Embryofetal death has been observed in rats and rabbits administered approximately 6 (rats) and 0.3 (rabbits) times the human sublingual dose of buprenorphine 16 mg/day during the period of organogenesis. In rats, increased neonatal deaths were observed at 0.3 times and higher and dystocia at approximately 3 times the human sublingual dose of buprenorphine 16 mg/day. Teratogenicity was not observed, but increased skeletal abnormalities have been observed. Untreated opioid addiction during pregnancy is associated with adverse obstetrical outcomes such as low birth weight, preterm birth, and fetal death. Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of prolonged opioid use during pregnancy. Buprenorphine use was studied in the MOTHER trial (Maternal Opioid Treatment Human Experimental Research), a trial in which opioid dependent mothers (n=175) received buprenorphine or methadone. Buprenorphine-treated neonates required less morphine, had shorter hospital stays, and required shorter treatment for NOWS compared with methadone, but due to an imbalance in discontinuations between groups, the results are difficult to interpret. There are no controlled data with this combination product in human pregnancy.

Chronic use of opioids may cause reduced fertility in females and males of reproductive potential; it is not known whether these effects on fertility are reversible.

AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus

AU TGA pregnancy category: C
US FDA pregnancy category: Not assigned

Risk Summary: Limited human data from randomized clinical trials do not show an increased risk of major malformations while there have been reports of congenital malformations from observational studies; animal data has identified adverse events at clinically relevant and higher doses. There is extremely limited data on sublingual naloxone exposure to evaluate a drug-associated risk.

Comments:
-Prolonged use of opioids during pregnancy can result in physical dependence in the neonate; women should be advised of the risk of neonatal abstinence syndrome and ensure that appropriate treatment will be available.
-Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes; many experts believe the benefits of
pharmacotherapy for opioid use disorder during pregnancy outweigh the risks of untreated opioid use disorder.
-Dose adjustments of buprenorphine may be required during pregnancy; withdrawal signs and symptoms should be monitored closely.

See references

Benefit should outweigh risk

Excreted into human milk: Yes (buprenorphine); Unknown (naloxone)
Excreted into animal milk: Yes (buprenorphine); Unknown (naloxone)

Comments:
-Breastfed infants should be monitored closely for increased drowsiness and breathing difficulties.
-The decision to use the combination buprenorphine/naloxone product while breastfeeding is a shared decision, but one that ultimately must be made by the patient once she understands the risks and benefits to herself and her newborn.

Low levels of buprenorphine are found in breast milk. In a study of 7 women taking a median buprenorphine dose of 7 mg/day, the exclusively breastfed infant (assuming milk consumption of 150 mL/kg/day) would receive an estimated mean of 0.55 mcg/kg/day of buprenorphine and 0.29 mcg/kg/day of norbuprenorphine, constituting 0.38% and 0.18% of the maternal weight-adjusted dose, respectively. A second study in 6 lactating women receiving a median buprenorphine dose of 0.29 mg/kg/day 5 to 8 days after delivery yielded mean infant breast milk doses of 0.42 mcg/kg/day of buprenorphine and 0.33 mcg/kg/day of norbuprenorphine, equivalent to 0.2% and 0.12% of the maternal weigh-adjusted dose, respectively. There is no information regarding naloxone in breast milk; however, naloxone is not orally bioavailable so it is unlike to affect the breastfed infant.

Pregnant mothers need to know when they should or should not breastfeed; a stable mother being treated for opioid use disorder is encouraged to breastfeed, although there are situations where breastfeeding is not recommended (e.g., the mother is HIV-positive, has tuberculosis, has cracked or bleeding nipples, is hepatitis C-positive, has returned to illicit drug use including cannabis). If breastfeeding is being considered, counseling should include:
-How to identify respiratory depression and sedation in their babies and when it may be necessary to seek immediate medical care.
-Use of other substances of abuse will expose the baby to additional risks; if other substances of abuse are being used, mothers should not breast-feed.

See references