What are the management steps for a patient with a Methotrexate overdose?

Management of Methotrexate Overdose

In a case of methotrexate overdose, immediate administration of leucovorin (folinic acid), aggressive hydration, and urinary alkalinization with sodium bicarbonate are essential first-line interventions to prevent serious toxicity. 1

Immediate Interventions

1. Leucovorin (Folinic Acid) Administration

   • Begin leucovorin as soon as possible after overdose identification 2
   • Initial dose: 100 mg/m² IV every 3 hours 2
   • Continue until serum methotrexate level is less than 0.05 micromolar 2
   • Effectiveness decreases with time since exposure, so immediate administration is critical 1

2. Hydration and Urinary Alkalinization

   • Administer IV fluids to maintain high urine output (target: 600 mL/hour) 1
   • Give sodium bicarbonate to achieve and maintain urine pH ≥7.5 1, 3
   • Monitor urine pH every 1-2 hours initially 1
   • Continue alkalinization until methotrexate levels are <0.05 μmol/L 1

3. For Recent Oral Ingestion

   • Administer activated charcoal if ingestion occurred within the past hour 1

Monitoring

1. Laboratory Assessment

   • Obtain baseline CBC, renal function, liver function tests, and methotrexate levels
   • Monitor CBC daily to assess for bone marrow suppression 4
   • Check renal function every 24 hours 2
   • Monitor serum methotrexate levels to guide treatment duration 2
   • Check electrolytes, particularly potassium levels 1

2. Clinical Monitoring

   • Assess for signs of myelosuppression (fever, signs of infection) 4
   • Monitor for mucositis and gastrointestinal symptoms 4
   • Watch for signs of hepatotoxicity and pulmonary toxicity 4
   • Monitor neurological status for signs of neurotoxicity 3

Management of Specific Complications

1. Bone Marrow Suppression

   • Continue leucovorin at higher doses if pancytopenia develops 5
   • Consider filgrastim (G-CSF) for severe neutropenia 6
   • Provide blood product support as needed 6
   • Initiate broad-spectrum antibiotics for febrile neutropenia 5

2. Renal Dysfunction

   • Maintain aggressive hydration and alkalinization 3
   • Consider hemodialysis using high-flux dialyzer in cases of severe toxicity with renal failure 3
   • Avoid nephrotoxic medications 7

3. Gastrointestinal Toxicity

   • Provide supportive care for mucositis and stomatitis 4
   • Consider parenteral nutrition if severe mucositis prevents adequate oral intake 6
   • Administer antiemetics for nausea and vomiting 4

Special Considerations

1. Risk Factors for Increased Toxicity

   • Advanced age 4
   • Renal impairment 4
   • Hypoalbuminemia 4
   • Drug interactions (especially NSAIDs) 7
   • Lack of folate supplementation 4

2. Treatment Duration

   • Continue leucovorin until methotrexate levels are <0.05 micromolar 2
   • For patients with delayed methotrexate elimination, extend leucovorin therapy 2
   • Continue monitoring CBC for at least 2 weeks after overdose 5

Pitfalls to Avoid

1. Do not rely solely on methotrexate levels to guide treatment decisions in acute overdose cases 6
2. Do not delay leucovorin administration while waiting for methotrexate levels 1
3. Do not administer leucovorin intrathecally 2
4. Do not mix leucovorin in the same infusion as 5-fluorouracil 2
5. Do not discontinue monitoring too early, as pancytopenia can develop up to 6 weeks after exposure 4
6. Do not administer glucarpidase and leucovorin within 2 hours of each other 3

This management approach prioritizes rapid intervention to prevent serious complications and mortality from methotrexate toxicity, with particular focus on leucovorin rescue, hydration, and alkalinization as the cornerstones of treatment.