G6PD Testing Before Starting Dapsone
Yes, measurement of G6PD levels is recommended before starting dapsone therapy. 1
Guideline Recommendations
The NCCN explicitly states that for patients receiving dapsone, measurement of G6PD levels is recommended before the start of therapy, noting that G6PD deficient patients may have an increased risk for hemolytic adverse reactions. 1
Multiple clinical infectious disease societies strongly recommend screening for G6PD deficiency before starting therapy with oxidant drugs (including dapsone) in patients with predisposing racial or ethnic backgrounds—specifically those of Mediterranean, African, Indian, or Southeast Asian descent. 2, 3
FDA Drug Label Position
The FDA label for dapsone clearly warns that hemolysis and Heinz body formation may be exaggerated in individuals with G6PD deficiency, and this reaction is frequently dose-related. 4 The label states dapsone should be given with caution to G6PD deficient patients, explicitly listing dapsone among drugs that have produced significant hemolysis in G6PD deficient patients. 4
Clinical Rationale
Risk Severity by Variant Type
- Mediterranean variant (Gdmed): Causes life-threatening hemolysis and requires strict avoidance of dapsone 2, 3
- African variant (GdA-): Produces milder, self-limited hemolysis but still poses significant risk 2, 3
- The Mediterranean variant is found predominantly in men from Mediterranean regions, India, and Southeast Asia, while the African variant affects 10-15% of Black individuals 2
Evidence of Hemolytic Risk
Research demonstrates that dapsone is a potent oxidant that can cause methemoglobinemia and red blood cell hemolysis by overcoming the reductive capacity of G6PD. 2 A study of antimalarial treatment showed patients with G6PD deficiency had a 10-fold higher risk of severe anemia requiring blood transfusion when receiving dapsone-containing regimens (RR = 10.2; 95% CI 1.8 to 59.3). 5
In lung transplant recipients, dapsone-induced hemolytic anemia occurred in 22.7% of patients despite normal G6PD levels, with a mean hemoglobin drop of 2.7 g/dL. 6 This suggests additional risk factors beyond G6PD deficiency alone.
Testing Approach
- Qualitative screening is sufficient for initial assessment to detect severe G6PD deficiency (enzyme activity <10% of normal) 3
- Quantitative testing may be needed to determine the degree of deficiency in borderline cases 1, 2
- Critical timing consideration: G6PD levels may be falsely elevated during acute hemolysis, so repeat testing after 3 months may be necessary for accurate diagnosis if initial testing occurs during a hemolytic episode 7
Important Caveats
Topical Dapsone Exception
For topical dapsone gel 5% used in acne treatment, the risk profile differs substantially. A controlled study of 64 G6PD-deficient subjects showed no clinical or laboratory evidence of drug-induced hemolytic anemia with topical application. 8 However, the acne treatment guidelines still note that "some subjects with G6PD deficiency developed changes suggestive of mild hemolysis" and recommend observing for signs and symptoms. 1
High-Risk Populations Requiring Screening
- Mediterranean, African, Indian, or Southeast Asian descent 2, 3
- Patients with renal impairment (increased odds ratio of 4.75 for hemolysis per 1.0 mg/dL creatinine increase) 6
- Low body weight patients receiving doses exceeding 1.5 mg/kg 6
Bottom line: Screen for G6PD deficiency before prescribing oral dapsone, particularly in at-risk ethnic populations. Do not use dapsone in patients with confirmed G6PD deficiency, especially those with the Mediterranean variant. 2, 4