Methotrexate

Methotrexate is an anti-cancer drug used solely or in combination with other anti-cancer drugs for the therapy of leukaemia and other malignancies. The initial high dose is given to the patient intravenously and over the next 72 hours. Methotrexate (~90%) is excreted unchanged via the kidney. Relatively low doses have been used in the treatment of rheumatoid arthritis, sarcoidosis and transplantation therapy. Chronic low dose can cause cirrhosis and reversible increase in ALT. High doses results in metabolites (7-hydroxy MTX) and polyglutamate metabolites accumulates intracellularly. Renal impairment worsens toxicity.
High plasma concentrations (>1 μmol/L) after 48 hours require high dose leucovorin rescue.