Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 175 mg/17.5 mL (generic)
- 250 mg/25 mL (generic)
injection, lyophilized powder for reconstitution
- 50mg/vial (Fusilev, generic); vial contains 64 mg levoleucovorin calcium pentahydrate (equivalent to 50 mg levoleucovorin)
- 175mg/vial (Khapzory, generic)
- 300mg/vial (Khapzory)
High-dose Methotrexate Rescue
Indicated for rescue after high-dose methotrexate therapy in osteosarcoma
Recommended initial dose of 7.5 mg q6hr based on methotrexate IV dose of 12 g/m²
Monitor serum creatinine and methotrexate levels at least once daily; continue levoleucovorin, hydration, and urinary alkalinization (pH ≥7) until methotrexate level <5 x 10-8 M (0.05 micromolar)
Normal methotrexate elimination
- Serum methotrexate level ~10 micromolar at 24 hr, 1 micromolar at 48 hr, and <0.2 micromolar at 96 hr post methotrexate infusion
- Initiate at 7.5 mg (~5 mg/m²) q6hr 24 hr after beginning methotrexate infusion for 60 hr (10 doses)
Delayed late methotrexate elimination
- Serum methotrexate levels >0.2 micromolar at 72 hr and >0.05 micromolar at 96 hr post methotrexate infusion
- Continue 7.5 mg IV q6hr until methotrexate level <0.05 micromolar
Delayed early methotrexate elimination and/or evidence of acute renal injury
- Serum methotrexate level ≥50 micromolar at 24 hr, ≥5 micromolar at 48 hr, or serum creatinine level increased ≥100% at 24 hr post methotrexate infusion
- 75 mg IV q3hr until methotrexate level is <1 micromolar, followed by 7.5 mg IV q3hr until methotrexate level is <0.05 micromolar
- Extend levoleucovorin treatment for an additional 24 hr (total of 14 doses) in subsequent cycles if there is significant clinical toxicity in the presence of impaired methotrexate elimination or renal impairment
Delayed methotrexate elimination due to third space fluid accumulation, renal insufficiency, or inadequate hydration
- May require higher levoleucovorin doses or prolonged administration
Folic Acid Antagonists Overdose or Impaired Elimination
Indicated for diminishing toxicity and counteracting effects of impaired methotrexate elimination and of inadvertent overdosage of folic acid antagonists
7.5 mg (~5 mg/m²) q6hr until methotrexate level is <0.05 micromolar
Start as soon as possible after methotrexate overdosage or 24 hr of delayed elimination
Increase dose 50 mg/m² q3hr until methotrexate level <0.05 micromolar for the following:
- If serum creatinine at 24 hr increases ≥50% compared to baseline
- If methotrexate level at 24 hr >5 x 10^6 M
- If methotrexate level at 48 hr >9 x 10^7 M
- Continue hydration (3 L/day) and urinary alkalinization with sodium bicarbonate Adjust bicarbonate dose to maintain urine pH at ≥7
Metastatic Colorectal Cancer
Indicated, in combination with 5-fluorouracil (5-FU), for palliative treatment in patients with advanced metastatic colorectal cancer
Regimens are used for treatment of colorectal cancer
- Levoleucovorin 100 mg/m² IV over a minimum of 3 min, followed by 5-FU 370 mg/m² qDay for 5 consecutive days OR
- Levoleucovorin 10 mg/m² IV followed by 5-FU 425 mg/m2 qDay for 5 consecutive days
- Repeat q4Weeks for 2 courses, then q4-5Weeks, if patient recovered from toxicity from the prior course
- Do not adjust levoleucovorin dosage for toxicity
Refer to fluorouracil prescribing information for information on dosage and dosage modifications for adverse reactions
Dosing Considerations
Fusilev is dosed at one-half the usual dose of racemic d,l-leucovorin
Limitations of use
- Not indicated for pernicious anemia and megaloblastic anemia secondary to lack of vitamin B12
- Refer to prescribing information for complete monitoring instructions
Dosage Forms & Strengths
injectable solution
- 175 mg/17.5 mL (generic)
- 250 mg/25 mL (generic)
injection, lyophilized powder for reconstitution
- 50mg/vial (Fusilev, generic); vial contains 64 mg levoleucovorin calcium pentahydrate (equivalent to 50 mg levoleucovorin)
- 175mg/vial (Khapzory, generic)
- 300mg/vial (Khapzory)
High-dose Methotrexate Rescue
<6 years: Safety and efficacy not established
≥6 years
- Indicated for rescue after high-dose methotrexate therapy in osteosarcoma
- Recommended initial dose of 7.5 mg q6hr based on methotrexate IV dose of 12 g/m²
- Monitor serum creatinine and methotrexate levels at least once daily; continue levoleucovorin, hydration, and urinary alkalinization (pH ≥7) until methotrexate level <5 x 10-8 M (0.05 micromolar)
Normal methotrexate elimination
- Serum methotrexate level ~10 micromolar at 24 hr, 1 micromolar at 48 hr, and <0.2 micromolar at 96 hr post methotrexate infusion
- Initiate at 7.5 mg (~5 mg/m²) q6hr 24 hr after beginning methotrexate infusion for 60 hr (10 doses)
Delayed late methotrexate elimination
- Serum methotrexate levels >0.2 micromolar at 72 hr and >0.05 micromolar at 96 hr post methotrexate infusion
- Continue 7.5 mg IV q6hr until methotrexate level <0.05 micromolar
