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Leucovorin Calcium 25 mg Tablet, 50,000-count — NDC 00555-0485-99 package photo

Leucovorin Calcium 25 mg Tablet, 50,000-count

by Teva Pharmaceuticals USA, Inc. · 50000 TABLET in 1 CONTAINER (0555-0485-99)
NDC 00555-0485-99
🏷️ FDA NDC (as labeled) 0555-0485-99 billing pads the labeler segment with a zero
This package
Contains50,000-count Pack sizes3 compare ↓
Also comes in: 25 tablets 00555-0485-27 500 tablets 00555-0485-04
On market Non-controlled
🗂️ Data synced Sep 17, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

🆔 Identity & classification

FDA NDC (as labeled) 0555-0485-99
Product NDC 0555-0485
11-digit billing NDC 00555048599
SPL Set ID 94669fc8-3c1c-4228-be27-09a1cd468c36
DEA schedule Non-controlled
Marketing category DRUG FOR FURTHER PROCESSING
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2021-06-10
Dosage form TABLET
Substance LEUCOVORIN CALCIUM
GPI-14 21755040100345
GPI class Leucovorin Calcium
GCN Seq No 044538
GCN 87557
HICL code 001063
Ingredient (HICL) Leucovorin Calcium
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1I
Therapeutic class — specific (HIC3) Chemotherapy Rescue/Antidote Agents
AHFS code 91:04.12.00
AHFS class Chemotherapy Antidotes/Protectants
FDB label name LEUCOVORIN CALCIUM 25 MG TAB
FDB brand name Leucovorin Calcium
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 0555-0485-99 — a 4-4-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the labeler segment → 00555-0485-99. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏭 Manufacturer & labeler

LabelerTeva Pharmaceuticals USA, Inc.
Labeler code00555
First marketedJun 2021
Product typeDrug For Further Processing
Portfolio504 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name LEUCOVORIN CALCIUM 25 MG TAB Ingredient Leucovorin Calcium
📗 Our plain-language guide HelloPharmacist
  • It depends on which chemo drug you're getting. If you're on methotrexate, leucovorin acts as a 'rescue' — it replenishes the folate that methotrexate blocks, protecting your health...
  • Why am I taking leucovorin alongside my chemotherapy?
  • You can take the leucovorin calcium tablet with or without food — whichever is easier on your stomach. If swallowing a whole tablet is difficult, you can crush it and mix it with f...
  • Can I take the tablet with food, or does it have to be on an empty stomach?
📖 Read our full Leucovorin guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

💊 What it looks like

Color white / green
ShapeRound
Imprintb;485
Size8 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

🧪 Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII M28OL1HH48
    Croscarmellose sodium is a plant-based substance derived from cellulose. It acts as a disintegrant, helping tablets and capsules break down quickly in the digestive system so the medicine can be absorbed.
  • UNII CQ3XH3DET6
    D&C Yellow No. 10 Aluminum Lake is a yellow colorant made by combining a dye with aluminum salts. It's used in medicines to add color for product identification and visual appeal.
  • UNII J9EQA3S2JM
    FD&C Blue No. 1 Aluminum Lake is a blue colorant made by combining FD&C Blue No. 1 dye with aluminum salts. It is used to color tablets, capsules, and other medicines for easy identification and appearance.
  • UNII EWQ57Q8I5X
    Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII ETJ7Z6XBU4
    Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.

7 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
ℹ️
No price is published for this exact package yet. CMS surveys NADAC per package size, so a different pack of the same drug often has one.
Try another pack size: 25 tablets 500 tablets
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Leucovorin Calcium 25 mg 00054-4499-11 Hikma 25 tablets $1.710 AB Availability likely —
Leucovorin Calcium 25 mg 00904-7584-10 Major 20 tablets $1.710 AB Availability likely —
Leucovorin Calcium 25 mg 42806-0359-25 Epic 25 tablets $1.710 AB Availability likely —
Leucovorin Calcium 25 mg 50742-0184-25 Ingenus 25 tablets $1.710 AB Availability likely —
Leucovorin Calcium 25 mg 60687-0227-94 American 20 tablets $1.710 AB Availability likely —
Leucovorin Calcium 25 mg 69315-0187-25 Leading 25 tablets $1.710 AB Availability likely —
Leucovorin Calcium 25 mgthis 00555-0485-99 Teva 50000 tablets — — FDA listed —
About this product: other versions of the same ingredient, strength and form are listed above, least expensive first, with FDA equivalence ratings where available.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

