G6PD Deficiency Drug Risk

Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is the most common human enzyme deficiency, affecting approximately 400 million people worldwide, predominantly males due to its X-linked recessive inheritance pattern. G6PD is essential for the pentose phosphate pathway, which generates NADPH — the primary antioxidant defence inside red blood cells. Without adequate G6PD activity, red blood cells cannot neutralise reactive oxygen species (ROS) generated by oxidative stress from drugs, infections, or certain foods. This leads to oxidative damage of haemoglobin and the red cell membrane, forming Heinz bodies (denatured haemoglobin aggregates) that are recognised and removed by the spleen, causing haemolytic anaemia. The WHO classifies G6PD deficiency into five classes based on the degree of enzyme deficiency and clinical severity: Class I (severe deficiency with chronic non-spherocytic haemolytic anaemia), Class II (severe deficiency, <10% residual activity, intermittent acute haemolysis), Class III (moderate deficiency, 10–60% activity, haemolysis only with triggers), Class IV (mildly reduced or normal activity, clinically insignificant), and Class V (increased enzyme activity). The G6PD haemolysis risk calculator helps clinicians assess the likelihood of acute haemolysis based on a patient's known G6PD status and exposure to oxidative drugs or foods. The most common variants include G6PD A- (Africa), G6PD Mediterranean (Middle East and southern Europe), G6PD Canton (Southeast Asia), and G6PD Mahidol (Myanmar and Thailand).

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1. 1Confirm G6PD deficiency status through enzyme activity assay (fluorescent spot test or quantitative spectrophotometry).
2. 2Classify the deficiency severity using WHO Class I–V based on residual enzyme activity and clinical history.
3. 3Assess current exposure to known oxidative triggers: drugs (dapsone, primaquine, rasburicase, high-dose aspirin, nitrofurantoin, phenazopyridine), infections, or fava beans (favism).
4. 4Evaluate haematological parameters: haemoglobin drop, reticulocyte count, LDH, bilirubin, and peripheral blood film for Heinz bodies and bite cells.
5. 5Determine haemolysis risk level: low (Class IV/V, no exposure), moderate (Class III with mild oxidative trigger), or high (Class I/II with strong oxidative trigger).
6. 6For high-risk situations, stop the offending agent, ensure adequate hydration, monitor for haemoglobinuria (dark urine), and assess need for blood transfusion.
7. 7Provide patient education on drugs and foods to avoid long-term.

• !Prescribing rasburicase for tumour lysis syndrome without screening for G6PD deficiency — it is absolutely contraindicated.
• !Testing G6PD activity during an acute haemolytic episode, which gives falsely normal results due to selective destruction of deficient cells.
• !Assuming female carriers have normal G6PD activity — extreme lyonisation can lead to significant deficiency in females.
• !Using high-dose aspirin (anti-inflammatory doses) in G6PD-deficient patients — safe at analgesic doses only.
• !Overlooking neonatal jaundice risk in G6PD-deficient newborns, where bilirubin can rise rapidly enough to cause kernicterus.
• !Not counselling patients with G6PD deficiency about fava beans and over-the-counter drugs that contain oxidant compounds.