What laboratory tests should be ordered for a patient on methotrexate (MTX)?

Laboratory Monitoring for Patients on Methotrexate

For patients on methotrexate therapy, complete blood count (CBC), liver function tests (LFTs), and renal function tests should be monitored within the first 1-2 months of starting treatment and every 3-4 months thereafter. 1

Initial Laboratory Tests (Before Starting Methotrexate)

• Baseline laboratory tests:
  • Complete blood count (CBC) with differential
  • Liver function tests (ALT, AST, alkaline phosphatase, albumin, bilirubin)
  • Renal function tests (BUN, creatinine, urinalysis)
  • Hepatitis B and C serologic studies (for patients with risk factors)
  • Tuberculosis screening (if considering combination with TNF inhibitors)

Ongoing Monitoring Schedule

First 1-2 Months

• CBC with differential
• Liver function tests
• Renal function tests

Stable Patients

• CBC, LFTs, and renal function tests every 3-4 months 1, 2
• Laboratory measurements should be obtained 1-2 days prior to the scheduled weekly dose to avoid transient elevations in liver enzymes 1

Management of Abnormal Laboratory Results

Liver Function Tests

• LFT elevation up to 2× upper limit of normal:

  • No specific action or recheck at shorter interval 1

• LFT elevation 2-3× upper limit of normal:

  • Decrease methotrexate dose or temporarily withhold medication
  • Consider gastroenterology consultation 1

• LFT elevation >3× upper limit of normal despite dose reduction:

  • Discontinue methotrexate 1

Complete Blood Count

• WBC <3×10⁹ cells/L, neutrophils <1×10⁹ cells/L, or platelets <100×10⁹ cells/L:
  • Withhold or decrease methotrexate dose
  • Consider hematology consultation 1

Renal Function

• Significant elevation in creatinine or decrease in GFR:
  • Withhold or decrease methotrexate dose
  • Methotrexate can cause subclinical decreases in glomerular filtration rate with each administration 3, 4

Special Considerations

Risk Factors for Methotrexate Toxicity

• Decreased renal function
• Concomitant use of NSAIDs or other nephrotoxic drugs
• Advanced age
• Dehydration
• Hypoalbuminemia

Important Recommendations

• Folic acid supplementation is strongly recommended in conjunction with methotrexate to mitigate adverse events and improve tolerability 1
• Patients should be educated about early signs of toxicity (mouth ulceration, unusual bruising, severe sore throat, dry cough)
• Caution should be used when NSAIDs and salicylates are administered concomitantly with methotrexate 2

Monitoring in Special Populations

Patients with Risk Factors for Liver Disease

• Consider more frequent monitoring
• Risk factors include: obesity, diabetes, hyperlipidemia, alcohol use, history of liver disease 1
• Consider non-invasive liver fibrosis assessment such as transient elastography (FibroScan) 1, 5

Elderly Patients

• Consider lower doses due to diminished hepatic and renal function
• Monitor more closely for early signs of toxicity 2

Regular laboratory monitoring is essential for early detection of methotrexate toxicity and has been shown to significantly reduce the risk of serious adverse events while maintaining treatment efficacy.