FDA-filed SPL labeling · retrieved through openFDA

Levoleucovorin Injection

Levoleucovorin injection is a folate analog used intravenously to protect the body during and after high-dose methotrexate chemotherapy, to counteract folic acid antagonist overdose, and to boost the effectiveness of fluorouracil in treating advanced colorectal cancer.

Brand names FusilevKhapzory
Drug classes ⓘ Folate Analog
Rx Form 1 Route Intravenous
Dr. Brian Staiger, PharmD, BCPS
Reviewed by Last reviewed Jul 10, 2026
🧬 Where this information comes from Click to expand

The clinical label records used on this page are FDA-filed Structured Product Labeling (SPL) retrieved through openFDA. We identified 9 clinical label sets within the page’s selected clinical scope after exact ingredient or ingredient-combination matching and applicable route/form matching. Forms, routes, brands, labelers, strengths, and NDC product-record counts are built separately from matching FDA National Drug Code Directory records. The linked DailyMed document is a representative official source for verification, not the page’s only clinical source. View the linked label on DailyMed →

At a glance
Linked label effectiveMar 17, 2026
Clinical labels in scope ⓘ9
AvailabilityRx
Earliest approval/marketing year ⓘ2008
FDA-listed product records ⓘ31
Boxed warningNone found in compared labels
How we combine label and product data →
✓No current FDA shortage listed · checked Sep 22, 2026
⭐ Levoleucovorin Injection at a glance The quick version — the full detail is in the Patient Information Guide below.
💊
HelloPharmacist Editorial Team Bottom Line
Levoleucovorin injection (Fusilev, Khapzory) is a hospital-administered folate medication that serves two key roles in cancer care: protecting the body from methotrexate toxicity during osteosarcoma treatment, and enhancing the effectiveness of 5-fluorouracil in advanced colorectal cancer. Because it significantly amplifies 5-FU's side effects — especially gut toxicity — it requires careful medical supervision, and any gastrointestinal symptoms must be addressed before continuing treatment. Always let your entire care team know every medication you take, and report any worsening symptoms right away.
How we write & review this content — our editorial policy →

📖 Levoleucovorin Injection: Patient Information Guide

A plain-language walkthrough of Levoleucovorin Injection — what it treats, how it works, how it’s taken, side effects, warnings and interactions. Tap any section to expand it.

🎯What it's used for▾

Levoleucovorin injection is a folate analog given intravenously in three distinct clinical situations in cancer care:

  • Methotrexate rescue in osteosarcoma: Given after high-dose methotrexate chemotherapy to protect healthy cells from methotrexate's toxic effects
  • Counteracting folic acid antagonist toxicity or overdose: Used when methotrexate or similar drugs are not clearing the body properly, or after an accidental overdose
  • Combination chemotherapy for colorectal cancer: Used alongside 5-fluorouracil (5-FU) for the palliative treatment of advanced metastatic colorectal cancer — to enhance 5-FU's cancer-fighting effect
  • Not approved for: Pernicious anemia or megaloblastic anemias caused by vitamin B12 deficiency — using it for these conditions without addressing B12 deficiency can mask blood problems while nerve damage continues
⚙️How it works▾

Levoleucovorin is the active form of a folate compound (a type of B vitamin). Unlike folic acid, it does not need to be processed by the enzyme that methotrexate blocks (dihydrofolate reductase). This means it can bypass the blockade and restore the folate activity that cancer chemotherapy has disrupted in healthy cells. When given with 5-fluorouracil, levoleucovorin converts in the body to a compound that helps 5-FU grip more tightly to its target enzyme (thymidylate synthase — essential for DNA replication), making the chemotherapy more effective at stopping cancer cell growth.

💊How it's taken▾

Levoleucovorin injection is given only intravenously (into a vein) by a healthcare professional — never at home, and never into the spinal fluid. The frequency depends on why it is being used: for methotrexate rescue, it may be given every 6 hours for multiple doses starting 24 hours after methotrexate; in colorectal cancer treatment, it is given once daily for five consecutive days in repeating cycles. Your care team will adjust the timing and duration based on your lab results (especially methotrexate blood levels and kidney function) and how well you tolerate treatment.

