What are the recommendations for managing drug-induced hemolysis in patients with Glucose-6-phosphate dehydrogenase (G6PD) deficiency?

From the Guidelines

The primary recommendation for managing drug-induced hemolysis in G6PD deficiency is immediate discontinuation of the offending medication. When hemolysis occurs, supportive care should be provided, including intravenous hydration to maintain adequate renal perfusion and prevent acute kidney injury from hemoglobinuria 1. Blood transfusions may be necessary for severe anemia (typically when hemoglobin falls below 7 g/dL or if the patient is symptomatic). Monitoring of complete blood count, reticulocyte count, lactate dehydrogenase, haptoglobin, and renal function is essential during the acute phase. Folic acid supplementation (1 mg daily) is often recommended to support new red blood cell production. Oxygen therapy may be required for patients with significant anemia and respiratory distress.

Key Considerations

• The hemolytic crisis is typically self-limiting once the triggering agent is removed, with recovery occurring within 8-10 days as the body replaces damaged red blood cells with new G6PD-normal cells.
• Prevention is crucial, so patients should receive education about medications to avoid, including antimalarials (primaquine, chloroquine), sulfonamides, nitrofurantoin, rasburicase, and certain NSAIDs 1.
• Patients should carry a medical alert card listing their G6PD deficiency and medications to avoid.
• Methylene blue should be avoided in patients with G6PD deficiency, and ideally, all patients should be tested for G6PD deficiency before methylene blue therapy is instituted 1.

Medication Precautions

• Primaquine and tafenoquine are contraindicated in patients with G6PD deficiency, except for those with mild to moderate G6PD deficiency (>30 < 70% activity), where primaquine (45 mg once weekly) can be given for 8 weeks 1.
• Chloroquine is also a concern in patients with G6PD deficiency, and its use should be carefully considered.

Patient Education

• Patients with G6PD deficiency should be educated about the risks of hemolysis associated with certain medications and the importance of carrying a medical alert card.
• They should also be informed about the symptoms of hemolysis, such as jaundice, dark urine, and fatigue, and seek medical attention immediately if they experience any of these symptoms.

From the FDA Drug Label

WARNINGS Hemolytic anemia and G6PD deficiency Due to the risk of hemolytic anemia in patients with G6PD deficiency, G6PD testing has to be performed before using primaquine. In case of mild to moderate G6PD deficiency, a decision to prescribe primaquine must be based on an assessment of the risks and benefits of using primaquine If primaquine administration is considered, baseline hematocrit and hemoglobin must be checked before treatment and close hematological monitoring (e. g. at day 3 and 8) is required. Discontinue the use of primaquine phosphate promptly if signs suggestive of hemolytic anemia occur (darkening of the urine, marked fall of hemoglobin or erythrocytic count)

The recommendations for managing drug-induced hemolysis in patients with Glucose-6-phosphate dehydrogenase (G6PD) deficiency are:

• G6PD testing must be performed before using primaquine.
• In patients with mild to moderate G6PD deficiency, a decision to prescribe primaquine must be based on an assessment of the risks and benefits.
• Baseline hematocrit and hemoglobin must be checked before treatment.
• Close hematological monitoring is required (e.g., at day 3 and 8).
• Discontinue primaquine promptly if signs suggestive of hemolytic anemia occur. 2

From the Research

Managing Drug-Induced Hemolysis in G6PD Deficiency

• The management of drug-induced hemolysis in patients with Glucose-6-phosphate dehydrogenase (G6PD) deficiency involves avoiding certain medications that can trigger hemolysis 3.
• Medications that should be avoided in individuals with G6PD deficiency include dapsone, methylthioninium chloride (methylene blue), nitrofurantoin, phenazopyridine, primaquine, rasburicase, and tolonium chloride (toluidine blue) 3.
• However, a real-world study found that many medications suspected to carry risks for hemolysis in G6PD-deficient patients have been prescribed safely to these patients, providing reassurance to patients, prescribers, and regulators 4.
• It is essential to note that drug-induced hemolysis can be severe and may lead to renal tubular injury and glomerular glycocalyx degradation, as seen in a case of primaquine-induced hemolysis 5.

Recommendations for Medication Use

• Medications can be divided into three groups: those that should be avoided, those that are considered unsafe by at least one source but can probably be given safely, and those where no evidence contraindicates their use in G6PD-deficient patients 3.
• For example, nitrofurantoin has been prescribed safely to many G6PD-deficient patients, and other medications such as ciprofloxacin, glibenclamide, and hydroxychloroquine have also been used without evidence of hemolysis 4.
• However, it is crucial to exercise caution when prescribing medications to patients with G6PD deficiency, as some medications can still cause hemolysis, even if the evidence is limited 6, 7.

Monitoring and Prevention

• Regular monitoring of patients with G6PD deficiency is essential to prevent hemolysis, especially when prescribing medications that may pose a risk 7.
• Patients should be educated on the importance of avoiding certain medications, foods, and infections that can trigger hemolysis, and healthcare providers should be aware of the potential risks associated with G6PD deficiency 7.
• Large neonatal screening programs and molecular studies can help detect cases of G6PD deficiency before the occurrence of acute hemolysis, allowing for early intervention and prevention 7.