Medications Contraindicated in G6PD Deficiency
Only seven medications have solid evidence for absolute contraindication in G6PD deficiency: dapsone, methylthioninium chloride (methylene blue), nitrofurantoin, phenazopyridine, primaquine, rasburicase, and tolonium chloride (toluidine blue). 1, 2
Absolutely Contraindicated Medications
High-Risk Oxidant Drugs
Dapsone is contraindicated as it is a potent oxidant that causes methemoglobinemia and red blood cell hemolysis by overcoming the reductive capacity of G6PD, with hemolysis and Heinz body formation exaggerated in G6PD-deficient individuals 1, 3
Methylene blue (methylthioninium chloride) is absolutely contraindicated as it causes severe hemolytic anemia in G6PD-deficient patients 1, 2
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) 4, 5
Rasburicase is explicitly contraindicated in G6PD-deficient individuals because hydrogen peroxide is a major by-product of uric acid conversion to allantoin, causing hemolysis within 2-4 days of treatment initiation 6
Nitrofurantoin, phenazopyridine, and tolonium chloride (toluidine blue) are definitively contraindicated based on evidence of hemolytic risk 1, 2
8-Aminoquinolines
Tafenoquine is contraindicated in G6PD deficiency (hemizygous males and homozygous females) and should only be given to those with G6PD activity >70% of the local population median 7
Both primaquine and tafenoquine are contraindicated during pregnancy regardless of G6PD status 4
Medications Safe at Normal Therapeutic Doses
Antimalarials
Chloroquine and hydroxychloroquine in standard doses appear relatively safe in most G6PD-deficient patients, though monitoring is prudent 1
Artemisinin-based combination therapies (ACTs) including artesunate, artemether-lumefantrine, and dihydroartemisinin-piperaquine can be used safely for malaria treatment 4
Commonly Used Medications
Benzodiazepines, codeine/codeine derivatives, propofol, fentanyl, and ketamine have not been shown to cause hemolytic crises in G6PD-deficient patients 8
Metronidazole and tinidazole are not among the seven definitively contraindicated medications and can be used with appropriate monitoring 9
Critical Clinical Management Principles
Pre-Treatment Screening
Screen for G6PD deficiency before starting any oxidant drug in patients of Mediterranean, African, Indian, or Southeast Asian descent 1, 9
Qualitative screening is sufficient for males, but quantitative testing is necessary for females to differentiate deficient, intermediate, and normal G6PD status 1, 7
Quantitative testing may be needed in borderline cases to determine the degree of deficiency 1
Variant-Specific Risk Stratification
Mediterranean variant (Gdmed) typically causes more severe, potentially life-threatening hemolysis and is found predominantly in men from Mediterranean regions, India, and Southeast Asia 1
African variant (GdA-) causes milder, self-limited hemolysis and is found in 10-15% of Black men and women 1
Monitoring for Hemolysis
Watch for signs of hemolysis including jaundice, dark urine, fatigue, and pallor, particularly within 2-4 days of drug initiation 9, 6
Consider baseline hemoglobin measurement before initiating treatment in patients with severe G6PD deficiency or multiple comorbidities 9
Immediately and permanently discontinue the offending drug if hemolysis or methemoglobinemia develops, and institute appropriate support measures including potential transfusion support 6
Common Pitfalls to Avoid
Do not confuse infection-related hemolytic episodes with drug-induced hemolysis - many compounds have been wrongly cited as causing hemolysis when administered during infections that themselves trigger hemolysis 2
Do not assume all antimicrobials are contraindicated - only the seven medications listed above have solid evidence for prohibition 2
Do not give tafenoquine or primaquine without quantitative G6PD testing in females - heterozygous females with intermediate activity are at risk for hemolysis 7
Avoid confusing G6PD contraindications with those of other conditions - the list is more limited than commonly believed 9