Leucovorin

Leucovorin, also known as folinic acid, is a medication used as a form of reduced folate in medicine. It is the calcium salt of 5-formyltetrahydrofolate and does not require activation by dihydrofolate reductase to participate in folate metabolism.

Mechanism and role in therapy: Leucovorin is converted in cells to tetrahydrofolate derivatives that support thymidylate and purine synthesis. This allows normal, healthy cells to recover their folate-dependent functions after inhibition of dihydrofolate reductase by methotrexate. In oncology, leucovorin is used in two main ways: as a rescue agent after high-dose methotrexate to reduce toxicity to healthy tissues, and as a biochemical modulator that enhances the effectiveness of fluoropyrimidine chemotherapy, such as 5-fluorouracil, in certain cancers.

Medical uses: The primary indication is leucovorin rescue following high-dose methotrexate therapy, with dosing guided by methotrexate plasma concentrations and renal function. It can also be co-administered with 5-fluorouracil–based regimens to improve antitumor response in colorectal cancer. Outside cancer therapy, leucovorin is used to prevent or treat folate deficiency and its related signs when natural folate intake is insufficient or when rapid folate replenishment is needed.

Administration and dosing: Leucovorin is given by intravenous, intramuscular, or oral routes, with dosing and duration determined by the specific chemotherapy protocol and MTX monitoring. In rescue use, administration starts after methotrexate and continues until MTX levels fall to safe ranges.

Adverse effects and interactions: Leucovorin is generally well tolerated, but can cause allergic reactions, rash, fever, or gastrointestinal upset in some individuals. It interacts with methotrexate dosing; improper timing can diminish MTX anticancer activity. Monitoring of renal function and MTX levels is recommended during high-dose regimens.