Known brand names include Trexall.
A pill, usually taken once a week, for rheumatoid arthritis, severe psoriasis, and juvenile arthritis, and part of chemotherapy for some blood cancers. It blocks an enzyme cells need to use folate, and taking a weekly dose every day by mistake has caused deaths.
High-alert medication. Oral methotrexate for nononcologic use is named on the ISMP acute care high-alert list, and oral chemotherapeutic agents are listed as a class, so the oral tablet is high-alert for every labeled use.
The label does not describe a narrow therapeutic index or direct dosing by measured blood levels of the drug. Methotrexate levels guide leucovorin and glucarpidase after overdose, not routine dosing.
Sources: [1]
Embryo-fetal toxicity, hypersensitivity, severe adverse reactions, and medication errors. It can cause fetal death and is contraindicated in pregnancy for non-neoplastic diseases; patients treated for cancer need effective contraception. It is contraindicated after severe hypersensitivity, including anaphylaxis. Serious and fatal toxicity of the marrow, GI tract, liver, lungs, skin, and kidneys calls for close monitoring and withholding or stopping as appropriate. Taking it once daily by mistake has caused deaths.
Sources: [1]
Leucovorin or levoleucovorin, started as soon as possible after an overdose, lessens methotrexate toxicity; serum creatinine and methotrexate levels guide their dosing. Glucarpidase treats toxic plasma levels (above 1 micromole per liter) with delayed clearance from impaired kidney function. Give hydration and urinary alkalinization. Standard hemodialysis and peritoneal dialysis have not been shown to help, though high-flux hemodialysis has cleared it.
Doses come from the FDA label. Study tool, not for clinical decisions.
Elimination falls and toxicity risk rises with renal impairment. Monitor closely for adverse reactions when CrCl is below 90 mL/min (Cockcroft-Gault), and reduce the dose or stop as appropriate. Check renal function at baseline and periodically. For toxic levels with delayed clearance from renal impairment, give glucarpidase.
Pharmacokinetics and safety in hepatic impairment are unknown; monitor closely and reduce the dose or stop as appropriate. It can cause fibrosis, cirrhosis, and fatal liver failure. In psoriasis, fibrosis can develop without symptoms or abnormal liver tests, usually after a cumulative dose of 1.5 g or more, and heavy alcohol use raises the risk.
A folic acid antagonist that inhibits dihydrofolate reductase, so dihydrofolates are not reduced to the tetrahydrofolates needed to make purine nucleotides and thymidylate. DNA synthesis, repair, and cell replication fall, and rapidly dividing tissues (malignant cells, marrow, fetal cells, oral and intestinal mucosa, bladder) are most sensitive. Its mechanism in rheumatoid arthritis and psoriasis is unknown. Oral bioavailability is about 60% at doses of 30 mg/m² or less, the half-life is about 3 to 10 hours, and elimination is mainly renal; polyglutamate metabolites persist in tissues.