Azulfidine

THE SAFETY OF SULFASALAZINE 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 MAY CAUSE HARM TO YOUR BABY:

Human studies suggest sulfasalazine has a low risk of causing birth defects. However, sulfasalazine may have potential toxicity in newborns and nursing infants due to an increased risk of neonatal jaundice. Due to the negative effects on folic acid absorption, pregnant women or women who plan to become pregnant while on sulfasalazine should take folic acid supplementation to prevent neural tube defects. Caution is recommended in nursing mothers who continue to take sulfasalazine.

What is sulfasalazine?

Sulfasalazine is a gastrointestinal, immunologic, and antirheumatic medication. It is a combination of sulfapyridine (a sulfonamide) and mesalamine [5-aminosalicylic acid; 5-ASA] (a salicylate). Sulfasalazine is available as a generic or brand name (Azulfidine™) medication. It is typically administered as an initial dose followed by a maintenance dose that is given in divided doses. Child and adolescent doses are either weight-based or fixed doses. Sulfasalazine is available as an oral tablet or a delayed release tablet and is only available by prescription from your doctor. 

What is sulfasalazine used to treat?

Sulfasalazine is used to treat ulcerative colitis and rheumatoid arthritis in adults. It is used off-label to treat conditions such as Crohn’s disease, ankylosing spondylitis, and psoriatic arthritis. In children and adolescents, sulfasalazine is used to treat inflammatory bowel disease (ulcerative colitis, Crohn’s disease) and juvenile idiopathic arthritis. Ulcerative colitis and rheumatoid arthritis are both chronic inflammatory, autoimmune disorders. Ulcerative colitis affects the colon and rheumatoid arthritis affects the joints. 

You can find out more about rheumatoid arthritis during pregnancy here or inflammatory bowel disease during pregnancy here.

How does sulfasalazine work?

Sulfasalazine and 5-aminosalicylic acid (5-ASA) work by altering the immune response and inhibiting certain inflammatory mediators in the body. 

If I am taking sulfasalazine, can it harm my baby?

Sulfasalazine is continued during pregnancy in some women; however, it should only be used during pregnancy if clearly needed. Other medication options may be available. Maintenance doses of sulfasalazine in women with inflammatory bowel disease, musculoskeletal conditions, or rheumatic disease who are planning to conceive can be continued. Remission before pregnancy is recommended. One study estimated that 38% of women taking sulfasalazine who become pregnant continue to take it during pregnancy.

Evidence from animal studies with sulfasalazine:

When given to pregnant rats and rabbits at six times the maximum recommended human dose, there was no evidence to suggest sulfasalazine increases the risk of birth defects in offspring. Studies in pregnant rats given 1.2-5 times the maximum recommended human dose of sulfasalazine reported decreased litter size. 

Evidence for the risks of sulfasalazine in human babies:

Sulfasalazine does cross the human placenta to reach the developing baby. There is no evidence from studies in human pregnancy showing sulfasalazine is associated with birth defects or neonatal toxicity. At least three case reports have described birth defects such as cleft palate, kidney defects, heart defects, stillbirth, head defects, and death in infants exposed to sulfasalazine during pregnancy; however, it is unknown if these defects arose from sulfasalazine exposure, the mother’s disease, or both. The Slone Epidemiology Center Birth Defects Study found second or third trimester use of sulfasalazine during pregnancy resulted in an increased risk of oral clefts and heart defects. A Swedish cohort study found evidence for an increased risk of birth defects with use of sulfasalazine in early pregnancy; however, other cohort studies, including a Danish study and a Norwegian study, failed to show an association between sulfasalazine use in pregnancy and birth defects. The Hungarian Case Control Surveillance of Congenital Abnormalities study compared 17 pregnant women who took sulfasalazine during pregnancy to 26 women in a control group not exposed to sulfasalazine during pregnancy, finding no difference in the occurrence of birth defects in pregnant women exposed or not exposed to sulfasalazine. A study in pregnant women exposed to antirheumatic medications including sulfasalazine found no statistically significant increase in birth defects, stillbirth, preterm delivery, low birth weight, or miscarriage with medication use. Studies in pregnant women with inflammatory bowel disease or ulcerative colitis who took sulfasalazine found no evidence of harm to the developing baby. The impact of sulfasalazine exposure in utero on child development is unknown. Although there have been no reports of kernicterus or severe neonatal jaundice in newborns exposed to sulfasalazine in utero, similar medications have been associated with the development of jaundice in newborns particularly when administered near the time of delivery. Agranulocytosis has been reported in an infant exposed to sulfasalazine in utero. There have also been reports of hemolytic anemia and neutropenia in newborns exposed to this medication in utero. Sulfasalazine is known as a folic acid antagonist, meaning it can negatively affect folic acid absorption in the body during pregnancy. Folic acid is essential during pregnancy to prevent neural tube birth defects, so folic acid supplementation is important in pregnant women or fertile women who could become pregnant, particularly if they are taking sulfasalazine. 

