What are the guidelines for medication use in pregnancy?

Guidelines for Medication Use in Pregnancy

Medication use during pregnancy should be a shared decision-making process between healthcare providers and patients, with treatment choices based on the most recent evidence regarding safety for both mother and fetus. 1

General Principles for Medication Use in Pregnancy

Pregnancy-Compatible Medications

• First-line medications considered safe throughout pregnancy:
  • Hydroxychloroquine, chloroquine
  • Azathioprine (up to 2 mg/kg/day)
  • Cyclosporine, tacrolimus (at lowest effective dose)
  • Sulfasalazine (up to 2 g/day with folic acid supplementation)
  • Colchicine (1-2 mg/day)
  • Low-dose glucocorticoids (≤10 mg/day prednisone or equivalent) 1, 2

Medications to Avoid During Pregnancy

• Teratogenic medications that must be discontinued before conception:

  • Methotrexate (discontinue 1-3 months before conception)
  • Mycophenolate (discontinue 1.5 months before conception)
  • Cyclophosphamide (discontinue 3 months before conception)
  • Thalidomide 1

• Medications contraindicated in specific trimesters:

  • NSAIDs: Strongly contraindicated in third trimester due to risk of premature closure of the ductus arteriosus 1
  • ACE inhibitors and ARBs: Strictly contraindicated throughout pregnancy, particularly in second and third trimesters due to severe fetotoxicity 1

Trimester-Specific Recommendations

First Trimester

• Nonselective NSAIDs (ibuprofen, diclofenac) may be used for short durations if needed 1
• Consider discontinuing NSAIDs if attempting conception due to possible interference with ovulation 1
• Avoid COX-2 inhibitors due to limited safety data 1

Second Trimester

• Short-term NSAID use (7-10 days) appears safe 1
• Prefer nonselective NSAIDs with short half-life (e.g., ibuprofen) at lowest effective dose 1
• For hypertension: methyldopa, labetalol, or nifedipine are preferred options 1, 3, 4

Third Trimester

• Discontinue all NSAIDs after gestational week 28 1
• For hypertension: continue methyldopa, labetalol, or nifedipine as needed 1, 3, 4
• Taper glucocorticoids to lowest effective dose (preferably <20 mg/day prednisone) 1

Management of Specific Conditions During Pregnancy

Hypertension

• First-line agents: methyldopa, labetalol, nifedipine 1, 3, 4
• Never use ACE inhibitors or ARBs due to severe fetotoxicity 1
• Non-pharmacological approaches (limitation of activities, left lateral positioning) should be considered for mild hypertension (140-150/90-99 mmHg) 1

Rheumatic Diseases

• Continue hydroxychloroquine throughout pregnancy, especially in SLE patients 1, 2
• For disease flares: consider short courses of glucocorticoids at lowest effective dose 1
• For severe, refractory disease: IV methylprednisolone pulses, pregnancy-compatible DMARDs, or IVIG may be used 1
• TNF inhibitors may be continued if needed for disease control, with consideration of timing for discontinuation before delivery based on transplacental passage 1

Important Considerations

Pre-Conception Planning

• Transition from teratogenic to pregnancy-compatible medications at least 3 months before planned conception 1, 2
• Ensure disease stability on pregnancy-compatible regimens before conception 1
• For women on leflunomide, perform cholestyramine washout if planning pregnancy 1

Disease Activity Monitoring

• Monitor disease activity at least once per trimester 1
• Untreated or poorly controlled disease often poses greater risks to mother and fetus than medication risks 2

Medication Adjustments During Pregnancy

• Aim to use the lowest effective dose of any medication 1
• For glucocorticoids, taper to ≤10 mg/day when possible; if higher doses needed, add steroid-sparing agents 1
• Consider physiological changes of pregnancy that may affect medication pharmacokinetics 5

Common Pitfalls to Avoid

1. Abrupt discontinuation of all medications upon pregnancy diagnosis - this can lead to disease flares that may harm both mother and fetus
2. Continuing teratogenic medications into pregnancy - methotrexate, mycophenolate, cyclophosphamide, and ACE inhibitors/ARBs must be discontinued
3. Failing to supplement with folic acid - especially important with sulfasalazine use 1, 2
4. Using NSAIDs in the third trimester - can cause premature closure of the ductus arteriosus 1
5. Inadequate disease monitoring - pregnancy can affect disease activity and medication requirements

By following these evidence-based guidelines and maintaining close collaboration between rheumatologists, maternal-fetal medicine specialists, and other healthcare providers, medication use during pregnancy can be optimized to ensure the best outcomes for both mother and child.