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Leucovorin Calcium 5 mg Tablet, 100-count — NDC 00555-0484-02 package photo

Leucovorin Calcium 5 mg Tablet, 100-count

by Teva Pharmaceuticals USA, Inc. · 100 TABLET in 1 BOTTLE (0555-0484-02)
NDC 00555-0484-02
🏷️ FDA NDC (as labeled) 0555-0484-02 billing pads the labeler segment with a zero
This package
Contains100-count Cost per ea$0.3430 NADAC Per package$34.30 / 100 tablets Pack sizes4 compare ↓
Also priced by: Medicaid pays $0.6453/unit · Part D plans $0.7402/unit — full pricing hub ↓
Also comes in: 30 tablets 00555-0484-01 1000 tablets 00555-0484-05 50000 tablets 00555-0484-99
Rx only Generic On market Non-controlled
🗂️ Data synced Jul 24, 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) 0555-0484-02
Product NDC 0555-0484
11-digit billing NDC 00555048402
NCPDP billing unit EA — each (per item)
RxCUI 197862, 197863
UNII RPR1R4C0P4
UPC 0305550484011
Application # ANDA071198
SPL Set ID 94669fc8-3c1c-4228-be27-09a1cd468c36
Established class (EPC) Folate Analog
Chemical class Folic Acid
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 1990-06-30
Route ORAL
Dosage form TABLET
Substance LEUCOVORIN CALCIUM
GPI-14 21755040100310
GPI class Leucovorin Calcium
GCN Seq No 044539
GCN 87558
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 5 MG TAB
FDB brand name Leucovorin Calcium
Legend status F — Federal legend — prescription drug or device
TE code (Orange Book) AB · RLD · RS
Why two NDCs? The FDA registers this code as 0555-0484-02 — 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 → 00555-0484-02. 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.

🏷️ RxNorm drug class

This medicine belongs to the Folate Analog class.

Pharmacologic class Folate Analog
Drug family (ATC) Detoxifying agents for antineoplastic treatment
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerTeva Pharmaceuticals USA, Inc.
Application holderBARR PHARMACEUTICALS
FDA applicationANDA071198 (ANDA)
Labeler code00555
First marketedJun 1990
Product typeHuman Prescription Drug
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 5 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 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.

5 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 eaPer package
Retail pharmacies payNADAC · weekly $0.343 $34.30 / 100 tablets
Medicaid paysCMS SDUD · 12 mo $0.6453 $64.53 / 100 tablets
Medicare drug plans payPart D · Q2 2026 $0.7402 $74.02 / 100 tablets
NADAC price history (per ea) — tap or hover for the price & month
Dec 2021 Jul 2022 Dec 2025 Aug 2026 $0.873 $0.302
▼ Down 53% over the last 24 months.
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 5 mg 00054-4496-13 Hikma 30 tablets $0.343 AB Availability likely —
Leucovorin Calcium 5 mg 00054-8496-19 Hikma 50 tablets $0.343 AB Availability likely —
Leucovorin Calcium 5 mgthis 00555-0484-02 Teva 100 tablets $0.343 AB Availability likely —
Leucovorin Calcium 5 mg 42806-0358-01 Epic 100 tablets $0.343 AB Availability likely —
Leucovorin Calcium 5 mg 50742-0181-01 Ingenus 100 tablets $0.343 AB Availability likely —
Leucovorin Calcium 5 mg 69315-0184-01 Leading 100 tablets $0.343 AB Availability likely —
Lederle Leucovorin 5 mg 00069-5886-24 Pfizer 24 tablets — — FDA listed —
Leucovorin Calcium 5 mg 71205-0908-00 Proficient 100 tablets — AB FDA listed —
Lederle Leucovorin 5 mg 73591-5886-01 FARMASIERRA 100 tablets — — FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
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

🏛️
1990
On the market since
Jun 1990
📍
2026
Currently FDA-listed
36 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