⏳ Availability & generic status

🏛️
2021
On the market since
Jun 2021
📍
2026
Currently FDA-listed
5 years listed
🔓
·
Generic versions listed
see equivalents
✅Generic appears available

FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

💊 Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
25 tablets00555-0485-27 128 Rx · $12,856
500 tablets00555-0485-04 No Medicaid data
50000 tablets this page00555-0485-99 No Medicaid data
Drug total (last 4 qtrs): 128 Rx · 5,015 units · $12,856 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

📊 Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Leucovorin Calcium (matched by generic name) — the program that covers self-administered drugs. 10 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Leucovorin Calcium. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$1.78M
Claims incl. refills
30.9K
Beneficiaries
21.1K
Spend / beneficiary
$84.30
Spend / claim
$57.57
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Leucovorin Calcium — the ingredient across all brands.

Top reported reactions

Diarrhoea1,799
Nausea1,388
Vomiting1,135
Neutropenia1,094
Pyrexia1,011
Fatigue873
Disease Progression772

Reporter sex

19,003 reports
Male · 54%
Female · 45%
Unknown · 1%

Serious outcomes

Death2,532
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 1,950 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Per unit Per pack Marketing startStatus
00555-0485-04 500 TABLET in 1 BOTTLE (0555-0485-04) — — 1990-06-30 Active
00555-0485-27 25 TABLET in 1 BOTTLE (0555-0485-27) $1.71 / ea $42.74 1990-06-30 Active
00555-0485-99 You're viewing this 50000 TABLET in 1 CONTAINER (0555-0485-99) — — — Active

You're viewing the largest of 3 pack sizes for this product.

This pack shows little to no recent Medicaid volume — the 25 tablets pack carries most fills. See all packs ↓

Pack size FAQ

What quantity is in NDC 00555-0485-99?
NDC 00555-0485-99 is a 50,000-count package — 50000 tablet in 1 container.
What is the difference between NDC 00555-0485-99 and NDC 00555-0485-27?
Both are Leucovorin Calcium 25 mg Tablet — the drug itself is identical. NDC 00555-0485-99 is the 50,000-count package, while NDC 00555-0485-27 is the 25 tablets package.
What NDC number is used to bill for this package of Leucovorin Calcium 25 mg Tablet?
Bill NDC 00555-0485-99 — the 11-digit billing format is 00555048599. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

🧭 About this NDC listing & data coverage

Listed for further processing / repackaging

What "drug for further processing" means

FDA lists this package under the "drug for further processing" marketing category: Teva Pharmaceuticals USA, Inc. supplies it to other companies for further processing or repackaging (blister cards that are later repackaged or co-packaged are a common example). The units themselves are a finished dosage form — which is why pricing or Medicaid data can still appear — but this exact package code may not be the presentation a retail pharmacy dispenses.

What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Is this NDC FDA-approved?
An NDC listing does not by itself establish FDA approval — the NDC Directory records that a product is listed with FDA, not that it was reviewed and approved. This listing's marketing category is "Drug For Further Processing". Products approved under an application carry an NDA, ANDA, or BLA number.
Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The FDA registers it as 0555-0485-99, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 00555-0485-99, written without dashes as 00555048599. The Identity section at the top of this page lists every form of this code.
What do the three segments of this NDC mean?
In 00555-0485-99, the first segment (00555) is the labeler code FDA assigned to Teva Pharmaceuticals USA, Inc.; the middle segment (0485) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (99) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Teva Pharmaceuticals USA, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 2 other package presentations of this same product, including 25 tablets (00555-0485-27), 500 tablets (00555-0485-04). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Teva Pharmaceuticals USA, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full FDA label FDA SPL

The complete FDA label for this product, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE Leucovorin calcium tablets are a folate analog indicated: To reduce the toxicity of: Methotrexate in adult patients with impaired methotrexate elimination, and Folic acid antagonists or dihydrofolate reductase (DHFR) inhibitors following an overdose in adult patients. ( 1.1 ) For the treatment of cerebral folate transport deficiency in adult and pediatric patients who have a confirmed variant in the folate receptor 1 gene (FOLR1-CFTD). ( 1.2 ) Limitations of Use Leucovorin calcium tablets are not recommended for use in patients with a deficiency of methenyltetrahydrofolate synthetase (MTHFS) because MTHFS is a primary enzyme in the metabolism of leucovorin to 5-methenyltetrahydrofolate.

