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Can Fam Physician
Vol. 54, No. 12, December 2008, pp.1689 - 1690
Copyright © 2008 by The College of Family Physicians of Canada
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Motherisk Update

Methadone exposure during lactation

Miguel Marcelo Glatstein, MD, Facundo Garcia-Bournissen, MD, Yaron Finkelstein, MD and Gideon Koren, MD FRCPC FACMT
Methadone is an opioid analgesic used in the treatment of narcotic dependency.1 Its usefulness is related to its long serum half-life, slow onset of action, and lower rate of euphoric effects compared with other opiates. The long elimination half-life of methadone allows gradual decrease in dose. Methadone has been shown to reduce the illicit use of opiates and associated crime,2 and maintenance programs have been shown to reduce the risk of acquiring sexually transmitted infections, including HIV.2 Methadone can be prescribed and legally dispensed for outpatient use, facilitating management of these patients.3

Although chemically different from morphine, methadone has similar clinical analgesic effects. It is well absorbed from the gastrointestinal tract, and therapeutic concentrations are evident in plasma 30 minutes after ingestion.4 Peak plasma concentrations are reached 2 to 4 hours after therapeutic doses. Typically, the elimination half-life ranges between 10 and 18 hours.5 Metabolism and clearance rate of methadone are highly variable. Liver metabolism by cytochrome P450 isoenzymes CYP 3A4 and CYP 2B66 is the main route of elimination.

There is sparse published evidence of exposure of infants to methadone through breast milk. Concentrations of methadone in breast milk are low and remain stable over time.7–9 Methadone doses of 25 to 180 mg/d produce concentrations in milk ranging from 27 to 260 ng/ mL, leading to an average daily methadone ingestion of 0.05 mg (based on an infant’s estimated milk intake of approximately 500 mL/d).10 This ingested amount would be equal, in a 5-kg baby, to the ingestion of less than 1% of the maternal weight–adjusted dose (typical adult dose is 40 to 180 mg/d).10 Even after correcting for slower clearance rate of methadone in neonates as compared with adults, the relative infant dose would not exceed 5% of the maternal weight–adjusted dose.

Methadone offers important therapeutic benefits to the population of opiate-dependent pregnant women that far outweigh the theoretical small risk posed by minimal excretion of the drug into breast milk.11 For 18 years, the American Academy of Pediatrics recommended that methadone was only compatible with breastfeeding at maternal doses below 20 mg/d12; in September 2001, based on the evidence available, the American Academy of Pediatrics lifted this dose restriction. The new statement considers methadone compatible with breastfeeding at any maternal dose.13

Infants born to women using methadone for maintenance can develop neonatal abstinence syndrome (NAS), attributable to methadone withdrawal in the first days of life.14 The commonly observed delay between delivery and appearance of NAS, compared with other opiates, can be explained by the fact that in the early neonatal period the concentrations of methadone in the infant and in the mother are similar. Thereafter, methadone levels decline slowly in the infant according to its long elimination half-life. Malpas et al have suggested that breastfeeding might be beneficial in the treatment of NAS,15,16 although it is not clear if this is because of the beneficial effects of breastfeeding itself or because of the low concentrations of methadone present in breast milk mitigating the withdrawal.

Conclusion

The very low concentrations of methadone in beast milk reported in the literature support the recommendation to not discourage breastfeeding women from using methadone treatment, regardless of the dose.


MOTHERISK

Motherisk questions are prepared by the Motherisk Team at the Hospital for Sick Children in Toronto, Ont. Drs Glatstein, Garcia-Bournissen, and Finkelstein are members and Dr Koren is Director of the Motherisk Program. Dr Koren is supported by the Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation. He holds the Ivey Chair in Molecular Toxicology in the Department of Medicine at the University of Western Ontario in London.

Do you have questions about the effects of drugs, chemicals, radiation, or infections in women who are pregnant or breastfeeding? We invite you to submit them to the Motherisk Program by fax at 416 813-7562; they will be addressed in future Motherisk Updates.

Published Motherisk Updates are available on the Canadian Family Physician website (www.cfp.ca) and also on the Motherisk website (www.motherisk.org).

 

Acknowledgment

Dr Garcia-Bournissen has received funding from the Clinician Scientist Training Program. This program is funded, fully or in part, by the Ontario Student Opportunity Trust Fund—Hospital for Sick Children Foundation Student Scholarship Program.

Footnotes

Competing interests

None declared

References

  1. Dawe S, Harnett P. Reducing potential for child abuse among methadone-maintained parents: results from a randomized controlled trial. J Subst Abuse Treat 2007;32(4):381–90. Epub 2006 Dec 8.[Medline]
  2. Daley M, Argeriou M, McCarty D, Callahan JJ Jr, Shepard DS, Williams CN. The costs of crime and the benefits of substance abuse treatment for pregnant women. J Subst Abuse Treat 2000;19(4):445–58.[Medline]
  3. Kintz P, Villain M, Dumestre-Toulet V, Capolaghi B, Cirimele V. Methadone as a chemical weapon: two fatal cases involving babies. Ther Drug Monit 2005;27(6):741–3.[Medline]
  4. Loimer N, Schmid R. The use of plasma level to optimize maintenance treatment. Drug Alcohol Depend 1992;30(3):241–6.[Medline]
  5. Robinson AE, Williams FM. The distribution of methadone in man. J Pharm Pharmacol 1971;23(5):353–8.[Medline]
  6. Totah RA, Sheffels P, Roberts T, Whittington D, Thummel K, Kharasch ED. Role of CYP2B6 in stereoselective human methadone metabolism. Anesthesiology 2008;108(3):363–74.[Medline]
  7. Wojnar-Horton RE, Kristensen JH, Yapp P, Ilett KF, Dusci LJ, Hackett LP. Methadone distribution and excretion into breast milk of clients in a methadone maintenance programme. Br J Clin Pharmacol 1997;44(6):543–7.[Medline]
  8. Liu AJ, Nanan R. Methadone maintenance and breastfeeding in the neonatal period. Pediatrics 2008;121(4):869–70.[Free Full Text]
  9. Abdel-Latif ME, Pinner J, Clews S, Cooke F, Lui K, Oei J. Effects of breast milk on the severity and outcome of neonatal abstinence syndrome among infants of drug-dependent mothers. Pediatrics 2006;117(6):e1163–9.[Abstract/Free Full Text]
  10. Meites E. Opiate exposure in breastfeeding newborns. J Hum Lact 2007;23(1):13.[Free Full Text]
  11. Geraghty B, Graham EA, Logan B, Weiss EL. Methadone levels in breast milk. J Hum Lact 1997;13(3):227–30.[Abstract/Free Full Text]
  12. American Academy of Pediatrics, Committee on Drugs. The transfer of drugs and other chemicals into human breast milk. Pediatrics 1983;72(3):375–83.[Abstract/Free Full Text]
  13. American Academy of Pediatrics, Committee on Drugs: The transfer of drugs and other chemical into human milk. Pediatrics 2001;108(3):776–89.[Abstract/Free Full Text]
  14. Philipp BL, Merewood A, O’Brien S. Methadone and breastfeeding: new horizons. Pediatrics 2003;111(6 Pt 1):1429–30.[Free Full Text]
  15. Malpas TJ, Horwood J, Darlow BA. Breastfeeding reduces the severity of neontatal abstinence syndrome. J Pediatr Child Health 1997;33:A38.
  16. Malpas TJ, Darlow BA. Neonatal abstinence syndrome following abrupt cessation of breastfeeding. N Z Med J 1999;112(1080):12–3.[Medline]




This Article
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