  • Always follow your prescriber's exact schedule — timing is critical, especially for methotrexate rescue
  • Lab monitoring (creatinine, methotrexate levels) is a required part of treatment, not optional
🤒Side effects — in detail▾

The most common side effects depend on how levoleucovorin is being used:

  • With high-dose methotrexate (methotrexate rescue): mouth sores (stomatitis), vomiting, nausea, diarrhea, stomach upset, skin rash
  • With 5-fluorouracil (colorectal cancer): mouth sores, diarrhea, nausea, vomiting, abdominal pain, fatigue, skin rash or dermatitis, hair loss (alopecia), decreased appetite
  • Allergic reactions (rash, itching, chills, fever, breathing difficulty) have been reported

Severe diarrhea, severe mouth sores, or signs of an allergic reaction require immediate medical attention — rapid deterioration from gut toxicity can be life-threatening, especially in older patients.

⚠️Warnings & precautions▾
  • Increased 5-FU toxicity: Levoleucovorin makes 5-fluorouracil significantly more toxic. Gut side effects (diarrhea, mouth sores, dehydration) can become severe and have caused deaths — especially in elderly or debilitated patients. Do not start or continue this combination if gastrointestinal symptoms are present.
  • Diarrhea monitoring: Patients with diarrhea must be monitored closely by their care team. Rapid worsening can be fatal.
  • IV rate limit: Because the solution contains calcium, there is a strict limit on how fast it can be infused — your healthcare team manages this.
  • Anti-epileptic drug interaction: Large folate doses may reduce the effectiveness of seizure medications like phenobarbital or phenytoin; monitoring is needed.
  • Trimethoprim-sulfamethoxazole: Using leucovorin products with this antibiotic for Pneumocystis pneumonia in HIV patients was linked to higher treatment failure rates.
  • Not for vitamin B12 deficiency anemias: Using levoleucovorin for pernicious anemia or B12-related megaloblastic anemia may mask blood changes while nerve damage quietly progresses.
🔀What it interacts with▾

Levoleucovorin injection has several important drug interactions that your care team will manage:

  • 5-Fluorouracil (5-FU): Levoleucovorin amplifies 5-FU's toxicity — gastrointestinal side effects can be severe and even fatal; careful dose management is essential
  • Methotrexate: Levoleucovorin is given intentionally to counteract methotrexate toxicity, but timing is critical — waiting too long reduces its protective effect
  • Anti-epileptic drugs (phenobarbital, phenytoin, primidone): High folate levels may reduce how well these seizure medications work and could increase seizure frequency in some patients
  • Trimethoprim-sulfamethoxazole: Concurrent use with leucovorin products for Pneumocystis pneumonia treatment in HIV patients was associated with increased treatment failure

This is not a complete list of interactions. Always talk with your doctor or pharmacist before starting, stopping, or changing any medication.

📋Before taking it▾
  • Severe allergy history: Do not use if you have had a severe allergic reaction to leucovorin products, folic acid, or folinic acid
  • Pregnancy: There are limited data on levoleucovorin itself in pregnancy; however, the drugs it is used with (methotrexate, 5-FU) are known to cause serious harm to a developing baby — discuss all risks with your doctor
  • Breastfeeding: No data exist on levoleucovorin in human milk; consult your prescriber, and refer to the labeling for the co-administered drugs
  • Children: Established as safe and effective in patients aged 6 and older for methotrexate rescue; not established for colorectal cancer treatment in pediatric patients
  • Older adults: Elderly patients receiving levoleucovorin with 5-FU face a higher risk of severe gastrointestinal toxicity and require closer monitoring
  • All medications: Tell your doctor about every drug you take, especially anti-seizure medications or trimethoprim-sulfamethoxazole
  • Pernicious anemia / B12 deficiency: This drug is not approved for those conditions and should not be used as a substitute for treating the underlying cause
🚑If you take too much▾

If levoleucovorin itself is involved in an error, your care team will manage next steps in a clinical setting. In the context of methotrexate overdose — the situation this drug is most often used for — levoleucovorin rescue must begin as soon as possible and ideally within 24 hours of methotrexate exposure; the longer the delay, the less effective it becomes. Blood levels of methotrexate and kidney function (creatinine) are monitored at least every 24 hours, and the dose of levoleucovorin may be increased and given more frequently if levels remain dangerously high or kidney function worsens. Extra IV fluids and urine alkalinization (keeping urine pH at 7 or above) are given at the same time to help clear methotrexate from the body.

