What medications are contraindicated in patients with Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

Medications Contraindicated in G6PD Deficiency

Patients with Glucose-6-phosphate dehydrogenase (G6PD) deficiency should strictly avoid primaquine, rasburicase, dapsone, nitrofurantoin, phenazopyridine, methylene blue, and tolonium chloride due to high risk of potentially life-threatening hemolytic anemia. 1

High-Risk Medications to Avoid

• Primaquine is absolutely contraindicated in G6PD deficiency as it can cause severe hemolytic anemia, particularly in those with the Mediterranean variant 2, 3
• Rasburicase is contraindicated in G6PD deficient patients as it produces hydrogen peroxide as a byproduct that can trigger severe hemolysis 4
• Dapsone should be avoided as it is a potent oxidant that can cause methemoglobinemia and red blood cell hemolysis by overcoming the reductive capacity of G6PD 5, 6
• Nitrofurantoin has solid evidence showing risk of hemolysis in G6PD deficient patients 1
• Phenazopyridine should be avoided due to documented cases of hemolysis 1, 7
• Methylene blue (methylthioninium chloride) is contraindicated as it can cause severe hemolytic anemia in affected patients 3, 1
• Tolonium chloride (toluidine blue) should be avoided based on evidence of hemolytic risk 1

Risk Factors and Severity

• The severity of G6PD deficiency varies based on genetic variant, with the Mediterranean variant (Gdmed) typically causing more severe reactions than the African variant (GdA-) 5
• The Mediterranean variant is found predominantly in men from Mediterranean regions, India, and Southeast Asia, while the GdA- variant is found in 10-15% of Black men and women 5
• Patients with the Mediterranean variant may experience life-threatening hemolysis, while those with the African variant typically have milder, self-limited hemolysis 5

Medium-Risk Medications (Use with Caution)

• Sulfonamides (including sulfamethoxazole/trimethoprim) should be used with caution, though recent real-world data suggests they may be safer than previously thought 7
• Quinolones like ciprofloxacin and ofloxacin have been prescribed safely to G6PD deficient patients in real-world studies, but caution is still advised 7
• Chloroquine/Hydroxychloroquine in standard doses appears to be relatively safe in most G6PD deficient patients 5, 7

Clinical Management

• Screening for G6PD deficiency is strongly recommended before starting therapy with oxidant drugs in patients with predisposing racial or ethnic backgrounds (Mediterranean, African, Indian, or Southeast Asian descent) 5
• Qualitative screening is sufficient for initial assessment, but quantitative testing may be needed to determine the degree of deficiency 5
• When treating G6PD-deficient patients, monitor for signs of hemolysis including jaundice, dark urine, fatigue, pallor, and declining hemoglobin 8
• Hemolytic crisis typically occurs 24-72 hours after exposure to triggering agents 8

Other Considerations

• Infections can also trigger hemolysis in G6PD deficient patients (12.4% of cases in one study), including pneumonia, tonsillitis, typhoid fever, and hepatitis A 8
• Certain foods, particularly fava beans, can trigger severe hemolysis (known as favism) in G6PD deficient patients 8
• Non-steroidal anti-inflammatory drugs like diclofenac and ibuprofen have been reported to cause hemolysis in some cases 8

Safe Medications

• Benzodiazepines, codeine/codeine derivatives, propofol, fentanyl, and ketamine have not been found to cause hemolytic crises in G6PD-deficient patients 9
• Most antibiotics not specifically listed above can be used safely in standard therapeutic doses 1, 7
• Many medications previously thought to be contraindicated have been used safely in real-world settings, suggesting that the list of truly dangerous medications may be smaller than historically believed 7, 10