Last update Jan. 27, 2022

Кодеин

Limited compatibility

Unsafe. Moderate/severe adverse effects. Compatible under certain circumstances. Follow-up recommended. Use safer alternative or discontinue breastfeeding from 5 to 7 T ½ . Read Commentary.

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 denied or called into question. (Zipursky 2020, 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. (Lamvu 2018, 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 3-4 days and monitoring for signs of sedation in mother and infant. (Ito 2018, 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

  • Dextromethorphan (Safe product and/or breastfeeding is the best option.)
  • Diclofenac (Safe product and/or breastfeeding is the best option.)
  • Fentanyl (Safe product and/or breastfeeding is the best option.)
  • Ibuprofen (Safe product and/or breastfeeding is the best option.)
  • Morphine (Fairly safe. Mild or unlikely adverse effects. Compatible under certain circumstances. Follow-up recommended. Read Commentary.)
  • Paracetamol (Safe product and/or breastfeeding is the best option.)
  • Tramadol (Safe product and/or breastfeeding is the best option.)

Suggestions made at e-lactancia are done by APILAM team of health professionals, and are based on updated scientific publications. It is not intended to replace the relationship you have with your doctor but to compound it. The pharmaceutical industry contraindicates breastfeeding, mistakenly and without scientific reasons, in most of the drug data sheets.

Jose Maria Paricio, Founder & President of APILAM/e-Lactancia

Your contribution is essential for this service to continue to exist. We need the generosity of people like you who believe in the benefits of breastfeeding.

Thank you for helping to protect and promote breastfeeding.

José María Paricio, founder of e-lactancia.

Other names

Кодеин is Codeine in Cyrillic.

Is written in other languages:

Кодеин is also known as

Groups

Кодеин belongs to these groups or families:

Tradenames

Main tradenames from several countries containing Кодеин in its composition:

Pharmacokinetics

Variable Value Unit
Oral Bioavail. 65 - 100 %
Molecular weight 299 daltons
Protein Binding 7 - 25 %
VD 3 - 6 l/Kg
Tmax 0.5 - 1 hours
3 - 4 hours
M/P ratio 1.3 - 2.5 -
Theoretical Dose 0.005 - 0.05 mg/Kg/d
Relative Dose 0.3 -1.2 %
Ped.Relat.Dose < 1.5 %