( 1.2) Limitations of Use Leucovorin calcium tablets are not indicated for the treatment of pernicious anemia or other megaloblastic anemias, due to the lack of vitamin B12, because of the risk of progression of neurologic manifestations despite hematologic remission. ( 1.3 )

1.1Reduction of Toxicity of Folic Acid Antagonists or Dihydrofolate Reductase Inhibitors Leucovorin calcium tablets are indicated to reduce the toxicity of: Methotrexate in adult patients with impaired methotrexate elimination, and Folic acid antagonists or dihydrofolate reductase (DHFR) inhibitors following an overdose in adult patients.

1.2Cerebral Folate Transport Deficiency with Folate Receptor 1 Genetic Variant Leucovorin calcium tablets are indicated for the treatment of cerebral folate transport deficiency in adult and pediatric patients who have a confirmed variant in the folate receptor 1 gene (FOLR1-CFTD). Limitations of Use Leucovorin calcium tablets are not recommended for use in patients with a deficiency of methenyltetrahydrofolate synthetase (MTHFS) because MTHFS is a primary enzyme in the metabolism of leucovorin to 5-methenyltetrahydrofolate (5-MTHF) [see Clinical Pharmacology ( 12.3 )] .

1.3Limitations of Use Leucovorin calcium tablets are not indicated for the treatment of pernicious anemia or other megaloblastic anemias, due to the lack of vitamin B12, because of the risk of progression of neurologic manifestations despite hematologic remission.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Leucovorin calcium tablets are for oral administration only and can be taken with or without food. Crushing of leucovorin tablets and mixing with food or liquid has been reported in literature. ( 2.1 ) Administer leucovorin calcium tablets as soon as possible after a folic acid antagonist or dihydrofolate reductase (DHFR) inhibitor overdose and within 24 hours of methotrexate use when there is impaired methotrexate elimination.

( 2.2 ) Recommended Dosage to Reduce Methotrexate Toxicity in Patients with Impaired Methotrexate Elimination 10 mg/m 2 (up to 25 mg) orally every 6 hours until the serum methotrexate levels are less than 10 -8 M (0.01 micromolar). If a dosage greater than 25 mg every 6 hours is needed, an injectable formulation of leucovorin should be administered parenterally. ( 2.2 ) Recommended Dosage to Reduce the Toxicity of Folic Acid Antagonists or DHFR Inhibitors in Patients Following an Overdosage 5 mg to 15 mg per day.

( 2.2 ) For patients with impaired methotrexate elimination and following a methotrexate overdose, administer intravenous fluids (3 L/day) and alkalinize the urine to maintain the urine pH at 7.0 or greater. ( 2.2 ) Recommended Dosage to Treat FOLR1-CFTD Initiate oral leucovorin calcium tablets as follows based on body weight: Less than 40 kg: 1 to 2 mg/kg/day and adjust to the maximum recommended dosage of 8.5 mg/kg/day. ( 2.3 ) 40 kg or more: 1 to 2 mg/kg/day and adjust to the maximum recommended dosage of 330 mg/day.

( 2.3 ) Administer the total daily dosage once daily or in divided doses up to 6 times per day. ( 2.3 ) Single doses of 25 mg or less are preferred; do not administer more than 75 mg as a single dose. ( 2.3 )

2.1Important Administration Instructions Each indication has a different method for calculating the dosage (i.e., fixed dosage, body surface area-based dosage, or body weight-based dosage). Ensure that the correct method for calculating the dosage is used [see Dosage and Administration ( 2.2 , 2.3 )]. Leucovorin calcium tablets are for oral administration only and can be taken with or without food [see Clinical Pharmacology ( 12.3 )].

Crushing of leucovorin tablets and mixing with food or liquid (e.g., water, breastmilk, infant formula) has been reported in literature. If administering via this method, administer immediately after mixing.

2.2Recommended Dosage to Reduce the Toxicity of Methotrexate in Patients with Impaired Methotrexate Elimination or to Reduce the Toxicity of Folic Acid Antagonists or Dihydrofolate Reductase Inhibitors Following Overdose Administer leucovorin calcium tablets as soon as possible after a folic acid antagonist or DHFR inhibitor overdose and within 24 hours of methotrexate administration when there is impaired methotrexate elimination. The effectiveness of leucovorin calcium tablets decreases as the time interval between leucovorin calcium tablets administration and the folic acid antagonist or DHFR inhibitor increases.

