Azathioprine _ 6-mercaptopurine

THE SAFETY OF AZATHIOPRINE | 6-MERCAPTOPURINE DURING PREGNANCY OR BREASTFEEDING

The information provided below is for readers based in the United States of America. Readers outside of the United States of America should seek the information from local sources.

THIS MEDICATION CAN CAUSE HARM TO YOUR BABY:

Azathioprine and mercaptopurine are not recommended during pregnancy unless clearly indicated. While it is hard to get an accurate assessment of birth defect risk, immunosuppression, toxicity, delayed growth, and premature delivery have been associated with in utero azathioprine and mercaptopurine exposure. Breastfeeding is not recommended in women taking azathioprine or mercaptopurine. This medication should be used with caution in pregnant women or nursing mothers. Your doctor can help you weight the risks to the baby vs the benefits to the mother.

What is azathioprine | 6-mercaptopurine?

Azathioprine and mercaptopurine, also known as 6-mercaptopurine or 6MP, are medications that are taken to control the body’s immune response. Mercaptopurine is also a by-product of azathioprine metabolism in the body. Azathioprine and mercaptopurine are currently available as generic and brand name medications. Azathioprine is available in solution for injection and tablet. Mercaptopurine is available in suspension for injection and tablet. Dosage regimens vary for both medications, but azathioprine is dosed based on body weight and mercaptopurine is dosed based on body surface area. Both are available as prescription medications. 

What is azathioprine | 6-mercaptopurine used to treat?

Azathioprine and mercaptopurine are immunosuppressant medications; mercaptopurine is also an anticancer (antineoplastic) medication. Azathioprine is used for immunosuppression in kidney transplantation and rheumatoid arthritis as well as many off-label uses in children and adults. Mercaptopurine is used for immunosuppression in acute lymphoblastic leukemia as well as off-label uses including Crohn’s disease and ulcerative colitis. Azathioprine and mercaptopurine are often used in combination with other medications. 

How does azathioprine | 6-mercaptopurine work?

Azathioprine is metabolized into 6-mercaptopurine in the body, which interferes with DNA replication and synthesis leading to immunosuppression and toxic effects. These effects can keep the body from rejecting a transplanted kidney, keep the immune system from attacking itself in rheumatoid arthritis, or kill cancer cells.

If I am taking azathioprine | 6-mercaptopurine, can it harm my baby?

If immunosuppression is required during pregnancy, azathioprine might be used. Potential adverse effects associated with azathioprine use during pregnancy include low birth weight, prematurity, respiratory distress syndrome, and jaundice. Azathioprine use during pregnancy has not been associated with a proven increased risk of birth defects. Mercaptopurine use during pregnancy has been associated with death of the developing baby, particularly during the first trimester. However, adverse effects have been reported with second and third trimester exposure to both azathioprine and mercaptopurine. The manufacturer for azathioprine and mercaptopurine recommends avoiding pregnancy during therapy with these medications.

Evidence from animal studies with Azathioprine | 6-Mercaptopurine:

Doses of azathioprine similar to recommended human doses have been associated with birth defects in rats and rabbits including skeletal defects, limb malformations, and defects of the internal organs. Doses of azathioprine several times higher than recommended human doses have been associated with defects of the arms and legs, eyes, and bones in mice and cleft palate in rabbits. 

Doses of mercaptopurine several times greater than recommended human doses have been associated with cleft palate, skeletal defects, urinary and genital defects, and abdominal hernia in mice and rats.

Evidence for the risks of Azathioprine | 6-Mercaptopurine in human babies:

Azathioprine has been used safely during pregnancy in women undergoing liver, kidney, and heart transplants. There are reports of women on azathioprine therapy during pregnancy having babies who developed birth defects, but most instances are not thought to be caused by azathioprine exposure. Infants exposed to azathioprine during the third trimester can suffer immunosuppression (e.g. neonatal anemia, thrombocytopenia, and lymphopenia) and poor growth in utero; poor growth is attributed to azathioprine exposure, but may also be due to underlying medical conditions and use of multiple medications in pregnant women requiring this medication.

