The Basics
What is Codeine?
Codeine is used to relieve mild to moderate pain. It is also used, usually in combination with other medications, to reduce coughing.
Brand names for Codeine
Codeine Sulfate
How Codeine is classified
Analgesic – Opioid, Narcotics, Antitussive Agents
Codeine During Pregnancy
Codeine pregnancy category
Category CNote that the FDA has deprecated the use of pregnancy categories, so for some medications, this information isn’t available. We still think it’s useful to list historical info, however, given what a common proxy this has been in the past.
What we know about taking Codeine while pregnant
There are no adequate and well-controlled studies that focus on Codeine in pregnancy. Codeine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Codeine has been shown to have embryolethal and fetotoxic effects (reduced fetal body weights and delayed or incomplete ossification) in the hamster, rat and mouse models at approximately 2-4 times the maximum recommended human dose of 360 mg/day based on a body surface area comparison. Maternally toxic doses that were approximately 7 times the maximum recommended human dose of 360 mg/day, were associated with evidence of resorptions and incomplete ossification, including meningioencephalocele and cranioschisis. In contrast, codeine did not demonstrate evidence of embrytoxicity or fetotoxicity in the rabbit model at doses up to 2 times the maximum recommended human dose of 360 mg/day based on a body surface area comparison [see Nonclinical Toxicology].
Taking Codeine While Breastfeeding
What are recommendations for lactation if you're taking Codeine?
Maternal use of codeine during breastfeeding can cause infant drowsiness, central nervous system depression and even death, with pharmacogenetics possibly playing a role.[1][2] Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. Once the mother’s milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of oral codeine to 2-4 days at a low dosage with close infant monitoring, especially in the outpatient setting.[2][3][4][5] If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately.[6] Excessive sedation in the mother often correlates with excess sedation in the breastfed infant. Following these precautions can lower the risk of neonatal sedation.[7] Numerous professional organizations and regulatory agencies recommend that other agents are preferred over codeine or to avoid codeine completely during breastfeeding;[8][9][10][11][12] however, other opioid alternatives have been studied less and may not be safer.[13]
Maternal / infant drug levels
Maternal use of codeine during breastfeeding can cause infant drowsiness, central nervous system depression and even death, with pharmacogenetics possibly playing a role.[1][2] Newborn infants seem to be particularly sensitive to the effects of even small dosages of narcotic analgesics. Once the mother’s milk comes in, it is best to provide pain control with a nonnarcotic analgesic and limit maternal intake of oral codeine to 2-4 days at a low dosage with close infant monitoring, especially in the outpatient setting.[2][3][4][5] If the baby shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately.[6] Excessive sedation in the mother often correlates with excess sedation in the breastfed infant. Following these precautions can lower the risk of neonatal sedation.[7] Numerous professional organizations and regulatory agencies recommend that other agents are preferred over codeine or to avoid codeine completely during breastfeeding;[8][9][10][11][12] however, other opioid alternatives have been studied less and may not be safer.[13]
Possible effects of Codeine on milk supply
Narcotics can increase serum prolactin.[31] However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.
Possible alternatives to Codeine
(Analgesia) Acetaminophen, Butorphanol, Hydromorphone, Ibuprofen, Morphine; (Antitussive) Dextromethorphan.
List of References
Lactation sources: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501922/1. Madadi P, Shirazi F, Walter FG, Koren G. Establishing causality of CNS depression in breastfed infants following maternal codeine use. Paediatr Drugs. 2008;10:399-404. PMID: 18998750
2. Willmann S, Edginton AN, Coboeken K et al. Risk to the breast-fed neonate from codeine treatment to the mother: a quantitative mechanistic modeling study. Clin Pharmacol Ther. 2009;86:634-43. PMID: 19710640
3. 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;198:256-61. PMID: 19628064
4. Madadi P, Moretti M, Djokanovic N et al. Guidelines for maternal codeine use during breastfeeding. Can Fam Physician. 2009;55:1077-8. PMID: 19910591
5. Ito S. Opioids in breast milk: Pharmacokinetic principles and clinical implications. J Clin Pharmacol. 2018;58 (Suppl 10):S151-S163. PMID: 30248201
6. U.S. Food and Drug Administration. Public Health Advisory. Use of codeine products in nursing mothers. 2007;Aug 17. http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm054717.htm
7. Kelly LE, Chaudhry SA, Rieder MJ et al. A clinical tool for reducing central nervous system depression among neonates exposed to codeine through breast milk. PLoS One. 2013;8:e70073. PMID: 23922910
8. Sachs HC and the American Academy of Pediatrics committee on Drugs. The transfer of drugs and therapeutics into human breast milk: An update on selected topics. Pediatrics. 2013;132:e796-809. PMID: 23979084
9. United States Food and Drug Administration. FDA Drug Safety Communication: FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women. 2017;April 20. https://www.fda.gov/Drugs/DrugSafety/ucm549679.htm
10. 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;104:550-6. PMID: 25809057
11. European Medicines Agency. Codeine-containing medicines. 2013;EMA/385716/2013. http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Codeine-containing_medicines/human_referral_prac_000008.jsp&mid=WC0b01ac05805c516f
12. Lamvu G, Feranec J, Blanton E. Perioperative pain management: An update for obstetrician-gynecologists. Am J Obstet Gynecol. 2017. PMID: 28666699
13. Halder S, Russell R, Quinlan J. Codeine and breast-feeding mothers. Int J Obstet Anesth. 2015;24:5-7. Editorial. PMID: 25578245
14. Madadi P, Koren G. Pharmacogenetic insights into codeine analgesia: implications to pediatric codeine use. Pharmacogenomics. 2008;9:1267-84. PMID: 18781855
15. Findlay JW, DeAngelis RL et al. Analgesic drugs in breast milk and plasma. Clin Pharmacol Ther. 1981;29:625-33. PMID: 7214793
16. Naumburg EG, Meny RG, Findlay J et al. Codeine and morphine levels in breast milk and neonatal plasma. Pediatr Res. 1987;21(4, pt 2):240A. Abstract.
