What to check before starting methotrexate (MTX)?

Pre-Methotrexate Assessment Requirements

Before starting methotrexate therapy, comprehensive laboratory testing including complete blood count, liver function tests, renal function tests, hepatitis B and C screening, and tuberculosis screening must be performed to minimize the risk of serious toxicity. 1, 2

Essential Baseline Laboratory Tests

• Complete Blood Count (CBC) with differential and platelets 2
• Liver Function Tests (LFTs) including:
  • ALT/AST (transaminases)
  • Alkaline phosphatase
  • Albumin
  • Bilirubin 1, 2
• Renal Function Tests:
  • Serum creatinine
  • BUN 2
• Hepatitis B and C serology (for patients with risk factors) 1, 3
• Chest X-ray (baseline assessment) 2
• Tuberculosis screening (Mantoux PPD skin test) before TNF-α inhibitor combination therapy 1, 3
• Serum PIIINP (procollagen III aminopeptide) for patients with psoriasis 1, 3

Additional Assessments

Risk Factor Evaluation

• Alcohol consumption history (limit alcohol intake) 1
• Pregnancy status (contraindicated in pregnancy) 1
• Obesity assessment (BMI >30 increases hepatotoxicity risk) 1
• Diabetes status (increases hepatotoxicity risk) 1
• Medication review for potential drug interactions:
  • NSAIDs (can increase methotrexate toxicity)
  • Salicylates
  • Probenecid
  • Sulfonamides
  • Phenytoin
  • Tetracyclines
  • Chloramphenicol 1, 2

Special Considerations

• Consider test dose in patients with risk factors, especially renal impairment 1
• Consider liver fibrosis assessment using non-invasive techniques like transient elastography (FibroScan) for patients with risk factors for liver disease 1, 3
• Baseline liver biopsy is NOT routinely recommended 1

Monitoring Schedule After Initiation

1. First month: CBC, LFTs, and renal function every 7-14 days 1
2. Stable therapy: CBC, LFTs, and renal function every 3-4 months 1
3. PIIINP measurement every 3 months for psoriasis patients 1, 3
4. Laboratory measurements should be obtained 1-2 days before the scheduled weekly dose 1, 3

Management of Abnormal Results

• For LFT elevation up to 2× upper limit of normal: No specific action or recheck at shorter interval
• For LFT elevation >2× upper limit of normal: Decrease methotrexate dose or temporarily withhold
• For LFT elevation >3× upper limit of normal despite dose reduction: Discontinue methotrexate 1, 3

Common Pitfalls to Avoid

1. Failure to prescribe folic acid supplementation with methotrexate (reduces adverse effects) 1, 3
2. Confusing daily vs. weekly dosing (methotrexate is typically given WEEKLY, not daily) 2
3. Overlooking renal function (85% of methotrexate is renally excreted) 2
4. Ignoring drug interactions that may increase methotrexate toxicity 2
5. Missing early signs of toxicity (fever, mouth ulcers, unexplained bruising, breathlessness) 1

By following this comprehensive pre-treatment assessment protocol, clinicians can significantly reduce the risk of serious methotrexate-related toxicity and improve patient outcomes.