Is salazopyrine (sulfasalazine) safe to use during breastfeeding?

Sulfasalazine (Salazopyrine) Use During Breastfeeding

Sulfasalazine is strongly recommended as compatible with breastfeeding and can be safely continued during lactation. 1

Primary Guideline Recommendations

Multiple high-quality rheumatology guidelines from 2020-2025 provide consistent, strong recommendations supporting sulfasalazine use during breastfeeding:

• The 2025 EULAR guidelines strongly recommend sulfasalazine as compatible with breastfeeding, placing it in the highest safety category alongside hydroxychloroquine, colchicine, and TNF inhibitors. 1

• The 2020 American College of Rheumatology guidelines strongly recommend sulfasalazine as compatible with breastfeeding, based on extensive clinical experience in rheumatic and musculoskeletal diseases. 1

• The 2010 Hepatology guidelines for autoimmune hepatitis note that sulfasalazine can be continued at doses up to 2 g/day throughout pregnancy, with the recommendation extending to breastfeeding based on safety profiles. 1

Pharmacokinetic Profile Supporting Safety

The safety of sulfasalazine during breastfeeding is supported by favorable pharmacokinetic data:

• Sulfasalazine itself appears in breast milk in insignificant amounts, while the active metabolite sulfapyridine reaches only 30-60% of maternal serum levels in milk. 2

• This limited transfer results in minimal infant exposure, well below levels that would cause concern for systemic effects. 2

Important Monitoring Considerations

While sulfasalazine is compatible with breastfeeding, specific monitoring is warranted:

• Monitor breastfed infants for bloody stools or diarrhea, as limited case reports have documented these symptoms in milk-fed infants of mothers taking sulfasalazine. 2

• If bloody stools or diarrhea occur, these symptoms typically resolve after discontinuation of either sulfasalazine or breastfeeding, though a definitive causal relationship has not been established. 2

• Theoretical kernicterus risk exists in newborns because sulfonamides compete with bilirubin for plasma protein binding sites, though sulfapyridine has poor bilirubin-displacing capacity. Monitor newborns specifically for signs of kernicterus. 2

Essential Folic Acid Supplementation

• Continue daily folic acid supplementation while taking sulfasalazine during breastfeeding, as sulfasalazine inhibits folate absorption even at the standard 2 g/day dose. 1

• This supplementation protects both maternal folate stores and ensures adequate folate in breast milk for the infant. 1

Clinical Decision Algorithm

For women with rheumatic diseases or inflammatory bowel disease requiring sulfasalazine:

1. Continue sulfasalazine during breastfeeding at the dose needed for disease control (typically up to 2 g/day). 1

2. Add or continue folic acid supplementation (typically 1-5 mg daily depending on indication). 1

3. Monitor the infant clinically for gastrointestinal symptoms, particularly bloody stools or diarrhea, especially in the first weeks of life. 2

4. If the infant is jaundiced or premature, exercise additional caution and monitor more closely for kernicterus, though the risk with sulfapyridine is low. 2

5. Do not discontinue breastfeeding based solely on sulfasalazine use, as the benefits of breastfeeding outweigh the minimal risks of medication exposure. 1

Common Pitfalls to Avoid

• Do not advise discontinuation of breastfeeding due to sulfasalazine use, as this contradicts current evidence-based guidelines and deprives the infant of breastfeeding benefits. 1

• Do not confuse sulfasalazine safety with other sulfonamides that may have different lactation profiles; sulfasalazine has specific data supporting its use. 2

• Do not discontinue disease-modifying therapy unnecessarily, as untreated maternal disease poses greater risks to both mother and infant than continued sulfasalazine exposure through breast milk. 1

Strength of Evidence

The recommendation for sulfasalazine compatibility with breastfeeding is based on:

• Strong consensus across multiple international guidelines (EULAR 2025, ACR 2020) representing the highest level of expert consensus. 1

• Decades of clinical experience with favorable safety profiles in breastfeeding women with inflammatory bowel disease and rheumatic conditions. 1, 2

• Pharmacokinetic data demonstrating minimal transfer to breast milk and low infant exposure. 2