Management of G6PD Deficiency
Patients with G6PD deficiency should avoid medications that can trigger hemolysis, including dapsone, methylene blue, nitrofurantoin, primaquine, rasburicase, phenazopyridine, and tolonium chloride, while using safe alternatives such as penicillins, cephalosporins, macrolides, and most tetracyclines. 1
Understanding G6PD Deficiency
G6PD deficiency is the most common human enzyme defect, affecting approximately 400 million people worldwide 2. This X-linked genetic disorder impairs the body's ability to protect red blood cells against oxidative stress, leading to hemolysis when exposed to certain triggers:
- Oxidative medications
- Infections
- Certain foods (particularly fava beans)
Medication Management
Medications to Strictly Avoid
The following medications have solid evidence contraindicating their use in G6PD deficiency 1, 3:
- Dapsone
- Methylene blue (methylthioninium chloride)
- Nitrofurantoin
- Primaquine
- Rasburicase
- Phenazopyridine
- Tolonium chloride (toluidine blue)
Medication Safety Considerations
- Dapsone: FDA labeling specifically warns that hemolysis may be exaggerated in individuals with G6PD deficiency, and the drug should be given with caution to these patients 4
- Methylene blue: Contraindicated in G6PD deficiency; ascorbic acid (0.5-1.0 g/day in divided doses) can be used instead for treating methemoglobinemia 1
- Antimalarials: 8-amino-antimalarials such as primaquine can cause significant hemolysis 4
Safe Medication Alternatives
The following medications are generally considered safe for patients with G6PD deficiency 1:
- Penicillins
- Cephalosporins
- Macrolides
- Most tetracyclines
- Most quinolones (though ciprofloxacin requires monitoring)
Diagnostic Testing
Proper diagnosis is essential for management:
- Gold standard: Quantitative enzyme activity assay measuring G6PD activity in U/g Hemoglobin 1
- Screening method: Fluorescent spot test (FST) with results interpreted as:
- Absent fluorescence: Severe deficiency
- Intermediate fluorescence: Partial deficiency
- Bright fluorescence: Normal activity
Important: Testing should be avoided during acute hemolytic episodes as results may be falsely normal. If G6PD deficiency is strongly suspected but initial test is normal during hemolysis, repeat testing should be performed 3 months after the hemolytic episode resolves 1
Management Protocol
- Confirm G6PD status through appropriate laboratory testing
- Review all medications and eliminate any with oxidative potential
- Substitute with safer alternatives from the same therapeutic class
- Establish monitoring protocol:
- Baseline complete blood count (CBC)
- Monitor for signs of hemolysis (pallor, jaundice, dark urine)
- Check hemoglobin levels and reticulocyte count if hemolysis is suspected
Dietary Considerations
- Fava beans are the most common dietary trigger for hemolytic episodes 1
- Patients should be educated about avoiding foods that cause oxidative stress
Special Considerations
Severity Variations
The severity of hemolysis depends on the specific G6PD variant 1:
- GdA- variant: Milder, self-limited hemolysis
- Gdmed variant: Associated with life-threatening hemolysis
Female Carriers
Heterozygous females with G6PD deficiency may have intermediate deficiency that can still cause clinical symptoms under severe oxidative stress 1
Complications
Acute hemolysis can lead to severe complications including 5:
- Severe anemia
- Jaundice
- Acute renal failure (most severe complication)
Monitoring for Hemolysis
Watch for signs and symptoms of hemolysis, which typically appear 24-72 hours after exposure to triggers 1:
- Pallor
- Jaundice
- Dark urine
- Fatigue
- Back or abdominal pain 6
By following these guidelines, clinicians can effectively manage patients with G6PD deficiency and prevent potentially life-threatening hemolytic episodes.