For patients with impaired methotrexate elimination, monitor serum methotrexate concentrations and serum creatinine to determine the recommended dosage and duration of leucovorin calcium tablets. For patients with impaired methotrexate elimination and in patients following a methotrexate overdose, administer intravenous fluids (3 Liters per day) and alkalinize the urine to maintain a urine pH of 7.0 or greater. The recommended leucovorin calcium tablets dosage to reduce methotrexate toxicity in patients with impaired methotrexate elimination: 10 mg/m 2 (up to 25 mg) orally every 6 hours until the serum methotrexate levels are less than 10 -8 M (0.01 micromolar).

When a dosage greater than 25 mg every 6 hours is needed for this use, leucovorin calcium tablets are not recommended because this dosage and the formulation may be inadequate to treat significant methotrexate toxicity, resulting in possible methotrexate toxicity fatalities. Refer to the prescribing information for leucovorin injection for…

💊 Dosage Forms and Strengths 60 words ▾

3 DOSAGE FORMS AND STRENGTHS Leucovorin calcium tablets, USP: 5 mg: White, round, biconvex tablets, debossed with “stylized b” on one side and 484 on the other side 25 mg: Pale green, round, biconvex tablets, debossed with “stylized b” on one side and 485 on the other side Tablets: 5 mg of leucovorin, 25 mg of leucovorin ( 3 )

⛔ Contraindications 116 words ▾

4 CONTRAINDICATIONS Leucovorin calcium tablets are contraindicated in patients with a history of hypersensitivity reaction depending on indication as described below, to leucovorin (folinic acid), levoleucovorin, folic acid, or any component of leucovorin calcium tablets [see Description ( 11 )]: Folic acid antagonist or DHFR inhibitor toxicity: history of severe hypersensitivity reaction FOLR1-CFTD: history of any hypersensitivity reaction Reactions have included anaphylactic reactions [see Warnings and Precautions ( 5.1 )] .

History of hypersensitivity reaction, depending on indication, to leucovorin (folinic acid), levoleucovorin, folic acid, or any component of leucovorin calcium tablets: folic acid antagonist or DHFR inhibitor toxicity: history of a severe hypersensitivity reaction FOLR1-CFTD: history of any hypersensitivity reaction. ( 4 , 5.1 )

⚠️ Warnings and Cautions 114 words ▾

5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions : Withhold or permanently discontinue leucovorin calcium tablets based on severity and indication. ( 4 , 5.1 )

5.1Hypersensitivity Reactions Hypersensitivity reactions, including anaphylactic reactions and urticaria, have been reported following the administration of leucovorin. Leucovorin calcium tablets are contraindicated for the treatment of folic acid antagonist or DHFR inhibitor toxicity in patients with a history of a severe hypersensitivity reaction and for the treatment of FOLR1-CFTD in patients with a history of any hypersensitivity reaction to leucovorin, levoleucovorin, folic acid, or any component of leucovorin calcium tablets [see Contraindications ( 4 )] .

Withhold or permanently discontinue leucovorin calcium tablets based on the severity of hypersensitivity.

🤒 Adverse Reactions 140 words ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )]. The following adverse reactions have been identified during postapproval use of leucovorin (d,l-leucovorin) or levoleucovorin (l-leucovorin). Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Dermatologic: Pruritus, rash. Respiratory: Dyspnea. Other Clinical Events: Rigors, temperature change.

Safety information for the treatment of FOLR1-CFTD with oral leucovorin is limited. The available evidence is based on published case reports [see Clinical Studies ( 14.1 )] . Adverse reactions included pruritus, rash, urticaria, dyspnea, hypersensitivity reactions, rigors, and temperature change.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS Certain Antiepileptic Drugs : Increase monitoring for seizure activity in leucovorin-treated patients taking certain concomitant antiepileptic drugs. Certain antiepileptic drugs may reduce the effectiveness of leucovorin calcium tablets. ( 7.1 , 7.2 ) Trimethoprim-Sulfamethoxazole : Avoid concomitant use of leucovorin calcium tablets with trimethoprim-sulfamethoxazole.

