Is Codeine compatible with breastfeeding? Do we have alternatives for Codeine?

Codeine

August 6, 2017 (High Risk)

Compound of cough and pain medication. The cytochrome P450-CYP2D6 enzyme catalyzes morphine.

It is excreted in breast milk in small amounts, much lower than the dose used for newborns and infants. The plasma levels of infants whose mothers take them are very low, less than usual therapeutic levels and assuming an insignificant relative dose, less than 1.5% (Meny 1993, Naumburg 1988, Findlay 1981), so it was considered safe for use during breastfeeding (Bar-Oz 2003, WHO 2002, AAP 2001, Moretti 2000, Spigset 2000, Mitchell 1999, Meny 1993).

However, excessive sedation in the mother or infant may occur if they are rapid metabolizers of codeine to morphine due to an excess of the gene linked to the P450-2D6 enzyme: this occurs in <1% of Chinese, Japanese and Hispanic people; 3% African Americans; 1-10% of Caucasians and 16-29% of North Africans, Ethiopians and Saudis (Halder 2015, Sachs 2013). The genetic diagnosis of this characteristic is not available in usual clinical practice (Madadi, 2011).

Codeine through breast milk has been linked to the appearance of neonatal apnea (Naumburg, 1988), drowsiness (Ito, 1993), neurological depression (Madadi, 2008) and, above all, a fatal outcome: a newborn whose mother had this genetic abnormality died at 13 days; the mother was taking 60 mg of codeine twice daily, morphine levels were normal in breast milk, but very high in the child's plasma (Madadi 2007, Koren 2006). Subsequently, the causality of codeine in this case has been called into question (Bateman 2008, Ferner RE 2008, Young 2007).

A link has been found between the use of codeine during pregnancy and breastfeeding and the risk of developing neuroblastoma in the infant (Cook, 2004).

Because of all this, and with newborns having a limited capacity for opioid elimination (Willmann, 2009) and the existence of more effective alternatives, many authors and institutions advocate completely discouraging its use in infants and breastfeeding mothers (FDA 2017, Al-Adhami 2016, Lazaryan 2015, AEMPS 2015, Sachs 2013, EMA 2013).

Other authors advocate cautious use (some even in the case of rapid metabolizers), using the lowest possible effective dose and for no more than 4 days and monitoring for signs of sedation in mother and infant (Royal Berkshire-NHS 2016, Halder 2015, Reece-Stremtan-ABM Protocol#21 2015, Chow 2015, Kelly 2013, UKMi NHS 2013, Rowe 2013, Montgomery-ABM protocol#15 2012, Amir 2011, Madadi 2009, Madadi 2007, FDA 2007).

The use of non-steroidal anti-inflammatory drugs (NSAIDs) better controls pain and with fewer side effects than codeine alone or in combination with paracetamol (Palanisamy 2014, Hendrickson 2012, van den Anker 2012, Madadi 2009, Nauta 2009, Willmann 2009), and codeine is not included either in international consensus on the treatment of migraines (Bordini 2016, Worthington 2013).

Follow WHO standards for childbirth attendance, reduce cesarean sections and episiotomies, and therefore the need for analgesics in the first few days.

Alternatives

Very Low Risk

Compatible. Not risky for breastfeeding or infant.

Low Risk

Moderately safe. Mild risk possible. Follow up recommended. Read the Comment.

High Risk

Poorly safe. Evaluate carefully. Use a safer alternative. Read the Comment.

Very High Risk

Not recommended. Cessation of breastfeeding or alternative.

Synonyms

  • Codeine Hydrochloride
  • Codeine Phosphate
  • Codeine Sulfate
  • Methylmorphine

Writings

  • كودين (Arabic)
  • Кодеин (Cyrillic)
  • 可待因 (Chinese)
  • コデイン (Japanese)
  • Codéine (French)
  • C18H21NO3,H2O (Molecular formula)
  • 7,8-Didehydro-4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol monohydrate (Chemical name)

