Co-Amoxiclav is Safe in G6PD Deficiency
Co-amoxiclav (amoxicillin-clavulanate) can be used safely in patients with G6PD deficiency at normal therapeutic doses, as penicillins including amoxicillin are not among the contraindicated medications. 1
Evidence-Based Safety Profile
Definitive Guideline Recommendations
- Penicillins, including amoxicillin, are explicitly listed as safe to use in normal therapeutic doses in G6PD-deficient patients according to American Journal of Kidney Diseases guidelines 1
- Only seven medications have solid evidence for absolute contraindication in G6PD deficiency: dapsone, methylthioninium chloride (methylene blue), nitrofurantoin, phenazopyridine, primaquine, rasburicase, and tolonium chloride 1, 2
- Co-amoxiclav does not appear on any contraindicated medication list in current guidelines 1, 3
Real-World Safety Data
- A large Israeli real-world study of 31,962 G6PD-deficient patients found only 71 cases (0.2%) of major hemolysis requiring hospitalization over 12 years 4
- Of these hemolytic episodes, 71.8% were caused by fava beans, 8.5% by infections, and only 4.2% possibly associated with medications (none were penicillins) 4
- This study demonstrated that many previously suspected medications have been prescribed safely to thousands of G6PD-deficient patients without causing hemolysis 4
Important Caveat: One Case Report
There is one published case report of severe hemolytic anemia possibly associated with amoxicillin exposure in a G6PD-deficient patient 5. However, this represents an extremely rare occurrence and should be interpreted cautiously:
- The patient received amoxicillin two weeks prior to hemolysis, making causality uncertain 5
- No other infectious or hematologic cause was identified 5
- This single case contrasts sharply with the large-scale safety data showing thousands of safe exposures 4
Clinical Approach
When Prescribing Co-Amoxiclav to G6PD-Deficient Patients:
- Prescribe at normal therapeutic doses without dose adjustment 1
- Monitor for signs of hemolysis when starting any new medication, including jaundice, dark urine, or pallor 1
- Consider that concurrent infections themselves can trigger hemolysis in G6PD deficiency, independent of medication exposure 4
- Educate patients about when to seek medical attention if symptoms of hemolysis develop 1
Variant-Specific Considerations:
- The Mediterranean variant (Gdmed) causes more severe hemolytic reactions than the African variant (GdA-), but this primarily matters for the seven definitively contraindicated medications 1, 3
- For penicillins, both variants can receive standard dosing 1
The overwhelming evidence supports safe use of co-amoxiclav in G6PD deficiency, with standard monitoring for any new medication in this population.