How do you monitor for methotrexate toxicity?

Monitoring for Methotrexate Toxicity

To monitor for methotrexate toxicity, complete blood count (CBC), liver function tests (LFTs), and renal function tests should be performed within the first 1-2 months of treatment initiation and every 3-4 months thereafter. 1

Baseline Testing Before Starting Methotrexate

• Obtain complete blood count with differential, liver function tests (ALT, AST), and renal function tests (BUN, creatinine, urinalysis) 1
• Screen for hepatitis B and C, especially in patients with risk factors for liver disease 1
• Consider pregnancy testing in women of childbearing potential as methotrexate is a known teratogen 1
• Perform chest X-ray to establish baseline pulmonary status 1

Regular Monitoring Schedule

Initial Monitoring

• CBC, LFTs, and renal function tests within first 1-2 months of starting therapy 1
• More frequent monitoring may be needed for patients with risk factors for toxicity 2

Ongoing Monitoring

• CBC, LFTs, and renal function tests every 3-4 months for maintenance therapy 1
• Avoid LFT testing within 2 days after methotrexate dose as transient elevations may occur 1
• For patients with risk factors (renal impairment, advanced age, drug interactions), consider more frequent monitoring 3

Specific Parameters to Monitor

Hematologic Toxicity

• Monitor for leukopenia (WBC <3000/mm³), thrombocytopenia (platelets <100,000/mm³), and anemia 2
• Significant drop in blood counts requires immediate discontinuation of methotrexate 2
• Consider folinic acid (leucovorin) rescue for significant hematologic toxicity 2, 4

Hepatotoxicity

• Monitor for elevated transaminases, decreased albumin, and increased bilirubin 2
• Risk factors include obesity, diabetes, alcohol consumption, and pre-existing liver disease 1
• For patients with risk factors for hepatotoxicity, consider additional monitoring with:
  • Fibrosis-4 (FIB-4) Index for Liver Fibrosis 1
  • Referral to gastroenterology or hepatology for vibration-controlled transient elastography in high-risk patients 1

Renal Toxicity

• Monitor creatinine, BUN, and urinalysis 2
• Renal impairment increases risk of all other toxicities due to decreased methotrexate clearance 3, 5
• For elderly patients or those with reduced muscle mass, consider calculating glomerular filtration rate rather than relying solely on creatinine 1

Management of Abnormal Results

• Decrease or hold methotrexate dose if clinically relevant elevation in LFTs or decreased neutrophil/platelet count is found 1
• For high-dose methotrexate regimens, monitor serum methotrexate levels to guide leucovorin rescue 5, 6
• For suspected overdose or severe toxicity, administer folinic acid (leucovorin) immediately 7, 4
• For severe toxicity with renal impairment, consider glucarpidase for patients with significantly delayed methotrexate clearance 5, 6

Preventive Measures

• Use folic acid or folinic acid supplementation with methotrexate to reduce adverse events and improve tolerability 1
• Ensure adequate hydration, especially with higher doses 5
• Review concomitant medications for potential interactions that may increase methotrexate toxicity:
  • NSAIDs may reduce renal clearance of methotrexate 2
  • Probenecid, salicylates, and sulfonamides can decrease renal tubular excretion 2
  • Antibiotics may interfere with enterohepatic circulation 2

Special Considerations

• Elderly patients require more careful monitoring due to decreased renal function, decreased folate stores, and increased risk of drug interactions 2, 3
• Patients with renal impairment may require dose reduction and more frequent monitoring 3, 7
• For patients receiving high-dose methotrexate (>500 mg/m²), more intensive monitoring protocols are required, including serum methotrexate levels 5

Remember that early detection of toxicity allows for prompt intervention, which can prevent serious complications and allow for continued methotrexate therapy when appropriate.