Antibiotics to Avoid in Patients with G6PD Deficiency
Patients with G6PD deficiency should avoid dapsone, nitrofurantoin, and co-trimoxazole (sulfamethoxazole-trimethoprim) due to risk of hemolytic anemia. 1, 2, 3
High-Risk Antibiotics
Definitively Contraindicated:
- Dapsone: Strong evidence shows it causes hemolysis in G6PD-deficient patients 2, 3
- Nitrofurantoin: Documented cases of hemolysis in G6PD deficiency 3, 4
- Primaquine: Although primarily an antimalarial, it has significant hemolytic potential in G6PD deficiency 1, 5
Moderate Risk:
- Sulfonamides/Co-trimoxazole: Includes sulfamethoxazole-trimethoprim combinations 4
- Phenazopyridine: Used for urinary tract symptom relief, can cause hemolysis 3, 6
Mechanism of Hemolysis
G6PD deficiency impairs the body's ability to protect red blood cells against oxidative stress. When exposed to certain medications:
- Reduced NADPH production occurs
- Decreased glutathione levels result
- Red blood cells become vulnerable to oxidative damage
- Hemolysis (red blood cell destruction) follows
Risk Factors for Severe Reactions
The severity of hemolytic reactions depends on:
- G6PD variant: Mediterranean variants (Gdmed) typically cause more severe reactions than African variants (GdA-) 1
- Medication dose: Higher doses increase risk
- Concurrent oxidative stressors: Infections, certain foods (especially fava beans), or multiple medications 4
Safer Antibiotic Alternatives
When treating infections in G6PD-deficient patients, consider:
- Penicillins: Generally safe (though rare cases of amoxicillin-associated hemolysis have been reported) 7
- Cephalosporins: Generally considered safe
- Macrolides: Generally considered safe
- Tetracyclines: Generally considered safe
- Quinolones: Most are considered safe, though caution is advised with ciprofloxacin 6
Clinical Monitoring
When prescribing any medication to G6PD-deficient patients:
- Monitor for signs of hemolysis: pallor, jaundice, dark urine
- Watch for symptoms typically appearing 24-72 hours after exposure 4
- Check hemoglobin levels and reticulocyte count if hemolysis is suspected
- Discontinue the offending medication immediately if hemolysis occurs
Recent Evidence
A 2024 real-world study found that many medications previously thought to be risky for G6PD-deficient patients were actually prescribed safely to thousands of patients, including ciprofloxacin and sulfamethoxazole 6. However, this study still identified cases of hemolysis with nitrofurantoin and phenazopyridine, confirming their risk.
Despite this reassuring data, it remains prudent to avoid medications with well-documented risk (dapsone, nitrofurantoin, primaquine) when alternatives exist, particularly in patients with severe G6PD deficiency variants.