: quantitative and qualitative HPLC analysis and microbiological study at regular intervals during storage at 4°C for 6 months. Maternal characteristics: age, opiate dose during pregnancy. Neonatal characteristics: gestational age at delivery, birth weight, Lipsitz scores. Morphine dose: daily morphine dose, maximum morphine dose, duration of NAS, and duration of treatment required to achieve stable Lipsitz scores below 4. Statistics: Kruskal–Wallis test for comparison of median values. Results Microbiological and HPLC analysis showed that the morphine preparation remained stable for 6 months at 4°C. Nine methadone-exposed infants and 13 buprenorphine-exposed infants were included in the study. All infants presented NAS requiring treatment with the morphine solution. Lipsitz scores at birth were significantly different in the methadone and buprenorphine groups (P < 0.05). The methadone group required significantly higher doses of morphine preparation than the buprenorphine group during the first 38 days of treatment (P < 0.05): 0.435 ± 0.150 mg/kg/day vs. 0.257 ± 0.083 mg/kg/day. Conclusion This hospital morphine solution is adequate for management of NAS. Preparations showed good stability and doses could be adjusted with a margin of 0.02 mg. The onset of NAS occurred within 24 h after birth in methadone-exposed infants (range 6–24 h) and within 48 h after birth in buprenorphine-exposed infants (range 24–168 h). Due to the possibility of delayed onset of NAS up to 7 days, infants born to mothers treated with buprenorphine should be kept in the hospital for an appropriate surveillance period. Treatment time was significantly longer (45 vs. 28 days) and the mean morphine doses were higher (1.7 fold) in methadone-exposed than buprenorphine-exposed infants.

Keywords

Buprenorphine Methadone Morphine Neonatal abstinence syndrome Opioid dependence Withdrawal 

Notes

Acknowledgments

The authors are grateful to the many people who actively cooperated in this project.

