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This combination consists of **leucovorin calcium** (racemic folinic acid) and **levoleucovorin** (the pharmacologically active levo-isomer of folinic acid). Both are folate analogs that are used in oncology as rescue agents to counteract the toxic effects of folic acid antagonists like methotrexate by bypassing the metabolic block caused by dihydrofolate reductase inhibition and supplying tetrahydrofolate for nucleic acid synthesis[1][2][5][7][8]. The two agents are sometimes administered separately based on drug availability or shortages; their indications include rescue after high-dose methotrexate in osteosarcoma, reducing toxicity after excessive exposure to folic acid antagonists, and in combination with 5-fluorouracil (5-FU) for advanced or metastatic colorectal cancer[1][2][5][7][8]. Levoleucovorin is considered slightly more pharmacologically active on a per-mg basis compared to racemic leucovorin, but clinically they are used for similar purposes, though not co-administered together in usual clinical practice.
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