References

  1. Zipursky J, Juurlink DN. The Implausibility of Neonatal Opioid Toxicity from Breastfeeding. Clin Pharmacol Ther. 2020 Nov;108(5):964-970. Abstract
  2. Ito S. Opioids in Breast Milk: Pharmacokinetic Principles and Clinical Implications. J Clin Pharmacol. 2018 Oct;58 Suppl 10:S151-S163. Abstract
  3. Lamvu G, Feranec J, Blanton E. Perioperative pain management: an update for obstetrician-gynecologists. Am J Obstet Gynecol. 2018 Feb;218(2):193-199. Abstract
  4. 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. Breastfeed Med. 2017 Nov;12(9):500-506. Full text (link to original source) Full text (in our servers)
  5. 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)
  6. Al-Adhami N, Whitfield K, North A. CHANGING PRESCRIBING CULTURE - A FOCUS ON CODEINE POSTPARTUM. Arch Dis Child. 2016 Abstract
  7. 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)
  8. Royal Berkshire Hospital. Codeine and breastfeeding. Maternity Information. 2016 Full text (link to original source) Full text (in our servers)
  9. Halder S, Russell R, Quinlan J. Codeine and breast-feeding mothers. Int J Obstet Anesth. 2015 Abstract
  10. 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)
  11. 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)
  12. Chow CK, Koren G. Sedating drugs and breastfeeding. Can Fam Physician. 2015 Abstract Full text (link to original source) Full text (in our servers)
  13. ABM. 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)
  14. 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
  15. 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)
  16. Dalal PG, Bosak J, Berlin C. Safety of the breast-feeding infant after maternal anesthesia. Paediatr Anaesth. 2014 Abstract
  17. EMA. Restrictions on use of codeine for pain relief in children – CMDh endorses PRAC recommendation. 2013 Full text (in our servers)
  18. 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 Sep;40(5 Suppl 3):S1-S80. Review. Abstract Full text (in our servers)
  19. Rowe H, Baker T, Hale TW. Maternal medication, drug use, and breastfeeding. Pediatr Clin North Am. 2013 Feb;60(1):275-94. Abstract
  20. Sachs HC; Committee On Drugs. The transfer of drugs and therapeutics into human breast milk: an update on selected topics. Pediatrics. 2013 Sep;132(3):e796-809. Abstract Full text (link to original source) Full text (in our servers)
  21. 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)
  22. 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)
  23. van den Anker JN. Is it safe to use opioids for obstetric pain while breastfeeding? J Pediatr. 2012 Abstract Full text (in our servers)
  24. 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)
  25. 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)
  26. Amir LH, Pirotta MV, Raval M. Breastfeeding--evidence based guidelines for the use of medicines. Aust Fam Physician. 2011 Sep;40(9):684-90. Review. Abstract Full text (link to original source) Full text (in our servers)
  27. 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)
  28. 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
  29. 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
  30. 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
  31. Madadi P, Shirazi F, Walter FG, Koren G. Establishing causality of CNS depression in breastfed infants following maternal codeine use. Paediatr Drugs. 2008 Abstract
  32. Bateman DN, Eddleston M, Sandilands E. Codeine and breastfeeding. Lancet. 2008 Abstract
  33. Ferner RE. Did the drug cause death? Codeine and breastfeeding. Lancet. 2008 Abstract
  34. Madadi P, Koren G. Pharmacogenetic insights into codeine analgesia: implications to pediatric codeine use. Pharmacogenomics. 2008 Abstract
  35. 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)
  36. 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)
  37. Young M. Morphine in breast milk. Can Fam Physician. 2007 Abstract Full text (link to original source) Full text (in our servers)
  38. 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
  39. 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
  40. Bar-Oz B, Bulkowstein M, Benyamini L, Greenberg R, Soriano I, Zimmerman D, Bortnik O, Berkovitch M. Use of antibiotic and analgesic drugs during lactation. Drug Saf. 2003 Abstract
  41. 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 Abstract Full text (link to original source) Full text (in our servers)
  42. AAP - American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics. 2001 Sep;108(3):776-89. Abstract Full text (link to original source) Full text (in our servers)
  43. Spigset O, Hägg S. Analgesics and breast-feeding: safety considerations. Paediatr Drugs. 2000 Abstract
  44. Moretti ME, Lee A, Ito S. Which drugs are contraindicated during breastfeeding? Practice guidelines. Can Fam Physician. 2000 Sep;46:1753-7. Review. Abstract Full text (link to original source) Full text (in our servers)
  45. Mitchell JL. Use of cough and cold preparations during breastfeeding. J Hum Lact. 1999 Abstract
  46. 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 May;168(5):1393-9. Abstract
  47. Meny RG, Naumburg EG, Alger LS, Brill-Miller JL, Brown S. Codeine and the breastfed neonate. J Hum Lact. 1993 Abstract
  48. Naumburg EG, Meny RG. Breast milk opioids and neonatal apnea. Am J Dis Child. 1988 Abstract
  49. Naumburg EG, Meny RG, Findlay J, Brill JL, Alger LS Codeine and morphine levels in breast milk and neonatal plasma. Pediatr Res. 1987;21(4, Pt 2):240A. Abstract 400 Full text (link to original source)
  50. Findlay JW, DeAngelis RL, Kearney MF, Welch RM, Findlay JM. Analgesic drugs in breast milk and plasma. Clin Pharmacol Ther. 1981 May;29(5):625-33. Abstract

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