What laboratory tests and intervals are recommended for a patient starting methotrexate (MTX) 12.5 mg per oral (PO) once a week, with folic acid 1 mg once daily (OD) except on methotrexate days?

Laboratory Monitoring for Methotrexate 12.5 mg Weekly with Folic Acid Supplementation

For a patient starting methotrexate 12.5 mg weekly with folic acid 1 mg daily (except methotrexate days), perform complete blood count (CBC), liver function tests (ALT/AST, albumin), and creatinine every 1-1.5 months until the dose is stable, then every 1-3 months thereafter. 1

Baseline Laboratory Testing (Before Starting Methotrexate)

Before initiating methotrexate, obtain the following baseline tests 1:

• Complete blood count (CBC) - to assess for baseline cytopenias 1
• Liver function tests: AST, ALT, albumin, alkaline phosphatase, bilirubin 1, 2
• Serum creatinine - to assess renal function 1, 2
• Hepatitis B and C serologic studies - to identify chronic viral hepatitis 1, 2
• Chest X-ray (if obtained within the previous year) 1
• Pregnancy test for women of childbearing potential 1

Additional baseline tests to consider include HIV serology, fasting glucose, and lipid profile 1.

Monitoring Schedule During Treatment

Initial Phase (First 1-1.5 Months)

Perform CBC, ALT/AST, albumin, and creatinine every 1-1.5 months when starting methotrexate or increasing the dose. 1 The British Association of Dermatologists recommends even more frequent monitoring during the first month, suggesting tests every 7-14 days for the first month 1.

This intensive early monitoring is critical because bone marrow suppression can occur early in treatment (first 4-6 weeks) and is reversible with cessation 1. The FDA drug label notes that leukopenia, thrombocytopenia, and pancytopenia have been observed in clinical trials 3.

Maintenance Phase (After Dose Stabilization)

Once the methotrexate dose is stable, perform CBC, ALT/AST, albumin, and creatinine every 1-3 months. 1 For dermatologic conditions, the British Association of Dermatologists recommends monitoring every 2-3 months once therapy is stabilized 1. The American Academy of Dermatology suggests every 3-6 months for psoriasis patients 1.

Specific Laboratory Parameters to Monitor

Hematologic Monitoring

• CBC with differential - monitor for leukopenia (WBC <3000/mm³), thrombocytopenia (platelets <100,000/mm³), or pancytopenia 1, 3
• Stop methotrexate immediately if there is a significant drop in blood counts 3

Hepatic Monitoring

• ALT and AST - primary markers of hepatotoxicity 1, 2
• Albumin - decreased albumin may indicate chronic liver damage 1, 2
• Alkaline phosphatase and bilirubin - additional liver function markers 2

Action thresholds for liver enzyme elevations 1:

• If ALT/AST increases to >3 times the upper limit of normal (ULN), stop methotrexate; may reinstitute at lower dose after normalization 1
• If ALT/AST persistently elevated up to 3 times ULN, adjust methotrexate dose 1
• If ALT/AST persistently >3 times ULN after discontinuation, consider diagnostic procedures 1

The American College of Rheumatology defines persistent abnormalities as elevations in AST in 5 of 9 determinations within a 12-month interval, or a decrease in serum albumin below normal range 2.

Renal Monitoring

• Serum creatinine - methotrexate is renally cleared, and impaired renal function increases toxicity risk 1
• Consider dose reduction if creatinine clearance is suboptimal (<20 mL/min) 1
• Avoid methotrexate in patients on dialysis 1

Clinical Assessment at Each Visit

At every visit, perform clinical assessment for side effects and risk factors 1:

• Symptoms of bone marrow suppression: fever/flu-like illness, unexplained bruising or bleeding, mouth ulceration 1
• Gastrointestinal symptoms: nausea, vomiting, abdominal pain 1
• Hepatic symptoms: dark urine, jaundice 1
• Respiratory symptoms: breathlessness, cough (to monitor for pulmonary toxicity) 1
• Alcohol intake assessment 1

Special Considerations for Your Dosing Regimen

Your folic acid regimen of 1 mg daily except on methotrexate days is appropriate and follows guideline recommendations 1, 4. The American Academy of Dermatology recommends folic acid 1-5 mg daily, given on all days except when methotrexate is administered 1, 4. This approach reduces gastrointestinal and hepatic adverse effects without compromising methotrexate efficacy 1, 4.

Common Pitfalls to Avoid

• Timing of laboratory tests: Draw labs at least 4-6 days after methotrexate dosing, as transient transaminase elevations can occur within 3-4 days of dosing 1
• Do not skip monitoring even with folic acid supplementation: Regular monitoring remains essential despite folic acid use 1, 4
• Do not ignore mild abnormalities: Persistent mild elevations in liver enzymes may precede fibrosis or cirrhosis 3, 2
• Patient education is critical: Patients unable to comply with regular blood test monitoring should not be given methotrexate 1

Summary Algorithm

1. Baseline: CBC, ALT/AST, albumin, creatinine, hepatitis B/C serology, chest X-ray, pregnancy test 1
2. Weeks 0-6: CBC, ALT/AST, albumin, creatinine every 1-1.5 months (or every 7-14 days per British guidelines) 1
3. After stabilization: CBC, ALT/AST, albumin, creatinine every 1-3 months 1
4. Every visit: Clinical assessment for toxicity symptoms and risk factors 1