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Methotrexate 2.5 mg Tablet, 100-count — NDC 42291-594-01 (Billing 42291-0594-01)

by AvKARE · 100 TABLET in 1 BOTTLE

This is a package of 100 tablets of Methotrexate 2.5 mg Tablet from AvKARE, marketed since Nov 2014 and currently FDA-listed. It is this product's only package size.

NDC 42291-0594-01
🏷️ FDA NDC (as labeled) 42291-594-01 billing pads the product segment with a zero
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Aug 13, 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

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 42291-594-01
Product NDC 42291-594
11-digit billing NDC 42291059401
NCPDP billing unit EA — each (per item)
RxCUI 105585
UNII 3IG1E710ZN
UPC 0342291594012
Application # ANDA081099
SPL Set ID 757d6cef-6696-7a1c-8074-01258aaa8bdd
Established class (EPC) Folate Analog Metabolic Inhibitor
Mechanism of action Folic Acid Metabolism Inhibitors
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2014-11-20
Route ORAL
Dosage form TABLET
Substance METHOTREXATE SODIUM
TE code (Orange Book) AB · RLD · RS

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GCN Seq No 036872
GCN 38489
HICL code 003905
Ingredient (HICL) Methotrexate Sodium
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1B
Therapeutic class — specific (HIC3) Antineoplastic - Antimetabolites
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name METHOTREXATE 2.5 MG TABLET
FDB brand name Methotrexate
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 036872
  • GCN: 38489
  • HICL (First Databank): 003905
  • AHFS class code: 10:00.00.00
  • RxCUI (RxNorm): 105585
Why two NDCs? The FDA registers this code as 42291-594-01 — a 5-3-2 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 product segment → 42291-0594-01. 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 Metabolic Inhibitor class.

Pharmacologic class Folate Analog Metabolic Inhibitor
Drug family (ATC) Folic acid analogues, Other immunosuppressants
How it works Folic Acid Metabolism Inhibitors
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.

Clinical

Label name METHOTREXATE 2.5 MG TABLET Ingredient Methotrexate Sodium
📗 Our plain-language guide HelloPharmacist
  • It treats certain cancers, rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and severe psoriasis. Which use applies depends on the product you were given. Otrexup...
  • For many uses, such as arthritis and psoriasis, it is taken once a week, not daily. Taking it daily by mistake has caused deaths. Follow your prescriber's schedule exactly, and ask...
  • Nausea, stomach upset, mouth sores, tiredness, dizziness, rash and hair loss are common. Call your doctor about a dry cough, bad diarrhea, fever, severe skin reactions or unusual b...
  • NSAIDs and aspirin can raise methotrexate levels and increase toxicity, so check with your prescriber or pharmacist first. This matters most at high methotrexate doses. Also tell u...
📖 Read our full Methotrexate guide →
1
Nutrient depletion considerations

Methotrexate may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.

🧪 Full Methotrexate nutrient depletion report →
An association is not a deficiency. Educational only — don't start or stop anything without professional guidance.
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.

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.
Medicare Part B allowsASP · NONE No ASP payment limit on file for NONE this quarter.
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.
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.

Billing & reimbursement

FDA NDC (as labeled)42291-594-01
11-digit billing NDC42291-0594-01
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeNONE
DescriptorMETHOTREXATE, 2.5 MG, ORAL
Billing units / pkg1 units
How the units are derivedThis package is 100 EA; the HCPCS unit is 2.5 MG, so one package = 1 billing unit.
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
42291-0594-01 You're viewing this Main listing 100 TABLET in 1 BOTTLE 2014-11-20 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Methotrexate 2.5 mg 00555-0572-02 Teva 100 tablets $0.158 AB Availability likely —
Methotrexate 2.5 mg 16729-0486-01 Accord 100 tablets $0.158 AB Availability likely —
Methotrexate 2.5 mg 62135-0772-35 Chartwell 36 tablets $0.158 AB Availability likely —
Methotrexate 2.5 mg 59651-0182-01 Aurobindo 100 tablets $0.158 AB Availability likely —
Methotrexate 2.5 mg 62332-0730-31 Alembic 100 tablets $0.158 AB Availability likely —
Methotrexate 2.5 mg 51079-0670-05 Mylan 20 tablets $0.158 AB Availability likely —
Methotrexate 2.5 mg 00378-0014-01 Mylan 100 tablets $0.158 AB Availability likely —
Methotrexate 2.5 mg 82804-0136-30 Proficient 30 tablets — AB FDA listed —
Methotrexate 2.5 mg 50090-5457-02 A-S 100 tablets — AB Discontinued —
Methotrexate 2.5 mg 68071-3991-09 NuCare 90 tablets — AB FDA listed —
Methotrexate 2.5 mg 71335-2221-01 Bryant 30 tablets — AB FDA listed —
Methotrexate 2.5 mg 46708-0730-31 Alembic 100 tablets — AB FDA listed —
Methotrexate 2.5 mg 51407-0121-01 Golden 100 tablets — AB FDA listed —
Methotrexate 2.5 mg 71335-0782-01 Bryant 30 tablets — AB FDA listed —
Methotrexate 2.5 mg 71335-1118-01 Bryant 30 tablets — AB FDA listed —
Methotrexate 2.5 mg 68071-3765-06 NuCare 60 tablets — AB FDA listed —
Methotrexate 2.5 mg 71335-1772-01 Bryant 30 tablets — AB FDA listed —
Methotrexate 2.5 mg 48433-0065-05 Safecor 20 tablets — AB FDA listed —
Methotrexate 2.5 mg 67046-1524-03 Coupler 30 tablets — AB FDA listed —
Methotrexate 2.5 mg 72162-2647-01 Bryant 100 tablets — AB FDA listed —
Methotrexate 2.5 mgthis 42291-0594-01 AvKARE 100 tablets — AB 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

