Ceftriaxone is Safe in G6PD Deficiency
Ceftriaxone can be used safely in patients with G6PD deficiency without special precautions or monitoring, as it is not an oxidant drug and has no documented association with hemolysis in this population.
Evidence-Based Safety Profile
The available evidence strongly supports the safety of ceftriaxone in G6PD-deficient patients:
Only seven medications have solid evidence for causing hemolysis in G6PD deficiency: dapsone, methylthioninium chloride (methylene blue), nitrofurantoin, phenazopyridine, primaquine, rasburicase, and tolonium chloride 1
Ceftriaxone is not listed among contraindicated or high-risk medications in any guideline recommendations for G6PD deficiency management 2, 3
Cephalosporins, including ceftriaxone, are not oxidant drugs and do not trigger the oxidative stress pathway that causes hemolysis in G6PD-deficient red blood cells 4
Understanding the Hemolysis Mechanism
The key to understanding medication safety in G6PD deficiency is recognizing which drugs cause oxidative stress:
G6PD-deficient patients lack adequate antioxidant protection because the enzyme catalyzes the first step in the pentose phosphate pathway, which produces antioxidants that protect red blood cells 4
Only oxidant drugs pose hemolytic risk by overwhelming the reduced antioxidant capacity in G6PD-deficient cells 2
Many medications have been wrongly cited as causing hemolysis because they were administered during infection-related hemolytic episodes, not because the drugs themselves caused hemolysis 1
Clinical Implications
No screening for G6PD deficiency is needed before prescribing ceftriaxone, as screening is only recommended before starting oxidant drugs (dapsone, primaquine, sulfonamides) in at-risk populations 3
No special monitoring is required when using ceftriaxone in G6PD-deficient patients, unlike the hemoglobin monitoring recommended for truly risky medications 5
The real-world safety data is reassuring: a large study of 31,962 G6PD-deficient patients found only 71 cases (0.2%) of major hemolysis requiring hospitalization, with 71.8% caused by fava beans, 8.5% by infections, and only 4.2% potentially medication-related (none involving cephalosporins) 6