Company:

Spectrum

Folate analogue

Levoleucovorin (as calcium pentahydrate) 50mg/vial; pwd for IV inj after reconstitution; contains mannitol 50mg/vial.

In osteosarcoma, to reduce toxicity of high-dose methotrexate (MTX) therapy. To reduce toxicity and counteract effects of impaired MTX elimination and of inadvertent overdose of folic acid antagonists.

Levoleucovorin is the pharmacologically active isomer of the racemic drug d,l-leucovorin, a derivative of folic acid. It can counteract the therapeutic and toxic effects of folic acid antagonists such as MTX which inhibit the activity of the enzyme dihydrofolate reductase. Levoleucovorin is dosed at 1/2 the usual dose for racemic leucovorin.

The safety and efficacy of levoleucovorin rescue following high-dose MTX was studied in 16 patients 6–21years of age who received 58 courses of therapy for osteogenic sarcoma. High-dose MTX was used as one component of several different combination chemotherapy regimens evaluated across several trials. Thirteen patients received MTX 12g/m² IV over 4 hours and levoleucovorin 7.5mg every 6 hours for 60 hours or longer beginning 24 hours after the completion of MTX. Three patients received MTX 12.5g/m² IV over 6 hours, then levoleucovorin 7.5mg every 3 hours for 18 doses starting 12 hours after completion of MTX therapy. The efficacy of levoleucovorin was based on the adverse reaction profile. Six patients (37.5%) reported stomatitis, with one (6.3%) having grade 3 or higher. Six patients (37.5%) reported vomiting while nausea occurred in 3 patients (18.8%). The number of patients who had other adverse reactions such as dyspnea, neuropathy, and dermatitis was reported as one. In the 58 courses of therapy, there was a total of 10 occurrences for stomatitis, 14 for vomiting, 3 for nausea, and 3 for abnormal renal function.

<6years: see literature. ≥6years: Give by IV inj; max rate 160mg/min. High-dose MTX rescue: Start 24hrs after the beginning of MTX infusion (based on MTX dose of 12g/m² over 4hrs). Normal MTX elimination: give levoleucovorin 7.5mg (approximately 5mg/m²) every 6hrs for 10 doses. Delayed late MTX elimination: continue levoleucovorin 7.5mg every 6hrs until MTX <0.05micromolar; delayed early MTX elimination and/or evidence of acute renal injury: levoleucovorin 75mg every 3hrs until MTX <1micromolar, then 7.5mg every 3hrs until MTX <0.05micromolar. May continue another 24hrs for subsequent courses in cases of significant clinical toxicity. Inadvertent MTX overdose: Start as soon as possible or within 24hrs if delayed MTX excretion. Levoleucovorin 7.5mg every 6hrs until MTX <0.05micromolar. See literature.

Not for treating pernicious anemia and megaloblastic anemia. Monitor serum creatinine and MTX levels every 24hrs. Delayed early MTX elimination may cause reversible renal failure; provide hydration, alkalinize urine with sodium bicarbonate, closely monitor fluid and electrolytes until serum MTX <0.05 micromolar and renal failure resolves. Pregnancy (Cat.C). Nursing mothers.

Potentiates 5-fluorouracil toxicity. Antagonizes TMP/SMZ. Antagonizes anticonvulsants (eg, phenobarbital, primidone, phenytoin). May be affected by drugs that affect MTX elimination.

Stomatitis, vomiting, nausea.

Single-use vial—1

8/1/08