Is it safe to give Amoxiclav (amoxicillin-clavulanate) to a patient with Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

Safety of Amoxiclav in G6PD Deficiency

Amoxiclav (amoxicillin-clavulanate) is safe to administer to patients with Glucose-6-phosphate dehydrogenase (G6PD) deficiency as it is not among the medications known to cause hemolytic anemia in these patients.

Evidence on Medication Safety in G6PD Deficiency

G6PD deficiency is the most common enzymatic disorder of red blood cells worldwide, affecting approximately 400 million people 1. This X-linked genetic disorder impairs the body's ability to protect red blood cells against oxidative stress, which can lead to hemolysis when exposed to certain triggers.

Medications Known to Cause Hemolysis in G6PD Deficiency

According to comprehensive evidence-based reviews, only a limited number of medications have solid evidence showing they cause hemolysis in G6PD-deficient patients. These include:

• Dapsone
• Methylthioninium chloride (methylene blue)
• Nitrofurantoin
• Phenazopyridine
• Primaquine
• Rasburicase
• Tolonium chloride (toluidine blue) 2

Notably, amoxicillin-clavulanate (Amoxiclav) is not included in this list of contraindicated medications.

Real-World Evidence

A large real-world study examining medication use in G6PD-deficient patients found that many medications previously thought to be risky were actually prescribed safely to thousands of G6PD-deficient patients without causing hemolytic episodes 3. Among the 31,962 G6PD-deficient patients studied, only 71 cases (0.2%) of major hemolysis requiring hospitalization were identified, with only 3 cases (4.2%) potentially associated with medications (specifically nitrofurantoin, phenazopyridine, and an unspecified "pain killer") 3.

Management Principles for G6PD-Deficient Patients

The most effective management strategy for G6PD deficiency is prevention through avoidance of known oxidative stressors 1, 4. These include:

1. Medications with established risk (the seven listed above)
2. Fava beans (the most common dietary trigger)
3. Certain infections that can trigger hemolysis

Clinical Implications for Amoxiclav Use

When treating infections in G6PD-deficient patients:

• Amoxiclav can be safely administered in standard therapeutic doses
• No dose adjustment is necessary based on G6PD status
• Regular monitoring for signs of hemolysis is not specifically required when using Amoxiclav

Signs of Hemolysis to Monitor (General Awareness)

Although not expected with Amoxiclav, clinicians should be aware of signs of hemolysis in G6PD-deficient patients:

• Sudden onset of pallor
• Jaundice
• Dark urine
• Fatigue
• Back/abdominal pain
• Laboratory findings: decreased hemoglobin, increased bilirubin, elevated LDH, decreased haptoglobin

Conclusion

Based on the available evidence, Amoxiclav does not pose a risk of hemolytic anemia in G6PD-deficient patients and can be safely prescribed at standard therapeutic doses. The focus should remain on avoiding the seven medications with established risk of causing hemolysis in these patients.