Drug is indicated for rescue of normal cells following high dose methotrexate administration for osteosarcoma. It is also indicated to diminish and counteract methotrexate toxicity if the drug is not effectively eliminated, or for inadvertent overdose of folic acid antagonists.
Approved Drugs: Levoleucovorin (Fusilev)
Indications
Drug is indicated for rescue of normal cells following high dose methotrexate administration for osteosarcoma. It is also indicated to diminish and counteract methotrexate toxicity if the drug is not effectively eliminated, or for inadvertent overdose of folic acid antagonists.
Mechanism of Action
Drug is a folate analogue and the active isomer of 5-formyl tetrahydrofolic acid. This drug “rescues normal cells” as it provides tetrahydrofolic acid directly to normal cells so that they can resume active cell division after having been stopped by methotrexate.
Cells that divide frequently, such as those lining the intestines, need tetrahydrofolic acid to make DNA and RNA.
Methotrexate is a folate antagonist which blocks the enzyme dihydrofolate reductase (DHFR) and prevents folic acid from being converted to tetrahydrofolic acid.
High dose methotrexate is a lethal dose of chemotherapy and patients depend upon levoleucovorin or leucovorin to rescue the normal cells so that normal body cells can continue to divide.
Metabolism
Peak levels of total tetrahydrofolate are found 0.9 hours after drug administration, with a mean terminal half-life of 5.1 hours.
Drug Administration
Guidelines for Levoleucovorin Dosage and Administration based on clinical situation:
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Adverse Reactions by System (most common are in boldface type)
CNS: Confusion, taste perversion
GI:Stomatitis, vomiting, nausea, diarrhea, dyspepsia, typhlitis
Neuro: neuropathy
Respiratory: Dyspnea
Skin: Dermatitis
Patient Education
Teach patient: Purpose of levoleucovorin and frequent blood tests (serum creatinine and MTX).
Interactions
Do not mix with other agents in the same admixture, as they may precipitate. Levoleucovorin has interactions with certain drugs:
Special Considerations
Contraindications/Precautions
Patients who have had allergic reactions to folic or folinic acid. Administer cautiously to nursing mothers, as it is not known if drug is excreted in human milk.
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