What can be given to a patient with glucose-6-phosphate dehydrogenase (G6PD) deficiency at risk of tumor lysis syndrome (TLS) to prevent it?

Prevention of Tumor Lysis Syndrome in Patients with G6PD Deficiency

For patients with G6PD deficiency at risk of tumor lysis syndrome, allopurinol is the appropriate agent for prevention, as rasburicase is absolutely contraindicated in these patients due to the risk of severe hemolytic anemia and methemoglobinemia.

Contraindication of Rasburicase in G6PD Deficiency

Rasburicase is explicitly contraindicated in patients with G6PD deficiency according to multiple guidelines:

• The Journal of Clinical Oncology guidelines clearly state that "rasburicase is contraindicated in patients with a known G6PD deficiency" 1
• The European Society for Medical Oncology consensus states that "rasburicase is contraindicated in patients with metahemoglobinemia, G6PDH deficiency or other metabolic disorders that can potentially cause hemolytic anemia" 1
• Praxis Medical Insights confirms that rasburicase has "contraindications in patients with G6PD deficiency, methemoglobinemia, or other metabolic disorders that may cause hemolytic anemia" 2

Mechanism of Harm

The contraindication exists because rasburicase can cause severe adverse reactions in G6PD-deficient patients:

• Rasburicase converts uric acid to allantoin, producing hydrogen peroxide as a byproduct
• In G6PD deficiency, red blood cells cannot adequately detoxify hydrogen peroxide
• This leads to oxidative damage resulting in potentially life-threatening hemolytic anemia and methemoglobinemia 3, 4

Appropriate Management for G6PD-Deficient Patients

For patients with G6PD deficiency at risk of TLS, guidelines recommend:

1. Allopurinol as the primary xanthine oxidase inhibitor:

   • Administer orally at 100 mg/m² three times daily (maximum 800 mg/day) 1, 2
   • For patients unable to take oral medications, IV allopurinol at 200-400 mg/m²/day in 1-3 divided doses (maximum 600 mg/day) 1

2. Aggressive hydration:

   • Maintain urine output of at least 100 mL/hour in adults (3 mL/kg/hour in children <10 kg) 1, 2
   • Begin hydration at least 48 hours before tumor-specific therapy when possible 1

3. Urine alkalinization:

   • Consider urine alkalinization for patients on allopurinol (unlike rasburicase, where it's not recommended) 1
   • Monitor urine pH to maintain appropriate alkalinity

Monitoring Recommendations

For patients with G6PD deficiency at risk of TLS:

• Monitor LDH, uric acid, sodium, potassium, creatinine, BUN, phosphorus, and calcium every 12 hours for the first three days, then every 24 hours 1
• If TLS develops, increase monitoring to every 6 hours for the first 24 hours for vital parameters, serum uric acid, electrolytes, and renal function 1
• Assess for signs of acute kidney injury, which may require renal replacement therapy

Important Considerations for Allopurinol Use

• Reduce allopurinol dose by 50% in patients with renal insufficiency 1
• If used concomitantly with 6-mercaptopurine or azathioprine, reduce those drugs by 50-70% 1
• Be aware of potential drug interactions with dicumarol, uricosuric agents, thiazide diuretics, ampicillin/amoxicillin, cyclophosphamide, chlorpropamide, and cyclosporine 1
• Unlike rasburicase, allopurinol only prevents new uric acid formation and does not reduce existing uric acid 1

Pitfalls to Avoid

1. Never administer rasburicase to patients with known G6PD deficiency - this can lead to life-threatening hemolytic anemia and methemoglobinemia 5, 3, 4

2. Do not use methylene blue to treat methemoglobinemia if it develops in G6PD-deficient patients - it can worsen the condition 4

3. Do not delay TLS prophylaxis - allopurinol should be started 1-2 days before chemotherapy when possible 1

4. Do not administer rasburicase and allopurinol concurrently - allopurinol reduces rasburicase efficacy by decreasing substrate availability 2