📡Pharmacodynamics — effects in the body▾

After entering the bloodstream, levoleucovorin is actively transported into cells and converted to its primary active form, 5-methyltetrahydrofolic acid (5-methyl-THF), which is the main circulating form of reduced folate in the body. Inside cells, both levoleucovorin and 5-methyl-THF are further processed into forms (polyglutamates) that participate directly in biochemical reactions requiring folate — including DNA synthesis and repair. This cellular activity is what allows levoleucovorin to restore normal folate function blocked by methotrexate, or to enhance the action of 5-fluorouracil against cancer cells. Small amounts can enter cerebrospinal fluid, primarily as 5-methyl-THF, though concentrations there remain far lower than typical methotrexate levels after spinal administration.

🔬Pharmacokinetics — how your body processes it▾

After intravenous administration, levoleucovorin reaches peak blood levels quickly. Its main active metabolite, (6S)-5-methyl-THF, peaks in the blood around 0.9 hours after injection. The body takes several hours to clear these compounds: the half-life (the time for blood levels to fall by half) is about 5 hours for total folate and about 6.8 hours for the primary metabolite. Studies comparing levoleucovorin to the older racemic form (d,l-leucovorin, which contains both active and inactive isomers) showed that at half the dose, levoleucovorin delivers equivalent blood exposure to the active form — confirming that the two are comparable in terms of how much active drug the body receives.

📦How to store it▾

Store in refrigerator at 2°C to 8°C (36°F to 46°F). Protect from light. Store in carton until contents are used.

📄 Written from Levoleucovorin Injection’s FDA-approved label information, summarized in plain language with AI, and reviewed by our pharmacy team before publication. Every point is grounded in that labeling — nothing is invented. How we use AI →

🩺 Pharmacist Counseling Corner

Quick, plain-English answers to the questions patients ask most about Levoleucovorin Injection — the kind of thing our pharmacy team would talk through with you at the counter.

Why am I getting levoleucovorin — is it a chemotherapy drug itself? ▾
Great question. Levoleucovorin is not a chemotherapy drug on its own — it's actually a form of folate, similar to a B-vitamin. Depending on why you're receiving it, it's either protecting your healthy cells from the damage caused by methotrexate, or it's being added to boost how well your 5-FU chemotherapy works against colorectal cancer. Think of it as a support player — it either shields your body or helps another drug do its job better.
What side effects should I expect, and which ones mean I need to call someone right away? ▾
Nausea, vomiting, mouth sores, and diarrhea are the most commonly reported side effects — especially when levoleucovorin is given with 5-fluorouracil. Mild discomfort is expected, but if your diarrhea becomes severe or doesn't stop, that's urgent — it can get dangerous very quickly, so don't wait it out. Also call your care team right away for signs of an allergic reaction like rash, chills, fever, or trouble breathing. Severe mouth sores that make it hard to eat or drink also need prompt attention.
I take phenytoin for seizures. Is it safe to use levoleucovorin? ▾
This is really important to flag with your neurologist and oncologist before starting treatment. High levels of folate-based drugs like levoleucovorin can sometimes reduce how well anti-seizure medications — including phenytoin, phenobarbital, and primidone — work. Your care team will want to monitor you closely for any changes in seizure control while you're on this treatment. Don't stop your seizure medication on your own — just make sure all your doctors know what you're taking.
I'm pregnant. Is this safe for my baby? ▾
There's very limited safety data on levoleucovorin itself during pregnancy. The bigger concern is the drugs it's used alongside — both methotrexate and 5-fluorouracil are known to be harmful to a developing baby. This is a serious conversation to have with your oncologist and OB provider together, so you fully understand the risks and can make the most informed decision for your situation. Please don't stop any cancer treatment without that conversation first.
Why does the nurse inject this so slowly? Does it matter how fast it goes in? ▾
Yes, it really does matter. Levoleucovorin solution contains calcium, and if it's given too quickly, that can cause problems. Your care team follows a strict limit on how fast it can be infused intravenously. Separately, when it's given with 5-fluorouracil, each drug has to go in as a separate infusion — mixing them in the same IV bag can cause the drugs to clump together (form a precipitate), which makes them ineffective. The nurses and pharmacists manage all of this carefully.
Can levoleucovorin treat my anemia or B12 deficiency? ▾
No — and this is actually a safety point worth knowing. Levoleucovorin is not approved to treat pernicious anemia or anemias caused by vitamin B12 deficiency. Using it for those conditions could mask the blood abnormalities and make things look better on a test, while nerve damage from the B12 deficiency quietly continues to worsen. If you have concerns about anemia or B12 levels, talk to your doctor about the right treatment for that specifically.
Is Levoleucovorin Injection available over the counter? ▾
Levoleucovorin Injection is dispensed by prescription according to its FDA labeling, so it isn't sold over the counter. Your prescriber and pharmacist will determine if it's appropriate for you.
When was Levoleucovorin Injection first available? ▾
Levoleucovorin Injection has been available in the United States since at least 2008, based on FDA approval history (Drugs@FDA) and product marketing records.
Who makes Levoleucovorin Injection? ▾
Levoleucovorin Injection is supplied by 13 manufacturers listed in the FDA NDC Directory, including Acrotech Biopharma LLC, Amneal Pharmaceuticals LLC, Acrotech Biopharma Inc.

