levoleucovorin calcium

(redirected from Fusilev)

levoleucovorin calcium

(lee-vo-loo-koe-vor-in kal-see-um ) ,

Fusilev

(trade name)

Classification

Therapeutic: antidotes
Pharmacologic: folic acid analogues
Pregnancy Category: C

Indications

Used as “rescue” following high-dose methotrexate treatment of osteosarcoma.Decreases toxicity which may follow impaired methotrexate elimination or unintended toxicity of other folic acid antagonists.In combination with 5–fluorouracil for the palliative treatment of advanced metastatic colorectal cancer.

Action

The reduced form of folic acid that serves as a cofactor in the synthesis of DNA and RNA; does not require dihydrofolate reductase for activity.

Therapeutic effects

Reversal of toxic effects of folic acid antagonists, including methotrexate, that inhibit dihydrofolate reductase.
Improved survival and performance status in patients with colorectal cancer.

Pharmacokinetics

Absorption: IV administration results on complete bioavailability.
Distribution: Transported actively and passively across cell membranes; enters CSF.
Metabolism and Excretion: Extensively converted to tetrahydrofolic derivatives.
Half-life: Total tetrahydrofolic acid—5.1 hr.

Time/action profile

ROUTEONSETPEAKDURATION
IVunknownend of infusion3–6 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity to folic acid or folinic acid.
Use Cautiously in: Concurrent use of anticonvulsants; may increase risk of seizures; Obstetric / Lactation: Use in pregnancy only if clearly needed, use cautiously during lactation; Pediatric: Has been used safely.

Adverse Reactions/Side Effects

(all patients also received methotrexate)

Central nervous system

  • confusion

Respiratory

  • dyspnea

Gastrointestinal

  • nausea (most frequent)
  • stomatitis (most frequent)
  • vomiting (most frequent)
  • altered taste
  • diarrhea
  • dyspepsia

Dermatologic

  • dermatitis

Genitourinary

  • abnormal renal function

Neurologic

  • neuropathy

Miscellaneous

  • allergic reactions

Interactions

Drug-Drug interaction

↑ risk of toxicity from fluorouracil.May ↓ effectiveness of phenobarbital , phenytoin, or primidone leading to ↑ risk of seizures.May ↓ effectiveness of trimethoprim-sulfamethoxazole when used to treat Pneumocustis carnii pneumonia in HIV-infected patients.

Route/Dosage

Levoleucovorin Rescue Following High-Dose Methotrexate—based on a methotrexate dose of 12 grams/m2 IV over 4 hr and concurrent with hydration and maintenance of urine pH ≥7.0

Intravenous (Adults) Normal methotrexate elimination—7.5 mg (5 mg/m2) every 6 hr for 10 doses starting 24 hr after the start of the methotrexate infusion; Delayed late methotrexate elimination—7.5 mg (5 mg/m2) every 6 hr starting 24 hr after the start of the methotrexate infusion; continue until methotrexate level <5 × 10–8 (0.05 micromolar); delayed early methotrexate elimination and/or evidence of acute renal injury—75 mg (5 mg/m2) every 3 hr starting 24 hr after the start of the methotrexate infusion; continue until methotrexate level is <1 micromolar, then 7.5 mg every 3 hr until 0.05 micromolar).

Levoleucovorin Rescue Following Inadvertent Overdosage of Methotrexate

Intravenous (Adults) 7.5 mg (approximately 5 mg/m2) every 6 hr until serum methotrexate level is less than 10−8 M. Determine creatinine and methotrexate levels at 24 hr intervals. If 24 hour serum creatinine has increased 50% over baseline or 24 hr methotrexate level is greater than 5 × 10−6 M or 48 hr level is greater than 9 × 10−7 M, ↑ dose to 50 mg/m2 IV every 3 hr until methotrexate level is less than 10−8 M. Maintain hydration and urinary alkalinization (pH ≥7.0). Initiate as soon as possible and within 24 hr of methotrexate when there is delayed excretion; as time interval increases, effectiveness ↓.

Palliative Treatment of Advanced Metastatic Colorectal Cancer (in combination with 5–fluorouracil)

Intravenous (Adults) 100 mg/m2 followed by 5–fluorouracil 370 mg/m2; regimen should be given daily for 5 days; repeat regimen q 4 wk for 2 courses (may then repeat course q 4–5 wk if patient tolerates)or levoleucovorin 10 mg/m2 followed by 5–fluorouracil 425 mg/m2; regimen should be given daily for 5 days; repeat regimen q 4 wk for 2 courses (may then repeat course q 4–5 wk if patient tolerates).

