Is drug safety in pregnancy still classified using the FDA A, B, C, D, and X categories?

FDA Pregnancy Letter Categories Are No Longer Used

The FDA discontinued the A, B, C, D, and X pregnancy risk category system in 2015, replacing it with the Pregnancy and Lactation Labeling Rule (PLLR) that provides narrative descriptions of medication risks instead of letter grades. 1

What Changed and When

The FDA established the original letter category system (A, B, C, D, X) in 1979, but officially replaced it on June 30,2015 with the PLLR. 1 The change occurred because:

• The letter system was being misinterpreted as a grading system (with "A" perceived as safest and "X" as most dangerous), providing an overly simplified view of actual medication risks 1
• The categories failed to capture the complexity of risk-benefit decisions needed during pregnancy 1
• The system was not used in product labeling outside the United States, further reinforcing its limitations 1

Current Labeling System (PLLR)

The new rule requires three main narrative sections instead of letter categories: 1

1. Pregnancy (including labor and delivery) - with subsections for risk summary, clinical considerations, and available data (human, animal, and pharmacological)
2. Lactation - describing risks to breastfed infants
3. Females and males of reproductive potential - addressing fertility and contraception needs

Implementation Timeline

• Drugs approved after June 30,2015: Must use the new PLLR format and are not assigned pregnancy letter categories 1
• Drugs approved before 2015: Staggered phase-in, with many older medications still showing legacy letter categories in some references 1

Clinical Reality: The Old System Persists

Despite the official change, 95% of prescribers continue to use the pregnancy letter category system to make prescribing decisions, and less than half of surveyed clinicians were even aware the system had been replaced. 2 This creates a critical gap where:

• Older medications retain their historical letter designations in clinical references and tables 1
• Newer medications (post-2015) have no letter category, which can cause confusion when comparing drugs 1
• International guidelines may still reference the old system for completeness, even while acknowledging its replacement 1

Common Pitfalls to Avoid

Do not assume letter categories provide adequate safety information. The categories were overly simplistic and failed to distinguish between:

• Quality and quantity of available data
• Dose-dependent risks
• Trimester-specific concerns
• Disease-specific risk-benefit calculations 1

Do not rely solely on letter categories for prescribing decisions. Instead, access the full PLLR narrative sections that describe:

• Actual human and animal study data
• Background risk rates for birth defects
• Disease-associated risks if the condition goes untreated
• Specific clinical considerations for timing and monitoring 1

Be aware that you may encounter both systems in practice. Older drug references, international guidelines, and legacy labeling may still show letter categories, while newer drugs will only have narrative descriptions. 1