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What is FUSILEV (levoleucovorin) for injection?
FUSILEV (levoleucovorin) for injection is a folate analog. FUSILEV is the pharmacologically active isomer of leucovorin (also called folinic acid), which is made up of a mixture of two isomers, one active, and one inactive.
FUSILEV can only be administered by your healthcare provider.
How is FUSILEV different?
FUSILEV contains the active isomer of leucovorin and does not contain the inactive isomer of leucovorin. Only one-half of the dose of FUSILEV needs to be given as compared with folinic acid.
What do folates do?
Folates are a group of vitamins that allow cells to reproduce. Specifically, they fuel the synthesis of purinic and pyrimidinic bases, the building blocks of DNA. Cells need to duplicate their own DNA before they can divide. Folate deficiency hinders DNA synthesis and cell division, most notably affecting rapidly proliferating tissues, such as normal bone marrow and cancer tissue.
The folate form most commonly found in nature, folic acid, has to be metabolized to the reduced active form, in order to exert its biologic activity. FUSILEV is a reduced, active folate.
Why is FUSILEV important to patients?
FUSILEV can enhance the efficacy of 5-fluorouracil, a chemotherapy agent used in the treatment of colorectal cancer. FUSILEV protects against the toxic effects of methotrexate, which is a type of chemotherapy that prevents folates from being metabolized to the reduced active form , therefore leading to cell death. Specifically, methotrexate is a folic acid antagonist which binds and inhibits one enzyme involved in an early step of the activation of folic acid to folinic acid. The administration of FUSILEV, therefore, bypasses the metabolic block effected by methotrexate.
What is FUSILEV approved for?
In combination with 5-fluorouracil for the palliative treatment of advanced metastatic colorectal cancer —Patients receive FUSILEV with a chemotherapy drug called 5-fluorouracil. This drug blocks an enzyme that is important in DNA repair and replication.
Rescue after high-dose methotrexate therapy in osteosarcoma—FUSILEV is used in patients with osteosarcoma who are treated with the folic acid antagonist methotrexate. This drug blocks the replication (copying) of DNA by preventing the active form of folate from being formed. Along with many types of cancer cells, some healthy cells like bone marrow and gastrointestinal mucosa cells also reproduce rapidly, which is why chemotherapy can have toxic effects. FUSILEV rescue therapy allows for a plan of administering a high dose of methotrexate in an attempt to kill more cancer cells while protecting the healthy cells with FUSILEV. This use of FUSILEV is described as rescue therapy.
To reduce the toxicity of methotrexate—FUSILEV is also used to diminish the toxicity of methotrexate in situations where the body is not able to rid itself of the drug normally. FUSILEV is also indicated for accidental overdosage of folic acid antagonists.
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
Contraindications
• 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.
Vomiting (38%), stomatitis (38%) and nausea (19%) were reported in patients
receiving FUSILEV as rescue after high dose methotrexate therapy.
The most common adverse reactions (>50%) in patients with advanced colorectal cancer receiving Fusilev in combination with 5-FU were diarrhea, nausea and stomatitis.
Drug Interactions
FUSILEV may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone, and increase the frequency of seizures in susceptible patients.
Reporting of Suspected Adverse Reactions
You are encouraged to report side effects of prescription drugs to the FDA.
Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
Please see the FUSILEV (levoleucovorin) for injection full prescribing information for complete safety information.
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