Bottom line: Although evidence on the safety of sulfasalazine during pregnancy is limited, this medication has not been associated with an increased risk of birth defects with use during pregnancy. Sulfasalazine use during pregnancy, particularly near the time of delivery may be associated with an increased risk of kernicterus or jaundice. Pregnant women who are taking sulfasalazine should also take folic acid supplementation due to the medication’s ability to interfere with folic acid absorption.

If I am taking sulfasalazine and become pregnant, what should I do?

If you are taking sulfasalazine and become pregnant, you should contact your doctor immediately. Your doctor will determine if your medication is medically necessary, or if it can be discontinued until after the birth of your baby.

If I am taking sulfasalazine, can I safely breastfeed my baby?

Sulfasalazine is excreted into breast milk. The amount of sulfasalazine and its byproducts reaching the nursing infant is expected to be 30%-40% of the mother’s concentration of the medication in the blood. Sulfasalazine may affect milk production or composition. There have been reports of bloody diarrhea in nursing infants whose mother took sulfasalazine. If sulfasalazine is needed by a nursing mother, breastfeeding should not be avoided. Other medication options may be available. However, nursing infants should be monitored for diarrhea and bloody stool. Discontinuation of sulfasalazine was required to stop the bloody diarrhea in the infant. The American Academy of Pediatrics classifies sulfasalazine as a medication that is “usually” compatible with breastfeeding, but should be used with caution in nursing mothers and may cause significant effects in nursing infants. The World Health Organization recommends mothers avoid breastfeeding while taking this medication. Breastfeeding while taking sulfasalazine should be avoided in premature infants as well as ill infants, infants with high bilirubin levels, and infants with G-6-PD deficiency. 

Bottom line: Caution is advised in women who continue breastfeeding while taking sulfasalazine. Nursing infants should be monitored for signs of bloody diarrhea. Breastfeeding while taking su
lfasalazine should be avoided in premature infants as well as ill infants, infants with high bilirubin levels, and infants with G-6-PD deficiency.

If I am taking sulfasalazine, will it be more difficult to get pregnant?

Studies in rats and rabbits administered up to six times the maximum recommended human dose of sulfasalazine experienced no impairments in female fertility. In male patients who take sulfasalazine to treat inflammatory bowel disease, the medication can have negative effects on sperm development, motility, and counts, and may require two or more months after discontinuing sulfasalazine for sperm levels to return to normal. In men with musculoskeletal or rheumatic disease, sulfasalazine may be continued during conception. However, if pregnancy doesn’t occur, semen analysis may be required. A study of the female partners of men treated with sulfasalazine 12 weeks prior to conception found no increased risk of adverse pregnancy outcomes or birth defects. A Dutch study found use of sulfasalazine before conception to treat rheumatoid arthritis did not negatively affect time to pregnancy.

If I am taking sulfasalazine, what should I know?

Limited available human studies suggest sulfasalazine has a low risk of causing birth defects. However, sulfasalazine may have an increased risk of causing neonatal jaundice. Due to the negative effects on folic acid absorption, pregnant women or women who plan to become pregnant while on sulfasalazine should take folic acid supplementation to prevent neural tube defects. Caution is recommended in nursing mothers who take sulfasalazine.

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

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

You may find Pregistry's expert report about ulcerative colitis here, rheumatoid arthritis here, Crohn’s disease here, ankylosing spondylitis 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 sulfasalazine during and after pregnancy, contact http://www.womenshealth.gov/ (800-994-9662 [TDD: 888-220-5446]) or check the following links:

U.S. National Library of Medicine: SULFASALAZINE

UpToDate: Patient education: Inflammatory bowel disease and pregnancy (Beyond the Basics)

UpToDate: Patient education: Rheumatoid arthritis and pregnancy (Beyond the Basics)

Read the whole report
Last Updated: 09-06-2020
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.