What tests should be prescribed before starting methotrexate (antifolate medication)?

Pre-Treatment Testing Before Starting Methotrexate

Before initiating methotrexate therapy, you must obtain complete blood count with differential, liver function tests (ALT, AST, alkaline phosphatase, albumin, bilirubin), serum creatinine, hepatitis B and C serologies, 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 assess baseline bone marrow function and risk of myelosuppression 1, 2, 3
• This is critical because bone marrow suppression typically occurs early in treatment (first 4-6 weeks) and accounts for the majority of methotrexate-associated fatalities 1, 4

Renal Function

• Serum creatinine measurement is required because methotrexate is eliminated almost entirely by the kidneys 1, 2, 3
• Renal insufficiency is a primary risk factor for methotrexate toxicity due to impaired drug clearance 4
• In elderly patients or those with low muscle mass, calculate glomerular filtration rate (GFR) rather than relying solely on serum creatinine, as creatinine levels may not accurately reflect renal function in these populations 2

Hepatic Function

• Liver function tests including ALT, AST, alkaline phosphatase, albumin, and bilirubin must be obtained to establish baseline hepatic function 1, 2, 3
• These tests are essential for monitoring hepatotoxicity, which is a major concern with methotrexate therapy 1

Infectious Disease Screening

• Hepatitis B and C serologic studies are recommended for all patients prior to initiating methotrexate, regardless of apparent risk factors 1, 2, 5
• This screening should not be skipped even in patients without obvious risk factors, as undiagnosed hepatitis significantly increases the risk of hepatotoxicity 2
• HIV serology should be considered based on individual circumstances and local epidemiology 1

Pulmonary Assessment

• Chest X-ray (obtained within the previous year) is required to establish baseline pulmonary status 1, 2, 6
• This is important because pulmonary fibrosis accounts for a significant proportion of methotrexate-associated fatalities 4

Additional Pre-Treatment Assessments

Non-Invasive Liver Fibrosis Assessment

• Non-invasive baseline liver fibrosis assessment is recommended before starting methotrexate in psoriasis patients 2
• For patients with BMI >28 kg/m² or alcohol intake >14 drinks per week, screening using transient elastography (FibroScan) is recommended 4
• Baseline liver biopsy is NOT recommended regardless of risk factors, as routine liver biopsies are no longer considered necessary 1, 2, 4

Clinical History Requirements

Alcohol Consumption:

• Document alcohol intake, as patients should limit consumption to well below national guidelines 2
• Excessive alcohol consumption is a major risk factor for hepatotoxicity 1, 4

Medication Review:

• Obtain a comprehensive medication history to identify potential drug interactions, particularly NSAIDs, salicylates, sulfonamides, trimethoprim-sulfamethoxazole, penicillins, and probenecid 2, 3
• These medications can reduce tubular secretion of methotrexate or displace it from serum albumin, enhancing toxicity 3

Reproductive Planning:

• Pregnancy testing must be performed in women of childbearing potential before initiating therapy 2, 6
• Counsel both male and female patients about the need for effective contraception, as methotrexate is pregnancy category X 1
• Methotrexate should not be used for at least 3 months before planned pregnancy for both men and women 1

Family History:

• Obtain family history of inheritable liver disease 2

Additional Laboratory Tests to Consider:

• Blood fasting glucose and lipid profile should be considered as part of the baseline assessment 1

Test Dose Consideration

• A test dose of 2.5-5 mg (or 1.25-5 mg in pediatric patients) should be considered, especially in patients with impaired kidney function, followed by a complete blood count 5 or 6 days later to check for acute idiosyncratic bone marrow toxicity 1, 2

Common Pitfalls to Avoid

• Do not skip hepatitis B and C screening even in patients without obvious risk factors, as undiagnosed viral hepatitis significantly increases hepatotoxicity risk 2
• Do not rely solely on serum creatinine in elderly patients or those with low muscle mass—calculate GFR to accurately assess renal function 2
• Do not perform routine baseline liver biopsies in psoriasis or rheumatoid arthritis patients, as this practice is no longer recommended 1, 2, 4
• Do not forget pregnancy testing in women of childbearing potential before initiating therapy 2
• Do not overlook the chest X-ray, as baseline pulmonary assessment is essential for detecting future methotrexate-induced lung disease 1, 2, 6