Delayed early methotrexate elimination and/or evidence of acute renal injury
- Serum methotrexate level ≥50 micromolar at 24 hr, ≥5 micromolar at 48 hr, or serum creatinine level increased ≥100% at 24 hr post methotrexate infusion
- 75 mg IV q3hr until methotrexate level is <1 micromolar, followed by 7.5 mg IV q3hr until methotrexate level is <0.05 micromolar
- Extend levoleucovorin treatment for an additional 24 hr (total of 14 doses) in subsequent cycles if there is significant clinical toxicity in the presence of impaired methotrexate elimination or renal impairment
Delayed methotrexate elimination due to third space fluid accumulation, renal insufficiency, or inadequate hydration
- May require higher levoleucovorin doses or prolonged administration
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Contraindicated (0)
Serious - Use Alternative (1)
- trimethoprim
levoleucovorin decreases effects of trimethoprim by pharmacodynamic antagonism. Avoid or Use Alternate Drug. Monitor for trimethoprim treatment failure or decreased efficacy when coadministered with levoleucovorin, especially when used with sulfamethoxazole for Pneumocystis jiroveci pneumonia in patients who are HIV positive .
Monitor Closely (0)
Minor (0)
Adverse Effects
>10% (Levoleucovorin)
Stomatitis (38%)
Vomiting (38%)
Nausea (19%)
>10% (Levoleucovorin/5-FU)
Stomatitis (72%)
Diarrhea (70%)
Nausea (62%)
Vomiting (40%)
Asthenia/fatigue/malaise (29%)
Dermatitis (29%)
Alopecia (26%)
Anorexia/decreased appetite (24%)
Abdominal pain (14%)
Grade 3-4
- Diarrhea (19%)
- Stomatitis (12%)
1-10% (Levoleucovorin/5-FU)
Grade 3-4
- Nausea (8%)
- Vomiting (5%)
- Asthenia/fatigue/malaise (5%)
- Anorexia/decreased appetite (4%)
- Abdominal pain (3%)
- Dermatitis (1%)
6% (Levoleucovorin)
Diarrhea
Dyspepsia
Typhlitis
Dyspnea
Dermatitis
Confusion
Neuropathy
Abnormal renal function
Taste perversion
Postmarketing Reports
Dyspnea
Pruritus, rash
Temperature change, rigors, allergic reactions
Warnings
Contraindications
Hypersensitivity reactions to leucovorin products, folic acid, or folinic acid
Cautions
Increased gastrointestinal toxicities with 5-FU; monitor patients for gastrointestinal toxicities; do not initiate or continue therapy with fluorouracil in patients with symptoms of gastrointestinal toxicity until those symptoms have resolved
Do not initiate or continue therapy with levoleucovorin and 5-FU in patients with symptoms of gastrointestinal toxicity until symptoms resolve; monitor patients with diarrhea until it resolves
Increased rates of treatment failure and morbidity with concomitant use of d,l-leucovorin with trimethoprim-sulfamethoxazole for Pneumocystis jiroveci pneumonia in patients with HIV
Exercise caution when taking folinic acid in combination with anticonvulsant drugs
Drug interaction overview
- Increased rates of failure and morbidity in the acute treatment of Pneumocystis jiroveci pneumonia in HIV patients when coadministered with trimethoprim-sulfamethoxazole
- Folic acid in large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin and primidone and increase frequency of seizures in susceptible children; it is not known whether folinic acid has the same effects; however, both folic and folinic acids share some common metabolic pathways; monitor patients taking folinic acid in combination with antiepileptic drugs
- Leucovorin products increase the toxicity of fluorouracil; do not initiate or continue therapy with fluorouracil in patients with symptoms of gastrointestinal toxicity until those symptoms have resolved; monitor patients with diarrhea until diarrhea has resolved, as rapid deterioration leading to death can occur
Pregnancy & Lactation
Pregnancy
There are limited data in pregnant women
Drug is administered in combination with methotrexate or fluorouracil, which can cause embryo-fetal harm; refer to methotrexate and fluorouracil prescribing information for additional information
Animal data
Animal reproduction studies not conducted
Lactation
There are no data on presence of levoleucovorin in human milk or effects on breastfed infant or on milk production
Levoleucovorin is administered in combination with methotrexate or fluorouracil; refer to methotrexate and fluorouracil prescribing information for additional information
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
Mechanism of Action
High dose methotrexate therapy
- An active isomer of 5-formyl tetrahydrofolic acid (THF)
- Counteracts therapeutic and toxic effects of folic acid antagonists (eg, methotrexate), which act by inhibiting dihydrofolate reductase
Combination with fluorouracil in colorectal cancer
- Enhances therapeutic and toxic effects of 5-FU
- 5-FU is metabolized to 5-fluoro-2'- deoxyuridine-5'-monophosphate (FdUMP), which binds to and inhibits thymidylate synthase
- Levoleucovorin converts to another reduced folate, 5,10-methylenetetrahydrofolate, which then acts to stabilize the binding of FdUMP to thymidylate synthase, thereby enhances inhibition of thymidylate synthase
