Paracetamol (Acetaminophen) is Safe to Use in Patients with G6PD Deficiency
Paracetamol can be safely administered to patients with G6PD deficiency at normal therapeutic doses, as there is no solid evidence linking it to hemolytic crises in these patients.
Evidence Supporting Safety
The most comprehensive evidence-based review found only seven medications with solid evidence to prohibit their use in G6PD deficiency: dapsone, methylthioninium chloride (methylene blue), nitrofurantoin, phenazopyridine, primaquine, rasburicase, and tolonium chloride 1. Paracetamol is notably absent from this list.
Prospective clinical trial data directly demonstrates paracetamol safety:
- A prospective study of 10 children with G6PD deficiency receiving paracetamol for 3 days post-operatively showed no evidence of hemolysis 2
- Mean hemoglobin decreased by only 0.2 g/dL (not statistically significant) 2
- While reticulocyte count increased slightly (0.1%), this was not correlated with hemoglobin changes or clinical signs of hemolysis 2
Real-world evidence from severe hemolysis confirms paracetamol safety:
- In a case of severe primaquine-induced hemolysis in a G6PD-deficient patient, regularly dosed paracetamol was given for its putative renoprotective effect and was demonstrated to be safe even in the context of severe oxidative hemolysis 3
Clinical Guidelines Perspective
Current guidelines on G6PD deficiency consistently list the seven contraindicated medications mentioned above, but do not include paracetamol among drugs to avoid 4, 5. The guideline-based evidence focuses on high-risk oxidant drugs like dapsone and methylene blue, which cause methemoglobinemia and overwhelm the reductive capacity of G6PD 6.
Common Pitfalls to Avoid
Do not confuse paracetamol with aspirin: Aspirin is explicitly contraindicated in G6PD deficiency as it can overwhelm the reduced antioxidant capacity in G6PD-deficient red blood cells 5. Paracetamol has a different mechanism of action and safety profile.
Historical misattribution: Many compounds have been wrongly cited as causing hemolysis because they were administered during infection-related hemolytic episodes, leading to confusion about true causative agents 1. Paracetamol appears to have been caught in this historical confusion.
Practical Recommendations
- Use paracetamol at standard therapeutic doses for pain and fever management in G6PD-deficient patients 2
- No special monitoring is required beyond routine clinical assessment 2
- Avoid the truly contraindicated medications (the seven listed above) 4, 1
- Screen patients of Mediterranean, African, Indian, or Southeast Asian descent before starting any oxidant drugs 4