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Levoleucovorin (Intravenous)

Medically reviewed by Last updated on Mar 15, 2022.

Commonly used brand name(s)

In the U.S.

  • Fusilev
  • Khapzory

Available Dosage Forms:

  • Powder for Solution
  • Solution

Therapeutic Class: Methotrexate Rescue

Uses for levoleucovorin

Levoleucovorin injection is used as a rescue treatment after high-dose methotrexate treatment in patients with osteosarcoma (bone cancer). It is also used to lessen the toxic effects of folic acid blocker overdose or methotrexate in patients who cannot eliminate this drug properly from their bodies. Levoleucovorin injection is also used together with fluorouracil to treat metastatic (cancer that has spread) colon or rectal cancer.

Levoleucovorin is to be given by or under the direct supervision of your doctor.

Before using levoleucovorin

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For levoleucovorin, the following should be considered:


Tell your doctor if you have ever had any unusual or allergic reaction to levoleucovorin or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.


Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of levoleucovorin injection in children as rescue treatment after high-dose methotrexate treatment in osteosarcoma.

Appropriate studies have not been performed on the relationship of age to the effects of levoleucovorin injection in children to treat metastatic colorectal cancer. Safety and efficacy have not been established.


Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of levoleucovorin injection in the elderly.


There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are receiving levoleucovorin, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using levoleucovorin with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

  • Capecitabine
  • Doxifluridine
  • Fluorouracil
  • Fosphenytoin
  • Phenobarbital
  • Phenytoin
  • Primidone
  • Tegafur

Interactions with food/tobacco/alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other medical problems

The presence of other medical problems may affect the use of levoleucovorin. Make sure you tell your doctor if you have any other medical problems, especially:

  • Ascites (abnormal fluid in the abdomen) or
  • Dehydration or
  • Kidney disease or
  • Pleural effusion (excess fluid in the lungs)—Use with caution. Dose may be increased because of slower removal of methotrexate in the body.
  • Hypercalcemia (high calcium in the blood) or
  • Stomach or bowel problems (eg, diarrhea, stomatitis)—Use with caution. May make these conditions worse.

Proper use of levoleucovorin

A nurse or other trained health professional will give you levoleucovorin in a medical facility. It is given through a needle placed into one of your veins.

Do not use levoleucovorin together with trimethoprim-sulfamethoxazole for the acute treatment of Pneumocystis jiroveci pneumonia in patients with HIV infection.

Precautions while using levoleucovorin

It is very important that your doctor check your progress closely while you are receiving levoleucovorin to make sure it is working properly. Blood and urine tests may be needed to check for unwanted effects.

Levoleucovorin may cause stomach or bowel problems when used with fluorouracil. Check with your doctor right away if you have swelling of the mouth, diarrhea, confusion, decreased urination, dizziness, dry mouth, fainting, increased heart rate, lightheadedness, rapid breathing, sunken eyes, thirst, unusual tiredness or weakness, or wrinkled skin, which may be severe or longer than usual.

Levoleucovorin side effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

More common

  • Belching
  • blistering, crusting, irritation, itching, or reddening of the skin
  • chest tightness
  • cracked, dry, scaly skin
  • fever
  • heartburn
  • indigestion
  • sores, ulcers, or white spots on the lips, tongue, or inside the mouth
  • stomach discomfort, upset, or pain
  • stomach distention
  • swelling of the mouth
  • troubled breathing
  • watery or bloody diarrhea

Incidence not known

  • Cough
  • difficulty swallowing
  • dizziness
  • fast heartbeat
  • feeling unusually cold
  • hives, itching, skin rash
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • shivering
  • unusual tiredness or weakness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  • Bad unusual or unpleasant (after)taste
  • burning, tingling, numbness or pain in the hands, arms, feet, or legs
  • change in taste
  • confusion
  • decreased appetite
  • nausea
  • sensation of pins and needles
  • stabbing pain
  • thinning or loss of hair
  • vomiting
  • weight loss

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Further information

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