Methotrexate is contraindicated in patients with active liver disease due to its potential to cause severe hepatotoxicity, exacerbating existing liver impairment.
Absolute contraindication in active alcoholic or other liver disease; baseline LFTs must be normal before starting.
Hepatotoxicity risk is dose-dependent and cumulative; monitor AST/ALT monthly during low-dose therapy.
Avoid in patients with history of liver dysfunction; alternative therapies should be prioritized.
Alcohol consumption further potentiates risk and should be prohibited.
Methotrexate inhibits dihydrofolate reductase, leading to folate deficiency and accumulation of toxic metabolites in the liver. In active liver disease, reduced hepatic metabolism and clearance increase drug exposure, promoting oxidative stress, inflammation, and fibrosis.
Risk of acute liver enzyme elevation, chronic hepatitis, hepatic fibrosis, cirrhosis, and potentially fatal liver failure; may worsen underlying liver pathology and increase mortality.
Avoid initiation in patients with active liver disease. If unavoidable (e.g., in oncology), obtain baseline liver function tests, use lowest effective dose, monitor LFTs frequently, and consider dose reduction or discontinuation if abnormalities occur. Hepatology consultation recommended.
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