( 7.1 ) Fluorouracil : Leucovorin may enhance the toxicity of fluorouracil. Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients. ( 7.1 )

7.1Effects of Leucovorin on Other Drugs Certain Antiepileptic Drugs Increase monitoring for seizure activity in leucovorin-treated patients taking certain concomitant antiepileptic drugs. Folic acid in high doses may reduce the effectiveness of certain antiepileptic drugs (e.g., phenobarbital, phenytoin, and primidone) and thereby increase the frequency of seizures in susceptible patients, including pediatric patients. It is not known whether folinic acid, including leucovorin calcium tablets, has the same effects; however, both folic and folinic acids, including leucovorin calcium tablets, share some common metabolic pathways.

Trimethoprim-Sulfamethoxazole Avoid concomitant use of leucovorin calcium tablets with trimethoprim-sulfamethoxazole. The effectiveness of trimethoprim-sulfamethoxazole can be decreased if used concomitantly with leucovorin calcium tablets, which was associated with increased rates of treatment failure and mortality in patients with HIV infection who receive trimethoprim-sulfamethoxazole for the acute treatment of Pneumocystis jirovecii pneumonia. Fluorouracil Leucovorin may enhance the toxicity of fluorouracil.

Deaths from severe enterocolitis, diarrhea, and dehydration have been reported in elderly patients receiving weekly leucovorin and fluorouracil. Concomitant granulocytopenia and fever were present in some but not all of the patients.

7.2Effect of Other Drugs on Leucovorin Certain antiepileptic drugs may reduce folate absorption and metabolism leading to folate deficiency. As folic acid and folinic acid share common metabolic pathways, certain antiepileptic drugs may reduce the effectiveness of leucovorin calcium tablets.

👥 Use in Specific Populations ~2 min read ▾

8 USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary Available data on the intermittent use of leucovorin for the treatment of folic acid antagonist or DHFR inhibitor toxicity during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are no adequate data on the use of leucovorin for the treatment of FOLR1-CFTD in pregnant women. Adequate animal reproductive and developmental studies have not been conducted with leucovorin.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Risks with Concomitant Use of Leucovorin calcium tablets and Chemotherapy Drugs administered in combination with leucovorin calcium tablets may cause fetal harm. Refer to the Prescribing Information for the chemotherapy administered in combination with leucovorin calcium tablets for additional information, as appropriate.

8.2Lactation Risk Summary There are no data on the presence of leucovorin in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for leucovorin calcium tablets and any potential adverse effects on the breastfed infant from leucovorin or from the underlying maternal condition. Refer to the Prescribing Information for chemotherapy administered in combination with leucovorin calcium tablets for breastfeeding recommendations, as appropriate.

8.4Pediatric Use Leucovorin calcium tablets are indicated for the treatment of cerebral folate transport deficiency in pediatric patients who have a confirmed variant in the folate receptor 1 gene (FOLR1-CFTD) [see Clinical Studies ( 14.1 )] . The safety and effectiveness of leucovorin calcium tablets have not been established to reduce the toxicity of methotrexate in pediatric patients with impaired methotrexate elimination or in pediatric patients to reduce the toxicity of folic acid antagonists or dihydrofolate reductase (DHFR) inhibitors following an overdose.

Folic acid in large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin, and primidone, and increase the frequency of seizures in susceptible pediatric patients [see Drug Interactions ( 7.1 )] .

8.5Geriatric Use There is insufficient information in patients 65 years of age and older on the use of leucovorin calcium tablets to reduce the toxicity of methotrexate, other folic acid antagonists, or DHFR inhibitors, and there is no information on the use of leucovorin calcium tablets to treat FOLR1-CFTD in patients 65 years of age and older to determine whether they respond differently from younger patients [see Clinical Studies ( 14.1 )] .

🤰 Pregnancy 142 words ▾

8.1Pregnancy Risk Summary Available data on the intermittent use of leucovorin for the treatment of folic acid antagonist or DHFR inhibitor toxicity during pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are no adequate data on the use of leucovorin for the treatment of FOLR1-CFTD in pregnant women. Adequate animal reproductive and developmental studies have not been conducted with leucovorin.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Risks with Concomitant Use of Leucovorin calcium tablets and Chemotherapy Drugs administered in combination with leucovorin calcium tablets may cause fetal harm. Refer to the Prescribing Information for the chemotherapy administered in combination with leucovorin calcium tablets for additional information, as appropriate.

