Medications Contraindicated in G6PD Deficiency

High-Risk Medications to Avoid

Dapsone should be avoided as it is a potent oxidant that can cause methemoglobinemia and red blood cell hemolysis by overcoming the reductive capacity of G6PD in patients with G6PD deficiency 1
Methylene blue (methylthioninium chloride) is contraindicated as it can cause severe hemolytic anemia in affected patients with G6PD deficiency 2

The severity of G6PD deficiency varies based on genetic variant, with the Mediterranean variant (Gdmed) typically causing more severe reactions than the African variant (GdA-) in patients with G6PD deficiency 3, 4
The Mediterranean variant is found predominantly in men from Mediterranean regions, India, and Southeast Asia, while the GdA- variant is found in 10-15% of Black men and women with G6PD deficiency 3, 4
Patients with the Mediterranean variant may experience life-threatening hemolysis, while those with the African variant typically have milder, self-limited hemolysis in the context of G6PD deficiency 3

Screening for G6PD deficiency is strongly recommended before starting therapy with oxidant drugs in patients with predisposing racial or ethnic backgrounds (Mediterranean, African, Indian, or Southeast Asian descent) by the Clinical Infectious Diseases society 3, 4
Qualitative screening is sufficient for initial assessment, but quantitative testing may be needed to determine the degree of deficiency in patients with G6PD deficiency 4

Chloroquine/Hydroxychloroquine in standard doses appears to be relatively safe in most G6PD deficient patients, according to the Clinical Microbiology and Infection society 5

The National Comprehensive Cancer Network recommends measurement of G6PD levels before starting dapsone therapy, noting that G6PD deficient patients may have an increased risk for hemolytic adverse reactions 6
The American Academy of Dermatology notes that some subjects with G6PD deficiency developed changes suggestive of mild hemolysis with topical dapsone gel 5% and recommends observing for signs and symptoms 7

Quantitative testing may be needed to determine the degree of deficiency in borderline cases, according to the National Comprehensive Cancer Network 6

Primaquine is contraindicated in severe G6PD deficiency and should only be used in mild to moderate deficiency (>30% to <70% activity) at reduced dosing (45 mg once weekly for 8 weeks) in patients, according to the Clinical Microbiology and Infection guideline 8
Both primaquine and tafenoquine are contraindicated during pregnancy regardless of G6PD status, as recommended by the Clinical Microbiology and Infection guideline 8
Artemisinin-based combination therapies (ACTs) including artesunate, artemether-lumefantrine, and dihydroartemisinin-piperaquine can be used safely for malaria treatment in G6PD-deficient patients, as stated in the Clinical Microbiology and Infection guideline 8

The Centers for Disease Control and Prevention recommends that primaquine may be considered in mild to moderate G6PD deficiency (>30% to <70% activity) at reduced dosing of 45 mg once weekly for 8 weeks, but only after G6PD testing and with close hematological monitoring, and notes that children of any age can develop hemolysis from contraindicated medications, and the same restrictions apply 9
The Centers for Disease Control and Prevention suggests that chloroquine may be used during pregnancy as it has not been found to have harmful effects on the fetus when used in recommended doses, though the fetus may be G6PD-deficient even if the mother is normal 9
The Centers for Disease Control and Prevention recommends that mefloquine is not indicated for children less than 15 kg (30 lbs) and doxycycline is contraindicated in children less than 8 years of age 9

Dapsone is a potent oxidant that can cause methemoglobinemia and hemolysis and must be avoided in patients with G6PD deficiency (strong evidence from a 2019 review in Blood Advances) 10

Patients with G6PD deficiency should be educated to recognize early signs of hemolysis, which include dark urine, sudden fatigue or pallor, jaundice, and abdominal or back pain (clinical guidance based on the same 2019 evidence) 10