What precautions should individuals with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency take to manage their condition?

Precautions in G6PD Deficiency

Individuals with Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency should avoid specific oxidant medications that can trigger hemolysis, undergo G6PD testing before starting potentially harmful drugs, and be aware of variant-specific risks. 1, 2

Key Medications to Avoid

• Absolutely contraindicated medications that should be strictly avoided in G6PD-deficient individuals include:

  • Primaquine (antimalarial) 2, 3
  • Dapsone 3
  • Methylene blue (methylthioninium chloride) 3
  • Nitrofurantoin 3
  • Phenazopyridine 3
  • Rasburicase 3
  • Tolonium chloride (toluidine blue) 3

• Antimalarials requiring special consideration:

  • For P. vivax or P. ovale malaria requiring radical cure, primaquine should only be used after G6PD testing 1
  • For those with intermediate G6PD deficiency (30-70% activity) and non-Mediterranean variants (A-), weekly primaquine (0.75 mg base/kg, maximum 45 mg) for 8 weeks with close monitoring for hemolysis may be considered 1
  • The Mediterranean variant (B-) has a very high risk of severe hemolysis even with extended dosing regimens 1

G6PD Testing

• Mandatory screening should be performed:

  • Upon entry into healthcare 1
  • Before starting therapy with any oxidant drug 1
  • Before primaquine administration for malaria treatment 2
  • Especially in individuals with predisposing racial or ethnic backgrounds (Mediterranean, African, Middle Eastern, South-East Asian, and Oceanian descent) 1, 4

• Testing considerations:

  • Qualitative screening is recommended for initial assessment 1
  • Quantitative G6PD testing is required before tafenoquine administration (do not use if <70% activity) 1
  • Even with negative testing, patients should be monitored for signs of hemolysis when taking potentially risky medications 2

Variant-Specific Precautions

• African variant (A-) 1:

  • Found in 10-15% of Black men and women
  • Associated with milder, more self-limited hemolysis
  • May tolerate certain oxidant drugs with careful monitoring

• Mediterranean variant (B-) 1:

  • Found predominantly in men from the Mediterranean, India, and Southeast Asia
  • Can cause life-threatening hemolysis
  • Requires stricter avoidance of oxidant medications

Monitoring During Treatment with Potentially Hemolytic Drugs

• Baseline testing before initiating treatment 2:

  • Complete blood count with hemoglobin determination
  • Hematocrit levels

• Ongoing monitoring 2:

  • Blood examinations during therapy (particularly blood cell counts and hemoglobin)
  • Monitor on days 3 and 8 when using potentially hemolytic drugs
  • Immediate discontinuation of the drug if signs of hemolysis occur

Warning Signs of Hemolysis

• Immediate discontinuation of any potentially hemolytic medication if the following occur 2:
  • Darkening of urine
  • Sudden decrease in hemoglobin concentration
  • Decrease in leukocyte count
  • Clinical symptoms of anemia (fatigue, pallor, shortness of breath)
  • Back/abdominal pain

Special Considerations

• Pregnancy: Primaquine is contraindicated in pregnant women, even if the mother is G6PD normal, as the fetus may be G6PD deficient 2

• Breastfeeding: Caution with oxidant drugs as they may be excreted in breast milk 2

• Infections: Infections can trigger hemolysis in G6PD-deficient individuals, requiring careful monitoring during febrile illnesses 5, 6

• Fava beans: Should be avoided as they are a common trigger of hemolysis in G6PD-deficient individuals (favism) 5

Recent Evidence on Medication Safety

• A 2024 real-world study found that several medications previously thought to be risky have been prescribed safely to G6PD-deficient patients, including ciprofloxacin, sulfamethoxazole/cotrimoxazole, and hydroxychloroquine 5

• However, this doesn't negate the need for caution, as the study also documented cases of hemolysis with nitrofurantoin and phenazopyridine 5

Family Screening

• First-degree relatives of patients with hereditary methemoglobinemia should be tested for G6PD deficiency 1

• Genetic counseling should be offered to families with G6PD deficiency 7

By following these precautions, individuals with G6PD deficiency can significantly reduce their risk of hemolytic episodes while effectively managing their condition.