Can sulfasalazine be given during pregnancy?

Sulfasalazine Use During Pregnancy

Sulfasalazine can be safely used throughout pregnancy at doses up to 2 g/day, with concomitant daily folic acid supplementation recommended due to its inhibition of folate absorption. 1

Safety Profile and Recommendations

• Sulfasalazine is classified as a pregnancy-compatible conventional synthetic disease-modifying antirheumatic drug (csDMARD) according to the 2025 EULAR recommendations 1
• Current evidence does not indicate an increased rate of congenital malformations or other adverse pregnancy outcomes with sulfasalazine use during pregnancy 1
• The FDA label notes that reproduction studies in rats and rabbits at doses up to 6 times the human maintenance dose revealed no evidence of impaired female fertility or fetal harm 2
• Sulfasalazine crosses the placenta, but this has not been associated with significant adverse outcomes in large pregnancy cohorts 2

Dosing and Administration

• The maximum recommended dose during pregnancy is 2 g/day 1
• Folic acid supplementation is essential when using sulfasalazine during pregnancy due to its inhibition of folate absorption 1
  • Recommended folic acid supplementation: 1 mg daily 1
  • Should be started at least 3 months before conception and continued throughout pregnancy 1

Clinical Considerations and Monitoring

• Sulfasalazine and its metabolite, sulfapyridine, pass through the placenta 2
• In newborns, sulfonamides can compete with bilirubin for binding sites on plasma proteins, potentially causing kernicterus, though sulfapyridine has poor bilirubin-displacing capacity 2
• Monitor newborns for jaundice if the mother was taking sulfasalazine during pregnancy 2
• For patients with inflammatory bowel disease (IBD), sulfasalazine has been shown to be safe during pregnancy with no increased risk of adverse pregnancy outcomes compared to the general population 1

Comparative Safety Among Antirheumatic Drugs

• Unlike methotrexate, leflunomide, and mycophenolate which are teratogenic and contraindicated during pregnancy, sulfasalazine is considered safe 1, 3, 4
• Sulfasalazine belongs to the same safety category as hydroxychloroquine, azathioprine, cyclosporine, tacrolimus, and colchicine - all considered compatible with pregnancy 1
• For patients with rheumatoid arthritis whose disease does not improve during pregnancy, sulfasalazine can be used as part of the treatment regimen 5

Important Considerations for Clinical Practice

• For patients planning pregnancy who are on teratogenic DMARDs (methotrexate, leflunomide), switching to sulfasalazine before conception is a safe alternative 4, 6
• When treating inflammatory conditions during pregnancy, sulfasalazine should be considered as a first-line option among DMARDs due to its established safety profile 3, 6
• There is some evidence that sulfasalazine may have beneficial effects in preeclampsia by reducing antiangiogenic factors and improving endothelial function, though more research is needed 7

Lactation Considerations

• Sulfasalazine is also compatible with breastfeeding, allowing for continuous treatment through pregnancy and the postpartum period 8, 6
• Folic acid supplementation should be continued during lactation if sulfasalazine therapy is maintained 8