Cefalexin (Cephalexin) is Safe for G6PD-Deficient Patients
Cefalexin can be used safely in patients with G6PD deficiency, as there is no evidence linking cephalosporin antibiotics to hemolytic crises in these patients.
Evidence-Based Safety Profile
The most comprehensive and recent real-world study examining medications in G6PD deficiency found that major hemolysis requiring hospitalization occurred in only 0.2% of G6PD-deficient patients, with the vast majority (71.8%) caused by fava bean ingestion, 8.5% by infections, and only 4.2% potentially associated with medications 1. Importantly, cefalexin and other cephalosporins were not identified as causative agents in any hemolytic episodes 1.
A systematic evidence-based review identified only seven medications with solid evidence to prohibit their use in G6PD deficiency: dapsone, methylene blue, nitrofurantoin, phenazopyridine, primaquine, rasburicase, and toluidine blue 2. Cefalexin is notably absent from this list of contraindicated medications 2.
High-Risk Medications to Actually Avoid
For context, the medications you should genuinely avoid in G6PD-deficient patients include:
- Dapsone - potent oxidant causing methemoglobinemia and hemolysis 3
- Methylene blue - causes severe hemolytic anemia 3, 4
- Primaquine - contraindicated in severe G6PD deficiency 3
- Nitrofurantoin, phenazopyridine, rasburicase, toluidine blue 2
Clinical Implications
The confusion about medication safety in G6PD deficiency stems from historical misattribution, where medications given during infection-related hemolytic episodes were incorrectly blamed for the hemolysis 2. Cefalexin has never been shown to cause oxidative stress sufficient to trigger hemolysis in G6PD-deficient red blood cells 5, 2.
When prescribing to G6PD-deficient patients, focus on avoiding the documented high-risk oxidant drugs listed above, while recognizing that common antibiotics like cefalexin pose no additional risk 3, 2, 1.