Animal studies have failed to reveal evidence of teratogenicity; however, reproductive and developmental studies in rats and rabbits have identified adverse events at clinically relevant and higher doses. Limited data from observational studies, case series, and case reports during pregnancy have not shown an increased risk of major malformations specifically due to buprenorphine, however, there are limitations in these studies (most studies were performed with doses used for opioid use disorder). Untreated opioid addiction in pregnancy is associated with adverse outcomes such as low birth weight, preterm birth, and fetal death. Buprenorphine doses adjustments are often needed during pregnancy, even if the patient has been maintained on a stable dose prior to pregnancy. There are no controlled data in human pregnancy.

Opioids cross the placenta and may produce respiratory depression in neonates. This drug is not recommended for use prior to labor, when shorter acting analgesic or other analgesic techniques are more appropriate. Opioid dependent women on buprenorphine may require additional analgesia during labor.

Chronic opioid use may cause reduced fertility in females and males of reproductive potential; it is unknown if these effects are reversible.

NMP, an excipient in Sublocade extended-release injection for subcutaneous use, has caused pre-implantation losses, delayed ossification, reduced fetal weight, developmental delays, and reduced cognitive function at doses equivalent to recommended human doses. Decreased pup survival and malformation and postimplantation losses were reported at 2 and 3 times the human NMP dose.

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.

Benefit should outweigh risk

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

Risk Summary:
-Limited data in women maintained on this drug for opioid dependence during pregnancy have not shown an increased risk of major malformations, however, these studies were not designed to appropriately assess risk.
-Prolonged use of opioids during pregnancy for medical or non-medical reasons can result in neonatal opioid withdrawal syndrome which may be life-threatening if not recognized and treated.
-Based on animal data, NMP (an excipient in the extended-release injection (Sublocade) poses a potential risk to the fetus.

Comments:
-Women should be advised of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available; due to the long half-life of buprenorphine, neonatal monitoring will be necessary for several days after birth.
-This drug is not recommended for chronic pain management during pregnancy; adequate contraception should be discussed.
-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; long-acting products are not recommended during pregnancy because the dose cannot be adjusted.

See references

This drug is excreted in low levels in breastmilk; it has poor oral bioavailability in breastfed infants with low concentrations found in the serum and urine. This drug may increase serum prolactin although the prolactin level in a mother with established lactation may not affect her ability to breastfeed. The manufacturer's product labeling for buprenorphine pain products advises against breastfeeding due to the potential for serious adverse reactions.
-Mothers requiring treatment for opiate addiction 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, and when it may be necessary to seek immediate medical care.
-Neonatal Abstinence syndrome (NAS): The amount of drug in breast milk may not be sufficient to prevent neonatal withdrawal; infant treatment for NAS may be required.
-If breastfeeding is stopped abruptly, observe for signs and symptoms of opioid withdrawal in the infant.

Not recommended unless benefit expected to outweigh risks

Excreted into human milk: Yes

Comments:
-In situations other than opioid dependence, breastfeeding is not recommended because of the potential for serious adverse reactions including excess sedation and respiratory depression.
-For use in patients with opiate dependence, the decision to breastfeeding is a shared decision, but one that ultimately must be made by the patient once she understands the risks and benefits to her and her newborn.
-If used, monitor for increased drowsiness and breathing difficulties, and if these develop, seek immediate medical attention.

See references