Can silver sulfadiazine be given to a patient with Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

Silver Sulfadiazine Should Be Avoided in G6PD-Deficient Patients

Silver sulfadiazine is contraindicated in patients with G6PD deficiency due to documented risk of acute hemolytic anemia, and alternative topical antimicrobials should be used for burn management in this population. 1, 2

Evidence for Contraindication

FDA Drug Label Warning

• The FDA label for sulfadiazine explicitly states: "Hemolysis may occur in individuals deficient in glucose-6-phosphate dehydrogenase. This reaction is dose related." 1
• Sulfonamides (including silver sulfadiazine) should be given with caution to patients with impaired renal or hepatic function and to those with severe allergy or bronchial asthma, but the G6PD warning is absolute regarding hemolysis risk 1

Case Report Evidence

• A documented case exists of a 20-year-old G6PD-deficient burn patient who developed acute hemolytic anemia 4 days after topical application of 1% silver sulfadiazine twice daily for 35% body surface area burns 2
• Complete recovery occurred following withdrawal of silver sulfadiazine, confirming the drug as the causative agent 2
• G6PD deficiency was confirmed by pathological Motulski tests in this patient 2

Classification of Sulfonamides in G6PD Deficiency

High-Risk Oxidant Drugs

• Sulfonamides are classified among the drugs most commonly used that can lead to hemolysis in G6PD deficiency, alongside dapsone and primaquine 3
• The 2023 Clinical Pharmacogenetics Implementation Consortium guideline systematically reviewed medications implicated as unsafe in G6PD deficiency and provides risk stratification 4
• A 2010 evidence-based review found solid evidence to prohibit seven medications in G6PD deficiency, though sulfonamides showed variable evidence depending on the specific compound 5

Real-World Safety Data for Some Sulfonamides

• In a large real-world study of 31,962 G6PD-deficient patients, sulfamethoxazole/cotrimoxazole and sulfasalazine were prescribed safely to hundreds/thousands of patients without major hemolysis 6
• However, this data does not extend to silver sulfadiazine, which has documented case reports of hemolysis 2

Pathophysiology of Risk

Mechanism of Hemolysis

• G6PD catalyzes the first step in the pentose phosphate pathway, producing antioxidants that protect red blood cells against oxidative damage 7
• G6PD-deficient patients lack the ability to protect red blood cells against oxidative stresses from certain drugs, including sulfonamides 7
• The hemolytic reaction is dose-related, which is particularly concerning with topical silver sulfadiazine applied to large burn surface areas 1

Variant-Specific Severity

• The Mediterranean variant (Gdmed) can cause life-threatening hemolysis, while the African variant (GdA-) typically produces milder, self-limited hemolysis 3, 8
• The Mediterranean variant is found predominantly in men from Mediterranean regions, India, and Southeast Asia, while GdA- is found in 10-15% of Black men and women 3, 8

Clinical Management Recommendations

Screening Before Treatment

• Qualitative screening for G6PD deficiency is recommended before starting therapy with oxidant drugs (including sulfonamides) in patients with predisposing racial or ethnic backgrounds (Mediterranean, African, Indian, or Southeast Asian descent) 3, 8
• Anyone suspected of G6PD deficiency should be screened before exposure to oxidative stressors 7

Monitoring for Hemolysis

• Patients should be instructed to report promptly the onset of sore throat, fever, pallor, purpura, or jaundice, as these may be early indications of serious blood disorders 1
• Complete blood counts should be done frequently in patients receiving sulfonamides 1
• Clinicians should monitor for signs of hemolysis including jaundice, dark urine, fatigue, and pallor when any new medication is started in G6PD-deficient patients 9

Management of Acute Hemolysis

• If acute hemolytic crisis is identified, the patient should be admitted for close observation and care 7
• Immediate discontinuation of the offending agent is essential 2
• The rare need for blood transfusion may arise in severe cases 7

Alternative Topical Antimicrobials for Burns

While the evidence provided does not specify alternative burn treatments, the clear documentation of hemolysis with silver sulfadiazine 2 combined with FDA warnings 1 mandates avoidance and selection of non-sulfonamide topical antimicrobials in G6PD-deficient burn patients.