Buprenorphine Pregnancy and Breastfeeding Warnings

Brand names: Belbuca, Brixadi, Buprenex, Butrans, Probuphine, Sublocade, Subutex

Medically reviewed by Drugs.com. Last updated on Mar 5, 2024.

Buprenorphine Pregnancy Warnings

For Opioid Dependence:
-Most products: This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus.
-Subcutaneous implant: Use is not recommended during pregnancy or in patients of childbearing potential not using contraception.

For Pain:
-Buccal film, transdermal system: Use is not recommended immediately prior to labor.
-IM/IV injection: According to some authorities, use is contraindicated.
-Sublingual tablets: Depending on the product, use is recommended only if clearly needed and the benefit outweighs the risk, use is not recommended, OR use is contraindicated.
-Transdermal patches: Depending on the product, use is contraindicated OR use is not recommended during pregnancy or in patients of childbearing potential not using contraception unless the benefit outweighs the risk to the fetus.

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

Risk Summary: Based on animal data, this drug can cause fetal harm; neonatal opioid withdrawal syndrome may occur in newborn infants of mothers receiving this drug.
-For Opioid Dependence: Limited data on use of this drug in pregnant women have not shown an increased risk of major malformations; however, these studies were not designed appropriately to assess the risk.
-For Pain: Insufficient data available on use of this drug in pregnant women to inform a drug-related risk.

Comments:
-Safety of the IM/IV injection has not been established during labor and delivery.
-Neonates should be closely monitored for signs of respiratory depression and for signs/symptoms of neonatal opioid withdrawal syndrome and should be managed accordingly.
---Due to the long half-life of this drug, neonatal monitoring for several days after birth should be considered.
-If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential harm to the fetus.
-Subcutaneous implant: This product is not considered an optimal treatment choice for pregnant women and should not be started in these patients; if pregnancy occurs during treatment, the benefit to the patient should be weighed against the risk to the fetus. In general, other treatments/formulations are considered more appropriate in this situation.

Animal studies have failed to reveal evidence of teratogenicity but have revealed evidence of adverse events at clinically relevant and higher doses. Increased postimplantation losses, embryofetal death, increases in skeletal abnormalities, increases in the number of stillborn offspring, reduced litter size, reduced offspring growth, preimplantation losses, increased litter incidence of malformation (external, visceral, and skeletal), and maternal toxicity (some resulting in mortality) have been reported at exposures lower than or higher than the maximum recommended human dose (depending on the species, formulation, and route of administration). This drug crosses the placenta in humans; this drug and its active metabolite (norbuprenorphine) have been detected in newborn blood, urine, and meconium after in utero exposure. Limited data from trials, observational studies, case series, and case reports on use of this drug in pregnancy have not shown an increased risk of major malformations specifically due to this drug; however, several factors complicate the interpretation of data. There are no controlled data in human pregnancy.

Clinical Considerations:
-Disease-associated maternal and embryofetal risk: Untreated opioid addiction in pregnancy is associated with adverse obstetrical outcomes (e.g., low birth weight, preterm birth, fetal death); in addition, untreated opioid addiction often results in continued or relapsing illicit opioid use.
-Dose adjustment during pregnancy and the postpartum period: When using this drug for opioid dependence, dose adjustments may be required during pregnancy, even if the patient was maintained on a stable dose before pregnancy; withdrawal signs/symptoms should be monitored closely and the dose adjusted as needed.
-Fetal/neonatal adverse reactions: Use of opioid analgesics for an extended duration during pregnancy for medical/nonmedical purposes can result in physical dependence in the neonate and neonatal opioid withdrawal syndrome shortly after birth; in addition, this syndrome may occur in newborn infants of mother receiving this drug for opioid dependence. Neonatal opioid withdrawal syndrome presents as irritability, hyperactivity and abnormal sleep pattern, high pitched cry, tremor, vomiting, diarrhea, and/or failure to gain weight. Signs of neonatal withdrawal generally occur in the first days after birth; the duration and severity of the syndrome may vary. Newborns should be observed for signs/symptoms of neonatal opioid withdrawal syndrome and managed accordingly.
-Labor or delivery: Opioid-dependent women on maintenance therapy for opioid dependence may require additional analgesia during labor. Opioids cross the placenta and may produce respiratory depression and psychophysiologic effects in neonates. An opioid antagonist (e.g., naloxone) must be available for reversal of opioid-induced respiratory depression in the neonate. This drug is not recommended for analgesia in women immediately prior to labor, when shorter-acting analgesics or other analgesic techniques are more appropriate. Opioid analgesics can prolong labor through actions that temporarily reduce the strength, duration, and frequency of uterine contractions; however, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor.

Chronic opioid use may cause reduced fertility in females and males of reproductive potential; it is not known if these effects 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.

See references

Buprenorphine Breastfeeding Warnings

LactMed: Use is considered acceptable.

For Opioid Dependence:
-Oral lyophilisate: Use is contraindicated.
-Subcutaneous implant: Breastfeeding should be discontinued during therapy.
-Subcutaneous injection, subdermal implant: Benefit should outweigh risk; caution is recommended.
-Sublingual tablets: Depending on the product, benefit should outweigh risk OR breastfeeding should be discontinued during therapy.
---According to some authorities: Use is contraindicated.

