What medication should be avoided in a 2-year-old boy with sudden jaundice, fever, dark urine, and a family history of genetic hemolytic anemia, such as G6PD (Glucose-6-Phosphate Dehydrogenase) deficiency?

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Aspirin Should Be Avoided in This Child with G6PD Deficiency

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

Clinical Reasoning

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

  • Sudden onset jaundice, fever, and dark urine (hemoglobinuria) 2
  • Anemia (Hb 9 g/L) with reticulocytosis (3%) indicating active hemolysis 2
  • Positive family history (brother with severe neonatal jaundice requiring exchange transfusion) 3
  • Symptoms appearing 24-72 hours after exposure to a precipitating factor 2

Medication Safety Profile in G6PD Deficiency

Absolutely Contraindicated: Aspirin (Answer A)

Aspirin is explicitly contraindicated in G6PD deficiency because it can overwhelm the reduced antioxidant capacity in G6PD-deficient red blood cells. 1 This medication acts as an oxidative stressor that can precipitate or worsen acute hemolysis in affected patients.

Controversial: Ibuprofen (Answer C)

Ibuprofen presents a moderate risk in G6PD deficiency. While NSAIDs are listed among drugs that can cause hemolysis 4, and ibuprofen was documented as a precipitating factor in 0.8% of hemolytic episodes in one Egyptian study 2, it is not on the absolute contraindication list like aspirin. However, given safer alternatives exist, caution is warranted.

Generally Safe: Acetaminophen (Answer D)

Acetaminophen is not listed among contraindicated medications in G6PD deficiency and represents the safest antipyretic/analgesic option for this child 5, 1.

Amoxicillin Consideration (Answer B)

Penicillins, including amoxicillin, are not among the contraindicated medications in G6PD deficiency and can be used in normal therapeutic doses. 1 While one case report documented severe hemolysis after amoxicillin exposure 6, this represents an extremely rare occurrence. Cephalosporins and penicillins are mentioned in general drug evaluation lists 4, but amoxicillin specifically is considered safe in standard guidelines 1.

High-Risk Medications to Absolutely Avoid

The following medications are definitively contraindicated and should never be used 5, 1:

  • Dapsone - potent oxidant causing methemoglobinemia and hemolysis 5
  • Methylene blue (methylthioninium chloride) - causes severe hemolytic anemia 5
  • Primaquine - contraindicated in severe deficiency 5
  • Rasburicase 1

Clinical Pitfalls

  • Do not test G6PD levels during acute hemolysis - reticulocytes and young RBCs may contain near-normal enzyme levels, potentially masking deficiency and causing false-negative results 7
  • Wait at least 50 days after any blood transfusion before performing enzyme assays 7
  • The severity varies by genetic variant: Mediterranean variant causes life-threatening hemolysis, while African variant produces milder, self-limited hemolysis 5, 7

Immediate Management Priorities

For this child's acute hemolytic crisis:

  • Immediately discontinue any potential oxidative stressors 8
  • Supportive care with hydration 8
  • Monitor hemoglobin levels closely 4
  • Consider transfusion if hemoglobin drops below 7-8 g/dL with symptoms 4
  • Provide folic acid supplementation (1 mg daily) 4

The correct answer is A (Aspirin) - this is the medication that must be strictly avoided in G6PD deficiency.

References

Guideline

Management of G6PD Deficiency in Children

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

Study of Glucose-6-Phosphate Dehydrogenase Deficiency: 5 Years Retrospective Egyptian Study.

Endocrine, metabolic & immune disorders drug targets, 2018

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Medications Contraindicated in G6PD Deficiency

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

G6PD Deficiency Diagnosis and Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

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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