Antibiotics to Avoid in G6PD Deficiency
Patients with G6PD deficiency must absolutely avoid dapsone, nitrofurantoin, and sulfonamides (including trimethoprim-sulfamethoxazole), while quinolone antibiotics should also be avoided despite limited evidence. 1, 2
Absolutely Contraindicated Antibiotics
High-Risk Antibiotics (Avoid Completely)
Dapsone is definitively contraindicated as it is a potent oxidant that causes methemoglobinemia and red blood cell hemolysis by overwhelming the reductive capacity of G6PD-deficient cells. 1, 3, 2
Nitrofurantoin has solid evidence demonstrating it causes hemolytic anemia in G6PD-deficient patients and should be strictly avoided. 2
Sulfonamides (including sulfamethoxazole/trimethoprim, co-trimoxazole) are explicitly listed as causing hemolysis in G6PD deficiency, though recent real-world data suggests they may be safer than previously thought. 4, 5, 6
- The FDA label for trimethoprim-sulfamethoxazole specifically warns that "in glucose-6-phosphate dehydrogenase deficient individuals, hemolysis may occur. This reaction is frequently dose-related." 6
- Despite emerging evidence suggesting possible safety, the conservative approach is to avoid these agents given regulatory warnings and documented cases of hemolysis. 4, 7
Chloramphenicol should be avoided based on established evidence of causing hemolysis in G6PD-deficient patients. 8
All quinolone antibiotics are contraindicated despite limited published evidence, as they are consistently listed among oxidant drugs to avoid. 8
Antibiotics Safe to Use
Low-Risk Antibiotics (Can Use Normally)
Penicillins (including amoxicillin) are not among contraindicated medications and can be used in normal therapeutic doses without concern for hemolysis. 3
Standard analgesics and anesthetics including benzodiazepines, codeine/codeine derivatives, propofol, fentanyl, and ketamine have not been shown to cause hemolytic crises. 9
Critical Clinical Considerations
Variant-Specific Risk Stratification
The Mediterranean variant (Gdmed) typically causes more severe, potentially life-threatening hemolysis compared to the African variant (GdA-), which usually produces milder, self-limited hemolysis. 1
The Mediterranean variant predominates in men from Mediterranean regions, India, and Southeast Asia, while the African variant affects 10-15% of Black individuals. 1
Pre-Treatment Screening
Screen all patients of Mediterranean, African, Indian, or Southeast Asian descent before starting any oxidant drug therapy. 1, 4
Qualitative screening is sufficient for initial assessment, though quantitative testing may be needed for borderline cases. 1, 3
Common Pitfalls to Avoid
Do not test during acute hemolysis - G6PD levels can be falsely elevated during active hemolysis because young reticulocytes have higher enzyme activity. 3
Avoid testing during or immediately post-transfusion - this will give falsely elevated results. 3
Repeat testing after 3 months may be necessary if initial testing occurs during acute hemolysis for accurate diagnosis. 3
Non-Antibiotic Triggers
Infections themselves (pneumonia, tonsillitis, typhoid fever, hepatitis A, urinary tract infections) are the second most common cause of hemolysis after dietary triggers. 7
Fava beans and legumes remain the most common dietary precipitant, causing hemolysis in 32.6% of cases in one large series. 7
NSAIDs including diclofenac sodium, ibuprofen, and aspirin can trigger hemolysis and should be used with extreme caution or avoided. 3, 7