🧒 Pediatric Use 115 words ▾

8.4Pediatric Use Leucovorin calcium tablets are indicated for the treatment of cerebral folate transport deficiency in pediatric patients who have a confirmed variant in the folate receptor 1 gene (FOLR1-CFTD) [see Clinical Studies ( 14.1 )] . The safety and effectiveness of leucovorin calcium tablets have not been established to reduce the toxicity of methotrexate in pediatric patients with impaired methotrexate elimination or in pediatric patients to reduce the toxicity of folic acid antagonists or dihydrofolate reductase (DHFR) inhibitors following an overdose.

Folic acid in large amounts may counteract the antiepileptic effect of phenobarbital, phenytoin, and primidone, and increase the frequency of seizures in susceptible pediatric patients [see Drug Interactions ( 7.1 )] .

🧓 Geriatric Use 74 words ▾

8.5Geriatric Use There is insufficient information in patients 65 years of age and older on the use of leucovorin calcium tablets to reduce the toxicity of methotrexate, other folic acid antagonists, or DHFR inhibitors, and there is no information on the use of leucovorin calcium tablets to treat FOLR1-CFTD in patients 65 years of age and older to determine whether they respond differently from younger patients [see Clinical Studies ( 14.1 )] .

🆘 Overdosage 17 words ▾

10 OVERDOSAGE Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for overdose management recommendations.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Levoleucovorin, a reduced folate and the pharmacologically active isomer of leucovorin (5-formyl- tetrahydrofolic acid), can mitigate the toxic effects of folate antagonists, including methotrexate and other agents that inhibit dihydrofolate reductase (DHFR). Inhibition of DHFR blocks the formation of tetrahydrofolate, an essential cofactor for DNA synthesis and repair. Levoleucovorin has been observed to increase levels of 5-MTHF, an active metabolite of folate, in case studies of FOLR1-CFTD [see Clinical Studies ( 14.1 )] .

12.2Pharmacodynamics Levoleucovorin and its metabolites (5,10-methenyltetrahydrofolate, 5,10-methylenetetrahydrofolate, and 5-MTHF) serve as cofactors in “one carbon” metabolism. These reactions are involved in the generation of nucleic acids and the regulation of gene expression.

12.3Pharmacokinetics Leucovorin is a racemic mixture of (l)- or levoleucovorin and (d)- or dextroleucovorin. Following oral administration of leucovorin to healthy adults, dextroleucovorin, levoleucovorin, and 5-MTHF exposures increased in a dose proportional manner with doses up to 25 mg, but in a less than dose proportional manner with doses greater than 25 mg. Absorption Following oral administration of leucovorin in adults, the apparent bioavailability of levoleucovorin is 97% for 25 mg, 75% for 50 mg, and 37% for 100 mg, and dextroleucovorin is approximately 19% for 25 mg, 20% for 50 mg, and 7% for 100 mg.

After a single oral 15 mg (7.5 mg/m 2 ) dose of leucovorin, time to peak serum folate concentration is 1.7 hours. Effect of Food: The effect of food on the pharmacokinetics of leucovorin has not been evaluated. As leucovorin is a highly soluble and well absorbed drug, and different immediate-release oral formulations of leucovorin (oral tablet and oral solution) showed relatively higher bioavailability of total folates (>95%), food is not expected to have a clinically significant effect on the pharmacokinetics of leucovorin or 5-MTHF.

Crushing of leucovorin tablets and mixing with food or liquid has been reported in literature. Distribution Levoleucovorin is minimally bound to human serum albumin. The reported human serum albumin binding of 5-MTHF ranges from 42-49%.

Leucovorin is not observed in cerebrospinal fluid (CSF) and 5-MTHF is reported to accumulate in CSF in children with leukemia. Elimination After intravenous administration of leucovorin in adults, the reported mean plasma elimination half-life in the literature was 0.5-1.3 hours for levoleucovorin and 3-7 hours for 5-MTHF. Metabolism: Following administration of oral leucovorin, levoleucovorin undergoes metabolism in intestinal cells via methenyltetrahydrofolate synthetase (MTHFS) and methylenetetrahydrofolate reductase (MTHFR) to its active metabolite, 5-MTHF.