💬 Answers drafted from Levoleucovorin Injection’s FDA-approved label information, summarized in plain language with AI, and reviewed by our pharmacy team before publication. Grounded in that labeling — nothing is made up. How we use AI →

🧰 Keep exploring

🌿Drug & Supplement CheckerLevoleucovorin Injection vs. vitamins & herbs 💬Ask a PharmacistFree answer, usually < 24h 🔎NDC & pricing lookupFind Levoleucovorin Injection NDCs & costs 🅰️Browse Drugs A–ZLook up any medication

💊 How Levoleucovorin Injection comes

Levoleucovorin Injection is available in 1 form. Different forms and brands can have different approved uses, doses, schedules, and directions. Follow the instructions for your exact product, and do not switch forms without guidance from your prescriber or pharmacist.

Injection

Into a vein
Brands Fusilev Khapzory
How this form is used
What it may be used for
  • Used intravenously as rescue therapy after high-dose methotrexate in osteosarcoma
  • Used intravenously to counteract toxicity from impaired methotrexate elimination or accidental overdose of folic acid antagonists
  • Used intravenously in combination with 5-fluorouracil for palliative treatment of advanced metastatic colorectal cancer
Important instructions
  • For intravenous use only — never administer into the spinal fluid (intrathecally)
  • Do not mix levoleucovorin injection in the same IV admixture as other medications, due to risk of precipitation; administer separately
  • Because the solution contains calcium, the infusion rate must be carefully controlled — your care team will manage this
  • When used with 5-fluorouracil, levoleucovorin injection and 5-FU must be given as separate infusions to avoid formation of a precipitate
Available strengths 8 strengths
10 mg 10 mg/mL 50 mg 50 mg/5 mL 175 mg/3.5 mL 175 mg/17.5 mL
Show 2 more strengths Show fewer strengths
250 mg/25 mL 300 mg/6 mL
31 FDA-listed product records ⓘ

📊 Levoleucovorin Injection across the U.S. market

How Levoleucovorin Injection appears in the FDA’s National Drug Code Directory — including its dosage forms, strengths, brand names, manufacturers, and FDA-listed product records. These are directory records, not sales or prescription volume.

1
Dose forms ⓘ
13
Manufacturers
4
Brand names
31
FDA-listed product records ⓘ
2008
First marketed ⓘ
Acrotech Biopharma LLC16%
Amneal Pharmaceuticals LLC16%
Acrotech Biopharma Inc10%
Dr.Reddy's Laboratories Inc6%
Fosun Pharma USA Inc.6%
Gland Pharma Limited6%
Other makers39%

Share of FDA-listed product records by manufacturer — FDA National Drug Code Directory. Record counts are not sales or prescription volume.

