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FUSILEV is levoleucovorin—
the pharmacologically active isomer in modulation of 5-FU1,2

FUSILEV is levoleucovorin—the pharmacologically active isomer in modulation of 5-FU.


FUSILEV is dosed at one-half the usual dose of the generic racemic leucovorin

FUSILEV is dosed at one-half the usual dose of generic racemic leucovorin.

There is potential for dosing errors when interchanging leucovorin and levoleucovorin.


FUSILEV enhances the therapeutic and toxic effects of 5-FU in mCRC

Levoleucovorin has unique pharmacologic properties

In pharmacokinetic studies, levoleucovorin was shown to have distinct characteristics in several dimensions1,3-6




Does not bind human serum albumin4


Converted to active metabolite1


Short plasma half-life (32 minutes)5


Potentiates 5-FU3


Actively transported into cells6


Is not excreted via kidneys1

Learn how FUSILEV works >

Indications and Usage

FUSILEV is a folate analog indicated for:

  • Rescue after high-dose methotrexate therapy in osteosarcoma.
  • Diminishing the toxicity and counteracting the effects of impaired methotrexate elimination and of inadvertent overdosage of folic acid antagonists.
  • Use in combination chemotherapy with 5-FU in the palliative treatment of patients with advanced metastatic colorectal cancer.

Limitations of Use

FUSILEV is not approved for pernicious anemia and megaloblastic anemias. Improper use may cause a hematologic remission while neurologic manifestations continue to progress.

Important Safety Information


FUSILEV is contraindicated for patients who have had previous allergic reactions attributed to folic acid or folinic acid.

Warnings and Precautions

  • Due to Ca++ content, no more than 16 mL (160 mg) of levoleucovorin solution should be injected intravenously per minute.
  • FUSILEV enhances the toxicity of fluorouracil. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly d,l-leucovorin and 5-fluorouracil. When these drugs are administered concurrently in the palliative treatment of advanced colorectal cancer, the dosage of 5-FU must be lower than usually administered. Although the toxicities observed in patients treated with the combination of FUSILEV and 5-FU are qualitatively similar to those observed with 5-FU alone, gastrointestinal toxicities (particularly stomatitis and diarrhea) are observed more commonly and may be of greater severity and of prolonged duration in patients treated with the combination.
  • Concomitant use of d,l-leucovorin with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in HIV patients was associated with increased rates of treatment failure in a placebo-controlled study.

Adverse Reactions

  • Allergic reactions were reported in patients receiving FUSILEV.
  • The most common adverse reactions (>50%) in patients with advanced colorectal cancer receiving FUSILEV in combination with 5-FU were diarrhea, nausea and stomatitis.
  • Vomiting (38%), stomatitis (38%) and nausea (19%) were reported in patients receiving FUSILEV as rescue after high dose methotrexate therapy.

Drug Interactions

FUSILEV may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone, and increase the frequency of seizures in susceptible patients.

FUSILEV adverse event profile

Adverse reactions (≥10% in either arm) in patients with advanced metastatic colorectal cancer

Adverse Reaction Levoleucovorin/5FU
Adverse Event N (%) Grade 1–4 Grade 3–4 Grade 1–4 Grade 3–4
Gastrointestinal Disorders
Stomatitis 229 (72%) 37 (12%) 221 (72%) 44 (14%)
Diarrhea 222 (70%) 61 (19%) 201 (65%) 51 (17%)
Nausea 197 (62%) 25 (8%) 186 (61%) 26 (8%)
Vomiting 128 (40%) 17 (5%) 114 (37%) 18 (6%)
Abdominal Pain* 45 (14%) 10 (3%) 57 (19%) 10 (3%)
General Disorders
Asthenia/Fatigue/Malaise 91 (29%) 15 (5%) 99 (32%) 34 (11%)
Metabolism and Nutrition
Anorexia/Decreased Appetite 76 (24%) 13 (4%) 77 (25%) 5 (2%)
Skin Disorders
Dermatitis 91 (29%) 3 (1%) 86 (28%) 4 (1%)
Alopecia 83 (26%) 1 (0.3%) 87 (28%) 3 (1%)

* Includes abdominal pain, upper abdominal pain, lower abdominal pain, and abdominal tenderness


Please click here to see full Prescribing Information for FUSILEV.

Reporting of Suspected Adverse Reactions

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.


  • Zittoun J. Pharmacokinetics and in vitro studies of l-leucovorin. Comparison with the d and d,l-leucovorin. Ann Oncol. 1993;4(suppl 2):S1-S5.
  • FUSILEV [package insert]. East Windsor, NJ: Acrotech Biopharma, LLC.
  • Bleyer WA. New vistas for leucovorin in cancer chemotherapy. Cancer. 1989;63:995-1007.
  • Mader RM, Steger GG, Rizovski B, et al. Different stereospecific protein binding of tetrahydrofolates to human serum albumin. J Pharm Sci. 1994;83(9):1247-1249.
  • Straw JA, Szapary D, Wynn WT. Pharmacokinetics of the diastereoisomers of leucovorin after intravenous and oral administration to normal subjects. Cancer Res. 1984;44:3114-3119.
  • Sirotnak FM, Chello PL, Moccio DM, et al. Stereospecificity at carbon 6 of formyltetrahydrofolate as a competitive inhibitor of transport and cytotoxicity of methotrexate in vitro. Biochem Pharmacol. 1979;28:2993-2997.

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