🏛️
2014
On the market since
Nov 2014
📍
2026
Currently FDA-listed
12 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.

What it looks like

Color yellow
ShapeOval
Imprintb;572
Size8 mm
ScoringScored — splits in 2
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 3SY5LH9PMK
    Anhydrous lactose is a milk sugar with no water content. It acts as a filler and binder in tablets and capsules, adding bulk and helping ingredients stick together.
  • 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 3NXW29V3WO
    Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
  • 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 3WJQ0SDW1A
    Polyethylene glycol is a synthetic liquid or solid polymer used in medicines as a solvent, lubricant, and humectant. It helps dissolve active ingredients, reduces friction during manufacturing, and retains moisture in the final product.
  • UNII 6DC9Q167V3
    Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
  • UNII 2A1Q1Q3557
    Sodium carbonate monohydrate is an inorganic salt containing sodium, carbon, and water. It acts as a pH buffer and alkalizing agent in medicines, helping maintain the proper acid-base balance needed for product stability and function.
  • UNII O8232NY3SJ
    A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
  • UNII 7SEV7J4R1U
    A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.

9 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.

Manufacturer & labeler

LabelerAvKARE
Application holderBARR LABORATORIES INC
FDA applicationANDA081099 (ANDA)
Labeler code42291
First marketedNov 2014
Product typeHuman Prescription Drug
Portfolio384 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.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🆘 Overdosage 🧬 Clinical Pharmacology 📦 How Supplied / Storage and Handling 📋 Description 🧪 Nonclinical Toxicology 📚 References 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~1 min read ▾

WARNING: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, SEVERE ADVERSE REACTIONS, AND RISK OF MEDICATION ERRORS • Methotrexate tablets can cause embryo-fetal toxicity, including fetal death. For non-neoplastic diseases, methotrexate tablets are contraindicated in pregnancy. For neoplastic diseases, advise females and males of reproductive potential to use effective contraception [see Contraindications (4), Warnings and Precautions (5.1), Use in Specific Populations (8.1, 8.3)]. • Methotrexate tablets are contraindicated in patients with a history of severe hypersensitivity reactions to methotrexate, including anaphylaxis [Contraindications (4), Warnings and Precautions (5.2)]. • Serious adverse reactions, including death, have been reported with methotrexate.

Closely monitor for adverse reactions of the bone marrow, gastrointestinal tract, liver, lungs, skin, and kidneys. Withhold or discontinue methotrexate tablets as appropriate [Warnings and Precautions (5.3, 5.4, 5.5, 5.6, 5.7, 5.8)]. • Methotrexate tablets when inadvertently administered once daily have resulted in death [Warnings and Precautions (5.9)]. WARNING: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, SEVERE ADVERSE REACTIONS, and RISK OF MEDICATION ERRORS See full prescribing information for complete boxed warning . • Methotrexate tablets can cause embryo-fetal toxicity, including fetal death.

For non-neoplastic diseases, methotrexate tablets are contraindicated in pregnancy. For neoplastic diseases, advise patients of reproductive potential of the potential risk to a fetus and to use effective contraception (4, 5.1, 8.1, 8.3). • Methotrexate tablets are contraindicated in patients with a history of severe hypersensitivity reactions to methotrexate, including anaphylaxis (4, 5.2). • Serious adverse reactions, including death, have been reported with methotrexate. Closely monitor for adverse reactions of the bone marrow, gastrointestinal tract, liver, lungs, skin, and kidneys.

