How to manage methotrexate (MTX) toxicity with eosinophilia?

Management of Methotrexate Toxicity with Eosinophilia

In cases of methotrexate toxicity with eosinophilia, immediate administration of leucovorin (folinic acid) is the cornerstone of treatment, along with supportive measures including hydration and urinary alkalinization. 1

Initial Management

• Administer leucovorin as promptly as possible - early treatment is life-saving and effectiveness decreases as time interval between methotrexate administration and leucovorin initiation increases 1, 2
• Initial leucovorin dose should be up to 100 mg/m² by intravenous infusion if methotrexate level is unknown 1
• Continue leucovorin with subsequent oral/intravenous doses every 6 hours based on methotrexate levels 1, 2
• Maintain aggressive hydration to improve renal elimination of methotrexate 1, 2
• Perform urine alkalinization with sodium bicarbonate to prevent methotrexate precipitation in renal tubules 1, 2

Specific Management for Eosinophilia

• For eosinophilia specifically, continue leucovorin until methotrexate levels are <0.05 μmol/L and hematological abnormalities have resolved 1
• Monitor complete blood count regularly to track eosinophil levels and other hematologic parameters 1, 3
• For bone marrow suppression (which may accompany eosinophilia): administer filgrastim (granulocyte colony-stimulating factor) subcutaneously at 5 μg/kg daily to accelerate myeloid recovery 1
• Continue monitoring until eosinophil counts normalize and other signs of toxicity resolve 3

Supportive Care

• Monitor liver function and renal function tests regularly, as methotrexate toxicity can affect multiple organ systems 3, 2
• Watch for mucositis, fever, diarrhea, erythema, and ulceration, which may take 6-23 days to manifest 1
• If renal function is impaired (a common cause of methotrexate toxicity), consider dose adjustments in future methotrexate therapy - avoid methotrexate in patients with creatinine clearance <20 mL/min and reduce dose by 50% for those with clearance between 20-50 mL/min 3, 4

Advanced Interventions (If Standard Treatment Fails)

• For severe cases with delayed methotrexate clearance due to impaired renal function, glucarpidase may be indicated 2, 5
• If glucarpidase is used, do not administer leucovorin within two hours before or after a dose of glucarpidase (leucovorin is a substrate for glucarpidase) 2
• In cases of extremely high methotrexate levels with delayed elimination, hemodialysis may be considered, though its effectiveness is variable 2, 5

Prevention of Future Toxicity

• For patients continuing on methotrexate therapy, ensure folic acid supplementation (1-5 mg daily) except on the day(s) of methotrexate administration 6, 3
• Regular monitoring of complete blood count, liver function, and renal function is essential even with folate supplementation 6, 3
• Adjust methotrexate dosing based on renal function to prevent recurrent toxicity 3, 4

Important Considerations

• Do not delay leucovorin administration while waiting for methotrexate levels - early treatment is critical 1
• Serum methotrexate levels do not always correlate with toxicity; therefore, folinic acid rescue therapy should be started as soon as toxicity is suspected 7
• Risk factors for methotrexate toxicity include renal insufficiency, advanced age, lack of folate supplementation, and drug interactions 7, 4