In a 30-year-old woman with systemic lupus erythematosus in remission for over 6 months who is taking mycophenolate mofetil, hydroxychloroquine, and low-dose prednisone and wishes to become pregnant, what is the most appropriate medication adjustment?

Discontinue Mycophenolate Mofetil and Start Azathioprine

The most appropriate action is to discontinue mycophenolate mofetil and start azathioprine (Option C), as mycophenolate mofetil is teratogenic and must be stopped at least 6 weeks before attempting pregnancy, while azathioprine is safe throughout pregnancy and maintains disease control in SLE. 1

Rationale for Medication Changes

Mycophenolate Mofetil Must Be Discontinued

• Mycophenolate mofetil is FDA Pregnancy Category D and is strongly contraindicated in pregnancy, causing first trimester pregnancy loss (45% spontaneous abortion rate) and congenital malformations (22% of live births), particularly external ear abnormalities, cleft lip/palate, and limb, heart, kidney, and nervous system anomalies. 2

• The American College of Rheumatology strongly recommends discontinuing mycophenolate mofetil at least 6 weeks before attempting conception to allow adequate washout and prevent teratogenic exposure. 1

• The patient must not be pregnant when stopping mycophenolate mofetil, and reliable contraception should be used during the 6-week washout period. 1

Azathioprine Is the Appropriate Replacement

• The American College of Rheumatology strongly recommends continuing azathioprine throughout pregnancy as it is safe and effective for maintaining SLE remission. 1

• Azathioprine at 2 mg/kg/day is pregnancy-compatible and maintains disease control in patients who have achieved remission with other immunosuppressants. 1

• Patients should switch from mycophenolate mofetil to azathioprine at least 3 months prior to conception to ensure stable disease control on the new medication before pregnancy. 1

Why Other Options Are Incorrect

Option A (Discontinue Prednisone, Start Cyclosporine)

• Prednisone at 5 mg/day should be continued, not discontinued, as low-dose glucocorticoids (≤7.5 mg/day) are safe in pregnancy and help maintain disease control. 1

• While cyclosporine is conditionally recommended as pregnancy-compatible, it is not superior to azathioprine for maintenance therapy and requires blood pressure monitoring. 1

• This option fails to address the critical issue: mycophenolate mofetil must be stopped. 1

Option B (Discontinue Hydroxychloroquine, Start Quinacrine)

• This is completely wrong—hydroxychloroquine should be strongly continued throughout pregnancy as it reduces disease activity, prevents flares, improves obstetrical outcomes, and is safe for the fetus. 1, 3

• The American College of Rheumatology gives hydroxychloroquine the highest recommendation (++) for use before, during, and after pregnancy. 1

• Quinacrine is not a standard pregnancy medication and this option again fails to address mycophenolate mofetil. 1

Option D (Discontinue Mycophenolate Mofetil, Start Methotrexate)

• Methotrexate is absolutely contraindicated in pregnancy (FDA Category X equivalent) and must be stopped 1-3 months before conception with folic acid 5 mg/day supplementation. 1

• This would replace one teratogen with another, potentially more dangerous one. 1

Complete Preconception Management Plan

Medication Adjustments (Starting Now)

• Discontinue mycophenolate mofetil immediately and start azathioprine 2 mg/kg/day (approximately 100-150 mg/day for a 30-year-old woman). 1

• Continue hydroxychloroquine 200 mg/day throughout preconception, pregnancy, and breastfeeding. 1

• Continue prednisone 5 mg/day, which is well below the 20 mg/day threshold requiring special precautions. 1

Timing of Conception Attempt

• Wait at least 6 weeks after stopping mycophenolate mofetil before attempting pregnancy to ensure adequate drug clearance. 1

• Ideally wait 3 months to confirm stable disease control on azathioprine before conception. 1

• The patient already has 6+ months of inactive disease, which meets the recommended stability period. 1, 3

Additional Preconception Interventions

• Start low-dose aspirin 81 mg daily by 16 weeks gestation (can start preconceptionally) to reduce pre-eclampsia risk, especially important given her SLE diagnosis. 3

• Ensure reliable contraception during the 6-week to 3-month transition period. 1

• Monitor disease activity closely during medication transition to detect any flares early. 1

Critical Pitfall to Avoid

Never allow a patient on mycophenolate mofetil to become pregnant without adequate washout time. The teratogenic effects are severe and well-documented, with nearly half of pregnancies ending in spontaneous abortion and over 20% of live births having major malformations. 2 This is a medical emergency requiring immediate medication adjustment and contraceptive counseling. 1