Approved March 7, 2008

LEVOLEUCOVORIN CALCIUM
(FDA Category 1S)

The recommended dose of levoleucovorin is 7.5 milligrams (mg) (approximately 5 mg/square meter m(2)) intravenously (IV) every 6 hours (hr) starting 24 hr after the beginning of the methotrexate (MTX) (12 grams/m(2) IV over 4 hr) infusion for 10 doses or until serum methotrexate level is less than 5 x 10(8) M (0.05 micromolar). For the use in inadvertent methotrexate overdosage, levoleucovorin 7.5 mg should be administered IV every 6 hr until serum methotrexate level is less than 10(-8) M.

PHARMACOKINETICS: Following a single 15 mg IV dose of levoleucovorin in health male volunteers, peak serum total tetrahydrofolate (THF) concentrations were 1722 nanogram/milliliter (ng/mL) and peak serum (6S)-5-methyl-5,6,7,8-THF concentrations were 275 ng/mL (mean time-to-peak concentration, 0.9 hr). The mean terminal half-lives of total THF and (6S)-5-methyl-5,6,7,8-THF were 5.1 and 6.8 hr, respectively.

CAUTIONS: Allergic reactions have been reported. The most common side effects are vomiting, stomatitis, and nausea.

FDA APPROVED INDICATIONS: Levoleucovorin is indicated following high-dose methotrexate therapy in patients with osteosarcoma, diminish the toxicity and counteract the effects of impaired methotrexate elimination, and of inadvertent overdosage of folic acid antagonists.