The Pharmacology of Opiates in Breastmilk
by Anne Eglash MD, IBCLC, FABM
This week’s question is on the technical side, based on a recent review The Pharmacology of Opiates in Breastmilk by Shinya Ito, MD, from the Division of Pharmacology and Toxicology at the Hospital for Sick Children in Toronto Canada. Given the epidemic proportions of opiate use, I thought I would address this topic, and provide an opportunity to brush up on some basic principles of lactation pharmacology.
The author explains that there is a difference between maternal use of narcotics during breastfeeding for pain control vs for opiate dependence. Infants whose mothers need opiates for pain control after a procedure, such as a cesarean section, have not typically been exposed to narcotics in the past, and are at risk for respiratory depression due to possible slow metabolism. It is hard to predict how an infant will metabolize opiates such as fentanyl, oxycodone, or hydrocodonedue to individual variation. In addition, infants’ brains vary greatly in terms of their sensitivity to low doses of narcotics. Some infants may become quite sedated despite low levels of opiates in breastmilk. For these reasons, around-the-clock maternal opiate use for pain control should be limited to no more than 2-3 days, especially in the outpatient setting where infant observation is limited.
Infants who were exposed to opiates during pregnancy likely have a higher tolerance to narcotics. Methadone and buprenorphine treatment during breastfeeding is thought to help prevent infant withdrawal symptoms. Infants whose mothers were treated with buprenorphine during pregnancy might have milder withdrawalas compared to methadone exposure. The levels of methadone and buprenorphine in breastmilk are lower than what these infants would need for opiate withdrawal if they were abruptly weaned, so these medications have been considered safe, although there are no clear maternal dose limitations. Infants of mothers using methadone and buprenorphine should be closely monitored for their health status.
- The Relative Infant Dose (RID) of a medication in breastmilk is the % of mom’s medication dose that the baby ingests.
- The Relative Infant Dose (RID)of a medication in breastmilk is the amount of medication that the infant ingests as a % of what would normally be a therapeutic infant dose.
- An RID of less than 10% is ideal for most medication.
- The RID of opiates used for pain control is typically over 10%.
- The FDA recommends avoidance of codeine and tramadol during breastfeeding because some mothers highly metabolize the medications into active metabolites that might cause excessive infant sedation and respiratory depression.
- Neonates in the first week of life are faster at clearing opiates from their bodies as compared to infants who are over 2 months of age.
See the Answer
Safety of maternal drug therapy during breastfeeding may be assessed from estimated levels of drug exposure of the infant through milk. Pharmacokinetic (PK) principles predict that the lower the clearance is, the higher the infant dose via milk will be. Drugs with low clearance (<1 mL/[kg·min]) are likely to cause an infant exposure level greater than 10% of the weight-adjusted maternal dose even if the milk-to-plasma concentration ratio is 1. Most drugs cause relatively low-level exposure below 10% of the weight-adjusted maternal dose, but opioids require caution because of their potential for severe adverse effects. Furthermore, substantial individual variations of drug clearance exist in both mother and infant, potentially causing drug accumulation over time in some infants even if an estimated dose of the drug through milk is small. Such PK differences among individuals are known not only for codeine and tramadol through pharmacogenetic variants of CYP2D6 but also for non-CYP2D6 substrate opioids including oxycodone, indicating difficulties of eliminating PK uncertainty by simply replacing an opioid with another. Overall, opioid use for pain management during labor and delivery and subsequent short-term use for 2-3 days are compatible with breastfeeding. In contrast, newly initiated and prolonged maternal opioid therapy must follow a close monitoring program of the opioid-naive infants. Until more safety data become available, treatment duration of newly initiated opioids in the postpartum period should be limited to 2-3 days in unsupervised outpatient settings. Opioid addiction treatment with methadone and buprenorphine during pregnancy may continue into breastfeeding, but infant conditions must be monitored.
The Relative Infant Dose (RID) of a medication is the % of mom’s medication dose that the infant ingests.It would be ideal if we could compare the % of medication that the infant ingests with what the expected infant therapeutic dose of the medication would be, but neonatal therapeutic medication levels are not available.
A RID less than 10% is considered safe for most medications, and the RID for narcotics tends to be low. However, even if the RID is low, the medication can still accumulate in the infant due to variability in excretion rates. Neonates in the first several weeks have less ability to excrete medication as compared to infants over 2 months. In addition, infants with pre-existing illnesses such as low kidney function may accumulate medications.
A mother should not typically be instructed to pump and dump if she is given narcotics for pain control. Rather, she should be counseled about the possible effects of narcotics on her infant, along with strategies to minimize narcotic use. She could be prescribed a non-narcotic pain medication as a complement, such as ibuprofen, acetaminophen, or gabapentin. Also, alternative options for pain could be discussed with her, including topical lidocaine, acupuncture, massage, ice, heat, homeopathy, and turmeric. Close followup of the infant would allow an opportunity for mom to share how she is feeling, and continued conversation on strategies for her pain.