What are the guidelines for monitoring a patient with methotrexate (MTX) toxicity?

From the Guidelines

Monitoring a patient with methotrexate toxicity requires regular laboratory tests, including complete blood count, liver function tests, and kidney function tests, to be performed every 1-3 months, with initially more frequent assessments when starting or increasing the dose, as recommended by the most recent guidelines 1. When monitoring a patient with methotrexate toxicity, it is essential to consider the following key points:

• Regular laboratory monitoring is crucial to detect potential toxicity early, including myelosuppression, hepatotoxicity, and nephrotoxicity.
• The frequency of monitoring may vary depending on the patient's risk factors, such as renal insufficiency, advanced age, and greater than moderate alcohol intake.
• A noninvasive baseline liver fibrosis assessment is recommended before starting treatment with methotrexate, and annual GI/hepatology referral or vibration-controlled transient elastography, or both, should be performed if methotrexate is continued despite abnormal baseline liver fibrosis laboratory results 1.
• The algorithm for methotrexate hepatotoxicity screening differs depending on whether patients do or do not have risk factors, and a test dose should be considered in patients with risk factors for developing complications, such as decreased kidney function 1.
• Monitoring laboratory tests should be performed at least 4-6 days after dosing to avoid making dosage adjustments based on transient elevations of hepatic transaminases 1. Some important considerations when monitoring methotrexate toxicity include:
• Ensuring adequate hydration and urinary alkalinization to enhance methotrexate excretion.
• Administering leucovorin (folinic acid) rescue therapy promptly if toxicity is suspected or confirmed.
• Temporarily discontinuing medications that may increase methotrexate toxicity, such as NSAIDs, sulfonamides, and proton pump inhibitors.
• Assessing for clinical signs of toxicity, including mucositis, skin rash, diarrhea, and neurological symptoms. It is also important to note that the guidelines for monitoring methotrexate toxicity may vary depending on the specific patient population, such as pediatric patients 1, and that the most recent guidelines should always be consulted to ensure optimal patient care.

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. If methotrexate therapy is reinstituted, it should be carried out with caution, with adequate consideration of further need for the drug and increased alertness as to possible recurrence of toxicity.

The guidelines for monitoring a patient with methotrexate (MTX) toxicity include:

• Baseline assessment: complete blood count, hepatic enzymes, renal function tests, and chest X-ray
• Regular monitoring:
  • Hematology: at least monthly
  • Renal function: every 1 to 2 months
  • Liver function: every 1 to 2 months
• Reinstatement of therapy: with caution and increased alertness for possible recurrence of toxicity 2

From the Research

Monitoring Guidelines for Methotrexate Toxicity

The following guidelines are recommended for monitoring patients with methotrexate (MTX) toxicity:

• Before starting low-dose methotrexate therapy, a full blood count, liver function tests, renal function tests, and chest radiography should be performed 3
• Blood counts and liver function tests should be repeated at regular intervals 3
• Therapeutic drug monitoring of methotrexate has also been suggested as a means of limiting toxicity 3
• Patients with renal deficiency require monitoring, and a more gradual dosage increase and a lower weekly maximum should be considered regarding their general health situation 4
• Methotrexate is contraindicated in patients with RA if the eGFR is <30 mL/minute 4
• Frequent monitoring of blood count and renal and liver function tests is recommended to detect early deterioration 5

Risk Factors for Methotrexate Toxicity

The following are risk factors for methotrexate toxicity:

• Poor renal function 3, 4, 6
• Age 3
• Concomitant use of certain medications, such as nonsteroidal anti-inflammatory drugs 3 and inhibitors of folate utilization or renal tubular secretion 3
• Impaired kidney function 4, 5
• Co-medication 5

Treatment of Methotrexate Toxicity

The following are recommended for the treatment of methotrexate toxicity:

• Clearance of MTX from the bloodstream 4
• Folinic acid therapy 4
• Organ treatment 4
• Administration of intravenous folinic acid if methotrexate intoxication is suspected 5
• Glucarpidase has been licensed for the treatment of high plasma MTX levels of >1 μmol/L in patients with compromised renal function who have delayed MTX elimination 4