AST Monitoring Frequency for Patients on Methotrexate
When starting methotrexate or increasing the dose, AST should be monitored every 1-1.5 months until a stable dose is reached, and then every 1-3 months thereafter. 1
Initial Monitoring Period
- AST (with or without ALT), creatinine, and complete blood count (CBC) should be checked every 1-1.5 months during the initial period of methotrexate therapy or when increasing the dose 1
- This more frequent initial monitoring is critical as the incidence of abnormal liver enzymes is higher in the first months of methotrexate therapy 1
- After a stable dose is established, the monitoring frequency can be decreased to every 1-3 months 1
- For patients with dose increases, more frequent monitoring is suggested for 4-6 weeks after the change, as pancytopenia may occur during this period 1
Ongoing Monitoring Schedule
- For patients with no risk factors for hepatotoxicity, monitor liver function tests monthly for the first 6 months and then every 1-3 months thereafter 1
- Clinical assessment for side effects and risk factors should be performed at each visit 1
- Two observational studies showed an optimal interval for identifying abnormal liver enzymes of 30-60 days 1
Management of Abnormal AST Results
- For elevations less than 2-fold upper limit of normal (ULN): repeat in 2-4 weeks 1
- For elevations ≥2-fold but <3-fold ULN: closely monitor, repeat in 2-4 weeks, and decrease dose as needed 1
- For confirmed increase in AST greater than 3 times ULN: methotrexate should be stopped but may be reinstituted at a lower dose following normalization 1
- If AST levels are persistently elevated up to 3 times ULN, the dose of methotrexate should be adjusted 1
- For persistent elevations in 5 of 9 AST levels during a 12-month period: consider liver biopsy 1, 2
Risk Factors Requiring More Vigilant Monitoring
- Patients with risk factors for hepatotoxicity may require more frequent monitoring 1
- Risk factors include: 1
- History of alcohol consumption
- Obesity (BMI > 30)
- Diabetes mellitus
- Hyperlipidemia
- Hepatitis B or C
- Family history of liver disease
- Advanced age
- Renal impairment
Factors That May Reduce Monitoring Frequency
- Some evidence suggests that monitoring every 12 weeks may be safe in selected patients with low risk 3
- Folate supplementation significantly reduces the risk of abnormal AST values and may allow for less frequent monitoring in compliant patients 4
- Initial methotrexate dosage is not associated with increased risk of hepatotoxicity, suggesting that monitoring frequency should be based on other risk factors rather than dose alone 5
Important Considerations
- The mean AST and percentage of elevated AST correlate with histological grades of liver disease in rheumatoid arthritis 1
- Cumulative incidence of abnormal ALT/AST was reported as 48.9% above ULN and 16.8% above two ULN after a mean of 3.3 years on methotrexate 1
- Methotrexate-induced serious fibrosis and cirrhosis are rare, especially in rheumatoid arthritis patients 1
- Consider other causal factors for elevated liver enzymes, including NSAIDs, obesity, and alcohol 1
Special Circumstances
- During hospitalization for acute illness or infection, methotrexate should be temporarily discontinued and liver function tests monitored closely 6
- When resuming methotrexate after prolonged discontinuation, consider more frequent monitoring initially 6
- For patients undergoing elective orthopedic surgery, methotrexate can be safely continued with standard monitoring 1