Is Codeine safe while breastfeeding?

Effects on the breastfed infant

Codeine was reported to be the possible cause of asymptomatic bradycardia 6 days following a single maternal 30 mg codeine dose in a week-old, term, exclusively breastfed infant.[ 20 ] This seems implausible.[ 7 ] Four probable cases of apnea associated with maternal codeine intake of 60 mg every 4 to 6 hours were reported in 4- to 6-day-old term and near-term breastfed infants. Apnea resolved 24 to 48 hours after withholding breast feeding and discontinuation of maternal codeine.[ 21 ] In a case-control study of 12 breastfed term newborns with unexplained episodes of apnea, bradycardia or cyanosis during the first week of life, maternal oral codeine use was determined to be the probable cause. A higher proportion of newborns with episodes, 83 vs 31%, had mothers using opiates, including codeine, for postpartum analgesia. The mean number of doses taken was also higher with mothers of case newborns taking a mean of 10 doses (range 4 to 22) vs. 5 doses (range 1 to 13) in the control group. There were no differences in other perinatal and demographic factors between cases and controls.[ 22 ] The authors recommended discontinuation of breastfeeding if infants of mothers taking opiate analgesics have unexplained negative cardiorespiratory symptoms. No apnea, bradycardia, or color changes occurred in 11 healthy, term, 1- to 3-day-old newborn breastfed infants exposed to codeine in milk. Their mothers had taken an average of 4 doses of oral codeine 60 mg every 4 to 6 hours prior to breastfeeding.[ 19 ] In one telephone follow-up study, 19% (5 of 26) of breastfeeding mothers taking multiple doses of codeine reported drowsiness in their infants. All infants were younger than 1 month. The authors added that the elimination half-life of codeine's metabolite, morphine, is prolonged in the newborn period which may explain why the adverse reaction was reported in only infants younger than 1 month.[ 23 ] A large case-control study of 504 children with neuroblastoma found a statist

Effects on milk supply

Narcotics can increase serum prolactin.[ 36 ] However, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.

Levels in milk

Codeine is metabolized via CYP2D6 to morphine (5%), norcodeine (15%), and further to codeine-6-glucuronide (80%) and morphine-6-glucuronide by UGT2B7. Codeine itself has very weak analgesic activity. The morphine and codeine-6-glucuronide metabolites are responsible for codeine's analgesic properties. Both CYP2D6 and UGT2B7 are subject to genetic variability, which can alter the amount of active narcotic excreted into breastmilk. The plasma clearance of morphine is prolonged in newborn infants compared to older infants and children.[ 10 , 13 , 16 ] Pharmacokinetic models of maternal codeine use during breastfeeding have shown that neonatal toxicity from codeine and morphine in milk is unlikely.[ 10 , 13 ] Maternal Levels. Two mothers who were 7 and 13 weeks postpartum were given a single 60 mg dose of oral codeine. Milk was collected over 12 hours in the first subject and over 48 hours in the second. Codeine and morphine were detected in the milk of both subjects with peak codeine levels in milk occurring 1 hour after the dose. The peak codeine milk level was 455 mcg/L in the first subject and about 450 to 550 mcg/L in the second. The half-life of codeine in breastmilk was 2.5 hours. Morphine milk levels were 16 mcg/L and 9 mcg/L 1 hour after the dose in the 2 subjects. Elimination of morphine from milk occurred very slowly over 36 hours. The authors calculated an average milk level from 0 to 12 hours after a single codeine 60 mg dose to be 140 mcg/L for codeine and 9 mcg/L for morphine. They also estimated an average steady-state codeine milk concentration of 351 mcg/L and morphine milk concentration of 42 mcg/L from a codeine dose of 60 mg every 4 hours.[ 17 ] Using the average milk level data from this study, including the contribution of the morphine metabolite, an exclusively breastfed infant would receive an estimated maximum dose of 11 mcg/kg in the 12 hours after a single 60 mg maternal dose and 59 mcg/kg daily from a maternal dosage regimen of 60 mg taken e

Alternatives LactMed lists

• Butorphanol
• Hydromorphone
• Ibuprofen