What baseline tests should be done before initiating methotrexate (antifolate medication) therapy?

Baseline Testing Before Initiating Methotrexate

Before starting methotrexate, you must obtain a complete blood count with differential and platelets, comprehensive metabolic panel including liver function tests (ALT, AST, alkaline phosphatase, albumin, bilirubin) and serum creatinine, hepatitis B and C serologic studies, and a chest X-ray. 1, 2, 3

Essential Laboratory Tests

Hematologic Assessment

• Complete blood count (CBC) with differential and platelet count is mandatory to establish baseline values and assess risk of myelosuppression 1, 2, 3
• This identifies patients with pre-existing bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia, which are absolute contraindications to methotrexate 1

Renal Function Assessment

• Serum creatinine and blood urea nitrogen (BUN) must be measured, as methotrexate is eliminated almost entirely by the kidneys 1, 2, 3, 4
• In elderly patients or those with low muscle mass, calculate creatinine clearance or glomerular filtration rate (GFR) rather than relying solely on serum creatinine, as declining renal function with age is an important predictor of toxicity 2, 4

Hepatic Assessment

• Liver function tests including ALT, AST, alkaline phosphatase, albumin, and bilirubin are required before initiation 1, 2, 3, 5
• Hepatitis B and C serologic studies should be obtained in all patients, not just those with obvious risk factors, as chronic viral hepatitis increases hepatotoxicity risk 2, 5
• Baseline liver biopsy is NOT recommended regardless of risk factors for hepatotoxicity 1, 2
• For psoriasis patients, consider non-invasive baseline liver fibrosis assessment (such as serum procollagen III peptide where available in Europe, or FIB-4 index in the United States) 1, 2

Pulmonary Assessment

• Chest X-ray should be performed to establish baseline pulmonary status, as methotrexate can cause interstitial pneumonitis 1, 6, 3
• This is particularly important in patients over 40 years of age who smoke or have underlying pulmonary disease 1

Additional Required Assessments

Pregnancy Testing

• Pregnancy test must be performed in all women of childbearing potential before starting therapy, as methotrexate is FDA pregnancy category X and is both an abortifacient and teratogen 1, 6
• Counsel patients that effective contraception is mandatory during therapy and for 3-6 months after discontinuation 1

Infection Screening

• Consider tuberculosis screening with PPD or interferon-gamma release assay in appropriate populations 1
• Consider HIV testing in selected high-risk patients 1

Clinical History Requirements

Risk Factor Assessment

Document the following risk factors that increase hepatotoxicity risk:

• Alcohol consumption history - alcoholism is an absolute contraindication, and excessive alcohol intake (>14 drinks/week for men, >7 drinks/week for women) is a relative contraindication 1, 7
• Obesity and diabetes mellitus - both increase risk of liver fibrosis 1
• Pre-existing liver disease or family history of inheritable liver disease 1, 2

Medication Review

• Identify potential drug interactions including NSAIDs, salicylates, sulfonamides (especially trimethoprim-sulfamethoxazole), penicillins, and probenecid, all of which can increase methotrexate toxicity 1, 3, 4
• Review use of other hepatotoxic agents (azathioprine, retinoids, sulfasalazine) 1

Test Dose Consideration

• A test dose of 2.5-5 mg should be considered, especially in patients with impaired kidney function, before proceeding to therapeutic dosing 1, 2

Common Pitfalls to Avoid

• Do not skip hepatitis B and C screening even in patients without obvious risk factors, as unrecognized chronic viral hepatitis significantly increases hepatotoxicity risk 2, 5
• Do not rely solely on serum creatinine in elderly patients or those with low muscle mass - calculate GFR to accurately assess renal function, as age-related decline in renal function is a major predictor of toxicity 2, 4
• Do not perform routine baseline liver biopsies in psoriasis or rheumatoid arthritis patients - these are only indicated for patients with history of significant liver disease, chronic hepatitis B or C, or persistently abnormal baseline liver function tests 1, 2, 5
• Do not forget pregnancy testing in women of childbearing potential, as methotrexate exposure during pregnancy causes severe fetal abnormalities 1, 6
• Ensure patients understand weekly dosing - mistaken daily use of the recommended weekly dose has led to fatal toxicity 1, 3