Codeine and CYP2D6: Why Genetics Matter During Breastfeeding
3 June 2026
Codeine is a commonly prescribed medication used to relieve mild to moderate pain. While it is generally considered safe when used as directed, some individuals may process codeine differently due to genetic variations.
One of the most important genes involved in codeine metabolism is CYP2D6. Variations in this gene can affect how quickly codeine is converted into morphine, potentially influencing both treatment effectiveness and the risk of side effects.
This becomes particularly important during breastfeeding, as morphine can pass into breast milk and be transferred to the infant.
A tragic case published in The Lancet in 2006 highlighted how genetic differences can influence medication safety and helped bring greater awareness to the role of pharmacogenomics in healthcare.
A Landmark Case: Morphine Poisoning in a Breastfed Infant
The mother had been taking 30mg of codeine before she managed to deliver her baby on April 2005.
Because of the recent surgery delivering her baby, the mother started taking 5oomg of acetaminophen post-surgery.
Analysis of the baby's blood revealed a high morphine level of 70ng/mL, which is unusual for breastfed infants, especially mothers who are undergoing codeine medication.
The baby passed because the mother had a gene variant, potentially causing the excessive codeine to morphine.
In April 2005, a healthy full-term baby boy was born. By the seventh day of life, he experienced difficulty breastfeeding and became increasingly drowsy. Although he appeared to improve temporarily, his condition deteriorated again. On the thirteenth day, the infant sadly passed away.¹
A postmortem examination revealed no anatomical abnormalities. However, laboratory analysis detected a morphine concentration of 70 ng/mL in the infant’s blood, significantly higher than what would typically be expected in breastfed infants whose mothers were taking codeine.¹
The mother had been prescribed a combination of codeine and acetaminophen following childbirth. During genetic testing, she was found to carry a CYP2D6 variant associated with the ultrarapid metaboliser phenotype.¹
As an ultrarapid metaboliser, her body converted codeine into morphine more quickly and extensively than expected, resulting in elevated morphine levels in her breast milk. The infant was exposed to these higher levels of morphine through breastfeeding, leading to a tragic outcome.
What Is CYP2D6?
CYP2D6 is a gene responsible for producing an enzyme involved in the metabolism of many commonly prescribed medications, including codeine.
Based on their genetic makeup, individuals may be classified into different metaboliser groups:
- Poor Metabolisers
- Intermediate Metabolisers
- Normal Metabolisers
- Ultrarapid Metabolisers
These genetic differences can influence how effectively medications work and whether an individual may be at increased risk of side effects.
For codeine specifically, CYP2D6 determines how efficiently the medication is converted into morphine, which is the active compound responsible for pain relief.
Why This Case Changed Clinical Practice
The 2006 Lancet case became one of the most widely cited examples in pharmacogenomics.
It demonstrated that the same medication and the same dose may not produce the same outcome in every individual. Following reports of serious toxicity associated with codeine use in ultrarapid metabolisers, health authorities and professional organisations introduced stronger warnings regarding codeine use during breastfeeding.
This case reinforced the importance of considering genetic differences when prescribing certain medications.
How Pharmacogenomics Helps Improve Medication Safety
Pharmacogenomics (PGx) studies how genetic variations influence an individual’s response to medications. By understanding genetic differences in drug metabolism, healthcare professionals may be able to identify medications that could require closer monitoring, dosage adjustments, or alternative treatment approaches.
For medications such as codeine, genetic information may provide valuable insights into how a patient processes the drug and whether there may be an increased risk of adverse reactions.
Why Pharmacogenomics Matters in Malaysia
Genetic variations affecting medication response are common across different populations, including Asians.
As awareness of pharmacogenomics continues to grow in Malaysia, DNA-guided prescribing is becoming an increasingly important component of personalised healthcare. Understanding genes such as CYP2D6 may help healthcare professionals make more informed prescribing decisions and support safer medication use.
Conclusion
The tragic case of morphine poisoning in a breastfed infant highlighted how genetic differences can influence medication safety.
Not everyone processes medications in the same way. Variations in genes such as CYP2D6 may affect how the body responds to codeine and many other commonly prescribed medications.
Understanding these genetic differences may help support more informed healthcare decisions and personalised treatment strategies. Interested in learning how your DNA may influence your response to medications?
PRECISE Pharmacogenomics (PGx) analyses clinically relevant genetic markers associated with medication metabolism and response, helping healthcare professionals gain additional insights when evaluating medication choices. Contact Precision Diagnostics to learn more about PRECISE PGx.
Reference
- Koren G, Cairns J, Chitayat D, Gaedigk A, Leeder SJ. (2006). Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother. Lancet. 19;368(9536):704.
