Important Safety Information  |  Full Prescribing Information
  • Text Size  A | A | A
  • FUSILEV Mechanism of Action

    FUSILEV traps 5-FU to block cell growth

    5-FU inhibits DNA synthesis, but can be reversed1,2

    Mechanism of action of 5-FU alone in mCRC treatment

    Click image to enlarge

    Thymidylate synthase (TS) is a key enzyme in the creation of thymine, a building block of DNA. 5-FU competes with the natural substrate to bind the TS active site. When bound to TS, 5-FU inhibits its activity, arresting DNA synthesis.

    5-FU can be displaced, enabling DNA synthesis in cancer cells to continue.

    FUSILEV traps 5-FU to block DNA synthesis1,2

    Mechanism of action of 5-FU + FUSILEV in mCRC treatment

    Click image to enlarge

    FUSILEV stabilizes the bond between 5-FU and thymidylate synthase. This “traps” the enzyme into an inhibited state, arresting DNA synthesis.

    Note: Mechanism of action pathway has been simplified for illustrative purposes.

    Indications and Usage

    FUSILEV is a folate analog indicated for:

    • Rescue after high-dose methotrexate therapy in osteosarcoma.
    • Diminishing the toxicity and counteracting the effects of impaired methotrexate elimination and of inadvertent overdosage of folic acid antagonists.
    • Use in combination chemotherapy with 5-fluorouracil in the palliative treatment of patients with advanced metastatic colorectal cancer.

    Limitations of Use

    • FUSILEV is not approved for pernicious anemia and megaloblastic anemias. Improper use may cause a hematologic remission while neurologic manifestations continue to progress.

    Important Safety Information


    • FUSILEV is contraindicated for patients who have had previous allergic reactions attributed to folic acid or folinic acid.

    Warnings and Precautions

    • Due to Ca++ content, no more than 16 mL (160 mg) of levoleucovorin solution should be injected intravenously per minute.
    • FUSILEV enhances the toxicity of fluorouracil.
    • Concomitant use of d,l-leucovorin with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in HIV patients was associated with increased rates of treatment failure in a placebo-controlled study.

    Adverse Reactions

    • Allergic reactions were reported in patients receiving FUSILEV.
    • The most common adverse reactions (>50%) in patients with advanced colorectal cancer receiving FUSILEV in combination with 5-FU were diarrhea, nausea and stomatitis.
    • Vomiting (38%), stomatitis (38%) and nausea (19%) were reported in patients receiving FUSILEV as rescue after high-dose methotrexate therapy.

    Drug Interactions

    • FUSILEV may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone, and increase the frequency of seizures in susceptible patients.

    Please click here to see full Prescribing Information for FUSILEV.

    1. Peters GJ, Van Der Wilt CL, Van Triest B, et al. Thymidylate synthase and drug resistance. Eur J Cancer. 1995;31A(7/8):1299-1305.
    2. Santi DV, McHenry CS, Sommer H. Mechanism of interaction of thymidylate synthetase with 5-fluorodeoxyuridylate.Biochemistry.1974;13(1):471-480.