References

  1. 1.
    Cairns PA. Drug misuse: conception into childhood. Curr Paediatr 2001;11:475–79.CrossRefGoogle Scholar
  2. 2.
    Ferraro F, Massard A. Conséquences de la toxicomanie à la cocaïne pendant la grossesse sur le développement de l’enfant. [Consequences of cocaïne addiction during pregnancy on the development in the child]. Arch Pediatr 1997;4(7):677–82.PubMedCrossRefGoogle Scholar
  3. 3.
    Lejeune C, Floch-Tudal C, Montamat S, Crenn-Hebert C, Simonpoli AM. Prise en charge des femmes enceintes toxicomanes et de leurs enfants. [Management of drug addict pregnant women and their children]. Arch Pediatr 1997;4(3):263–70.PubMedCrossRefGoogle Scholar
  4. 4.
    Sinha C, Ohadike P, Carrick P, Pairaudeau P, Armstrong D, Lindow SW. Neonatal outcome following maternal opiate use in late pregnancy. Int J Gynaecol Obstet 2001;74:241–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Regini P, Cutrone M, Donzelli F, Flora PG, Montesanto G. Neonatal buprenorphine withdrawal syndrome; what is the right therapy? Pediatr Med Chir 1998;20:67–9.PubMedGoogle Scholar
  6. 6.
    Marquet P. Pharmacologie périnatale des opiacés. [Perinatal pharmacology of opiates] Arch Pediatr 2000;7(Suppl 2):287s–89s.PubMedCrossRefGoogle Scholar
  7. 7.
    Theis JG, Selby P, Ikizler Y, Koren G. Current management of the neonatal abstinence syndrome: a critical analysis of the evidence. Biol Neonate 1997;71:345–56.PubMedCrossRefGoogle Scholar
  8. 8.
    American Academy of Pediatrics. Committee On Drugs. Neonatal drug withdrawal. Pediatrics 1998;101:1079–88.CrossRefGoogle Scholar
  9. 9.
    Coghlan D, Milner M, Clarke T, Lambert I, McDermott C, McNally M, et al. Neonatal abstinence syndrome. Med J 1999;92(1):232–6.Google Scholar
  10. 10.
    Coyle MG, Ferguson A, Lagasse L, Ob W, Lester B. Diluted tincture of opium (DTO) and phenobarbital versus DTO alone for neonatal opiate withdrawal in term infants. J Pediatr 2002;140:561–4.PubMedCrossRefGoogle Scholar
  11. 11.
    Johnson RE, Jones HE, Fischer G. Use of buprenorphine in pregnancy: patient management and effects on the neonate. Drug Alcohol Depend 2003;70:S87–101.PubMedCrossRefGoogle Scholar
  12. 12.
    Amirat-Combralier V, Jentile B, Elias R, Dejode JM, Lagier P, Bues-Charbit M, et al. Preparation and use of morphine capsules in paediatric patients with burns. J Pharm Belg 1997;52(6):217–8.PubMedGoogle Scholar
  13. 13.
    Anderson IB, Kearney TE. Use of methadone. West J Med 2000;172:43–6.PubMedCrossRefGoogle Scholar
  14. 14.
    Ward J, Hall W, Mattick RP. Role of maintenance treatment in opioid dependence. Lancet 1999;353:221–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Osborn DA, Jeffery HE, Cole MJ. Sedatives for opiate withdrawal in newborn infants. In: National Institute of Child Health and Human Development, 2002. http://www.nichd.nih.gov/cochrane (15 February 2005).
  16. 16.
    Lipsitz PJ. A proposed narcotic withdrawal score for use with newborn infants: a pragmatic evaluation of its efficacy. Clin Pediatr 1975;14:592–4.CrossRefGoogle Scholar
  17. 17.
    Perelman R, Amiel-Tison CL, Desbois JC. Périnatologie-Pédiatrie pratique. [Practical perinatology and paediatrics]. Paris: Imprimerie Maloine; 1985.Google Scholar
  18. 18.
    Kandall SR, Gaines J. Maternal substance use and subsequent sudden infant death syndrome (SIDS) in offspring. Neurotoxicol Teratol 1991;13(2):235–40.PubMedCrossRefGoogle Scholar
  19. 19.
    Marquet P. Pharmacology of opiates during pregnancy. In: Kintz P, Marquet P, editors. Buprenorphin therapy of opiate addicts. Totowa-New Jersey: Human Press; 2002.p. 119–24.CrossRefGoogle Scholar
  20. 20.
    Jernite M, Viville B, Escande B, Brettes JP, Messer J. Grossesse et buprénorphine, à propos de 24 cas. [Buprenorphine and pregnancy. Analysis of 24 cases]. Arch Pediatr 1999;11:1179–85.CrossRefGoogle Scholar
  21. 21.
    Levy M, Spino M. Neonatal withdrawal syndrome: associated drugs and pharmacologic management. Pharmacotherapy 1993;13:202–11.PubMedGoogle Scholar
  22. 22.
    Lejeune C, Simmat-Durand L, Aubisson S, Gourarier L, Picquet M. Grossesse et substitution. Enquête sur les femmes enceintes substituées à la méthadone ou à la buprénorphine haut dosage et caractéristiques de leurs nouveau-nés. Observatoire Français des Drogues et des Toxicomanies (OFDT) [Pregnancy and substitutive treatment. Report on pregnant women treated by methadone or high dose buprenorphine and newborn characteristics. In: French Monitoring Center for Drugs and Drug Addiction (OFDT) library]. 2003. http://www.ofdt.fr/BDD/publications/docs/epfxclj7.pdf (15 February 2005).
  23. 23.
    Micard S, Brion F. Prise en charge du syndrome de sevrage du nouveau-né de mère toxicomane aux opiacés: enquête française et européenne. [Management of the opioid withdrawal in the neonates: French and European survey] Arch Pediatr 2003;10(3):199–203.PubMedCrossRefGoogle Scholar
  24. 24.
    Sutton LR, Hinderliter SA. Diazepam abuse in pregnant women on methadone maintenance. Implications for the neonate. Clin Pediatr 1990;29:108–11.CrossRefGoogle Scholar
  25. 25.
    Dashe JS, Jackson GL, Olscher DA, Zane EH, Wendel GD. Opioid detoxification in pregnancy. Obstet Gynecol 1998;92(5):854–58.PubMedCrossRefGoogle Scholar
  26. 26.
    Mazurier E, Sarda P, Boulot P. Traitement par Buprénorphine (Temgésic®) de la dépendance aux opiacés chez la femme enceinte. 26è Journées Nationales de la Société Française de Médecine Périnatale. [Treatment of opioid dependence in pregnant woman using Buprenorphine (Temgesic®). In: 26th Congress of the French Society of Perinatology] [Proceedings]. Brest (France), 1996.Google Scholar
  27. 27.
    Fischer G, Etzersdorfer P, Eder H, Jagsch R, Langer M, Weninger M. Buprenorphine maintenance in pregnant opiate addicts. Eur Addict Res 1998;4:32–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Fischer G, Johnson RE, Eder H, Jagsch R, Peternell A, Weninger M, et al. Treatment of opioid-dependent pregnant women with buprenorphine. Addiction 2000;95:239–44.PubMedCrossRefGoogle Scholar
  29. 29.
    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(1):97–103.PubMedCrossRefGoogle Scholar
  30. 30.
    Nanovskaya T, Deshmukh S, Brooks M, Ahmed MS. Transplacental transfer and metabolism of buprenorphine. J Pharmacol Exp Ther 2002;300(1):26–33.PubMedCrossRefGoogle Scholar
  31. 31.
    Tran JH. Treatment of neonatal abstinence syndrome. J Pediatr Health Care 1999;13(6):295–300.PubMedCrossRefGoogle Scholar
  32. 32.
    Choo RE, Huestis MA, Schroeder JR, Shin AS, Jones HE. Neonatal abstinence syndrome in methadone-exposed infants is altered by level of prenatal tobacco exposure. Drug Alcohol Depend 2004;75(3):253–60.PubMedCrossRefGoogle Scholar
  33. 33.
    Auerbach JG, Hans SL, Marcus J, Maeir S. Maternal psychotropic medication and neonatal behavior. Neurotoxicol Teratol 1992;14(6):399–406.PubMedCrossRefGoogle Scholar
  34. 34.
    Lundsberg LS, Bracken MB, Saftlas AF. Low-to-moderate gestational alcohol use and intra-uterine growth retardation, low birthweight, and pre-term delivery. Ann Epidemiol 1997;7(7):498–508.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Nathalie Colombini
    • 1
    Email author
  • Riad Elias
    • 1
  • Muriel Busuttil
    • 2
  • Myriam Dubuc
    • 3
  • Marie-Ange Einaudi
    • 2
  • Martine Bues-Charbit
    • 1
  1. 1.Hospital PharmacyMarseilles University Hospital SystemMarseille Cedex 20France
  2. 2.Department of NeonatologyMarseilles University Hospital SystemMarseilleFrance
  3. 3.Department of Statistical AnalysisMarseilles University Hospital SystemMarseilleFrance

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