TheraRadar
Data updated: Jun 28, 2026

LEVOLEUCOVORIN CALCIUM · MEITHEAL

Oncology Approved 2008-03-07

Levoleucovorin calcium is a folate analog indicated for rescue therapy following high-dose methotrexate administration in adult and pediatric patients with osteosarcoma. It is also used to diminish toxicity associated with folic acid antagonist overdosage or impaired methotrexate elimination in both adult and pediatric populations. Additionally, it is indicated for the treatment of adults with metastatic colorectal cancer when used in combination with fluorouracil. **Limitations of Use:** It is not indicated for the treatment of pernicious anemia or megaloblastic anemias secondary to vitamin B12 deficiency, as it may allow neurological progression despite hematologic remission.

How LEVOLEUCOVORIN CALCIUM Works

Levoleucovorin is the pharmacologically active isomer of 5-formyl tetrahydrofolic acid. Unlike folic acid, it does not require reduction by the enzyme dihydrofolate reductase (DHFR) to participate in folate-dependent reactions; this allows it to bypass the methotrexate-induced block of DHFR and provide the necessary "one-carbon" moieties for DNA/RNA synthesis. When used with fluorouracil, levoleucovorin is converted to 5,10-methylenetetrahydrofolate, which stabilizes the binding of the fluorouracil metabolite FdUMP to thymidylate synthase. This stabilization enhances the inhibition of thymidylate synthase, further disrupting DNA repair and replication.

12
Indications
--
Phase 3 Trials
18
Years on Market

Details

Status
Discontinued
First Approved
2008-03-07
Routes
INTRAVENOUS
Dosage Forms
POWDER, SOLUTION

LEVOLEUCOVORIN CALCIUM Approval History

2016
2017
2018
2019
2020
2021
2022
2023
2024
2025
2026
Original
New Indication
New Form
Label Update
44 FDA actions from 2015 to 2023
Sep 2023 SUPPL
Label · Labeling
Jul 2023 SUPPL
Label · Labeling
May 2023 ORIGINAL
Update

What LEVOLEUCOVORIN CALCIUM Treats

4 indications

LEVOLEUCOVORIN CALCIUM is approved for 4 conditions since its original approval in 2015. These indications span multiple therapeutic areas including oncology, immunology, and more.

  • Osteosarcoma
  • Folic Acid Antagonist Overdose
  • Methotrexate Elimination Impairment
  • Colorectal Cancer
Source: FDA Label

LEVOLEUCOVORIN CALCIUM Competitive Set

Pro

Three rings of competition based on shared molecular targets and treated indications.

Unlock 16 more competitors across all three rings.
Upgrade to Pro

Filters applied: drops same-active-ingredient (505(b)(2) reformulations), route-mismatch (topical vs systemic), and cross-therapeutic-area matches in same-indication rings.

What's emerging in LEVOLEUCOVORIN CALCIUM's indications

See all emerging drugs →

Phase 3 candidates targeting molecules with no FDA-approved drug, in indications LEVOLEUCOVORIN CALCIUM treats. First-in-class if their pivotal trials read out positive.

Drugs Similar to LEVOLEUCOVORIN CALCIUM

3 of 12

FDA-approved drugs for similar conditions. Compare mechanisms and indications to understand treatment alternatives.

ALYMSYS
BEVACIZUMAB-MALY
1 shared
AMNEAL PHARMS
Shared indications:
AVASTIN
BEVACIZUMAB
1 shared
Roche
Shared indications:
CAPECITABINE
CAPECITABINE
1 shared
SHILPA
Shared indications:
📋

Clinical Trial Registry

2 trials
Trial Sponsor ID Phase Status Title
NCT04060017 DOD Leucovorin Ph 2 active not recruiting Early Treatment of Language Impairment in Young Children With Autism Spectrum Disorder With Leucovorin Calcium
NCT04060030 AS Leucovorin Ph 2 recruiting Treatment of Social and Language Deficits With Leucovorin for Young Children With Autism
🔬

Active Pipeline

Pro

Ongoing clinical trials by development phase

Loading...

Key Completed Trials

Pro

Completed studies with published results, ranked by significance

Loading...
📊

Trial Timeline

Full development history with FDA approval milestones

|
Loading...
Understanding FDA Approval Types
Count Type What it means
- ORIG Original approval - drug first enters market
- SUPPL - Efficacy New indication (new disease/condition approved)
- SUPPL - Labeling Label text changes (warnings, dosing updates)
- SUPPL - Manufacturing Production changes (new facility)
- SUPPL - Chemistry Formulation changes (new dosage strength)

Green lines in the timeline show ORIG and Efficacy approvals - the clinically meaningful milestones.

LEVOLEUCOVORIN CALCIUM FDA Label Details

Indications & Usage

FDA Label (PDF)

Levoleucovorin injection is indicated for: rescue after high-dose methotrexate therapy in adult and pediatric patients with osteosarcoma. diminishing the toxicity associated with overdosage of folic acid antagonists or impaired methotrexate elimination in adult and pediatric patients. the treatment of adults with metastatic colorectal cancer in combination with fluorouracil. Limitations of Use Levoleucovorin injection is not indicated for pernicious anemia and megaloblastic anemia secondary to the lack of vitamin B 12 , because of the risk of progression of neurologic manifestations despite he...

Looking for the branded version?

FUSILEV

Full clinical data, patents, trials, and competitive landscape for levoleucovorin calcium.

See FUSILEV

Data Sources

Data sourced from official FDA and NIH databases. Click links to verify on original sources.