Why are certain drugs not tolerated in Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency?

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Last updated: February 11, 2025View editorial policy

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From the Guidelines

Certain drugs are not tolerated in Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency because they can cause hemolysis.

Reasons for Intolerance

  • G6PD deficiency is a genetic condition that may result in hemolysis after exposure to oxidant drugs such as dapsone, primaquine, and sulfonamides 1.
  • The condition has many variants, but the most common ones are GdA– and Gdmed, which are found in different populations and can cause varying degrees of hemolysis, with Gdmed being potentially life-threatening 1.
  • Patients with GdA– variant may experience milder and more self-limited hemolysis, which may not preclude the use of oxidant drugs 1.

Clinical Implications

  • Screening for G6PD deficiency is recommended before starting therapy with an oxidant drug, especially in patients with a predisposing racial or ethnic background 1.
  • This is a strong recommendation based on moderate quality evidence, highlighting the importance of considering G6PD deficiency in clinical practice 1.

From the Research

Overview of G6PD Deficiency

  • G6PD deficiency is a genetic disorder that affects the enzyme glucose-6-phosphate dehydrogenase, which protects red blood cells from oxidative damage 2.
  • It is estimated that about 400 million people are affected by this deficiency, with the highest prevalence reported in Africa, southern Europe, the Middle East, Southeast Asia, and the central and southern Pacific islands 2.

Drug-Induced Hemolysis

  • Certain drugs can cause hemolysis in G6PD-deficient patients, including sulphonamides, quinolones, nitrofurantoin, and primaquine 3, 4, 5.
  • The risk and severity of hemolysis is almost always dose-related, and different genetic variants of G6PD deficiency entail different susceptibility to the hemolytic risk from drugs 4.
  • Some drugs, such as benzodiazepines, codeine/codeine derivatives, propofol, fentanyl, and ketamine, have been found to be safe for use in G6PD-deficient patients and do not cause hemolytic crises 2.

Medications to Avoid

  • The following medications should be avoided in individuals with G6PD deficiency:
    • Dapsone
    • Methylthioninium chloride (methylene blue)
    • Nitrofurantoin
    • Phenazopyridine
    • Primaquine
    • Rasburicase
    • Tolonium chloride (toluidine blue) 3, 5.
  • Other medications may be used with caution, but it is essential to consider the individual's G6PD status and the potential risk of hemolysis 4.

Management and Prevention

  • The most effective management strategy is to prevent hemolysis by avoiding oxidative stressors 2.
  • Patients with G6PD deficiency should be informed of the risks and signs and symptoms of an acute hemolytic crisis, and clinicians should be able to identify both laboratory and clinical signs of hemolysis 2.
  • G6PD testing can be done to reconcile safety with cost, especially in populations where G6PD deficiency is common 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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