What laboratory tests should be monitored in a patient on methotrexate (MTX)?

From the Guidelines

Patients on methotrexate should have their ALT with or without AST, creatinine, and CBC monitored every 1–1.5 months until a stable dose is reached and every 1–3 months thereafter. This monitoring is crucial to prevent and detect potential toxicity associated with methotrexate use, including hepatotoxicity, nephrotoxicity, and hematological toxicity 1. The choice of labs to monitor is based on the correlation between AST and histological grades of liver disease in rheumatoid arthritis, as well as the importance of monitoring renal function and hematological parameters 1.

Some key points to consider when monitoring patients on methotrexate include:

• The use of ALT alone may detect 90% of elevated AST or paired tests, making it a useful marker for hepatotoxicity 1
• Alkaline phosphatase may be oversensitive for monitoring hepatotoxicity and is not recommended as a primary marker 1
• Renal function should be monitored regularly, as impaired renal function can increase the risk of methotrexate toxicity 1
• CBC is essential for monitoring hematological toxicity, including bone marrow suppression 1

It is also important to note that the frequency of monitoring may need to be adjusted based on individual patient factors, such as age, renal function, and presence of other hepatotoxic medications 1. However, the general recommendation is to monitor labs every 1–1.5 months until a stable dose is reached and every 1–3 months thereafter 1.

From the FDA Drug Label

Patients undergoing methotrexate therapy should be closely monitored so that toxic effects are detected promptly. Baseline assessment should include a complete blood count with differential and platelet counts, hepatic enzymes, renal function tests and a chest X-ray During therapy of rheumatoid arthritis and psoriasis, monitoring of these parameters is recommended: hematology at least monthly, renal function and liver function every 1 to 2 months. Assessment of hematologic, hepatic, renal, and pulmonary function should be made by history, physical examination, and laboratory tests before beginning, periodically during, and before reinstituting methotrexate therapy

The labs to monitor in a patient on methotrexate are:

• Hematology: complete blood count with differential and platelet counts, at least monthly
• Renal function tests: every 1 to 2 months
• Liver function tests: hepatic enzymes, every 1 to 2 months
• Pulmonary function tests: if methotrexate-induced lung disease is suspected, especially if baseline measurements are available 2

From the Research

Labs to Monitor in Patients on Methotrexate

• Full blood cell counts: to monitor for potential hematologic toxicity 3, 4, 5
• Serum transaminase levels: to monitor for potential liver toxicity 3
• Serum creatinine with computation of creatinine clearance: to monitor for potential kidney toxicity 3
• Chest radiograph: to monitor for potential pulmonary toxicity, especially in patients with a history of respiratory disease or current respiratory symptoms 3
• Serological tests for hepatitis viruses B and C: to monitor for potential liver toxicity 3
• Serum albumin assay: to monitor for potential liver toxicity 3
• Lung function tests with determination of the diffusing capacity for carbon monoxide: to monitor for potential pulmonary toxicity, especially in patients with a history of respiratory disease or current respiratory symptoms 3

Frequency of Monitoring

• Full blood cell counts, serum transaminase, and creatinine assays should be obtained at least once a month for the first 3 months, then every 4-12 weeks 3

Additional Considerations

• Folate supplementation can be given routinely to patients treated with methotrexate to reduce potential toxicity 3
• Methotrexate levels can be monitored from central venous access, which may replace the need for peripheral venipuncture in some cases 6