Guidelines for maternal codeine use during breastfeeding

Parvaz Madadi, PhD, Myla Moretti, MSc, Nada Djokanovic, MD MSc, Pina Bozzo, Irena Nulman, MD FRCPC, Shinya Ito, MD FRCPC and Gideon Koren, MD FRCPC FACMT

November 2009

Postpartum use

A review of the pharmacologic mechanism of codeine analgesia sheds light on issues surrounding its postpartum use.⁶ Codeine is a prodrug that must be metabolized via the cytochrome P450 2D6 (CYP 2D6) enzyme into morphine to elicit an analgesic effect^7,8; however, the CYP 2D6 gene is highly polymorphic.⁹ While codeine is effective for most individuals worldwide who possess 2 functional copies of the gene, about 8% of Europeans do not possess any active gene copies, and thus are unable to receive analgesia.¹⁰ On the other hand, functional duplications of the CYP 2D6 gene (which range from 2% to 40% of individuals, depending on ethnic background¹⁰) enhance morphine biotransformation from codeine¹¹ and have been associated with adverse events,^12,13 including death in a breastfed infant.^4,5 There are commercial tests available for CYP 2D6 genetic screening; however, clinical trials supporting its introduction in the hospital setting have not yet been performed.

While maternal genotype should certainly be considered before codeine is prescribed, patient education might be an equally important preventive measure. Newborn infants appear to be most sensitive to the effects of narcotic opioids as compared with older infants^5,14–16; however, many mothers are unaware of the symptoms of central nervous system (CNS) depression and what to look for in their babies. In any case in which a baby is not fed well, does not wake up to be fed, does not gain weight, or shows limpness, he or she should be examined by a physician. These symptoms tend to appear after 4 days^3,5 of continuous breastfeeding while using codeine and are likely due to the accumulation of morphine in the infant.¹⁷ It follows that higher maternal codeine dose is associated with a higher risk of neonatal adverse events.^3,5 Thus, if pain still necessitates codeine after 4 days, an attempt should be made to decrease the dose or to switch to non-codeine painkillers (eg, non-steroidal anti-inflammatory drugs).⁵ There is also a strong correlation between CNS depression in the mother and the breastfed baby,⁵ which can serve as a warning flag for mothers; if a mother herself feels groggy or sedated, her baby should be examined by a physician for signs of CNS depression as well.

Conclusion

As the postpartum length of hospital stay has decreased in Canada,¹⁸ the onus for providing a safe and effective analgesic for maternal outpatient use has increased. The strategy of replacing codeine with another opioid analgesic is troublesome in the absence of safety data and clinical experience. However, if codeine is to remain the first-line treatment of postpartum pain, practitioners, as well as patients, should be educated on its risks.

MOTHERISK

Motherisk questions are prepared by the Motherisk Team at the Hospital for Sick Children in Toronto, Ont. Dr Madadi, Ms Moretti, Ms Bozzo, and Drs Djokanovic and Ito are members of the Motherisk Program. Dr Nulman is Associate Director and Dr Koren is Director of the Motherisk Program. Dr Koren is supported by the Research Leadership for Better Pharmacotherapy during Pregnancy and Lactation. He holds the Ivey Chair in Molecular Toxicology in the Department of Medicine at the University of Western Ontario in London.

Can Fam Physician
Vol.55, No. 11, November 2009, pp.1077 - 1078
Copyright © 2009 by The College of Family Physicians of Canada

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