5-MTHF is the main active metabolite in plasma after oral administration of leucovorin. Excretion: Leucovorin is mainly excreted by the kidney as unchanged dextroleucovorin, levoleucovorin, or as 5-MTHF, the metabolic product of levoleucovorin. Specific Populations Patients with Renal Impairment: The kidney is reported to contribute to the elimination of dextroleucovorin, levoleucovorin and its active metabolite, and plasma concentrations of dextroleucovorin, levoleucovorin, and 5-MTHF may be increased in patients with renal impairment.

However, clinical studies on the impact of renal impairment have not been conducted. Patients with Hepatic Impairment: The liver is reported to contribute to the metabolism of levoleucovorin, and plasma concentrations of levoleucovorin and 5-MTHF may be increased in patients with hepatic impairment. However, clinical studies on the impact of hepatic impairment have not been conducted.

🧬 Mechanism of Action 78 words ▾

12.1Mechanism of Action Levoleucovorin, a reduced folate and the pharmacologically active isomer of leucovorin (5-formyl- tetrahydrofolic acid), can mitigate the toxic effects of folate antagonists, including methotrexate and other agents that inhibit dihydrofolate reductase (DHFR). Inhibition of DHFR blocks the formation of tetrahydrofolate, an essential cofactor for DNA synthesis and repair. Levoleucovorin has been observed to increase levels of 5-MTHF, an active metabolite of folate, in case studies of FOLR1-CFTD [see Clinical Studies ( 14.1 )] .

📦 How Supplied / Storage and Handling 122 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Leucovorin calcium tablets, USP contain: 5 mg: White, round, biconvex tablets, debossed with “stylized b” on one side and 484 on the other side, packaged in bottles of 30 (NDC 0555-0484-01) and 100 (NDC 0555-0484-02) tablets. 25 mg: Pale green, round, biconvex tablets, debossed with “stylized b” on one side and 485 on the other side, packaged in bottles of 25 (NDC 0555-0485-27) tablets.

16.2Storage and Handling Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP, with a child-resistant closure (as required). Protect from light and moisture. Keep this and all medications out of the reach of children.

📋 Description 172 words ▾

11 DESCRIPTION Leucovorin is a racemic mixture of the 5-formyl derivative of tetrahydrofolic acid. The biologically active compound of the mixture is the (-)- L -Levoisomer, known as Citrovorum factor , or (-)-folinic acid or levoleucovorin. Leucovorin is a water soluble form of reduced folate in the folate group.

The chemical name of leucovorin, a folate analog, is the calcium salt of N -[4-[[(2-amino-5-formyl-1,4,5,6,7,8- hexahydro-4-oxo-6-pteridinyl)methyl] amino]benzoyl]- L -glutamic acid. The structural formula of leucovorin calcium is: C 20 H 21 CaN 7 O 7 M.W. 511.5 g/mol Leucovorin calcium tablets, USP are for oral administration.

Each 5 mg tablet contains 5 mg of leucovorin (equivalent to 5.4 mg of leucovorin calcium, USP), and each 25 mg tablet contains 25 mg of leucovorin (equivalent to 27.01 mg of leucovorin calcium, USP). The 5 mg and 25 mg tablets contain the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, and microcrystalline cellulose. Additionally, the 25 mg tablet contains D&C yellow no.10 aluminum lake and FD&C blue no.1 aluminum lake.

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💬 Information for Patients 143 words ▾

17 PATIENT COUNSELING INFORMATION Administration Instructions Advise patients or caregivers that leucovorin tablets may be dissolved in an age-appropriate liquid (e.g., water, breastmilk, or infant formula) or crushed and mixed with soft food before administration. If leucovorin is to be administered in this manner, instruct patients or caregivers to administer the dissolved or mixed product immediately after mixing [see Dosage and Administration ( 2.1 )] . Hypersensitivity Reactions Advise patients to inform their healthcare provider if they develop a hypersensitivity reaction while taking leucovorin calcium tablets [see Warnings and Precautions ( 5.1 )] .

Drug Interactions Advise patients to inform their healthcare providers of all concomitant drugs, including prescription drugs, nonprescription drugs, vitamins, and herbal products [see Drug Interactions ( 7 )] . Manufactured In Bulgaria By: Balkanpharma Dupnitsa AD Dupnitsa 2600, Bulgaria Manufactured For: Teva Pharmaceuticals Parsippany, NJ 07054 Rev. D 3/2026

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
← 00555-0484-01 · Teva 00555-0572-02 · Teva →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.