What Disease-Modifying Antirheumatic Drugs (DMARDs) are safe for patients attempting conception?

DMARDs Safe for Patients Attempting Conception

Hydroxychloroquine, chloroquine, azathioprine, cyclosporine, tacrolimus, sulfasalazine, and colchicine are the DMARDs that are safe and compatible with pregnancy for patients attempting conception. 1

Safe DMARDs Before and During Conception

First-line Options (Highest Safety Profile)

• Hydroxychloroquine/Chloroquine

  • Considered pregnancy-compatible with extensive safety data
  • Can be continued at standard doses throughout pregnancy
  • No increased rate of congenital malformations or adverse pregnancy outcomes
  • Particularly beneficial for patients with SLE as it may reduce flare risk

• Sulfasalazine

  • Safe to continue at doses up to 2 g/day throughout pregnancy 1, 2
  • Requires daily folic acid supplementation (2 mg) due to its inhibition of folate absorption 1, 2
  • Continuing treatment significantly reduces flare risk (26.5% flare rate with continued treatment vs. 56.3% with decreased/discontinued therapy) 2

• Azathioprine/Mercaptopurine

  • Can be used at doses up to 2 mg/kg throughout pregnancy in patients with normal thiopurine metabolism 1
  • Consider TPMT and NUDT15 testing before use to identify patients at risk for myelosuppression 3

• Calcineurin Inhibitors

  • Both cyclosporine and tacrolimus can be used during pregnancy at the lowest effective dose 1
  • Monitoring of trough levels may be recommended

• Colchicine

  • Compatible with pregnancy at doses of 1-2 mg/day 1

DMARDs to Avoid Before Conception

Must Be Discontinued

• Methotrexate

  • Teratogenic and embryotoxic - must be discontinued at least 3 months before conception 1, 4
  • Associated with increased risk of miscarriage and birth defects 4

• Mycophenolate

  • Teratogenic - must be discontinued before pregnancy 1
  • Associated with specific pattern of malformations

• Cyclophosphamide

  • Teratogenic - must be discontinued before pregnancy 1
  • Also associated with infertility risk in both men and women

• Leflunomide

  • Insufficient safety data - should be avoided until further evidence is available 1
  • Requires cholestyramine washout procedure before conception

Special Considerations for Male Partners

For male patients with rheumatic diseases attempting to conceive with their partners:

• Safe to Continue: Hydroxychloroquine, azathioprine, mercaptopurine, colchicine, cyclosporine, tacrolimus, TNF inhibitors 1

• Conditionally Safe for Men: Methotrexate, mycophenolate, leflunomide, and sulfasalazine can be continued in male patients attempting conception 1

  • Note: Sulfasalazine may affect sperm count/quality (but not teratogenicity) - consider semen analysis if conception is delayed 1, 2

• Avoid in Men: Cyclophosphamide (associated with dose-related risk of irreversible infertility) 1

Biologics and Pregnancy

• TNF Inhibitors: Generally considered compatible with conception and early pregnancy 1

  • May need to be discontinued in late pregnancy depending on specific agent and transplacental passage

• Other Biologics: Limited data available - decisions should be individualized based on disease activity and available alternatives 1

Clinical Approach for Patients Planning Conception

1. Optimize disease control before conception - active disease during pregnancy is associated with worse maternal and fetal outcomes than medication risks 2

2. Transition from teratogenic to pregnancy-compatible DMARDs at least 3-6 months before planned conception

3. Continue folic acid supplementation (especially with sulfasalazine)

4. Monitor disease activity throughout pregnancy - untreated disease poses significant risks to both mother and fetus

5. Shared decision-making between healthcare providers and patients regarding treatment choices before, during, and after pregnancy is essential 1

Remember that the benefits of controlling rheumatic disease activity during pregnancy often outweigh the potential risks of medication, as uncontrolled disease activity is associated with increased risk of adverse pregnancy outcomes 1.