What are the risks and precautions for hemolysis in patients with G6PD (Glucose-6-phosphate dehydrogenase) deficiency taking metronidazole?

Hemolysis Risk with Metronidazole in G6PD Deficiency

Direct Answer

Metronidazole is NOT contraindicated in G6PD deficiency and does not appear on established lists of medications that cause hemolysis in G6PD-deficient patients. The FDA label for metronidazole does not mention G6PD deficiency as a contraindication or precaution, and current guidelines do not identify metronidazole as a hemolytic trigger 1.

Evidence-Based Assessment

Medications That ARE Contraindicated in G6PD Deficiency

The following medications pose documented hemolytic risk and should be avoided:

• Dapsone - potent oxidant causing methemoglobinemia and hemolysis 2
• Methylene blue - causes severe hemolytic anemia and is absolutely contraindicated 3, 2, 4
• Primaquine - contraindicated in severe G6PD deficiency; may be used cautiously in mild-moderate deficiency (>30% to <70% activity) at reduced weekly dosing with close monitoring 2
• Tafenoquine - contraindicated in G6PD deficiency 3

Metronidazole Safety Profile

• The FDA label for metronidazole lists multiple precautions including blood dyscrasias and recommends leukocyte monitoring, but makes no mention of G6PD deficiency or hemolytic risk 1
• Metronidazole does not appear in comprehensive guideline-based lists of medications contraindicated or requiring caution in G6PD deficiency 2, 4
• Real-world data from 31,962 G6PD-deficient patients showed that major hemolysis requiring hospitalization occurred in only 0.2% of patients, with 71.8% caused by fava beans, 8.5% by infections, and only 4.2% potentially medication-related (nitrofurantoin, phenazopyridine, and unspecified "pain killer" - not metronidazole) 5

Clinical Management Approach

For patients requiring metronidazole:

• No routine G6PD testing is required before prescribing metronidazole, as it is not an established oxidant drug 2
• Standard metronidazole dosing and monitoring per FDA label is appropriate 1
• Monitor for general hematologic effects as recommended for all patients (leukopenia), not specifically for hemolysis 1

For patients with known G6PD deficiency requiring antibiotics:

• Avoid the truly high-risk medications: dapsone, methylene blue, primaquine, and tafenoquine 2, 4
• Medications previously thought risky but shown safe in real-world data include: nitrofurantoin, sulfamethoxazole/cotrimoxazole, ciprofloxacin, and hydroxychloroquine 5, 6
• The severity of G6PD deficiency varies by genetic variant - Mediterranean variant (B-) carries higher hemolytic risk than African variant (A-) 2, 4

Important Caveat

• If hemolysis occurs in a G6PD-deficient patient on metronidazole, consider alternative causes first: fava bean ingestion (most common), concurrent infection, or other medications 5
• The most common precipitant of hemolysis in G6PD deficiency is fava beans (71.8% of cases), not medications 5