THIS MEDICATION CAN CAUSE HARM TO YOUR BABY:
Untreated opioid use disorder is dangerous for pregnant women and their developing babies. There is limited information available on the safety of buprenorphine use during pregnancy. Some studies have reported an increased risk of neonatal withdrawal syndrome with the use of this medication during pregnancy; however, the risk of neonatal withdrawal syndrome is expected to be less with buprenorphine than with methadone. There have been no reports of birth defects associated with buprenorphine; however, animal studies suggest there may be developmental changes in offspring exposed to buprenorphine in utero. Caution is advised if continuing to breastfeed while taking buprenorphine. The manufacturer advises women who are taking buprenorphine to avoid breastfeeding their infants. Nursing infants should be monitored for signs of low weight gain and neonatal withdrawal syndrome.
What is buprenorphine?
Buprenorphine is classified as a controlled substance in the U.S., and is an analgesic opioid medication available as a generic or brand name (Belbuca™, Butrans™, Buprenex™, Probuphine™) medication. Buprenorphine is also available in a combination medication with naloxone (Suboxone™). Buprenorphine is available as intravenous (IV) or subcutaneous (SC) injection, sublingual tablet, buccal film, subcutaneous implant, transdermal patch, and is taken as 0.3–0.6 mg intramuscular (IM) or IV repeated up to every 6 hours (SC, buccal, subdermal implant, sublingual tablet, transdermal patch may be dosed differently). It is only available by prescription from your doctor.
What is buprenorphine used to treat?
Buprenorphine is used to treat acute pain (by IM or IV injection), moderate to severe chronic pain (by buccal film or transdermal patch), and opioid use disorder (by SC injection, subdermal implant, or sublingual tablet) in children, adolescents, and adults. Buprenorphine may be dosed based on weight in children and adolescents under 18 years of age. Buprenorphine is used off-label to treat opioid withdrawal in heroin dependent patients in the hospital and for anesthesia. Buprenorphine is available through a restricted access program from your provider. Buprenorphine has a boxed warning for risk of respiratory depression, abuse potential, overdose, and death particularly when used with benzodiazepines or other CNS (central nervous system) depressants.
You can find out more about opioid abuse in pregnancy here.
How does buprenorphine work?
Buprenorphine works in the central nervous system to bind to receptors and act as both an opioid and a non-opioid that inhibits the opioid response.
If I am taking buprenorphine, can it harm my baby?
Buprenorphine is expected to cross the placenta during pregnancy. Buprenorphine use during pregnancy has not been associated with an increased risk of birth defects; however, long-term behavioral changes and neonatal withdrawal syndrome are risks with use. Pregnant women should be advised about the risk of buprenorphine use to the developing baby. Opioid use during pregnancy has been associated with birth defects including neural tube, heart, and gastrointestinal defects as well as poor fgrowth, stillbirth, and preterm delivery. Opioid use during pregnancy is also associated with dependence and respiratory depression. Buprenorphine is recommended in pregnant women with opioid use disorder. Buccal or sublingual buprenorphine is preferred over the use of subcutaneous implants in pregnant women. Pregnant women who are receiving buprenorphine for opioid use disorder should be maintained on their regular dose of buprenorphine, and should receive standard analgesia during labor and delivery; however, buprenorphine should not be used for labor analgesia in these women. Pregnant women on buprenorphine should be monitored for signs of sleepiness and sedation.
Buprenorphine has been used for pain relief for labor (for example, during cesarean section) and to treat heroin dependence in pregnant women. Buprenorphine use during the time the labor and delivery has been associated with prolonged labor and decreased strength of contractions. Buprenorphine combined with naloxone has been used without harmful effects on the mother or child to treat opioid use disorder during pregnancy. It is currently being investigated for use as an alternative to methadone for opioid dependence, particularly in pregnancy. In pregnant women, buprenorphine is thought to be associated with less respiratory depressionin the baby, toxicity, withdrawal symptoms on discontinuation, and less abuse potential compared to the use of methadone in pregnant women.
Evidence from animal studies with buprenorphine:
When given to pregnant animals, there was no evidence to suggest buprenorphine increases the risk of birth defects in offspring. However, embryo, fetal, and maternal toxicity as well as changes in behavior were noted. Rats and rabbits administered 5 mg/kg IM of buprenorphine during pregnancy had no reports of adverse effects in offspring. Pregnant rats exposed to doses of buprenorphine 3-300 times greater than recommended human doses had offspring with growth restrictions, but no birth defects. Pregnant rats given 10-1000 (SC or IM) or 160 (IV) times the recommended human doses of buprenorphine had no offspring with birth defects; however, early fetal deaths were reported. Pregnant rabbits given IM doses of buprenorphine 1000 times the recommended human doses of the medication had offspring with development of an extra rib, and pregnant rats given 3 times the recommended human dose of buprenorphine had offspring with dystocias. One study in pregnant rats given 0.3, 1.0, and 3.0 mg/kg/day from early gestation through pregnancy reported no maternal toxicity and no negative effects on death, birth weight, or growth in offspring. Higher doses of buprenorphine (0.6 mg/kg) in pregnant rats impacted the behavioral development of offspring.
