Guideline for Safe Use of DMARDs and Related Medications During Lactation

Benefits of Breastfeeding vs. Medication Risks

• Breastfeeding provides protection against infectious morbidity, inflammatory bowel disease, obesity, diabetes, and certain childhood cancers, and should not be discouraged when compatible medications are used【1】【2】【3】.

Risks of Untreated Maternal Rheumatic Disease

• Active, untreated rheumatic disease in the postpartum period is associated with significant adverse maternal and infant outcomes, outweighing the theoretical risks of compatible therapies【1】【2】【3】.

Shared Decision‑Making

• Therapeutic decisions should be made jointly by clinicians and the patient to ensure informed choices about medication use while lactating【1】【2】【3】.

Strongly Recommended Medications (Robust Evidence)

Conventional Synthetic DMARDs

• Hydroxychloroquine – Considered compatible with breastfeeding; only limited transfer to breast milk has been demonstrated【4】.
• Sulfasalazine – Compatible; daily doses up to 2 g are safe, and daily folic‑acid supplementation is required because sulfasalazine impairs folate absorption【4】【1】.
• Colchicine – Compatible; doses of 1–2 mg per day are safe for lactating mothers【4】【1】.

Biologic Agents

• All TNF‑α inhibitors (e.g., infliximab, etanercept, adalimumab) – Strongly recommended as compatible; they exhibit minimal or absent transfer into breast milk【4】.
• Rituximab – Strongly recommended as compatible with lactation【4】.

Corticosteroids

• Prednisone < 20 mg/day – Compatible with breastfeeding without special precautions【4】.
• Prednisone ≥ 20 mg/day – Breastfeeding should be delayed for at least 4 hours after dosing, or expressed milk should be discarded, to limit infant exposure to higher steroid levels【4】.

Conditionally Recommended Medications (Moderate Evidence)

Conventional Synthetic DMARDs

• Azathioprine/6‑Mercaptopurine – Acceptable when the mother has normal thiopurine methyltransferase activity; doses up to 2 mg/kg/day may be used【4】【1】.

Calcineurin Inhibitors

• Cyclosporine or Tacrolimus – May be used at the lowest effective dose with therapeutic drug monitoring; infant serum levels have been reported as undetectable in exposed infants【4】【1】.

Additional Biologic Agents (Conditional)

• Anakinra, Belimumab, Abatacept, Tocilizumab, Secukinumab, Ustekinumab – Conditionally recommended as compatible with breastfeeding【4】.

Contraindicated Medications (Strong or Conditional)

• Cyclophosphamide, Leflunomide, Thalidomide – Strongly contraindicated during lactation【4】.
• Mycophenolate mofetil – Strongly contraindicated; insufficient safety data for lactation despite tolerability in men planning conception【4】【5】.
• Methotrexate – Conditionally contraindicated; although transfer into milk is minimal, the drug can accumulate in neonatal tissues【4】.

Non‑Steroidal Anti‑Inflammatory Drugs (NSAIDs)

• Ibuprofen – First‑line NSAID; extensively studied and considered safe for breastfeeding infants【6】.
• Diclofenac – Small quantities detected in milk; regarded as safe【6】.
• Naproxen – Widely used after cesarean delivery with normal breastfeeding outcomes【6】.
• Celecoxib – Very low infant exposure; compatible with lactation【6】.
• Etoricoxib – Should be avoided due to insufficient safety data; alternative NSAIDs are preferred【6】.

Monitoring Recommendations

• Infants younger than 6 weeks should be monitored closely when the mother uses NSAIDs, given their immature hepatic and renal function【6】.
• Observe for any unusual behavioral changes in the infant that could suggest drug exposure【6】.

Clinical Decision Algorithm (Key Points)

• First‑line (strongly recommended) – Hydroxychloroquine, sulfasalazine, colchicine, TNF‑α inhibitors, rituximab【4】.
• Second‑line (conditionally recommended) – Azathioprine/6‑MP, cyclosporine or tacrolimus, other non‑TNF biologics【4】.
• Avoid – Methotrexate, mycophenolate, cyclophosphamide, leflunomide, thalidomide【4】【5】.

All statements are based on cited evidence; strength of evidence is indicated where provided.

Guideline Recommendations for DMARD Use During Breastfeeding

Evidence Gap for Iguratimod

• The 2020 American College of Rheumatology (ACR) reproductive health guidelines do not contain any recommendation on the use of iguratimod during lactation, reflecting a complete lack of safety data in nursing mothers and infants. 7
• Although the ACR guidelines comprehensively address breastfeeding compatibility for conventional DMARDs, biologics, and small‑molecule agents, iguratimod is notably absent from all recommendations, underscoring the uncertainty surrounding its use while breastfeeding. 8

Breastfeeding‑Compatible DMARDs (Strong Recommendations)

• Hydroxychloroquine is strongly recommended by the ACR as compatible with breastfeeding, supported by robust safety data in lactating women and infants. 7
• Sulfasalazine is strongly recommended as compatible with breastfeeding when used at standard therapeutic doses (up to 2 g daily) together with folic acid supplementation. 7
• Tumor necrosis factor (TNF) inhibitors—including adalimumab, etanercept, and infliximab—are strongly recommended as breastfeeding‑compatible because they exhibit minimal transfer into breast milk. 7

Breastfeeding‑Compatible DMARDs (Conditional Recommendations)

• Azathioprine is conditionally recommended (up to 2 mg/kg/day) for lactating patients, with evidence indicating negligible infant exposure. 7

DMARDs to Avoid or Use with Caution During Breastfeeding

• Methotrexate is conditionally recommended against during lactation due to the risk of neonatal tissue accumulation. 7
• Leflunomide is strongly contraindicated for breastfeeding mothers because of its potential for significant infant exposure. 7

Clinical Management Guidance

• For patients with active disease who require DMARD therapy while breastfeeding, the ACR advises transitioning to hydroxychloroquine, sulfasalazine, or a TNF inhibitor based on the underlying disease phenotype and therapeutic goals. 7

Pharmacologic Considerations for Iguratimod

• Iguratimod, as a small‑molecule DMARD, is theoretically expected to cross into breast milk in a manner similar to other small molecules, raising concerns about infant exposure. 9

Counseling and Planning

• Women of reproductive age should receive counseling about breastfeeding‑compatible DMARD alternatives before conception to allow adequate washout of non‑compatible agents and seamless transition to safe therapies during lactation. [7][8]