What medication should be avoided in a 2-year-old boy with suspected Glucose-6-phosphate dehydrogenase (G6PD) deficiency, presenting with jaundice, fever, and dark urine?

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Aspirin Should Be Avoided in This Patient with G6PD Deficiency

Aspirin is contraindicated in patients with G6PD deficiency and should be avoided in this 2-year-old boy presenting with acute hemolytic crisis. 1

Clinical Presentation Confirms G6PD Deficiency

This child's presentation is classic for acute hemolytic crisis in G6PD deficiency:

  • Acute jaundice with dark urine indicates intravascular hemolysis 2
  • Anemia (Hb 9 g/L) with elevated reticulocytes (3%) demonstrates active red blood cell destruction and compensatory bone marrow response 2
  • Positive family history of severe neonatal jaundice requiring exchange transfusion strongly suggests inherited G6PD deficiency 2
  • Fever as a trigger - infections are well-documented precipitants of hemolytic crises in G6PD-deficient patients 3, 4

Why Aspirin Must Be Avoided

Aspirin is explicitly contraindicated in G6PD deficiency according to the American Family Physician guidelines, which list "G6PD-deficiency" as a specific contraindication for aspirin use 1. This is because:

  • Aspirin is a potent oxidant that can overwhelm the reduced antioxidant capacity in G6PD-deficient red blood cells 5, 3
  • The Mediterranean variant of G6PD deficiency (common in the patient's geographic origin) typically causes more severe hemolytic reactions than the African variant 5, 2
  • Administering aspirin during an active hemolytic crisis could precipitate life-threatening hemolysis 5

Safety Profile of Other Medications

Ibuprofen (Option C) - Safe to Use

  • Recent systematic review found ibuprofen to be safe in children with G6PD deficiency, with extremely low incidence of hemolysis (approximately 1/100,000 affected children per year) 6
  • A prospective study showed no evidence of hemolysis from perioperative NSAID exposure in G6PD-deficient children at high risk 6
  • While ibuprofen appears on some medium-risk lists, the evidence does not support avoiding it 6

Amoxicillin (Option B) - Safe to Use

  • Penicillins are not among the seven definitively contraindicated medications in G6PD deficiency 5, 7, 4
  • The comprehensive evidence-based review found no solid evidence to prohibit penicillin use in normal therapeutic doses 4
  • Penicillin-related concerns in CKD guidelines relate to crystalluria and neurotoxicity at high doses in renal failure, not G6PD deficiency 1

Acetaminophen (Option D) - Safe to Use

  • Not listed among contraindicated medications for G6PD deficiency 5, 7, 4
  • The definitive list of only seven contraindicated medications includes: dapsone, methylthioninium chloride (methylene blue), nitrofurantoin, phenazopyridine, primaquine, rasburicase, and tolonium chloride 5, 7, 4
  • Acetaminophen does not appear on this evidence-based list 4

Critical Management Principles

The most effective strategy is preventing further hemolysis by avoiding oxidative stressors 3. In this acute presentation:

  • Immediate discontinuation of any potential oxidant drugs is essential 3
  • Monitor for signs of worsening hemolysis: increasing jaundice, darkening urine, falling hemoglobin, rising indirect bilirubin 2
  • Screening confirmation should be performed, though G6PD levels may be falsely elevated during acute hemolysis, requiring repeat testing after 3 months 2
  • Patient and family education about avoiding oxidant triggers is crucial for preventing future crises 2, 3

Common Pitfall to Avoid

Many medications have been wrongly cited as causing hemolysis because they were administered during infection-related hemolytic episodes 4. The fever in this case suggests infection as the primary trigger, but aspirin remains contraindicated regardless of the precipitating cause 1.

Answer: A. Aspirin

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Management of G6PD Deficiency in Children

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Medications Contraindicated in G6PD Deficiency

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Miralax Safety in G6PD Deficiency

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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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