What is the management and treatment for Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

Management and Treatment of G6PD Deficiency

The cornerstone of G6PD deficiency management is strict avoidance of oxidative triggers—particularly high-risk medications, fava beans, and certain infections—combined with mandatory G6PD screening before prescribing any potentially hemolytic drug. 1

Screening and Diagnosis

Who Should Be Screened

• Screen all individuals with Mediterranean, African, Indian, or Southeast Asian ancestry before starting any oxidant medication 1, 2
• Screen upon entry into healthcare systems and before therapy with any oxidant drug 1
• Test first-degree relatives of affected patients 1

Testing Approach

• Use qualitative screening for initial assessment 1, 2
• Quantitative G6PD testing is required before tafenoquine administration and for borderline cases 1, 2
• Avoid testing during acute hemolytic episodes, as G6PD levels can be falsely elevated due to young reticulocytes having higher enzyme activity 3
• Avoid testing during or immediately after blood transfusion, which gives falsely elevated results 3
• If testing occurs during acute hemolysis, repeat testing after 3 months for accurate diagnosis 3

Absolutely Contraindicated Medications

High-Risk Drugs That Must Be Avoided

• Dapsone - potent oxidant causing methemoglobinemia and severe hemolysis 2
• Methylene blue (methylthioninium chloride) - causes severe hemolytic anemia 2, 3
• Primaquine - contraindicated in severe G6PD deficiency; only use in mild-moderate deficiency (>30% to <70% activity) at reduced dosing of 45 mg once weekly for 8 weeks 2
• Rasburicase - definitively contraindicated 3
• Aspirin - explicitly contraindicated as it overwhelms reduced antioxidant capacity 3

Pregnancy-Specific Contraindications

• Both primaquine and tafenoquine are contraindicated during pregnancy regardless of G6PD status 2

Safe Medications

Antimalarials

• Artemisinin-based combination therapies (ACTs) including artesunate, artemether-lumefantrine, and dihydroartemisinin-piperaquine can be used safely 2
• Chloroquine/hydroxychloroquine in standard doses appears relatively safe in most G6PD deficient patients 2

Anesthesia and Analgesia

• Benzodiazepines, codeine/codeine derivatives, propofol, fentanyl, and ketamine are safe and do not cause hemolytic crises 4

Antibiotics and Other Medications

• Penicillins (including amoxicillin) can be used in normal therapeutic doses 3
• Real-world data from 31,962 G6PD-deficient patients showed safe use of nitrofurantoin (1,366 patients), ciprofloxacin, ofloxacin, sulfamethoxazole/cotrimoxazole, sulfasalazine, hydroxychloroquine, and mesalazine 5

Variant-Specific Risk Stratification

Mediterranean Variant (Gdmed)

• Found predominantly in men from Mediterranean regions, India, and Southeast Asia 2
• Can cause life-threatening hemolysis requiring stricter avoidance of oxidant medications 1, 2

African Variant (GdA-)

• Found in 10-15% of Black men and women 1, 2
• Associated with milder, self-limited hemolysis 1, 2

Monitoring During Treatment with Potentially Hemolytic Drugs

Baseline Testing

• Complete blood count with hemoglobin determination before initiating treatment 1

Ongoing Monitoring

• Blood examinations during therapy, particularly blood cell counts and hemoglobin 1
• For intermediate G6PD deficiency with non-Mediterranean variants receiving weekly primaquine, close monitoring for hemolysis is required 1

Warning Signs of Hemolysis

• Immediately discontinue any potentially hemolytic medication if signs of hemolysis occur: 1
  • Back or abdominal pain 1
  • Jaundice 3
  • Elevated indirect bilirubin (>1.0 mg/dL when total bilirubin is ≤5 mg/dL) 3

Management of Acute Hemolytic Crisis

Recognition and Response

• If acute hemolytic crisis is identified, admit the patient for close observation and care 4
• Monitor for signs requiring blood transfusion, though this is rarely needed 4

Common Triggers

• Fava bean ingestion is the most common cause (71.8% of major hemolysis cases requiring hospitalization) 5
• Infections account for 8.5% of major hemolysis cases 5
• Medications account for only 4.2% of major hemolysis cases in real-world data 5

Patient Education

Critical Information to Provide

• Educate patients about oxidative stressors to avoid, including specific medications and fava beans 4
• Teach recognition of hemolysis signs and symptoms (jaundice, dark urine, back/abdominal pain) 1, 3
• Instruct when to seek immediate medical attention 3
• Inform patients of risks before starting any new medication 4

Clinical Pitfalls to Avoid

• Never prescribe primaquine for P. vivax or P. ovale malaria without prior G6PD testing 1
• Do not rely on testing performed during acute hemolysis or recent transfusion 3
• Recognize that most G6PD-deficient individuals remain asymptomatic throughout life unless exposed to triggers 5, 6
• Consider genetic testing when enzymatic activity is borderline (30-70% of normal) to determine specific variant and predict severity 3