What medications should be avoided in patients with Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

Medications to Avoid in G6PD Deficiency

Seven medications are definitively contraindicated in G6PD deficiency: dapsone, methylthioninium chloride (methylene blue), primaquine, rasburicase, nitrofurantoin, phenazopyridine, and tolonium chloride (toluidine blue). 1, 2

High-Risk Medications (Must Avoid)

• Primaquine: Contraindicated in severe G6PD deficiency due to risk of hemolytic anemia. In mild to moderate deficiency, use requires careful risk-benefit assessment with baseline hematocrit/hemoglobin testing and close monitoring. 3

• Rasburicase: Absolutely contraindicated in G6PD deficiency. The FDA label explicitly warns against administration to G6PD-deficient patients and recommends screening patients at higher risk (e.g., those of African or Mediterranean ancestry) prior to starting therapy. 4

• Dapsone, Methylthioninium chloride (methylene blue), Nitrofurantoin, Phenazopyridine, and Tolonium chloride (toluidine blue): These medications have solid evidence supporting their prohibition in G6PD-deficient patients due to risk of hemolysis. 2

Risk Factors and Monitoring

• The severity of hemolytic reactions depends on the G6PD variant:

  • Mediterranean variant (Gdmed) - found in individuals from Mediterranean regions, India, and Southeast Asia - can cause potentially life-threatening hemolysis 5, 6
  • African variant (GdA-) - found in 10-15% of Black men and women - typically causes milder, self-limited hemolysis 5, 6

• When starting any medication in G6PD-deficient patients:

  • Obtain baseline complete blood count with hemoglobin determination 6
  • Monitor for signs of hemolysis including dark/reddish urine, jaundice, back/abdominal pain, or marked decrease in hemoglobin 5, 1
  • Immediately discontinue any potentially hemolytic medication if signs of hemolysis occur 6

Other Precipitating Factors

• Beyond medications, be aware that certain foods (particularly fava beans) and infections are common triggers of hemolytic crises in G6PD-deficient patients 7

• In a real-world study, fava bean ingestion (71.8%) and infections (8.5%) were more common causes of hemolysis requiring hospitalization than medications (4.2%) 8

Testing Recommendations

• G6PD testing is recommended:

  • Before starting therapy with oxidant drugs 5, 6
  • Especially in individuals with predisposing racial or ethnic backgrounds (Mediterranean, African, Indian, Southeast Asian) 6, 1
  • For first-degree relatives of patients with G6PD deficiency 6

• Qualitative screening is suitable for initial assessment, but quantitative G6PD testing is required before administering certain medications like tafenoquine 6

Clinical Pearls

• Despite long lists of "risky" medications in many sources, recent evidence suggests that many medications previously considered dangerous can be safely administered to G6PD-deficient patients in normal therapeutic doses 2, 8

• A recent real-world study found that medications like ciprofloxacin, sulfamethoxazole/cotrimoxazole, hydroxychloroquine, and several others have been prescribed safely to hundreds or thousands of G6PD-deficient patients 8

• The Clinical Pharmacogenetics Implementation Consortium now classifies medications as high, medium, or low-to-no risk based on systematic review of evidence 9

• The most effective management strategy is prevention of hemolysis by avoiding known oxidative stressors 10