What are the recommended avoidance measures and acute management for a patient with G6PD (glucose‑6‑phosphate dehydrogenase) Mediterranean deficiency?

G6PD Mediterranean Deficiency: Avoidance and Acute Management

Absolutely Contraindicated Medications

The Mediterranean variant (G6PD-B⁻) carries a very high risk of severe, potentially life-threatening hemolysis and requires strict avoidance of specific oxidant medications. 1

High-Risk Medications to Avoid Completely:

• Dapsone - potent oxidant causing methemoglobinemia and severe hemolysis 2
• Methylene blue (methylthioninium chloride) - causes severe hemolytic anemia 2
• Primaquine - contraindicated in severe G6PD deficiency; may only be considered in mild-moderate deficiency (>30% to <70% activity) at reduced dosing of 45 mg once weekly for 8 weeks with close monitoring 2
• Tafenoquine - contraindicated in G6PD deficiency <70% activity 1
• Rasburicase - definitively contraindicated 3
• Aspirin - explicitly contraindicated 3

Medium-Risk Medications (Use with Extreme Caution):

• NSAIDs including ibuprofen - moderate risk of hemolysis 3
• Chloroquine/Hydroxychloroquine - relatively safe in standard doses for most G6PD deficient patients, but Mediterranean variant requires closer monitoring 2

Safe Antimalarial Options:

• Artemisinin-based combination therapies (ACTs) including artesunate, artemether-lumefantrine, and dihydroartemisinin-piperaquine can be used safely for malaria treatment 2

Critical Avoidance Measures

Environmental and Dietary Triggers:

• Fava beans - must be strictly avoided as they trigger acute hemolysis in Mediterranean variant 4, 5
• Infections - oxidative stress from infections can precipitate hemolysis 4

Pre-Treatment Screening:

Screen for G6PD deficiency before starting any oxidant drug in patients of Mediterranean, African, Indian, or Southeast Asian descent. 2 Qualitative screening is sufficient initially, but quantitative testing determines the degree of deficiency 2

Acute Hemolytic Crisis Management

Recognition of Hemolysis:

Educate patients to recognize early signs: dark urine, sudden fatigue or pallor, jaundice, and abdominal or back pain. 2

Immediate Management Steps:

1. Stop the offending agent immediately - hemolysis is self-limited once the oxidative stressor is removed 4

2. Monitor hemoglobin levels closely - especially during acute crisis 3

3. Consider transfusion if hemoglobin drops below 7-8 g/dL with symptoms 3

4. Provide supportive care:

   • Hydration to maintain renal perfusion
   • Monitor for complications including acute kidney injury from hemoglobinuria 1

5. Folic acid supplementation (1 mg daily) - recommended for patients with G6PD deficiency 3

Neonatal Considerations:

Neonatal hyperbilirubinemia may require phototherapy or exchange transfusion to prevent kernicterus 4

Special Clinical Pitfalls

Testing During Acute Hemolysis:

Avoid G6PD testing during acute hemolytic episodes - reticulocytes and young RBCs have higher G6PD activity, leading to falsely normal results. 6 Repeat testing after 3 months may be necessary for accurate diagnosis 3

Pregnancy Considerations:

• Primaquine and tafenoquine are contraindicated during pregnancy regardless of G6PD status 2
• Chloroquine is safe during pregnancy and has not been found harmful to the fetus in recommended doses 2
• The fetus may be G6PD-deficient even if the mother has normal enzyme activity 2

Severity Distinction:

The Mediterranean variant typically causes more severe, potentially life-threatening hemolysis compared to the African variant (GdA⁻), which usually produces milder, self-limited episodes. 2, 6 This distinction is critical for risk stratification and counseling.