Safety of Benadryl (Diphenhydramine) and Paracetamol (Acetaminophen) in G6PD Deficiency
Paracetamol (acetaminophen) and Benadryl (diphenhydramine) can be safely used in patients with G6PD deficiency as neither medication has been shown to cause hemolysis in these patients.
Safety of Paracetamol (Acetaminophen) in G6PD Deficiency
- Paracetamol (acetaminophen) has been demonstrated to be safe for use in patients with G6PD deficiency and does not increase the risk of hemolysis when administered in therapeutic dosages 1
- A prospective study specifically evaluating paracetamol in children with G6PD deficiency found no significant decrease in hemoglobin concentration after administration 1
- While a small increase in reticulocyte count was observed in the study, it was not correlated with changes in hemoglobin concentration or accompanied by clinical signs of hemolysis 1
- Recent comprehensive reviews of medications in G6PD deficiency do not list paracetamol among medications that should be avoided 2, 3
- A 2024 real-world study examining medications in G6PD-deficient patients did not identify paracetamol as a cause of hemolysis requiring hospitalization 4
Safety of Benadryl (Diphenhydramine) in G6PD Deficiency
- Diphenhydramine (Benadryl) is not included in any evidence-based lists of medications that should be avoided in G6PD deficiency 2, 3
- Comprehensive reviews of medications contraindicated in G6PD deficiency do not mention diphenhydramine as a medication of concern 2
- Unlike medications such as rasburicase, dapsone, methylene blue, nitrofurantoin, phenazopyridine, primaquine, and tolonium chloride which are definitively contraindicated in G6PD deficiency, diphenhydramine has no documented risk 2
Medications Definitively Contraindicated in G6PD Deficiency
For context, medications that are definitively contraindicated in G6PD deficiency include:
- Rasburicase - contraindicated due to risk of severe hemolysis 5
- Methylene blue (methylthioninium chloride) - can induce hemolysis and paradoxically worsen methemoglobinemia in G6PD deficiency 5
- Dapsone, nitrofurantoin, phenazopyridine, primaquine, and tolonium chloride - all have solid evidence showing risk of hemolysis 2
Clinical Approach to Medication Use in G6PD Deficiency
- Assess the patient's G6PD deficiency status - severity can vary based on genetic variant and ethnic background 5
- Consider alternative medications if there is any concern about a specific drug's safety profile 2
- Monitor for signs of hemolysis when starting any new medication in G6PD-deficient patients, including jaundice, dark urine, fatigue, and pallor 5
- In cases of suspected medication-induced hemolysis, immediately discontinue the offending agent 5
Key Points for Clinical Practice
- Both paracetamol and diphenhydramine can be used at standard therapeutic doses in patients with G6PD deficiency 2, 1
- Unlike certain medications that have clear evidence of causing hemolysis in G6PD deficiency, neither paracetamol nor diphenhydramine appears on evidence-based lists of contraindicated medications 2, 3
- When treating G6PD-deficient patients with any medication, maintain vigilance for early signs of hemolysis, though this is not expected with either paracetamol or diphenhydramine 5
- For pain management in G6PD-deficient patients, paracetamol is considered a safe option, as supported by clinical studies 1