Availability

Lyophylized powder for injection (requires reconstitution: 50 mg/vial (contains mannitol)
Solution for injection: 10 mg/mL

Nursing implications

Nursing assessment

  • Assess patient for nausea and vomiting secondary to methotrexate therapy or folic acid antagonists (pyrimethamine and trimethoprim) overdose.
    • Monitor for development of allergic reactions (rash, urticaria, wheezing). Notify health care professionalif these occur.
  • Lab Test Considerations: Monitor serum methotrexate and creatinine at least once daily levels to determine dosage and effectiveness of therapy. Leucovorin calcium levels should be equal to or greater than methotrexate level. Rescue continues until serum methotrexate level is <5 × 10−8 M.
    • Monitor electrolytes and hydration status, and urine pH every 6 hr during therapy; pH should be maintained >7 to decrease nephrotoxic effects of high-dose methotrexate.

Potential Nursing Diagnoses

Risk for injury (Indications)
Imbalanced nutrition: less than body requirements (Indications)

Implementation

  • Levoleucovorin is dosed at one-half the usual dose of the racemic form.
  • Intravenous Administration
  • Intermittent Infusion: Reconstitute 50 mg vial with 5.3 mL of 0.9% NaCl without preservatives for a concentration of 10 mg/mL. Diluent: Dilute further immediately with 0.9% NaCl or D5W. Concentration: 0.5 mg/mL–5 mg/mL. Initial reconstitution or dilutions in 0.9% NaCl are stable at room temperature for 12 hr. Dilutions in D5W are stable for 4 hrs at room temperature. Do not administer solutions that are cloudy or contain a precipitate.
  • Rate: Administer at no more than 16 mL of reconstituted solution (160 mg levoleucovorin) per min; due to calcium content of solution.
  • Additive Incompatibility: Do not admix with other solutions.

Patient/Family Teaching

  • Explain purpose of medication to patient.

Evaluation/Desired Outcomes

  • Reversal of toxic effects of methotrexate or in overdose of folic acid antagonists.
References in periodicals archive ?
M2 EQUITYBITES-October 28, 2015-Mylan introduces generic Fusilev for Injection for treating high-dose methotrexate therapy in osteosarcoma
M2 PHARMA-October 28, 2015-Mylan introduces generic Fusilev for Injection for treating high-dose methotrexate therapy in osteosarcoma
The day after she did so, Spectrum issued a press release that announced its reduced sales expectations for the drug Fusilev, along with its expectation of the reduced revenue to follow; the stock price dropped more than 35% after the announcement.
Table Ia: PLR formatted USPI records: Proposed typologies of 'limitations of use' (see text for search criterion; data culled on 29 July 2009) Typology Examples: product name (a) and USPI text Explicit forbidden use * Vectical (calcitriol) ointment: ('should not be used'; 'Vectical ointment should not be 'not indicated') applied to the eyes, lips or facial skin' Explicit risk of use * Fusilev (levoleucovorin calcium) ('may cause') injection, powder, lyophilized, for solution: 'Fusilev is not approved for pernicious anemia and megaloblastic anemias secondary to the lack of vitamin BI2.
Fusilev, freeze-dried powder sold in vials, was approved in March 2008 for use after high-dose methotrexate therapy in patients with a bone tumor called osteosarcoma.
M2 PHARMA-December 12, 2011-Spectrum Pharmaceuticals affirms solid patent protection for FUSILEV (levoleucovorin) by end-2019(C)2011 M2 COMMUNICATIONS
Biotechnology company Spectrum Pharmaceuticals (NasdaqGS:SPPI) has submitted a supplemental New Drug Application with the US Food and Drug Administration (FDA) for a Ready-to-Use formulation of FUSILEV (levoleucovorin) for Injection.
He will be in charge of leading and managing the company's cross-functional brand efforts for FUSILEV and ZEVALIN, as well as brand planning for apaziquone and belinostat.
25 January 2010 - US biopharmaceutical company Spectrum Pharmaceuticals Inc (NASDAQ: SPPI) said today it has met with the US Food and Drug Administration (FDA) regarding its supplemental New Drug Application (sNDA) for FUSILEV (levoleucovorin) for injection for the treatment of patients with advanced metastatic colorectal cancer.