## Sulfasalazine and G6PD Deficiency **Key Point:** Sulfasalazine is contraindicated in G6PD deficiency because its active metabolite, 5-aminosalicylic acid (5-ASA), generates oxidative stress that precipitates hemolysis in G6PD-deficient red blood cells. G6PD deficiency impairs the pentose phosphate pathway, reducing NADPH production and antioxidant defense. ### Why Sulfasalazine Causes Hemolysis in G6PD Deficiency 1. Sulfasalazine is cleaved by colonic bacteria to sulfapyridine + 5-ASA 2. 5-ASA and sulfapyridine generate reactive oxygen species (ROS) 3. ROS overwhelm the already-compromised antioxidant system in G6PD-deficient cells 4. Hemoglobin oxidation → Heinz body formation → Hemolysis **High-Yield:** G6PD deficiency screening is essential before initiating sulfasalazine, especially in populations with higher prevalence (African, Mediterranean, Asian descent). ### DMARD Safety in G6PD Deficiency | DMARD | G6PD Safe? | Rationale | |-------|-----------|----------| | Sulfasalazine | **No** | Metabolites generate oxidative stress | | Methotrexate | **Yes** | No oxidative stress mechanism | | Hydroxychloroquine | **Yes** | Antimalarial; safe in G6PD | | Azathioprine | **Caution** | Mild risk; monitor closely | | Leflunomide | **Yes** | No oxidative stress | | TNF inhibitors | **Yes** | No oxidative stress | **Clinical Pearl:** Acute hemolytic episodes in G6PD-deficient patients on sulfasalazine present with dark urine, jaundice, and reticulocytosis. Discontinue immediately and provide supportive care. **Warning:** Do not confuse sulfasalazine with 5-ASA monotherapy (mesalamine) used in IBD — mesalamine alone is safer in G6PD but still carries some risk. 
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