What Disease-Modifying Antirheumatic Drugs (DMARDs) are safe for patients planning pregnancy or already pregnant?

DMARDs Safe During Pregnancy and Preconception Planning

Hydroxychloroquine, sulfasalazine, azathioprine, cyclosporine, tacrolimus, and colchicine are the DMARDs considered safe during pregnancy and should be continued for maintenance of remission or treatment of disease flares in pregnant women with rheumatic diseases. 1

Safe DMARDs for Pregnancy and Preconception

First-line Options

• Hydroxychloroquine - Can be safely continued throughout pregnancy and is strongly recommended for SLE patients 1
• Sulfasalazine - Safe at doses up to 2 g/day throughout pregnancy, but requires daily folic acid supplementation due to its inhibition of folate absorption 1
• Azathioprine - Can be used at doses up to 2 mg/kg daily in women with normal thiopurine metabolism 1
• Cyclosporine/Tacrolimus - Can be used during pregnancy at the lowest effective dose, which may be monitored by trough levels 1
• Colchicine - Compatible with pregnancy at doses of 1-2 mg/day 1

Biologic DMARDs

• TNF inhibitors - All TNF inhibitors can be used throughout pregnancy based on individualized risk-benefit assessment 1
  • Certolizumab has minimal placental transfer and can be continued throughout pregnancy 1
  • Infliximab, etanercept, adalimumab, and golimumab should be continued through first and second trimesters but discontinued in the third trimester 1

DMARDs to Avoid During Pregnancy

• Methotrexate - Teratogenic and must be discontinued 1-3 months before conception 1, 2
• Leflunomide - Contraindicated in pregnancy due to teratogenicity 2
• Mycophenolate - Teratogenic and should be discontinued before pregnancy 1
• Cyclophosphamide - Teratogenic and should be discontinued at least 12 weeks prior to conception 1

DMARDs During Breastfeeding

• Compatible with breastfeeding: Hydroxychloroquine, sulfasalazine, azathioprine, colchicine, cyclosporine, tacrolimus, NSAIDs (ibuprofen preferred), and all TNF inhibitors 1
• Not recommended during breastfeeding: Methotrexate (limited data suggest low transfer) 1

Special Considerations

• Disease activity management: Active rheumatic disease increases risk of adverse pregnancy outcomes, so optimal disease control should be achieved before conception 1
• Medication transitions: When discontinuing teratogenic DMARDs, transition to pregnancy-compatible alternatives should be completed before conception 1
• Folic acid supplementation: Essential when using sulfasalazine due to its inhibition of folate absorption 1
• Shared decision-making: Treatment choices before, during, and after pregnancy should involve both healthcare providers and the patient 1

Paternal DMARD Use

• Safe for men planning conception: Hydroxychloroquine, azathioprine, colchicine, TNF inhibitors, NSAIDs 1
• Requires discontinuation before conception: Cyclophosphamide (12 weeks prior), methotrexate, mycophenolate 1
• Sulfasalazine: May affect male fertility; semen analysis recommended if conception is delayed 1

Common Pitfalls to Avoid

• Abrupt discontinuation: Don't stop all medications when pregnancy is diagnosed, as disease flares can harm both mother and fetus 1
• Overlooking folic acid: Always prescribe folic acid with sulfasalazine 1
• Delayed planning: Disease activity should be controlled before conception; don't wait until pregnancy to optimize treatment 1
• Ignoring breastfeeding benefits: Women should not be discouraged from breastfeeding while taking compatible medications 1

The management of DMARDs during pregnancy requires balancing disease control with medication safety. The evidence strongly supports continuing hydroxychloroquine, sulfasalazine, azathioprine, cyclosporine, tacrolimus, and colchicine throughout pregnancy while discontinuing methotrexate, leflunomide, mycophenolate, and cyclophosphamide before conception.