Documente Academic
Documente Profesional
Documente Cultură
Number 742
Obstetric Practice, in collaboration with the American College of Nurse-Midwives liaison member Tekoa L. King, CNM, MPH; American Academy of
Family Physicians liaison member Beth Choby, MD; and committee member Yasser Y. El-Sayed, MD.
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but is, on average, approximately 4–5% (46, 47, 50). Given interindividual variation in metabolism of
Conversely, approximately 6% of individuals in the opioids, as well as the risk of maternal and neonatal
United States are poor metabolizers, and, therefore, adverse effects in women who are ultra-rapid metabolizers
receive insufficient pain control with codeine. Given of codeine, monitoring for excessive sedation and other
interindividual variation in rates of metabolism, empiric adverse effects in infants is prudent for women who are
doses of codeine are associated with producing excessive prescribed opiates (55). The Motherisk Program at the
sedation or insufficient pain relief. Hospital for Sick Children in Toronto has published
On April 20, 2017, the U.S. Food and Drug guidelines for monitoring lactating women and infants
Administration (FDA) issued a Drug Safety Communi- for central nervous system depression while using medi-
cation that announced label revisions of all prescription cations that contain codeine (Box 1). In a study of 238
medicines that contained codeine and tramadol. Among breastfeeding women using these guidelines, neonatal
the label changes is a strengthened warning that breast- sedation was reported in 2.1% of infants and was not
feeding is not recommended while using medicines that associated with differences in genotype (55). These results
contain codeine or tramadol because of the potential for suggest that such safety guidelines reduce the risk of neo-
serious adverse effects in the infant due to opioid over- natal sedation with maternal opioid use.
dose (49). The FDA did not find any published reports of Although the FDA recommendations underscore
toxicity in breastfed infants after maternal use of trama- the need for anticipatory guidance regarding opioid
dol. However, tramadol was included in the FDA advi- effects in all patients, obstetrician–gynecologists and
sory because it has pharmacologic properties that are other obstetric care providers should ensure that the
similar to codeine, including metabolism through the application of this guidance does not interfere with pain
CYP2D6 pathway to produce analgesic effects. control or disrupt breastfeeding during the postpartum
Although not addressed in the FDA guidance, period. The American College of Obstetricians and Gy-
oxycodone and hydrocodone are also partially metabo- necologists recommends that obstetrician–gynecologists
lized by CYP2D6 to the more potent opioid metabolites and other obstetric care providers adopt the following
oxymorphone and hydromorphone, respectively. After two strategies to enable adequate pain control and con-
oxycodone administration, ultra-rapid metabolizers tinued breastfeeding if opioid analgesia is required:
may experience more pronounced pain relief (51). Hy- 1. If a codeine-containing medication is the selected choice
drocodone metabolism to hydromorphone also varies by for postpartum pain management, medication risks and
CYP2D6 activity (52). Because hydromorphone is not benefits, including patient education regarding newborn
metabolized by CYP2D6, effects of the drug in breast-
signs of toxicity, should be reviewed with the family.
feeding mother–infant dyads are not influenced by
maternal or infant CYP2D6 genotype (53). 2. Regardless of the medication selected, it is prudent to
As with all opioids, morphine given intravenously or counsel women who are prescribed opioid analgesics
orally, as opposed to neuraxial administration, appears in about the risk of central nervous system depression in the
higher amounts in breast milk. Once the woman’s milk woman and the breastfed infant. Duration of use of opiate
comes in, it is best to provide pain control with a nonopioid prescriptions should be limited to the shortest reasonable
analgesic and limit maternal intake of morphine to the first course expected for treating acute pain.
few days at a low dosage with close infant monitoring if the Additional strategies to encourage use of regional
infant is receiving the woman’s breast milk (54). anesthetic techniques, NSAIDs, and acetaminophen can
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This information is designed as an educational resource to aid clinicians in providing obstetric and gynecologic care, and use of this information is
voluntary. This information should not be considered as inclusive of all proper treatments or methods of care or as a statement of the standard of care. It
is not intended to substitute for the independent professional judgment of the treating clinician. Variations in practice may be warranted when, in the
reasonable judgment of the treating clinician, such course of action is indicated by the condition of the patient, limitations of available resources, or
advances in knowledge or technology. The American College of Obstetricians and Gynecologists reviews its publications regularly; however, its pub-
lications may not reflect the most recent evidence. Any updates to this document can be found on www.acog.org or by calling the ACOG Resource Center.
While ACOG makes every effort to present accurate and reliable information, this publication is provided “as is” without any warranty of accuracy,
reliability, or otherwise, either express or implied. ACOG does not guarantee, warrant, or endorse the products or services of any firm, organization, or
person. Neither ACOG nor its officers, directors, members, employees, or agents will be liable for any loss, damage, or claim with respect to any liabilities,
including direct, special, indirect, or consequential damages, incurred in connection with this publication or reliance on the information presented.
All ACOG committee members and authors have submitted a conflict of interest disclosure statement related to this published product. Any potential
conflicts have been considered and managed in accordance with ACOG’s Conflict of Interest Disclosure Policy. The ACOG policies can be found on
acog.org. For products jointly developed with other organizations, conflict of interest disclosures by representatives of the other organizations are ad-
dressed by those organizations. The American College of Obstetricians and Gynecologists has neither solicited nor accepted any commercial involvement
in the development of the content of this published product.
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