Evidence for the risks of buprenorphine in human babies:
There have been successful reports of buprenorphine use for opioid use disorder in pregnant women. Buprenorphine has a boxed warning for risk of neonatal withdrawal syndrome in newborns exposed to this medication during pregnancy. Symptoms of neonatal withdrawal syndrome can include irritability, hyperactivity, abnormal sleep pattern, high-pitched cry, tremor, vomiting, diarrhea, and failure to gain weight. The severity of neonatal withdrawal syndrome depends on how long the mother uses buprenorphine during pregnancy. Case reports and prospective studies suggest buprenorphine use during pregnancy may be associated with a transient neonatal withdrawal syndrome in newborns which includes symptoms such as agitation, tremor, yawning, changes in sleep, fever, and/or breathing difficulties.
Reports of sublingual or epidural use of buprenorphine during pregnancy have found no evidence of negative effects on the baby. Studies have reported no negative impact of buprenorphine exposure in utero on head circumference, with one study reporting an increased head size with buprenorphine compared to methadone exposure. A study in 25 children exposed to buprenorphine during pregnancy found decreased motor skills, attention, and memory at 5-6 years old, but normal weight and head circumference. A study in 122 children followed from birth to five years of age found in utero exposure to buprenorphine was not associated with increased death, emergency department use, or cancer diagnoses compared to control. However, hospital admissions for musculoskeletal diagnoses or blood disorders were greater and mental health treatments were higher in children with in utero exposure to buprenorphine.
Buprenorphine has been associated with a similar or lower risk of neonatal withdrawal syndrome compared to methadone. A study in 131 pregnant women found a similar risk of neonatal withdrawal syndrome symptoms and similar neonatal head circumference in infants exposed to buprenorphine or methadone during pregnancy. However, infants exposed to buprenorphine required less hospital treatment for neonatal withdrawal syndrome. A study in pregnant opioid dependent women found an increased risk of preterm labor with methadone versus buprenorphine. A Norwegian study in pregnant women who were part of an opioid treatment program found no difference in ne
onatal withdrawal syndrome for women on buprenorphine versus methadone. In a study of Finnish women who took buprenorphine during pregnancy, there was an increased need for neonatal intensive care, lower birth weight, sudden infant death syndrome, and a greater risk of neonatal withdrawal syndrome compared to pregnant women in the general Finnish population. A study in pregnant women on Massachusetts Medicaid found a greater risk of low birth weight, preterm birth, and infant hospitalization with methadone versus buprenorphine exposure. A study in 18 pregnant opioid-dependent women reported an earlier onset of neonatal withdrawal syndrome with oral methadone versus sublingual buprenorphine use. A study by the same authors in 15 opioid dependent pregnant women found less risk of neonatal withdrawal syndrome in women receiving sublingual buprenorphine. A study in pregnant opioid dependent women found buprenorphine was associated with normal birth outcomes and “mild” neonatal withdrawal syndrome, which first occurred 12 hours after birth and resolved itself after 120 hours. Buprenorphine has been associated with fewer changes in the heart rate of the developing baby compared to methadone when used in pregnant opioid dependent women. A systematic review including 18 studies found buprenorphine is associated with less risk of preterm birth, greater birth weight, and larger head circumference compared to methadone in pregnant opioid dependent women.
Bottom line: Buprenorphine use during pregnancy has not been associated with an increased risk of birth defects; however, long-term behavioral changes and neonatal withdrawal syndrome may be potential risks with use. Pregnant women should be advised about the risk of buprenorphine use to the developing baby. Buprenorphine is associated with fewer negative effects on the baby than methadone in opioid dependent pregnant women.
If I am taking buprenorphine and become pregnant, what should I do?
If you are taking buprenorphine and become pregnant, you should contact your doctor immediately. Your doctor will determine if your medication is medically necessary, or if it should be discontinued until after the birth of your baby. Before taking buprenorphine for opioid use disorder, women are encouraged to take a pregnancy test. Contraception counseling is recommended in women taking buprenorphine since it can increase fertility.
If I am taking buprenorphine, can I safely breastfeed my baby?