Absorption
Mean peak serum total tetrahydrofolate (total-THF) concentration: 1722 ng/mL
Mean peak serum (6S)-5-methyl-5, 6, 7, 8-tetrahydrofolate concentration: 275 ng/mL (0.9-hr postinjection
Elimination
Half-life: 5.1 hr (total-THF); 6.8 hr ([6S]-5-methyl-5, 6, 7, 8-tetrahydrofolate)
Administration
IV Compatibilities
0.9% NaCl
D5W
IV Incompatibilities
Due to precipitation risk, do not coadminister Fusilev with other agents in the same admixture
IV Preparation
Reconstitution with NaCl solutions with preservatives (eg, benzyl alcohol) not studied
Fusilev: Reconstitute with 5.3 mL of 0.9% NaCl to yield a concentration of 10 mg/mL
Khapzory: Reconstitute with 3.6 mL (175-mg vial) and 6.2 mL (300-mg vial) of 0.9% NaCl, to obtain a clear, colorless to yellowish solution (final concentration: 50 mg/mL levoleucovorin)
Dilute reconstituted solution immediately (if possible), to concentrations of 0.5-5 mg/mL in 0.9% NaCl or D5W
Visually inspect for particulate matter and discoloration prior to administration; discard if particulate matter or discoloration is observed
IV Administration
IV use only
Do not administer intrathecally
Fusilev: Inject ≤16 mL/min (160 mg/min), because of calcium content of reconstituted solution
Storage
Fusilev
- Protect from light
- Unused vials: Refrigerate at 2-8°C (36-46°F)
- Dilutions in D5W: Store at room temperature for ≤4 hr
- Reconstituted vials or dilutions in 0.9% NaCl: Store at room temperature for ≤12 hr
Khapzory
- Protect from light
- Unused vials: Store at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)
- Reconstituted vials and diluted solutions: Store at room temperature for ≤12 hr
Images
BRAND | FORM. | UNIT PRICE | PILL IMAGE |
---|---|---|---|
levoleucovorin calcium intravenous - | 10 mg/mL vial | ![]() | |
levoleucovorin calcium intravenous - | 50 mg vial | ![]() | |
levoleucovorin calcium intravenous - | 10 mg/mL vial | ![]() | |
levoleucovorin calcium intravenous - | 50 mg vial | ![]() | |
Fusilev intravenous - | 50 mg vial | ![]() |
Copyright © 2010 First DataBank, Inc.
Patient Handout
levoleucovorin calcium intravenous
LEVOLEUCOVORIN - INJECTION
(LEE-voe-LOO-koe-VOR-in)
COMMON BRAND NAME(S): Fusilev, Khapzory
USES: This medication is used to treat or prevent serious blood cell disorders (such as thrombocytopenia, neutropenia, anemia) caused by certain drugs (folic acid antagonists such as methotrexate, trimethoprim, pyrimethamine). Some brands may also be used with a certain cancer drug (5-fluorouracil) to treat patients with colon cancer.
HOW TO USE: This medication is given by injection into a vein as directed by your doctor, usually every 3 or 6 hours. For the treatment of colon cancer, it is usually given once daily. Do not inject this medication into the spine. The dosage is based on your medical condition, body size, and response to treatment.If you are using this medication at home, learn all preparation and usage instructions from your health care professional and the product package. Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Learn how to store and discard medical supplies safely.Use this medication regularly to get the most benefit from it. To help you remember, use it at the same time(s) each day.
SIDE EFFECTS: Nausea, vomiting, diarrhea, or mouth sores may occur. If any of these effects last or get worse, tell your doctor or pharmacist promptly.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
PRECAUTIONS: Before using levoleucovorin, tell your doctor or pharmacist if you are allergic to it; or to leucovorin; or to folic acid or folinic acid; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: certain anemias (due to vitamin B12 deficiency).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this medication passes into breast milk. Consult your doctor before breast-feeding.
DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Levoleucovorin is very similar to leucovorin. Do not use medications containing leucovorin while using levoleucovorin.
OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.
NOTES: Do not share this medication with others.Lab and/or medical tests (such as kidney function, complete blood count, folic acid antagonist blood levels) should be done while you are using this medication. Keep all medical and lab appointments. Consult your doctor for more details.
MISSED DOSE: It is important to get each dose of this medication as scheduled. If you miss a dose, ask your doctor or pharmacist right away for a new dosing schedule. Do not double the dose to catch up.
STORAGE: Different brands of this medication have different storage needs. Check the product package for instructions on how to store your brand, or ask your pharmacist. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.
Information last revised December 2022. Copyright(c) 2023 First Databank, Inc.
IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.