Possible negative side effects in babies exposed to azathioprine include the following:

  • Thymic atrophy
  • Leukopenia
  • Anemia
  • Thrombocytopenia
  • Chromosome abnormalities
  • Infections

The Swedish Medical Birth Register study in pregnant women exposed to azathioprine for treatment of inflammatory bowel disease noted an increased risk of delayed growth, preterm delivery, and heart defects; however, the cause of the defects could not conclusively be attributed to azathioprine therapy. An Australian study in women with inflammatory bowel disease exposed to azathioprine or 6-mercaptopurine during pregnancy found no increase risk of preterm delivery birth defects, or low birth weight. Evidence on the long-term neurobehavioral development of infants exposed to azathioprine is limited. 

The development of birth defects due to mercaptopurine exposure in utero has not been proven. A study in women who became pregnant after taking 6-mercaptopurine versus before taking 6-mercaptopurine found no difference in birth defects, spontaneous abortion, or infection. Neonatal toxicity including pancytopenia (too few red blood cells, white blood cells, and platelets), microangiopathic hemolytic anemia (loss of red blood cells), and severe bone marrow hypoplasia (decrease in bone marrow cells), has been reported in infants exposed to mercaptopurine and other chemotherapeutic agents. Mercaptopurine exposure has been associated with low birth weight and preterm delivery.  

A Danish study compared outcomes in women exposed to azathioprine or mercaptopurine during pregnancy versus outcomes in women not exposed to these medications during pregnancy. The odds of birth defects, death, and preterm birth were greater for infants exposed to these medications 30 days before conception through the first trimester of pregnancy. The authors of this study noted that the effects of medical condition and other medication use on these outcomes was unknown. 

Complications in the developing baby, including miscarriage, were noted in a review of 140 pregnancies with paternal exposure to azathioprine or 6-mercaptopurine within 3 months of conception.

Bottom line: Pregnancy should be avoided in women taking azathioprine or 6-mercaptopurine. Human and animal studies suggest there may be negative side effects associated with use during pregnancy.

If I am taking azathioprine | 6-mercaptopurine and become pregnant, what should I do?

If you are taking azathioprine | 6-mercaptopurine 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. 

If I am taking azathioprine | 6-mercaptopurine, can I safely breastfeed my baby?

The World Health Organization states breastfeeding is not recommended in women who are taking azathioprine or mercaptopurine. However, British and European guidance advises that these medications are compatible with breastfeeding. The metabolic product of azathioprine, 6-mercaptopurine, is not detectable in breast milk. However, there are theoretical risks for nursing infants to develop immunosuppression, cancer, and slowed growth with exposure to these medications through breast milk. It is important to weigh the benefits and risks of discontinuing breastfeeding while on these medications or discontinuing these medications while breastfeeding. Women who continue to breastfeed while on mercaptopurine therapy should make sure their infants are mo
nitored. 

Bottom line: Breastfeeding is not recommended in women who are taking azathioprine or 6-mercaptopurine. In breastfeeding moms taking this medication, caution is advised due to unknown effects on breastfeeding babies.

If I am taking azathioprine | 6-mercaptopurine, will it be more difficult to get pregnant?

Azathioprine can interfere with efficacy of intrauterine devices (IUDs) so an effective backup form of contraception is recommended in women on azathioprine therapy. Mercaptopurine has been associated with decreased sperm and testicular function in males on active therapy; sperm function returned to normal after stopping mercaptopurine therapy. Ovarian function and reproductive ability are not negatively affected by mercaptopurine therapy in women. 

If I am taking azathioprine | 6-mercaptopurine, what should I know?

Azathioprine and 6-mercaptopurine should only be used during pregnancy if clearly indicated. Human studies suggest there is an increased risk of immunosuppression, toxicity, premature delivery, and delayed growth with in utero exposure.

Breastfeeding is not recommended in women who are taking azathioprine or 6-mercaptopurine due to the potential for negative side effects in nursing infants.

If I am taking any medication, what should I know?

This report provides a summary of available information about the use of azathioprine | 6-mercaptopurine during pregnancy and breastfeeding. Content is from the product label unless otherwise indicated.

You may find Pregistry's expert report about cancer here, Crohn’s disease here, ulcerative colitis here, rheumatoid arthritis here and reports about the individual medications used to treat immune disorders here.   Additional information can also be found in the resources below. 

For more information about azathioprine | 6-mercaptopurine during and after pregnancy, contact http://www.womenshealth.gov/ (800-994-9662 [TDD: 888-220-5446]) or check the following links:

U.S. Food and Drug Administration: Azathioprine Prescribing Information

U.S. Food and Drug Administration: Mercaptopurine Prescribing Information

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Last Updated: 04-02-2020
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.