📈 How widely Levoleucovorin Injection is used

A general measure of how commonly Levoleucovorin Injection is prescribed, based on Medicaid — one of the largest public drug programs. The figure below is prescriptions filled in Q1–Q4 2025, summed across every form and brand of the drug.

Think of this as a proxy for how widely Levoleucovorin Injection is used, drawn from freely available public data. Medicaid is just one program — these numbers don’t include Medicare, other government coverage, or commercial and cash-pay prescriptions, so real-world use is higher than what’s shown here.

424
Medicaid prescriptions filled (Q1–Q4 2025)
$133,217 gross Medicaid reimbursement (before mandatory rebates — net cost is lower)

How commonly is Levoleucovorin Injection prescribed? Of the 1,596 medications we measure, Levoleucovorin Injection ranks #1,378 by Medicaid prescriptions — more than 14% of them.

Where Levoleucovorin Injection ranks among the drugs we measure · Q1–Q4 2025 · neighbors ±5
Total prescriptions — #1,378 of 1,596
#1,373 Eliglustat 453 Rx #1,374 Interferon Gamma-1b In... 438 Rx #1,375 Olanzapine Injection 436 Rx #1,376 Demeclocycline 434 Rx #1,377 Peginterferon Alfa-2a... 431 Rx #1,378 Levoleucovorin Injecti... 424 Rx #1,379 Methsuximide 417 Rx #1,380 Fostamatinib 407 Rx #1,381 Carbidopa 402 Rx #1,382 Quinine 401 Rx #1,383 Istradefylline 400 Rx

Utilization by Levoleucovorin Injection product

Pick a product to see its own Medicaid numbers. Each chip is one clinical product — a specific strength & dosage form as defined by RxNorm — with brand-name and generic versions combined.

The 17.5 mL / 10 mg/mL injection is the most-dispensed Levoleucovorin Injection product — about 63% of these Medicaid prescriptions.

17.5 ML levoleucovorin 10 MG/ML Injection Most dispensed

269 Medicaid prescriptions (Q1–Q4 2025) 63% of Levoleucovorin Injection prescriptions shown $18,102 gross reimbursement (before rebates) ≈ $67 per prescription (gross)

Summed across the 2 of 11 listed NDC products with Medicaid activity — every brand and generic of this exact strength & form. RxNorm 1720765

levoleucovorin 175 MG Injection

155 Medicaid prescriptions (Q1–Q4 2025) 37% of Levoleucovorin Injection prescriptions shown $115,115 gross reimbursement (before rebates) ≈ $743 per prescription (gross)

Summed across the 1 of 2 listed NDC products with Medicaid activity — every brand and generic of this exact strength & form. RxNorm 1858561

Shares are of the Medicaid prescriptions shown here. Product grouping follows RxNorm (the National Library of Medicine’s drug terminology), so “one product” means one strength & dosage form regardless of manufacturer. Dollar figures are gross Medicaid reimbursement before mandatory rebates — rebates (often large, especially for brand-name drugs) are confidential, so actual net cost to Medicaid is lower than shown.

Source: Medicaid State Drug Utilization Data (CMS), aggregated by generic ingredient — summed across every NDC (all brands, strengths, salt forms and dosage forms) of Levoleucovorin Injection, and across all states and both fee-for-service and managed-care claims. A general popularity signal; it excludes Medicare, commercial insurance and cash prescriptions, so it is not total U.S. use. Based on the 3 of 13 listed Levoleucovorin Injection NDCs with Medicaid activity.

🔍 Compare Levoleucovorin Injection products

A representative set of FDA-listed product records for Levoleucovorin Injection — across manufacturers, strengths, and dosage forms, grouped by form with each product’s manufacturer and how the FDA approved it. The same medicine may be made and packaged by different companies, so a single drug can have many directory entries. (It’s also why a refill can look different — a new shape, color, or box — even though it contains the same medication.)

