Management of G6PD Deficiency – Evidence‑Based Recommendations

Medication Risk Stratification

Avoid high‑risk oxidant drugs (primaquine > 5 days, dapsone, sulfonamides, rasburicase, methylene‑blue) in all individuals with G6PD deficiency because they precipitate severe hemolysis. [CDC MMWR 1992] 1, 2
Primaquine ≤ 5 days may be used with caution only in patients with the milder African A‑ variant; longer courses are contraindicated. [CDC MMWR 1992] 1, 5
Sulfonamides are classified as medium‑risk and should be prescribed only after careful risk‑benefit assessment. [IDSA 2024] 2, 3, 4
Acetaminophen/paracetamol is considered low‑risk and can be used safely in G6PD‑deficient patients. [CDC MMWR 1992] 5

Mediterranean (B‑) variant carries a very high risk of life‑threatening hemolysis; all oxidant drugs must be avoided. [CDC MMWR 1992] 1, 9
African (A‑) variant shows milder deficiency; short‑course primaquine (≤5 days) may be tolerated, but other high‑risk agents remain contraindicated. [CDC MMWR 1992] 1, 2, 4
Quantitative G6PD activity testing (30‑70 % of normal) should guide therapeutic decisions, especially for intermediate‑deficiency individuals. [Clinical Microbiology Infection 2024] 9

Immediately discontinue the offending oxidant agent when hemolysis is identified. [ASH 2021] 6
Provide supportive care with intravenous hydration and close laboratory monitoring (hemoglobin, reticulocyte count, bilirubin). [CDC MMWR 1992] 5
Administer supplemental oxygen for patients with respiratory symptoms or hypoxia. [ASH 2021] 10
Severe hemolysis may require exchange transfusion to rapidly reduce circulating hemoglobin‑bound toxins. [ASH 2021] 6, 10

Chloroquine is safe for malaria treatment in pregnant women with G6PD deficiency. [CDC MMWR 1992] 1, 5
Primaquine must be avoided throughout pregnancy due to unknown fetal safety. [Clinical Microbiology Infection 2024] 9
Methylene‑blue is contraindicated because of teratogenic risk (intestinal atresia) and potential fetal hemolysis; alternatives include high‑dose ascorbic acid or exchange transfusion. [ASH 2021, AHA 2023] 6, 7, 8, 10

Absolute contraindication in G6PD deficiency: can trigger severe hemolytic anemia and paradoxically worsen methemoglobinemia due to insufficient NADPH for reduction. [ASH 2021, AHA 2023] 6, 7, 8
Alternative therapies for methemoglobinemia in this population include high‑dose vitamin C or exchange transfusion. [ASH 2021] 6, 7

Mandatory G6PD testing before prescribing any oxidant drug to individuals of African, Mediterranean, Middle Eastern, or Southeast Asian ancestry. [IDSA 2024] 2, 3
Screen prior to initiating dapsone, primaquine, or sulfonamides. [IDSA 2024] 2, 3, 4
Quantitative enzymatic assays are preferred over qualitative spot tests for accurate classification, especially in females and intermediate‑deficiency cases. [Clinical Microbiology Infection 2024] 9, 4

Provide a written list of high‑risk medications (e.g., primaquine > 5 days, dapsone, methylene‑blue) to all patients diagnosed with G6PD deficiency. [Clinical Microbiology Infection 2024] 9
Instruct patients to seek immediate medical attention if they develop signs of hemolysis such as dark urine, jaundice, fatigue, dyspnea, or back pain. [Clinical Microbiology Infection 2024] 9