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What is methotrexate rescue?
One treatment of osteosarcoma is to administer a high dose of methotrexate, an antimetabolite and folic acid antagonist. Normally, such high doses of methotrexate would be too toxic to administer to a patient because too many healthy cells would be destroyed. The use of FUSILEV rescue therapy after high-dose methotrexate allows protection of the normal tissues with tolerable toxicity.
How does FUSILEV rescue normal tissues and not the tumor?
The rationale for this therapy is based on the mechanism of action of methotrexate, which exerts its biologic activity by binding to an enzyme involved in the activation of folic acid to folinic acid. Administration of folinic acid reverses this inhibition and displaces methotrexate from its binding to the enzyme.
The binding of methotrexate to the enzyme is tighter in cancer cells than in normal cells and therefore the displacement by folinic acid occurs to a lesser degree in cancer cells.
How is FUSILEV used as methotrexate rescue in patients with osteosarcoma?
The doctor will prescribe FUSILEV at the appropriate time(s) to patients receiving methotrexate for osteosarcoma. Patients should contact their physicians or health care practitioners regarding the use of FUSILEV.
How often is FUSILEV given to patients undergoing high-dose methotrexate therapy?
The dosage and frequency of dosing of FUSILEV will depend on the dose of methotrexate and several other factors. Patients should contact their physicians or heathcare practitioners, who will be able to provide specific information and who will make adjustments to dosages as necessary.
How is FUSILEV used in delayed methotrexate elimination?
Dose adjustments may be required if methotrexate is not able to be cleared from the system normally. The doctor will need to have the levels of methotrexate in the body monitored carefully, such as through blood sampling and other types of tests, and will use this information to determine how to best give FUSILEV.
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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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