Showing 31 of 31 products — FDA National Drug Code Directory. See every product, package size and price: browse all 31 Levoleucovorin Injection NDCs →

RxNorm Concept Web — From Ingredient to Every Form and Strength

This page starts with one ingredient concept (IN). The branches below show its dose-form concepts (SCDF), then the available clinical drug and strength concepts (SCD). Combination products remain separate concepts with their own pages.

Ingredient (IN) Levoleucovorin Injection RxCUI 877015 1 dose form · 5 strengths

Look up RxCUI 877015 in the RxCUI Atlas →

RxNorm is the U.S. National Library of Medicine’s normalized drug vocabulary. Its concept hierarchy can include forms that are not currently marketed; the status on each branch compares that concept with current FDA listings. RxCUIs identify vocabulary concepts, not individual packages or manufacturers.

🏷️ Sold under these brand names

Fusilev Khapzory

🏭 Manufacturers & labelers

Acrotech Biopharma LLC 5 Amneal Pharmaceuticals LLC 5 Acrotech Biopharma Inc 3 Dr.Reddy's Laboratories Inc 2 Fosun Pharma USA Inc. 2 Gland Pharma Limited 2 Hainan Poly Pharm. Co., Ltd. 2 Meitheal Pharmaceuticals Inc 2 Meitheal Pharmaceuticals Inc. 2 NorthStar RxLLC 2 Slate Run Pharmaceuticals 2 Hikma Pharmaceuticals USA Inc. 1 Sandoz Inc 1

RxNorm drug class

Levoleucovorin Injection belongs to the Folate Analog class.

Pharmacologic class Folate Analog

Classified by RxNorm RxClass — the U.S. National Library of Medicine's standardized drug-classification service (Established Pharmacologic Class from the FDA, the ATC drug family from the WHO, and mechanism of action). Reference only, not medical advice.

🔬 Where this comes from

Core label, product, RxNorm, safety, and utilization data on this page come from the sources identified below. AI-written, editorial, and licensed sections are labeled separately.

📄
FDA-filed drug labels (SPL) Uses, dosing, warnings & side effects from SPL records retrieved through openFDA; the linked representative set can be verified on DailyMed. ✓ Linked label effective Mar 17, 2026
🏭
Forms, brands & labelersAggregated from ingredient-matched FDA National Drug Code Directory product records for Levoleucovorin Injection.
📈
Real-world reportsThe FDA Adverse Event Reporting System (FAERS), served through openFDA.
🚨
Recalls & shortagesopenFDA drug-enforcement reports and the FDA drug-shortage database.
🧾 Clinical label set — FDA-filed SPL labels retained for Levoleucovorin Injection after exact ingredient or ingredient-combination matching and applicable route/form matching
Clinical labels in scope
9
NDC products indexed
31
Distinct labelers/manufacturers represented
13
Linked representative label ⓘ
Acrotech Biopharma LLC
Linked label effective
Mar 17, 2026
Composite sections available
21
Linked SPL Set ID
344f65ac-9f04-49d7-b7c3-4ba19bd7b429
Linked SPL Document ID
4b8997a9-ddf8-4618-966a-291d583f24f7
Open the linked representative label on DailyMed ↗

How we combine label and product data

HelloPharmacist combines public FDA and NLM records; we don’t author the underlying clinical facts. We identified 9 FDA-filed SPL label sets within the page’s selected clinical scope after exact ingredient or ingredient-combination matching and applicable route/form matching. The representative label is the starting point for the displayed reference monograph; the 12 largest stored in-scope SPL records, which may include that representative, are compared section by section, and the longest available version of each section is retained. Forms, routes, brands, labelers, product-listed strengths, and product-record counts are aggregated separately from ingredient-matched FDA NDC Directory records; package records listed above are associated with the linked SPL; and the normalized concept hierarchy comes from NLM RxNorm.

Where a section is identified as AI-written, its plain-language text is generated from bounded label evidence. New draft drug pages remain in the admin review queue before first publication. Acrotech Biopharma LLC is the representative DailyMed label linked for verification and dates; it is not the sole source used for the page.

This is general education, not medical advice — always consult your doctor or pharmacist about your medications and any medical condition. For the exact wording of the linked representative label, view that label on DailyMed; some displayed composite sections may come from other in-scope SPL labels. Learn how we use AI and our data sources & update cadence.