Codeine poses extra risk during breastfeeding

Codeine can present a threat to breastfed infants, according to research published online Aug. 20 in Clinical Pharmacology and Therapeutics.

Parvaz Madadi, of the University of Western Ontario in London, Ontario, Canada, and colleagues discuss a case of fatal opioid toxicity in a newborn breastfed by a mother who was an ultrarapid metabolizer due to gene duplication, which can affect the efficacy of codeine. The authors analyzed outcomes from 72 mothers whose infants were exposed to codeine through breastfeeding.

Seventeen infants (24%) reportedly showed CNS depression, with a decrease in alertness, while their mothers used codeine, the researchers report. Mothers of these infants used a mean 59% greater dose of codeine than mothers of infants who didn't exhibit these effects, they report. Two mothers of symptomatic children were “CYP2D6 ultrarapid metabolizers” in combination with another applicable issue, having the UGT2B7*2/*2 genotype, the report indicates.

“Our study suggests that there may be a dose-response relationship between maternal codeine use and neonatal toxicity. Neonatal toxicity was reported with a daily maternal dose of codeine as low as 0.63 mg/kg. Mothers with CYP2D6 ultrarapid metabolizers, when combined with UGT2B7*2/*2, may have a high risk of neonatal opioid poisoning. Because of the gradual accumulation of morphine in breastfed infants, it appears that neonatal risk may increase with prolonged maternal codeine use. If the mother needs codeine for long periods of time, it is advisable that the baby be periodically monitored by an experienced pediatrician,” the authors conclude.

Madadi P, Ross CJ, Hayden M, et al. Pharmacogenetics of Neonatal Opioid Toxicity Following Maternal Use of Codeine During Breastfeeding: A Case-Control Study. Clin Pharmacol Ther. 2008. doi:10.1038/clpt.2008.157.