17. Meny RG, Naumburg EG, Alger LS et al. Codeine and the breastfed neonate. J Hum Lact. 1993;9:237-40. PMID: 8260056
18. Koren G, Cairns J, Chitayat D et al. Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet. 2006;368:704. PMID: 16920476
19. Madadi P, Ross CJ, Pape T et al. A toxicogenetic case-control study of codeine toxicity during breastfeeding. Clin Pharmacol Ther. 2008;83 (Suppl 1):S2. DOI: doi:10.1038/sj.clpt.2008.36
20. Schaefer C, Peters P, Miller RK, eds. Drugs during pregnancy and lactation. Treatment options and risk assessment, 2nd ed. Amsterdam; Boston: Elsevier Academic Press. 2007:644-5.
21. Smith JW. Codeine-induced bradycardia in a breast-fed infant. Clin Res. 1982;30:259A. Abstract.
22. Davis JM, Bhutani VK. Neonatal apnea and maternal codeine use. Pediatr Res. 1985;19(4 pt 2):170A. Abstract.
23. Naumburg EG, Meny RG. Breast milk opioids and neonatal apnea. Am J Dis Child. 1988;142:11-2. Letter. PMID: 3341293
24. Ito S, Blajchman A, Stephenson M et al. Prospective follow-up of adverse reactions in breast-fed infants exposed to maternal medication. Am J Obstet Gynecol. 1993;168:1393-9. PMID: 8498418
25. Cook MN, Olshan AF, Guess HA et al. Maternal medication use and neuroblastoma in offspring. Am J Epidemiol. 2004;159:721-31. PMID: 15051581
26. Madadi P, Ross C, Hayden M et al. Pharmacogenetics of neonatal opioid toxicity following maternal use of codeine during breastfeeding: a case-control study. Clin Pharmacol Ther. 2009;85:31-5. PMID: 18719619
27. Ciszkowski C, Madadi P, Sistonen J et al. The incidence of CNS depression of neonates breastfed by mothers receiving codeine for postpartum analgesia. Clin Pharmacol Ther. 2011;89 (Suppl 1):S94. Abstract. DOI: doi:10.1038/clpt.2010.335
28. Lam J, Kelly L, Ciszkowski C et al. Central nervous system depression of neonates breastfed by mothers receiving oxycodone for postpartum analgesia. J Pediatr. 2012;160:33-37.e2. PMID: 21880331
29. Juurlink DN, Gomes T, Guttmann A et al. Postpartum maternal codeine therapy and the risk of adverse neonatal outcomes: A retrospective cohort study. Clin Toxicol (Phila). 2012;50:390-5. PMID: 22537257
30. Lam J, Matlow JN, Ross CJ et al. Postpartum maternal codeine therapy and the risk of adverse neonatal outcomes: The devil is in the details. Ther Drug Monit. 2012;34:378-80. PMID: 22777151
31. Moranta F. [Pharmaceutical enquiry by drowsiness in breastfed baby]. Farmaceuticos Comunitarios. 2016;8:42-44. DOI: doi:10.5672/FC.2173-9218.(2016/Vol8).004.06
32. Tolis G, Dent R, Guyda H. Opiates, prolactin, and the dopamine receptor. J Clin Endocrinol Metab. 1978;47:200-3. PMID: 263291
Disclaimer: This material is provided for educational purposes only and is not intended for medical advice, diagnosis, or treatment. Consult your healthcare provider with any questions.
