Methotrexate Toxicology Intravenous leucovorin (folinic acid) treatment serves as a cofactor necessary for synthesis of thymidylate and purine nucleotides that are essential for DNA synthesis. Do not wait for the serum MTX level to return prior to initiating therapy with leucovorin. Folic acid is ineffective because MTX inhibits dihydrofolate reductase, the enzyme required to convert folate to tetrahydrofolate and subsequently synthesize DNA and RNA. Leucovorin dosing is repeated every 6 hours and is based on calculation of Body Surface Area (BSA). Options for determining intravenous dosing: • Administer mg-to-mg dose of leucovorin to MTX ingested, up to 100 mg/m2 of leucovorin every 6 hours. • If ingested dose of MTX is unknown, empirically give 100 mg/m2of leucovorin every 6 hours (should be effective in all but the most severe overdoses). Leucovorin can be discontinued when one of the following has occurred: • MTX level is less than 0.05 µmol/L • If evidence of marrow toxicity, continue leucovorin until recovery of bone marrow, even if the MTX level is undetectable • If MTX levels are not available, continue leucovorin for at least 12 doses (3 days) By Dr. Kathryn Watson @Kat_Watson #Methotrexate #Leucovorin #Antidote #Toxicology #Toxicity #Management #Pharmacology