References

  1. FDA. FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women. Drug Safety Communications. 2017 Full text (link to original source) Full text (in our servers)
  2. Reece-Stremtan Sarah, Campos Matilde, Kokajko Lauren, and The Academy of Breastfeeding Medicine. Breastfeeding Medicine. ABM Clinical Protocol #15: Analgesia and Anesthesia for the Breastfeeding Mother, Revised 2017. Breastfeeding Medicine. 2017 Full text (link to original source) Full text (in our servers)
  3. Bordini CA, Roesler C, Carvalho Dde S, Macedo DD, Piovesan É, Melhado EM, Dach F, Kowacs F, Silva Júnior HM, Souza JA, Maciel JA Jr, Carvalho JJ, Speciali JG, Barea LM, Queiroz LP, Ciciarelli MC, Valença MM, Lima MM, Vincent MB. Recommendations for the treatment of migraine attacks - a Brazilian consensus. Arq Neuropsiquiatr. 2016 Abstract Full text (link to original source) Full text (in our servers)
  4. Al-Adhami N, Whitfield K, North A. CHANGING PRESCRIBING CULTURE - A FOCUS ON CODEINE POSTPARTUM. Arch Dis Child. 2016 Abstract
  5. Royal Berkshire Hospital. Codeine and breastfeeding. Maternity Information. 2016 Full text (link to original source) Full text (in our servers)
  6. AEMPS. Codeína: Nuevas restricciones de uso como antitusígeno en Pediatría. Recomendaciones del Comité para la Evaluación de Riesgos en Farmacovigilancia europeo-PRAC. 2015 Full text (in our servers)
  7. Halder S, Russell R, Quinlan J. Codeine and breast-feeding mothers. Int J Obstet Anesth. 2015 Abstract
  8. Lazaryan M, Shasha-Zigelman C, Dagan Z, Berkovitch M. Codeine should not be prescribed for breastfeeding mothers or children under the age of 12. Acta Paediatr. 2015 Abstract
  9. Chow CK, Koren G. Sedating drugs and breastfeeding. Can Fam Physician. 2015 Abstract Full text (link to original source) Full text (in our servers)
  10. ABM Protocolo clínico de la ABM n.º 21: Pautas para la lactancia y el consumo de sustancias o trastorno por consumo de sustancias, revisado en 2015. Breastfeed Med. 2015 Full text (link to original source) Full text (in our servers)
  11. Reece-Stremtan S, Marinelli KA. ABM Clinical Protocol #21: Guidelines for Breastfeeding and Substance Use or Substance Use Disorder, Revised 2015. Breastfeed Med. 2015 Abstract Full text (link to original source) Full text (in our servers)
  12. Palanisamy A, Bailey CR. Codeine in mothers and children: where are we now? Anaesthesia. 2014 Abstract Full text (link to original source) Full text (in our servers)
  13. Kelly LE, Chaudhry SA, Rieder MJ, 't Jong G, Moretti ME, Lausman A, Ross C, Berger H, Carleton B, Hayden MR, Madadi P, Koren G. A clinical tool for reducing central nervous system depression among neonates exposed to codeine through breast milk. PLoS One. 2013 Abstract Full text (link to original source) Full text (in our servers)
  14. EMA. Restrictions on use of codeine for pain relief in children – CMDh endorses PRAC recommendation. 2013 Full text (in our servers)
  15. Worthington I, Pringsheim T, Gawel MJ, Gladstone J, Cooper P, Dilli E, Aube M, Leroux E, Becker WJ; Canadian Headache Society Acute Migraine Treatment Guideline Development Group. Canadian Headache Society Guideline: acute drug therapy for migraine headache. Can J Neurol Sci. 2013 Abstract Full text (in our servers)
  16. NHS - UKMi. Codeine and breastfeeding: Is it safe and what are the alternatives? 2013 Full text (link to original source) Full text (in our servers)
  17. Rowe H, Baker T, Hale TW. Maternal medication, drug use, and breastfeeding. Pediatr Clin North Am. 2013 Feb;60(1):275-94. 2013 Abstract
  18. Sachs HC; Committee On Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics. 2013 Abstract Full text (link to original source) Full text (in our servers)
  19. van den Anker JN. Is it safe to use opioids for obstetric pain while breastfeeding? J Pediatr. 2012 Abstract Full text (in our servers)
  20. Hendrickson RG, McKeown NJ. Is maternal opioid use hazardous to breast-fed infants? Clin Toxicol (Phila). 2012 Abstract Full text (link to original source) Full text (in our servers)
