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

Medications to Avoid in G6PD Deficiency

Patients with G6PD deficiency must avoid certain medications that can trigger hemolysis, with the most definitively contraindicated drugs being dapsone, primaquine, rasburicase, nitrofurantoin, phenazopyridine, and methylene blue. 1, 2, 3, 4

High-Risk Medications (Absolutely Contraindicated)

• Rasburicase: FDA explicitly warns against use in G6PD deficiency patients due to risk of severe hemolysis. Must be immediately discontinued if hemolysis occurs. 2

• Primaquine: Contraindicated in severe G6PD deficiency. Can cause significant hemolysis, requiring G6PD testing before administration. 3, 1

• Dapsone: Causes significant hemolysis in G6PD-deficient individuals. 1, 4

• Methylene blue (methylthioninium chloride): Contraindicated due to high risk of hemolysis. 1, 4

• Nitrofurantoin: Should be avoided based on evidence of hemolytic risk. 4, 5

• Phenazopyridine: Associated with hemolysis in G6PD-deficient patients. 4, 6

• Tolonium chloride (toluidine blue): Should be avoided due to hemolytic risk. 4

Medications Requiring Caution

• Sulfonamides (including sulfamethoxazole/cotrimoxazole):

  • Traditionally considered risky, but recent evidence suggests lower hemolytic risk than previously thought 1
  • May be used with caution and monitoring in certain populations 7
  • Consider risk-benefit ratio in serious infections like Pneumocystis jirovecii pneumonia 7

• Quinolones:

  • Most are safe, but ciprofloxacin requires monitoring 1

• NSAIDs:

  • Some case reports of hemolysis with diclofenac sodium, ibuprofen, and acetylsalicylic acid 5

Safe Medication Alternatives

• Penicillins: Generally safe for G6PD-deficient patients 1

• Cephalosporins: Safe alternatives for infections 1

• Macrolides: Can be used safely 1

• Tetracyclines: Generally safe, but avoid in children <8 years 1

• Benzodiazepines: No evidence of hemolytic risk 8

• Opioids (codeine/derivatives, fentanyl): Safe for pain management 8

• Propofol and Ketamine: No hemolytic risk reported 8

Monitoring and Management

• Screen patients at higher risk for G6PD deficiency (e.g., those of African or Mediterranean ancestry) before administering high-risk medications 2

• Monitor for signs of hemolysis when using medications with potential risk:

  • Darkening of urine
  • Pallor
  • Fatigue
  • Jaundice
  • Falling hemoglobin levels 1, 3

• Discontinue offending agent immediately if signs of hemolysis appear 1

• Provide supportive care including IV hydration and possible blood transfusion for severe anemia 1

• Document G6PD status prominently in medical records 1

Special Considerations

• Mediterranean variant (B-) of G6PD deficiency has higher risk of severe hemolysis compared to African variant (A-) 1

• Fava beans are a common dietary trigger and should be avoided (most common non-drug trigger) 1, 5

• Infections can also trigger hemolysis in G6PD-deficient patients (second most common cause after dietary triggers) 5

• Pregnancy: Avoid primaquine in pregnant women due to risk to the fetus, even if the mother is G6PD normal 3

• Breastfeeding women should avoid primaquine or discontinue nursing 1

By following these guidelines and being vigilant about medication choices, healthcare providers can minimize the risk of hemolytic crises in patients with G6PD deficiency.