What Is Leucovorin?

Leucovorin (Leucovorin Calcium) is a reduced form of Folic Acid used to protect healthy cells during high-dose Methotrexate therapy, to enhance the effectiveness of chemotherapy for colorectal cancer, and to treat certain types of anemia.

Also known as Folinic Acid or Citrovorum Factor, Leucovorin is sold under the brand name Wellcovorin. It belongs to the folic acid analog drug class. Multiple generic manufacturers produce it, including Teva, Fresenius Kabi, and Sagent, while Pfizer makes the brand-name version.

Leucovorin is not a controlled substance and does not require DEA scheduling. It has been available in the United States for decades and is considered an essential medication in cancer care.

What Is Leucovorin Used For?

Leucovorin has several FDA-approved uses:

1. Methotrexate Rescue

When patients receive high-dose Methotrexate (commonly for osteosarcoma or certain lymphomas), Leucovorin is given afterward to "rescue" healthy cells from the toxic effects. Methotrexate works by blocking an enzyme called dihydrofolate reductase, which cells need to make DNA. Leucovorin bypasses this blockage, providing healthy cells with the folate they need to survive. For a deeper explanation, read our guide on how Leucovorin works.

2. Colorectal Cancer Treatment

Leucovorin is used in combination with 5-Fluorouracil (5-FU) for the palliative treatment of advanced colorectal cancer. It enhances the cancer-killing effects of 5-FU by stabilizing the bond between 5-FU and an enzyme called thymidylate synthase. This is one of the most common uses of Leucovorin in oncology.

3. Megaloblastic Anemia

When a patient has megaloblastic anemia caused by Folic Acid deficiency and cannot take oral Folic Acid, Leucovorin can be used as a substitute. However, it must not be used for anemia caused by vitamin B12 deficiency — doing so can mask the deficiency while neurological damage continues.

4. Methotrexate Overdose

In cases of accidental Methotrexate overdose or impaired Methotrexate elimination (such as from kidney problems), Leucovorin is given as an emergency rescue agent.

Off-Label Uses

Doctors also prescribe Leucovorin off-label for:

• Advanced esophageal, gastric, and pancreatic cancer (with 5-FU-based regimens)
• Prevention of blood toxicity from Pyrimethamine in HIV/AIDS patients with toxoplasmosis
• Treatment of ectopic pregnancy (alongside Methotrexate)
• Methanol or formic acid poisoning

How Is Leucovorin Taken?

Leucovorin comes in several forms:

• Oral tablets — Available in 5 mg, 10 mg, 15 mg, and 25 mg strengths. Can be taken with or without food.
• Powder for injection — Available in 50 mg, 100 mg, 200 mg, 350 mg, and 500 mg vials. Reconstituted and given IV or intramuscularly in a clinical setting.
• Solution for injection — 10 mg/mL, given IV or IM.

The dosage varies significantly depending on the reason for use:

• Methotrexate rescue: Typically 15 mg (about 10 mg/m²) every 6 hours for 10 doses, starting 24 hours after Methotrexate administration. Timing is critical — rescue must begin within 24 to 42 hours of the Methotrexate dose.
• Colorectal cancer: 200 mg/m² given IV over 2 hours, followed by 5-FU.
• Megaloblastic anemia: Up to 1 mg per day orally.

Important: Doses above 25 mg should be given by injection because oral absorption saturates at that level — meaning your body can't absorb more than about 25 mg at a time when taken by mouth.

Who Should Not Take Leucovorin?

Leucovorin should not be used by people who have:

• Pernicious anemia or B12-deficient megaloblastic anemia — Leucovorin can improve blood test results while hiding ongoing nerve damage from B12 deficiency
• Known allergy to Leucovorin or Folic Acid — Allergic reactions including anaphylaxis have been reported

Additionally, Leucovorin must never be given intrathecally (into the spinal canal), as this can be fatal.

Patients taking anti-seizure medications like Phenytoin, Phenobarbital, or Primidone should use Leucovorin with caution, as high doses of folates can reduce the effectiveness of these drugs and increase seizure risk. Learn more about Leucovorin drug interactions.

How Much Does Leucovorin Cost?

The cost of Leucovorin varies depending on the form, strength, and where you buy it:

• Generic oral tablets (5 mg, 12 tablets): $24 to $36 with a discount card like GoodRx
• Oral tablets without insurance: $24 to $150+ depending on the pharmacy
• Injection vials: $30 to $500+ depending on the strength (50 mg to 500 mg)

Generic Leucovorin Calcium is available and significantly cheaper than brand Wellcovorin. Most insurance plans cover Leucovorin — injectable forms administered in a clinic are typically covered under your medical benefit (Medicare Part B), while oral tablets fall under your pharmacy benefit (Medicare Part D).

If cost is a barrier, Prescription Hope offers brand Wellcovorin for $70 per month. There are also discount cards and patient assistance programs available. Read our complete guide on saving money on Leucovorin.

Availability in 2026

Leucovorin has been subject to recurring shortages since 2008. As of 2026, the 500 mg injection vials are on back order from multiple manufacturers, and oral tablets are intermittently unavailable. The FDA has allowed temporary importation of Leucovorin tablets from Canada to help bridge supply gaps.

If you're having trouble finding Leucovorin, Medfinder can help you locate pharmacies with it in stock. If it's completely unavailable, your doctor may consider Levoleucovorin (Fusilev), which is clinically equivalent at half the dose.

Final Thoughts

Leucovorin is a critical medication in cancer treatment and Methotrexate rescue therapy. Understanding what it is, how it's used, and what it costs puts you in a better position to work with your healthcare team and navigate any supply challenges. If you need help finding Leucovorin near you, start with Medfinder.