Naproxen Use in G6PD Deficiency
Naproxen (Naprosyn) can be safely used in patients with G6PD deficiency, including those with concurrent BPH, as there is no credible evidence linking NSAIDs like naproxen to hemolytic crises in G6PD-deficient individuals.
Evidence-Based Safety Profile
Direct Clinical Evidence
A case report specifically documents successful treatment with naproxen in a G6PD-deficient patient who initially developed severe hemolytic anemia from high-dose aspirin for adult-onset Still's disease; after switching to naproxen, the patient recovered completely with restoration of hematologic parameters 1.
A comprehensive evidence-based review of medications in G6PD deficiency found only seven medications with solid evidence for causing hemolysis: dapsone, methylthioninium chloride (methylene blue), nitrofurantoin, phenazopyridine, primaquine, rasburicase, and tolonium chloride—notably, NSAIDs including naproxen are not on this list 2.
NSAIDs as a class have been safely administered to G6PD-deficient patients, with ketoprofen lysine salt specifically studied in 34 G6PD-deficient children (19 females with intermediate deficiency, 14 hemizygote males, and 1 completely deficient female) showing no hemolysis or adverse events 3.
Real-World Safety Data
A large real-world study of 31,962 G6PD-deficient patients identified only 71 cases (0.2%) of major hemolysis requiring hospitalization over 13 years, with 71.8% caused by fava beans, 8.5% by infections, and only 4.2% potentially medication-related (nitrofurantoin, phenazopyridine, and an unspecified "pain killer"—not NSAIDs) 4.
The same study demonstrated that hundreds to thousands of G6PD-deficient patients safely received various medications previously suspected of causing hemolysis, providing reassurance that many historical concerns were unfounded 4.
Clinical Management Algorithm
Pre-Treatment Assessment
Screen patients at risk for G6PD deficiency (males of African, Mediterranean, Middle Eastern, or Southeast Asian ancestry) before initiating any potentially oxidative medication 5, 6.
Obtain baseline complete blood count to establish hemoglobin, hematocrit, and reticulocyte count before starting therapy 6.
Safe Prescribing of Naproxen
Naproxen can be prescribed at standard therapeutic doses without special precautions beyond routine NSAID monitoring (gastrointestinal, cardiovascular, and renal considerations) 2, 1.
No dose adjustment or special monitoring for hemolysis is required when prescribing naproxen to G6PD-deficient patients 2.
Patient Education
Inform patients about signs of hemolytic crisis (dark urine, jaundice, severe fatigue, shortness of breath) even though the risk with naproxen is negligible 6.
Counsel patients to avoid true oxidative stressors: fava beans (most common trigger), infections (second most common), and the seven medications with solid evidence for causing hemolysis 4, 2.
BPH Management Considerations
Concurrent BPH Treatment Options
Alpha-blockers (alfuzosin, doxazosin, tamsulosin, terazosin, silodosin) are safe in G6PD deficiency and appropriate for managing BPH-related lower urinary tract symptoms 5, 7.
5-alpha-reductase inhibitors (finasteride, dutasteride) are safe in G6PD deficiency and effective for patients with demonstrable prostatic enlargement (>30cc) 5, 8.
Naproxen can be used concurrently with BPH medications for pain management or anti-inflammatory needs without concern for drug-drug interactions related to G6PD status 2.
Common Pitfalls to Avoid
Historical Misconceptions
Many medications have been wrongly cited as causing hemolysis because they were administered during infection-related hemolytic episodes, leading to false attribution 2.
Avoid perpetuating outdated contraindication lists that lack evidence-based support; rely on the seven medications with solid evidence for prohibition 2.
Infection as Confounding Factor
Recognize that infections themselves can trigger hemolysis in G6PD-deficient patients (8.5% of hospitalized hemolytic cases), which may be incorrectly attributed to concurrent medications 4.
If hemolysis occurs during naproxen therapy, investigate for underlying infection or fava bean exposure before attributing causation to the NSAID 4, 1.
Unnecessary Restrictions
Do not withhold naproxen or other NSAIDs from G6PD-deficient patients based on theoretical concerns unsupported by clinical evidence 2, 1.
Standard NSAID precautions apply (gastroprotection in high-risk patients, monitoring renal function, cardiovascular risk assessment) but G6PD deficiency does not add additional contraindications 2.