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Generic name: levoleucovorin [ LEE-voe-LOO-koe-voe-rin ]
Brand names: Fusilev, Khapzory
Drug class: Antidotes

Medically reviewed by Philip Thornton, DipPharm. Last updated on Jul 26, 2023.

What is levoleucovorin?

Levoleucovorin is used to treat or prevent toxic effects of methotrexate in people who have received methotrexate to treat bone cancer.

Levoleucovorin is also used to treat or prevent toxic effects of methotrexate in people whose bodies do not eliminate methotrexate properly after the drug is metabolized. It may also be used to treat toxic effects of an overdose of methotrexate or certain other medications.

Levoleucovorin is also used in combination chemotherapy with fluorouracil to treat colorectal cancer that has spread to other parts of the body. Levoleucovorin treats only the symptoms of colorectal cancer but does not treat the cancer itself.

Levoleucovorin should not be used to treat anemia that is caused by a lack of vitamin B12.


You should not be treated with this medication if you are allergic to levoleucovorin or to folic acid or folinic acid.

Tell your doctor if you are taking sulfa drugs, seizure medication, a cancer medication called fluorouracil (5FU), or a multivitamin or mineral supplement than contains folic acid.

In an emergency situation, it may not be possible before you are treated to tell your caregivers about all of your medical conditions or if you are pregnant or breast-feeding. However, make sure any doctor caring for you afterward knows that you have received levoleucovorin.

Tell your doctor or caregivers at once if you have fever, chills, white patches or sores inside your mouth or on your lips, severe or ongoing diarrhea, confusion, urination problems, or if you feel very thirsty or hot, if you are unable to urinate, and you have heavy sweating or hot and dry skin.

Before taking this medicine

You should not receive this medicine if you are allergic to levoleucovorin, folic acid, or folinic acid.

If possible, before you receive levoleucovorin, tell your doctor or caregivers if you have:

It is not known whether levoleucovorin will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It may not be safe to breastfeed while using levoleucovorin. Ask your doctor about any risk.

In an emergency, you may not be able to tell caregivers if you are pregnant or breast feeding. Make sure any doctor caring for your pregnancy or your baby knows you received this medicine.

How is levoleucovorin given?

Levoleucovorin is given as an infusion into a vein. A healthcare provider will give you this injection.

For use with methotrexate, levoleucovorin is usually given every 3 to 6 hours.

For colorectal cancer, levoleucovorin is usually given daily as a 5-day treatment, repeated every 4 to 5 weeks.

After treatment with this medicine, you will be watched to make sure this medicine has been effective.

You will need frequent medical tests to help your doctor determine how long your treatment will continue for.

What happens if I miss a dose?

If this medication is given by a healthcare professional in an clinical setting, you are not likely to miss a dose.

If you are receiving levoleucovorin daily in 4-week treatment cycles, call your doctor for instructions if you miss an appointment for your scheduled injection.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while receiving levoleucovorin?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Levoleucovorin side effects

Get emergency medical help if you have any signs of an allergic reaction to levoleucovorin: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Tell your doctor or caregivers at once if you have:

Common levoleucovorin side effects may include:

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Dosing information

Usual Adult Dose for Methotrexate Rescue:

Levoleucovorin Rescue After High Dose Methotrexate Therapy:

Dose: 7.5 mg (approximately 5 mg/m2) IV every 6 hours for 10 doses starts 24 hours after the beginning of the methotrexate infusion. (The recommendations for levoleucovorin rescue are based on a methotrexate dose of 12 grams/m2 administered by intravenous infusion over 4 hours.)

Serum creatinine and methotrexate levels should be determined at least once daily. Levoleucovorin administration, hydration, and urinary alkalinization (pH of 7.0 or greater) Dosage should be adjusted or rescue extended based on the following guidelines:

Guidelines - Dosage and Administration
Clinical Situation 1) Normal Methotrexate Elimination
Laboratory Findings: Serum methotrexate level approximately 10 micromolar at 24 hours after administration, 1 micromolar at 48 hours, and less than 0.2 micromolar at 72 hours.
Levoleucovorin Dosage and Duration: 7.5 mg IV every 6 hours for 60 hours (10 doses starting at 24 hours after start of methotrexate infusion).

Clinical Situation 2) Delayed Late Methotrexate Elimination
Laboratory Findings: Serum methotrexate level remaining above 0.2 micromolar at 72 hours, and more than 0.05 micromolar at 96 hours after administration.
Levoleucovorin Dosage and Duration: Continue 7.5 mg IV every 6 hours, until methotrexate level is less than 0.05 micromolar.

