Is it safe to use codeine (opioid analgesic) while breastfeeding?

Codeine and Breastfeeding: Safety Considerations

Codeine should not be used by breastfeeding women due to the risk of severe neonatal depression and potential infant death, particularly in women who are ultrarapid metabolizers of CYP2D6. 1

Risk Assessment

• Codeine is a prodrug metabolized to morphine by the CYP2D6 enzyme system, with significant genetic variability in metabolism rates across populations 1
• Women who are ultrarapid metabolizers (up to 28% in Middle Eastern/North African populations, up to 10% in Caucasians) produce much higher concentrations of morphine in breast milk 1
• This variability creates unpredictable infant exposure, with documented cases of severe neonatal depression and death 1
• Codeine is secreted in breast milk due to high lipophilicity and weak protein binding, with potential for metabolism by the infant 1

Regulatory Guidance

• The US Food and Drug Administration (FDA) and European Medicines Agency advise against codeine use in breastfeeding women 1
• The FDA drug label specifically states pregnant or breastfeeding women should consult a healthcare professional before use 2
• While the UK Medicines and Healthcare Products Regulatory Agency (MHRA) suggests codeine may be suitable in moderation for short durations, the Association of Anaesthetists recommends against its use given the availability of safer alternatives 1

Management Recommendations

• Alternative analgesics for breastfeeding mothers:

  • Dihydrocodeine may be preferred if a weak opioid is needed, due to its cleaner metabolism compared to codeine 1
  • Morphine is recommended as the opioid of choice if strong analgesia is required 1
  • Non-opioid options like paracetamol (acetaminophen) and ibuprofen are considered safe during breastfeeding 3

• If codeine has been taken by a breastfeeding woman:

  • Discard breast milk for 15 hours to allow full clearance from maternal plasma 1
  • Monitor the infant for signs of opioid toxicity including increased sleepiness, difficulty breastfeeding, respiratory depression, and decreased alertness 1

Special Considerations

• Short-term opioid use (2-3 days) for pain management during labor, delivery, and immediate postpartum period generally poses lower risk than prolonged use 4
• Genetic testing for CYP2D6 ultrarapid metabolizer status is not routinely available, making it impossible to predict which mother-infant pairs may experience severe adverse effects 1
• The proportion of ultrarapid metabolizers varies significantly by ethnicity (1% in Asians to 28% in Middle Eastern/North African populations), creating variable risk profiles 1

Common Pitfalls

• Assuming all opioids carry equal risk during breastfeeding - different opioids have different safety profiles 1, 4
• Failing to recognize that even moderate codeine doses that appear safe in most women can cause severe toxicity in infants of ultrarapid metabolizers 1
• Not considering that the benefits of breastfeeding generally outweigh risks of most medications, but codeine represents a special case where safer alternatives exist 5, 1