Codeine & Breastfeeding: Implications of Pharmacogenomics (PGx)
24th June 2024
Pharmacogenomics is transforming the way we approach codeine use during breastfeeding. It provides a personalised approach to medicine, allowing healthcare providers to make safer and more effective treatment decisions. For breastfeeding mothers, understanding their genetic predisposition to codeine metabolism can mean the difference between a safe and successful breastfeeding experience and potential risks to their infants. As pharmacogenomic research continues to advance, it holds great promise in optimising healthcare decisions for both mothers and their newborns.
CASE STUDY
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 7th day, he had trouble breastfeeding and became drowsy. On the 11th day, he seemed to be recovering, but by the 12th day, he showed signs of distress and reduced milk intake. Sadly, he passed away on the 13th day, and no abnormalities were found during the postmortem examination. Analysis of the baby’s blood revealed a high morphine level of 70 ng/mL, which is unusual for breastfed infants whose mothers take codeine. ¹
The mother had been taking 30 mg of codeine and 500 mg of acetaminophen post-surgery. She initially took two tablets every 12 hours but reduced it by half on the 2nd day due to drowsiness and constipation, continuing for two weeks. Inadequate breastfeeding led to stored milk with a high morphine concentration of 87 ng/mL.
Genotyping showed that the mother had a gene variant making her an “Ultrarapid metaboliser” of codeine to morphine, explaining her drowsiness.
While breastfeeding, the mother initially took two tablets of acetaminophen/codeine twice daily. This dose could potentially produce 120 mg of morphine. She reduced it to 60 mg of codeine per day due to excessive drowsiness. The baby’s milk intake had declined for at least 24 hours before his tragic passing, occurring 11 days later. ¹
Pharmacogenomics (PGx) sheds light on Drug Safety
Pharmacogenomics explores genetic variations among individuals in drug metabolism and response. These variations can influence drug absorption, distribution, metabolism, and excretion, thereby affecting drug efficacy and safety.
Codeine is a widely used analgesic for mild to moderate pain relief. It is metabolised in the body to its active metabolite, morphine, which is responsible for its analgesic (pain relieve) effects. Pharmacogenomics research has revealed that codeine metabolism depends primarily on the expression and function of the CYP2D6 gene. Poor metabolisers metabolise less codeine into morphine, potentially weakening its efficacy. Conversely, ultrarapid metabolisers can convert codeine to morphine more rapidly, leading to higher drug concentrations in the body and an increased risk of adverse reactions.
Regarding breastfeeding, codeine can be transferred to infants through breast milk. Due to their limited ability to metabolize codeine, infants might be more susceptible to its effects. Infants, especially those with variant CYP2D6 genotypes, could be at risk of excessive analgesia (too much pain relief) or adverse reactions after codeine intake. Therefore, for breastfeeding infants, particularly those with variant CYP2D6 genotypes, doctors may advise against using codeine or limit its dosage to ensure the safety of the infants.
In conclusion, pharmacogenomics research indicates that genetic variations in drug metabolism and response can impact how drugs are processed and their effects within the body. For drugs like codeine, especially when breastfeeding is involved, infants could be affected by the drug. Thus, before using codeine, the infant’s CYP2D6 genotype and other relevant factors should be thoroughly considered to ensure safe drug use. Consult a physician or healthcare professional for advice and guidance specific to individual cases.
Reference
¹ 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.
