Dosing and uses of Levoleucovorin (Fusilev)
Adult dosage forms and strengths
powder for injection
- 50mg
Methotrexate Inadvertent Overdose
7.5 mg (approximately 5 mg/m²) intravenously (IV) every 6 hours until the serum methotrexate level is less than 0.01 micromolar
Measure methotrexate and creatinine levels at 24 hours interval; increase dose of levoleucovorin to 50 mg/m² IV every 3 hours until the methotrexate is less than 0.01 micromolar if methotrexate level is > 5 micromolar or serum creatinine has increased 50% over baseline after 24 hr of initiating treatment or if the 48 hr methotreaxate level is >0.9 micromolar
Aggressive hydration and urinary alkalinization (with sodium bicarbonate) should be maintained during the treatment period
High Dose Methotrexate Rescue
7.5 mg or 5 mg/m² IV q6hr for 10 doses starting 24 hr after initiating methotrexate infusion
Renal failure may occur in patients with delayed early methotrexate elimination; such patients require continuing hydration and urinary alkalization (with sodium bicarbonate); fluid and electrolyte monitoring is necessary until serum methotrexate has fallen to below 0.05 micromolar and renal failure has resolved
Advanced Colorectal Cancer
Indicated in combination with 5-fluorouracil in the palliative treatment of patients with advanced metastatic colorectal cancer
100 mg/m² by slow IV injection over a minimum of 3 minutes, followed by 5-FU at 370 mg/m² by IV injection, Or
10 mg/m² by slow IV injection followed by 5-FU at 425 mg/m² by IV injection
Repeat daily for 5 days at 4-week intervals for 2 cycles, and then repeat at 4-5 week intervals provided that the patient has completely recovered from the toxic effects of the prior treatment course
5-FU dose may need to be adjusted downward by 20-30% according to toxicities or upward by 10% if no toxicities experienced
Administer levoleucovorin separate from 5-FU to avoid precipitant
Pediatric dosage forms and strengths
powder for injection
- 50mg
Methotrexate Inadvertent Overdose
7.5 mg (approximately 5 mg/m²) intravenously (IV) every 6 hours until the serum methotrexate level is less than 0.01 micromolar
Measure methotrexate and creatinine levels at 24 hours interval; increase dose of levoleucovorin to 50 mg/m² IV every 3 hours until the methotrexate is less than 0.01 micromolar if methotrexate level is > 5 micromolar or serum creatinine has increased 50% over baseline after 24 hr of initiating treatment or if the 48 hr methotreaxate level is >0.9 micromolar
Aggressive hydration and urinary alkalinization (with sodium bicarbonate) should be maintained during the treatment period
High Dose Methotrexate Rescue
7.5 mg or 5 mg/m² IV q6hr for 10 doses starting 24 hr after initiating methotrexate infusion
Renal failure may occur in patients with delayed early methotrexate elimination; such patients require continuing hydration and urinary alkalization (with sodium bicarbonate); fluid and electrolyte monitoring is necessary until serum methotrexate has fallen to below 0.05 micromolar and renal failure has resolved
Levoleucovorin (Fusilev) adverse (side) effects
Frequency not defined
Fatigue
Dermatitis
Alopecia
Diarrhea
Nausea
Vomiting
Abdominal pain
Stomatitis
Weakness/malaise
Confusion
Neuropathy
Dyspnea
Thrombocytosis
Anaphylaxis
Wheezing
Urticaria
Warnings
Contraindications
Documented hypersensitivity to drug or related products
Cautions
Seizures and/or syncope reported
May increase toxicity of 5-fluorouraciL
May increase treatment failure of sulfamethoxazole-trimethoprim therapies
Should not be used to treat pernicious anemia or megaloblastic anemia secondary to vitamin B12 deficiency
Risk of severe neurological complications in patients with undiagnosed anemia
Administer as soon as possible following accidental folinic acid antagonist overdose
Monitor methotrexate serum concentrations to determine appropriate dose and duration of levoleucovorin therapy
Pregnancy and lactation
Pregnancy category: C
Lactation: Not known whether distributed in breast milk; not recommended
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Levoleucovorin (Fusilev)
Mechanism of action
Levoleucovorin does not require reduction by dihydrofolate reductase. Counteracts the toxic effects of folic acid antagonists. Supplies the necessary cofactor blocked by methotrexate.
Stabilizes the binding of 5-fluoro-2-deoxyuridine-5-monophosphate to thymidylate synthetase resulting in its inhibition.
Pharmacokinetics
Peak plasma time: 0.9 hr (IV)
Half-life elimination: 5-7 hr (15mg); 16-30 hr (300mg)
Administration
IV Incompatibilities
Coadministration with other agents could cause precipitation
Administer 5-FU and levoleucovorin separately to avoid formation of precipitate
IV Compatibilities
NS, D5W
Y-site: Granisetron
IV Preparation
Lyphilized powder: Reconstitute 50 mg vial w/ 5.3 mL NS to obtain 10 mg/mL solution
May further dilute to 0.5 mg/mL w/ NS or D5W
Stable 12 hr in NS & 4 hr in D5W at room temp
Ready-to-use solution: 10 mg/mL; may dilute further with Ns
IV Administration
IV injection not to exceed 160 mg/min
Not for intrathecal use