Buprenorphine is excreted into breast milk. The amount of medication reaching the nursing infant is expected to be less than1% of the mother's dose. Buprenorphine has the potential to affect milk production in some women. One study described decreased weight gain in nursing infants exposed to buprenorphine and bupivacaine during cesarean delivery and breastfeeding. Nonopioid analgesics are recommended in breastfeeding women requiring pain relief after labor and delivery surgery. However, low dose, short duration buprenorphine may be used for pain relief after surgery in breastfeeding women. Some recommendations state breastfeeding is safe to continue in women on buprenorphine for opioid use disorder as long as the nursing infant can tolerate the mother’s medication dose and the mother is not taking other illicit drugs. However, other sources including the manufacturer recommend that women who are taking buprenorphine should avoid breastfeeding due to the potential for low weight gain as well as an increased risk for respiratory depression and sedation in nursing infants. There have been reports of nursing infants who showed withdrawal symptoms after exposure to buprenorphine in the breast milk. Nursing infants should be monitored for development and withdrawal symptoms including sleepiness, sedation, feeding difficulties, and poor muscle tone particularly when breastfeeding or buprenorphine are discontinued. In women who choose to continue breastfeeding while on this medication, they should be informed of the potential risks to the nursing infant. It is important to weigh the risks versus benefits of buprenorphine before using it while breastfeeding.
Bottom line: Nursing infants should be monitored for developmental changes and withdrawal symptoms including sleepiness, sedation, feeding difficulties, and poor muscle tone particularly when breastfeeding or buprenorphine are discontinued. In women choosing to continue breastfeeding while on this medication, they should be informed of the potential risks to the nursing infant. The manufacturer does not recommend breastfeeding while taking this medication. It is important to weigh the risks versus benefits of buprenorphine before using it while breastfeeding.
If I am taking buprenorphine, will it be more difficult to get pregnant?
Long-term opioid use has been associated with decreased male fertility and female amenorrhea (lack of menstrual periods) as well as decreased female fertility. However, animal studies suggest buprenorphine is not associated with impaired fertility. Initiation of buprenorphine maintenance therapy may increase fertility.
If I am taking buprenorphine, what should I know?
Buprenorphine is an opioid analgesic that is used for pain relief and to treat opioid use disorder. Neonatal withdrawal syndrome is a possible side effect associated with the use of buprenorphine during pregnancy. Animal studies have shown buprenorphine increases the risk of toxicity in both mother and baby as well as behavioral changes. However, there is no evidence that buprenorphine increases the risk of birth defects. Further study is needed to determine the safety of using buprenorphine in pregnant women. Breastfeeding while taking buprenorphine is not widely encouraged, and women should be advised about the potential for low weight gain and neonatal withdrawal symptoms in nursing infants exposed to this medication through breast milk.
If I am taking any medication, what should I know?
This report provides a summary of available information about the use of buprenorphine during pregnancy and breastfeeding. Content is from the product label unless otherwise indicated.
You may find Pregistry's expert reports about the individual medications used to treat pain here, and our report about pain here. Additional information can also be found in the resources below.
For more information about buprenorphine during and after pregnancy, contact http://www.womenshealth.gov/ (800-994-9662 [TDD: 888-220-5446]) or check the following links:
Suboxone dot com: Suboxone prescribing information
U.S. National Library of Medicine: LACTMED: BUPRENORPHINE
General information
It is very common for women to worry about having a miscarriage or giving birth to a child with a birth defect while they are pregnant. Many decisions that women make about their health during pregnancy are made with these concerns in mind.
For many women these concerns are very real. As many as 1 in 5 pregnancies end in a miscarriage, and 1 in 33 babies are born with a birth defect. These rates are considered the background population risk, which means they do not take into consideration anything about the health of the mom, the medications she is taking, or the family history of the mom or the baby’s dad. A number of different things can increase these risks, including taking certain medications during pregnancy.
It is known that most medications, including over-the-counter medications, taken during pregnancy do get passed on to the baby. Fortunately, most medicines are not harmful to the baby and can be safely taken during pregnancy. But there are some that are known to be harmful to a baby’s normal development and growth, especially when they are taken during certain times of the pregnancy. Because of this, it is important to talk with your doctor or midwife about any medications you are taking, ideally before you even try to get pregnant.
If a doctor other than the one caring for your pregnancy recommends that you start a new medicine while you are pregnant, it is important that you let them know you are pregnant.
If you do need to take a new medication while pregnant, it is important to discuss the possible risks the medicine may pose on your pregnancy with your doctor or midwife. They can help you understand the benefits and the risks of taking the medicine.
Ultimately, the decision to start, stop, or change medications during pregnancy is up to you to make, along with input from your doctor or midwife. If you do take medications during pregnancy, be sure to keep track of all the medications you are taking.