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Medications to Avoid in Patients with G6PD Deficiency Due to Risk of Hemolysis

Summary:

  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a well-known, X-linked genetic disorder that most commonly affects up to 25% of primarily male patients from Africa, Asia, and the Mediterranean.
  • A number of different factors can trigger these patients to develop hemolytic anemia and most commonly include medications, fava beans, and/or an infection.
  • For those taking or preparing for board or specialty exams, those medications or substances that are stared (*) in the table above are the most common to know.

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA
Last Reviewed:
August 2015

Explanation

  • Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a well-known, X-linked genetic disorder that most commonly affects up to 25% of primarily male patients from Africa, Asia, and the Mediterranean.1-2  The most common clinical manifestation is jaundice due to hemolysis of red blood cells (RBC).1  A number of different factors can trigger these patients to develop hemolytic anemia, which most commonly includes medications, fava beans, and/or an infection.1  When placed under some type of stressor, RBCs must maintain the level of nicotinamide adenine dinucleotide phosphate (NADPH) in order to allow glutathione to protect the RBC from undergoing damage in the presence of oxidative metabolites.  It is the presence of a functionally active G6PD enzyme that allows the RBC to maintain adequate amounts of NADPH and thus allows glutathione to act as protector against oxidative stressors.

    As it relates to the oxidative stressors mentioned above, medications and other chemicals are commonly associated with the development of this in type of hemolytic anemia and are summarized below.3-9

    • Chloroquine (Aralen)* - Antimalarial Agent
    • Dapsone* - Antimycobacterial Agent
    • Fava Beans* - Natural Supplement
    • Flutamide (Eulexin) - Anti-androgen (Non-steroidal Oral Agent)
    • Methylthioninium chloride (Methylene Blue) - Antidote
    • Nitrofurantoin (Macorbid)* - Antibiotic
    • Pegloticase (Krystexxa) - Recombinate Urate-Oxidase Enzyme
    • Phenazopyridine (Pyridium) - Analgesic (Urinary Tract)
    • Primaquine Phosphate* - Antimalarial Agent
    • Rasburicase (Elitek)* - Recombinate Urate-Oxidase Enzyme
    • Trimethoprim/Sulfamethoxazole (Bactrim; Bactrin DS; Septra)* - Inhibitor of Dihydrofolate Reductase/Dihydropteroate Synthetase
    • Note:
      • Red blood cells (RBC) on histologic examination reveal "bite cells" or Heinz bodies due to oxidative damage to RBC membranes.
      • * = Medications most common or classically associated with hemolysis if used in G6PD deficient patients.

    For those taking or preparing for board or specialty exams, those medications or substances that are stared (*) are the most common to know.  If a patient should develop acute, new onset jaundice, a complete blood cell count (CBC) with differential, reticulocyte count, a peripheral smear looking for the presence of "bite cells" or Heinz bodies, indirect bilirubin, and measurement of G6PD enzyme are helpful in establishing a diagnosis.  If it is determined that a patient has hemolytic anemia from the use of any of these medications, the medication should be stopped, the patient should rest or even be put on bed rest for a few days, and if necessary add supplemental oxygen if the pulse ox is < 90% and/or if other comorbidities exist that might be exacerbated by a period of hypoxia.

    References:

    1. Beutler E. Glucose-6-phosphate dehydrogenase deficiency. N Engl J Med 1991;324:169-74.  
    2. Nkhoma ET, Poole C, Vannappagari V, et al. The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis. Blood Cells Mol Dis  2009;42:267-78.  
    3. Grossman S, Budinsky R, Jollow D.  Dapsone-induced hemolytic anemia: role of glucose-6-phosphate dehydrogenase in the hemolytic response of rat erythrocytes to N-hydroxydapsone.  J Pharmacol Exp Ther 1995;273:870-7.  
    4. Fanello CI, Karema C, Avellino P et al.  High risk of severe anaemia after chlorproguanil-dapsone+artesunate antimalarial treatment in patients with G6PD (A-) deficiency.  PLoS One  2008;3:e4031.  
    5. Schuurman M, van Waardenburg D, Da Costa J et al.  Severe hemolysis and methemoglobinemia following fava beans ingestion in glucose-6-phosphate dehydrogenase deficiency: case report and literature review.  Eur J Pediatr  2009;168:779-82.  
    6. Tishler M, Abramov A.  Phenazopyridine-induced hemolytic anemia in a patient with G6PD deficiency.  Acta Haematol  1983;70:208-9.  
    7. Browning LA, Kruse JA.  Hemolysis and methemoglobinemia secondary to rasburicase administration.  Ann Pharmacother  2005;39:1932-5.  
    8. Youngster I, Arcavi L, Schechmaster R et al.  Medications and glucose-6-phosphate dehydrogenase deficiency: an evidence based review.  Drug Saf 2010;33:713-726.  
    9. Chisholm-Burns MA, Patanwala AE, Spivey CA.  Aseptic meningitis, hemolytic anemia, hepatitis, and orthostatic hypotension in a patient treated with trimethoprim-sulfamethoxazole.  Am J Health Syst Pharm 2010;67:123-7.

MESH Terms & Keywords

  • G6PD Deficiency, Medications to Avoid in G6PD