For Pain:
-Buccal film, transdermal system: Breastfeeding is not recommended during use of this drug.
-IM/IV injection: Depending on the product, use is contraindicated OR breastfeeding is not recommended during use of this drug.
-Sublingual tablets: Depending on the product, use is contraindicated or not recommended.
-Transdermal patches: Use is not recommended.
---For some transdermal patches: If used, caution is recommended.

Excreted into human milk: Yes

Comments:
-This drug and its metabolite (norbuprenorphine) are present in low levels in human milk and infant urine.
-Infants should be monitored for drowsiness, respiratory depression, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants.
---Although unlikely, if the neonate shows signs of increased sleepiness (more than usual), difficulty breastfeeding, breathing difficulties, or limpness, a physician should be contacted immediately.
-Infants should be observed for withdrawal signs if breastfeeding is stopped abruptly.
-Women who received this drug for opiate abuse during pregnancy and are stable should be encouraged to breastfeed their infants postpartum, unless there is another contraindication (e.g., use of street drugs).
-For Opioid Dependence:
---Developmental and health benefits of breastfeeding should be considered as well as the mother's clinical need for this drug.
---This drug has been used without apparent harmful effects in the nursing infant; potential adverse effects in the breastfed child due to this drug or the mother's underlying condition should be considered.
---Breastfeeding women should be advised to monitor the infant for increased drowsiness and breathing difficulties.
-For Pain:
---There is the potential for serious adverse reactions, including excess sedation and respiratory depression in breastfed infants; a risk to the neonate/infant cannot be excluded.
---Infants exposed to this drug through breast milk should be monitored for excess sedation and respiratory depression.
---Withdrawal symptoms can occur in breastfed infants when maternal use of this drug is stopped or when breastfeeding is stopped.

Because of the low levels of this drug in breast milk, its poor oral bioavailability in infants, and low drug levels found in the serum and urine of breastfed infants, its use is considered acceptable in nursing mothers. This drug can increase serum prolactin; however, the prolactin level in a mother with established lactation may not affect her ability to breastfeed.

The long-term outcome of infants breastfed during maternal use of this drug for opiate abuse has not been well studied. The breastfeeding rate among mothers taking this drug for opiate dependency may be lower than in other mothers, especially with multiple attempts to start this drug; however, among women taking this drug as part of an abstinence program, the retention rate may be better in nursing mothers than in non-nursing mothers.

At 4 days postpartum, 4 mothers taking this drug (0.4, 2, 4, or 6 mg orally once a day) as maintenance during pregnancy and lactation had their milk collected 2, 4, 6, and 12 hours after a dose. Peak milk levels occurred 2 hours after dosing with 2 and 4 mg/day and 4 hours after dosing with 6 mg/day; peak levels were 0.8, 7.8, and 5.8 mcg/L, respectively. Milk levels of parent drug and metabolite (norbuprenorphine) were undetectable (lower limit of the assay not given) with 0.4 mg/day; milk levels with 2, 4, and 6 mg/day averaged 0.4, 3.5, and 4.4 mcg/L of parent drug and 0.57, 0.45, and 1.15 mcg/L of norbuprenorphine, respectively. Based on the average milk levels reported, an exclusively breastfed infant would receive less than 1% of the maternal weight-adjusted dosage. Dosages were on the low end of the usual dosage range for treatment of opiate withdrawal; furthermore, the doses were given by the oral route, which has poor bioavailability. The combination of low dose and oral route may have contributed to the low milk levels.

During the first 5 to 8 days postpartum, 6 women received this drug (median dose: 0.29 mg/kg/day) sublingually for opiate abstinence and had hindmilk samples obtained 6 to 8 times over a 24-hour period; their 6 nursing infants had 1 urine sample collected between 4 and 20 hours after the previous maternal dose. Breast milk contained estimated median infant doses of 0.42 mcg/kg/day of parent drug and 0.33 mcg/kg/day of norbuprenorphine, which were equal to 0.2% and 0.12% of the maternal weight-adjusted dosage; the range of parent drug plus metabolite was 0.18% to 0.77% of the maternal weight-adjusted dosage. This drug was undetectable (less than 0.187 mcg/L) in 3 infants, while the other 3 had urine levels of about 0.468 mcg/L; norbuprenorphine urine levels ranged from 0.414 to 1.987 mcg/L (median: 0.952 mcg/L). Of the 6 infants, 4 had signs of opioid abstinence, indicating that the amounts of this drug in breast milk were inadequate to prevent withdrawal. At 1 month after discharge from the hospital, all infants had normal development and weight gain.

An average of 1.12 months after delivery, 7 lactating women taking this drug (median dose: 7 mg/day [range: 2.4 to 24 mg/day]) sublingually for opiate substitution during pregnancy and lactation collected foremilk and hindmilk samples with each feeding for 24 hours. The milk concentrations of this drug and norbuprenorphine averaged 3.65 and 1.94 mcg/L, respectively, which corresponded to infant dosages of 0.55 and 0.29 mcg/kg/day, respectively, and weight-adjusted dosages of 0.38% and 0.18% of the maternal dosage, respectively. The women's breastfed infants were followed-up at 3 and 4 weeks of age; 4 infants were exclusively breastfed and 3 were partially/mostly breastfed. At the follow-up visits, infants were assessed for weight gain, sleeping patterns, skin color, and elimination and hydration patterns; all infants had values within normal limits for these parameters. At an average of 1.12 months of age (range: 0.58 to 1.85 months), infants had no apparent drug-related adverse effects and showed satisfactory developmental progress.

See references

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