FUSILEV
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FUSILEV (FUSILEV).
FUSILEV (levoleucovorin) is the pharmacologically active isomer of folinic acid. It bypasses dihydrofolate reductase inhibition by dihydrofolate reductase inhibitors (e.g., methotrexate), providing reduced folate that is used in DNA synthesis and repair. It also enhances the efficacy of fluorouracil by stabilizing the ternary complex of thymidylate synthase, thereby inhibiting DNA synthesis.
| Metabolism | Primarily hepatic metabolism; undergoes rapid conversion to 5-methyl-tetrahydrofolate. Partially metabolized by dihydrofolate reductase and other folate-metabolizing enzymes. |
| Excretion | Primarily hepatic metabolism; renal excretion of metabolites accounts for approximately 40-60% of the dose; fecal excretion is negligible. |
| Half-life | The terminal elimination half-life of the active metabolite, 5-methyltetrahydrofolate (5-MTHF), is approximately 6-8 hours in healthy adults; clinically, this supports twice-daily or daily dosing schedules. |
| Protein binding | Approximately 50-70% bound, primarily to albumin. |
| Volume of Distribution | 0.5-0.7 L/kg, indicating distribution into total body water and some tissue binding. |
| Bioavailability | Oral bioavailability is 10-20% due to saturable intestinal absorption and first-pass metabolism. |
| Onset of Action | Intravenous administration: 5-15 minutes; intramuscular: 30-60 minutes; oral: 30-60 minutes. |
| Duration of Action | Up to 24 hours based on effect on methotrexate rescue and folate levels; clinical duration may extend to 48 hours for rescue protocols. |
| Molecular Weight | 601.6 |
Leucovorin (Fusilev) 200 mg/m2 IV over 2 hours, followed by 5-fluorouracil bolus and infusion, repeated every 2 weeks in combination regimens for advanced colorectal cancer.
| Dosage form | SOLUTION |
| Renal impairment | No specific dose adjustment required for mild to moderate renal impairment. Use caution in severe renal impairment (CrCl <30 mL/min) as leucovorin is eliminated renally; consider dose reduction and monitoring. |
| Liver impairment | No specific dose adjustment based on Child-Pugh score; however, monitor liver function in patients with hepatic impairment. |
| Pediatric use | Safety and efficacy not established in pediatric patients. Limited data from clinical trials suggest similar dosing per body surface area as adults, but not recommended for use. |
| Geriatric use | No specific dose adjustment required; elderly patients may be more sensitive to myelosuppression and gastrointestinal toxicity; monitor closely. |
| 1st trimester | Teratogenic in animal studies; avoid use unless clearly needed. |
| 2nd trimester | May cause fetal harm; potential for megaloblastic anemia. |
| 3rd trimester | May cause fetal harm; use only if benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for FUSILEV (FUSILEV).
| Placental transfer | Levoleucovorin crosses the placenta; extent not fully quantified but fetal exposure occurs. |
| Breastfeeding | Excreted in breast milk in low amounts; caution advised due to potential for interference with folate metabolism in nursing infants. |
| Lactation Rating | L3 (Moderately Safe) |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
Hypersensitivity to leucovorin or any componentPernicious anemia or other megaloblastic anemias secondary to vitamin B12 deficiency
| Precautions | Increased risk of severe toxicity when used with fluorouracil, including myelosuppression, stomatitis, and diarrhea, Potential for calcium precipitation when administered intravenously at high doses; avoid mixing with calcium-containing solutions, Hypersensitivity reactions reported, May mask pernicious anemia and other megaloblastic anemias due to vitamin B12 deficiency |
| Food/Dietary | No specific food interactions. However, alcohol consumption should be limited as it may worsen side effects such as nausea. Maintain adequate nutrition and hydration during treatment. |
Loading safety data…
| Teratogenic Risk | Pregnancy Category C. First trimester: Folate antagonist; associated with neural tube defects and fetal death. Second and third trimesters: Limited data; potential for fetal myelosuppression and methotrexate-like effects if used with fluorouracil. |
| Fetal Monitoring | Monitor complete blood counts, liver function tests, and serum creatinine prior to and during therapy. Assess for signs of bleeding or infection. Fetal monitoring with ultrasound if used during pregnancy. |
| Fertility Effects | Limited data; leucovorin is a folate analogue and may theoretically affect ovarian or testicular function, but no definitive evidence of fertility impairment in humans. |
| Clinical Pearls | Fusilev (levoleucovorin) is the active isomer of leucovorin and does not require metabolic activation. It is used to counteract the toxic effects of folic acid antagonists such as methotrexate. Do not administer intrathecally due to risk of neurotoxicity. Monitor serum creatinine and methotrexate levels during rescue therapy. Adjust dose in renal impairment. |
| Patient Advice | Take this medication exactly as prescribed, usually intravenously under medical supervision. · Inform your doctor if you experience symptoms of an allergic reaction (rash, itching, swelling). · Avoid taking folic acid supplements without consulting your doctor. · Stay well hydrated and follow your doctor's instructions for monitoring blood tests. · Report any unusual bleeding, bruising, or signs of infection to your doctor. |