Clinical Situation 3) Delayed Early Methotrexate Elimination and/or Evidence of Acute Renal Injury
Laboratory Findings: Serum methotrexate level of 50 micromolar or more at 24 hours, or 5 micromolar or more at 48 hours after administration, or; a 100% or greater increase in serum creatinine level at 24 hours after methotrexate administration (e.g., an increase from 0.5 mg/dL to a level of 1 mg/dL or more).
Levoleucovorin Dosage and Duration: 75 mg IV every 3 hours until methotrexate level is less than 1 micromolar; then 7.5 mg IV every 3 hours until methotrexate level is less than 0.05 micromolar.

Patients who experience delayed early methotrexate elimination are likely to develop reversible renal failure. In addition to appropriate levoleucovorin therapy, these patients require continuing hydration, urinary alkalinization, and close monitoring of fluid and electrolyte status, until the serum methotrexate level has fallen to below 0.05 micromolar and the renal failure has resolved.

Some patients will have abnormalities in methotrexate elimination or renal function following methotrexate administration, which are significant but less severe than the abnormalities described above. These abnormalities may or may not be associated with significant clinical toxicity. If significant clinical toxicity is observed, levoleucovorin rescue should be extended for an additional 24 hours (total of 14 doses over 84 hours) in subsequent courses of therapy. The possibility that the patient is taking other medications which interact with methotrexate (e.g., medications which may interfere with methotrexate elimination or binding to serum albumin) should always be reconsidered when laboratory abnormalities or clinical toxicities are observed.

Delayed methotrexate excretion may be caused by accumulation in a third space fluid collection (i.e., ascites, pleural effusion), renal insufficiency, or inadequate hydration. Under such circumstances, higher doses or prolonged administration may be indicated.

Although levoleucovorin may ameliorate the hematologic toxicity associated with high dose methotrexate, this medicine has no effect on other established toxicities of methotrexate such as the nephrotoxicity resulting from drug and/or metabolite precipitation in the kidney.

Usual Adult Dose for Methotrexate Overdosage:

Dosing Recommendations for Inadvertent Methotrexate Overdosage

Dose: 7.5 mg (approximately 5 mg/m2) should be administered IV every 6 hours until the serum methotrexate level is less than 10^-8 M.

Levoleucovorin rescue should begin as soon as possible after an inadvertent overdosage and within 24 hours of methotrexate administration when there is delayed excretion. As the time interval between antifolate administration (e.g., methotrexate) and levoleucovorin rescue increases, levoleucovorin effectiveness in counteracting toxicity may decrease.

Serum creatinine and methotrexate levels should be determined at 24 hour intervals. If the 24 hour serum creatinine has increased 50% over baseline or if the 24 hour methotrexate level is greater than 5 x 10^-6 M or the 48 hour level is greater than 9 x 10^-7 M, the dose of levoleucovorin should be increased to 50 mg/m2 IV every 3 hours until the methotrexate level is less than 10^-8 M. Hydration (3 L/day) and urinary alkalinization with NaHCO3 should be employed concomitantly. The bicarbonate dose should be adjusted to maintain the urine pH at 7.0 or greater.

Usual Adult Dose for Colorectal Cancer:

For use in combination chemotherapy with 5-fluorouracil in the palliative treatment of patients with advanced metastatic colorectal cancer:
Regimen 1: 100 mg/m2 by slow intravenous injection over a minimum of 3 minutes, followed by 5-FU at 370 mg/m2 by intravenous injection.
Regimen 2: 10 mg/m2 by intravenous injection followed by 5-FU at 425 mg/m2 by intravenous injection.

Treatment is repeated daily for five days. This five day treatment course may be repeated at 4 week (28 day) intervals, for 2 courses and then repeated at 4 to 5 week (28 to 35 day) intervals provided that the patient has completely recovered from the toxic effects of the prior treatment course.

In subsequent treatment courses, the dosage of 5-FU should be adjusted based on patient tolerance of the prior treatment course. The daily dosage of 5-FU should be reduced by 20% for patients who experienced moderate hematologic or gastrointestinal toxicity in the prior treatment course, and by 30% for patients who experienced severe toxicity. For patients who experienced no toxicity in the prior treatment course, 5-FU dosage may be increased by 10%. Levoleucovorin dosages are not adjusted for toxicity.

What other drugs will affect levoleucovorin?

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with levoleucovorin, especially:

This list is not complete. Other drugs may interact with levoleucovorin, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.