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 & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for 00555-0484-02, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q4 2025 · 4 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
2.1K
Units reimbursed last 4 qtrs
110K
Gross reimbursed last 4 qtrs
$71K
Avg / prescription
$34.23
Avg / unit
$0.6452
Latest quarter Q4 2025
1.1KRx
Medicaid pays / ea
$0.6452
gross reimbursed
vs
NADAC / ea
$0.3430
acquisition cost
=
Spread
+$0.3022
+88% vs cost
What Medicaid paid per ea (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
60% FFS 40% MCO
Fee-for-service · 1,251 Rx Managed care · 823 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: 7,008 units · 89.7 per 100k residents WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: 869 units · 15.1 per 100k residents MN Wisconsin: 6,232 units · 105 per 100k residents WI Michigan: no data reported MI New York: 4,900 units · 25.0 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: 1,532 units · 36.2 per 100k residents OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: 1,773 units · 14.1 per 100k residents IL Indiana: no data reported IN Ohio: 1,955 units · 16.6 per 100k residents OH Pennsylvania: 1,314 units · 10.1 per 100k residents PA New Jersey: 588 units · 6.3 per 100k residents NJ Massachusetts: no data reported MA California: 43,704 units · 112 per 100k residents CA Utah: no data reported UT Colorado: 2,081 units · 35.4 per 100k residents CO Nebraska: no data reported NE Missouri: 1,147 units · 18.5 per 100k residents MO Kentucky: 2,252 units · 49.8 per 100k residents KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: 639 units · 8.6 per 100k residents AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: 1,230 units · 40.1 per 100k residents AR Tennessee: 1,213 units · 17.0 per 100k residents TN North Carolina: 3,091 units · 28.5 per 100k residents NC South Carolina: 1,884 units · 35.1 per 100k residents SC Delaware: no data reported DE Oklahoma: 658 units · 16.2 per 100k residents OK Louisiana: 690 units · 15.1 per 100k residents LA Mississippi: no data reported MS Alabama: 1,260 units · 24.7 per 100k residents AL Georgia: 1,434 units · 13.0 per 100k residents GA D.C.: no data reported DC Hawaii: 15,000 units · 1,045 per 100k residents HI Texas: 4,813 units · 15.8 per 100k residents TX Florida: 2,742 units · 12.1 per 100k residents FL
Units reimbursed · per 100k residents
6.31,045
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Hawaii 1,045 /100k
2 California 112 /100k
3 Wisconsin 105 /100k
4 Washington 89.7 /100k
5 Kentucky 49.8 /100k
6 Arkansas 40.1 /100k
7 Oregon 36.2 /100k
8 Colorado 35.4 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

💊 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.
100 tablets this page00555-0484-02 2,074 Rx · $70,983
30 tablets00555-0484-01 1,337 Rx · $40,917
1000 tablets00555-0484-05 No Medicaid data
50000 tablets00555-0484-99 No Medicaid data
Drug total (last 4 qtrs): 3,411 Rx · 172,213 units · $111,901 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 — 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
00555-0484-01 30 TABLET in 1 BOTTLE (0555-0484-01) $0.3430 / ea $10.29 1990-06-30 Active
00555-0484-02 You're viewing this 100 TABLET in 1 BOTTLE (0555-0484-02) $0.3430 / ea $34.30 1990-06-30 Active
00555-0484-05 1000 TABLET in 1 BOTTLE (0555-0484-05) — — 1990-06-30 Active
00555-0484-99 50000 TABLET in 1 CONTAINER (0555-0484-99) — — — Active

You're viewing one of 4 pack sizes for this product.

This pack effectively ties for the lowest per-ea cost of the 2 priced pack sizes ($0.3430 NADAC).

In Medicaid, this is the most-dispensed pack of this product — about 61% of fills over the last four reported quarters. See all packs ↓

Pack size FAQ

What quantity is in NDC 00555-0484-02?
NDC 00555-0484-02 is a 100-count package — 100 tablet in 1 bottle.
What is the difference between NDC 00555-0484-02 and NDC 00555-0484-01?
Both are Leucovorin Calcium 5 mg Tablet — the drug itself is identical. NDC 00555-0484-02 is the 100-count package, while NDC 00555-0484-01 is the 30 tablets package.
What NDC number is used to bill for this package of Leucovorin Calcium 5 mg Tablet?
Bill NDC 00555-0484-02 — the 11-digit billing format is 00555048402. 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.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, 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 ↗
← 00555-0483-02 · Teva 00555-0485-04 · 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.