  21. Amir LH, Pirotta MV, Raval M. Breastfeeding--evidence based guidelines for the use of medicines. Aust Fam Physician. 2011 Abstract Full text (link to original source) Full text (in our servers)
  22. Madadi P, Ciszkowski C, Gaedigk A, Leeder JS, Teitelbaum R, Chitayat D, Koren G. Genetic transmission of cytochrome P450 2D6 (CYP2D6) ultrarapid metabolism: implications for breastfeeding women taking codeine. Curr Drug Saf. 2011 Abstract Full text (in our servers)
  23. Nauta M, Landsmeer ML, Koren G. Codeine-acetaminophen versus nonsteroidal anti-inflammatory drugs in the treatment of post-abdominal surgery pain: a systematic review of randomized trials. Am J Surg. 2009 Abstract
  24. Madadi P, Moretti M, Djokanovic N, Bozzo P, Nulman I, Ito S, Koren G. Guidelines for maternal codeine use during breastfeeding. Can Fam Physician. 2009 Abstract Full text (in our servers)
  25. Madadi P, Ross CJ, Hayden MR, Carleton BC, Gaedigk A, Leeder JS, Koren G. Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: a case-control study. Clin Pharmacol Ther. 2009 Abstract
  26. Willmann S, Edginton AN, Coboeken K, Ahr G, Lippert J. Risk to the breast-fed neonate from codeine treatment to the mother: a quantitative mechanistic modeling study. Clin Pharmacol Ther. 2009 Abstract
  27. Madadi P, Shirazi F, Walter FG, Koren G. Establishing causality of CNS depression in breastfed infants following maternal codeine use. Paediatr Drugs. 2008 Abstract
  28. Ferner RE. Did the drug cause death? Codeine and breastfeeding. Lancet. 2008 Abstract
  29. Bateman DN, Eddleston M, Sandilands E. Codeine and breastfeeding. Lancet. 2008 Abstract
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  31. Public Health Advisory: Use of Codeine By Some Breastfeeding Mothers May Lead To Life-Threatening Side Effects In Nursing Babies FDA 2007 Full text (in our servers)
  32. Madadi P, Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder JS, Teitelbaum R, Karaskov T, Aleksa K. Safety of codeine during breastfeeding: fatal morphine poisoning in the breastfed neonate of a mother prescribed codeine. Can Fam Physician. 2007 Abstract Full text (in our servers)
  33. Young M. Morphine in breast milk. Can Fam Physician. 2007 Abstract Full text (link to original source) Full text (in our servers)
  34. Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder SJ. Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet. 2006 Abstract
  35. Cook MN, Olshan AF, Guess HA, Savitz DA, Poole C, Blatt J, Bondy ML, Pollock BH. Maternal medication use and neuroblastoma in offspring. Am J Epidemiol. 2004 Abstract
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  37. WHO / UNICEF. BREASTFEEDING AND MATERNAL MEDICATION Recommendations for Drugs in the Eleventh WHO Model List of Essential Drugs. Department of Child and Adolescent Health and Development (WHO/UNICEF) 2002 Full text (link to original source) Full text (in our servers)
  38. AAP - American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics. 2001 Abstract Full text (link to original source) Full text (in our servers)
  39. Moretti ME, Lee A, Ito S. Which drugs are contraindicated during breastfeeding? Practice guidelines. Can Fam Physician. 2000 Abstract Full text (link to original source) Full text (in our servers)
  40. Spigset O, Hägg S. Analgesics and breast-feeding: safety considerations. Paediatr Drugs. 2000 Abstract
  41. Mitchell JL. Use of cough and cold preparations during breastfeeding. J Hum Lact. 1999 Abstract
  42. Meny RG, Naumburg EG, Alger LS, Brill-Miller JL, Brown S. Codeine and the breastfed neonate. J Hum Lact. 1993 Abstract
  43. Ito S, Blajchman A, Stephenson M, Eliopoulos C, Koren G. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol. 1993 Abstract
  44. Naumburg EG, Meny RG. Breast milk opioids and neonatal apnea. Am J Dis Child. 1988 Abstract
  45. Findlay JW, DeAngelis RL, Kearney MF, Welch RM, Findlay JM. Analgesic drugs in breast milk and plasma. Clin Pharmacol Ther. 1981 Abstract