Withhold or discontinue methotrexate tablets as appropriate (5.3, 5.4, 5.5, 5.6, 5.7, 5.8). • Methotrexate tablets when inadvertently administered once daily have resulted in death (5.9).

🎯 Indications and Usage 210 words ▾

INDICATIONS AND USAGE Methotrexate tablets are a dihydrofolate reductase inhibitor indicated for the: • Treatment of adults and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen (1.1) • Treatment of adults with mycosis fungoides (1.1) • Treatment of adults with relapsed or refractory non-Hodgkin lymphoma as part of a metronomic combination regimen (1.1) • Treatment of adults with rheumatoid arthritis (1.2) • Treatment of pediatric patients with polyarticular juvenile idiopathic arthritis (pJIA) (1.3) • Treatment of adults with severe psoriasis (1.4)

1.1 Neoplastic Diseases

1.1Neoplastic Diseases Methotrexate tablets are indicated for the: • treatment of adults and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy maintenance regimen • treatment of adults with mycosis fungoides (cutaneous T-cell lymphoma) as a single agent or as part of a combination chemotherapy regimen • treatment of adults with relapsed or refractory non-Hodgkin lymphomas as part of a metronomic combination chemotherapy regimen

1.2Rheumatoid Arthritis Methotrexate tablets are indicated for the treatment of adults with rheumatoid arthritis.

1.3Polyarticular Juvenile Idipathic Arthritis Methotrexate tablets are indicated for the treatment of pediatric patients with polyarticular Juvenile Idiopathic Arthritis (pJIA).

1.4Psoriasis Methotrexate tablets are indicated for the treatment of adults with severe psoriasis.

⏱️ Dosage and Administration ~3 min read ▾

DOSAGE AND ADMINISTRATION • Instruct patients and caregivers to take the recommended dosage as directed, because medication errors have led to deaths. (2.1, 5.9) • Verify pregnancy status in females of reproductive potential before starting methotrexate tablets (4, 5.1). • ALL: The recommended dosage is 20 mg/m2 orally once weekly as a part of a combination chemotherapy maintenance regimen. (2.2) • Mycosis fungoides: The recommended dosage is 25 to 75 mg orally once weekly as monotherapy; 10 mg/m2 orally twice weekly as part of combination chemotherapy.

(2.2) • Relapsed or refractory non-Hodgkin lymphoma: The recommended dosage is 2.5 mg orally two to four times per week as part of metronomic combination chemotherapy. (2.2) • Rheumatoid Arthritis: The recommended starting dosage is 7.5 mg orally once weekly; adjust dose to achieve an optimal response (2.3) • pJIA: The recommended starting dosage is 10 mg/m2 orally once weekly; adjust dose to achieve an optimal response (2.4) • Psoriasis: The recommended dosage is 10 to 25 mg orally once weekly until adequate response is achieved.

(2.5)

2.1Important Dosage and Safety Information Verify pregnancy status in females of reproductive potential before starting methotrexate tablets [see Contraindications (4), Warnings and Precautions (5.1)]. Instruct patients and caregivers to take the recommended dosage as directed, because medication errors have led to deaths [see Warnings and Precautions (5.9)]. When switching the dosing regimen from oral administration to intravenous, intramuscular, or subcutaneous administration, an alternative dosing regimen may be necessary.

Do not administer to patients who are unable to swallow a tablet. Methotrexate tablets are a cytotoxic drug. Follow applicable special handling and disposal procedures.1

2.2Recommended Dosage for Neoplastic Diseases Acute Lymphoblastic Leukemia The recommended starting dosage of methotrexate tablets is 20 mg/m2 orally once weekly, as part of a combination chemotherapy maintenance regimen. After initiating methotrexate tablets, periodically monitor absolute neutrophil count (ANC) and platelet count and adjust the dose to maintain ANC at a desirable level and for excessive myelosuppression. Mycosis Fungoides The recommended dosage of methotrexate tablets is 25 to 75 mg orally once weekly when administered as a single agent or 10 mg/m2 orally twice weekly as part of a combination chemotherapy regimen.

Relapsed or Refractory Non-Hodgkin Lymphomas The recommended dosage of methotrexate tablets is 2.5 mg orally 2 to 4 times per week (maximum 10 mg per week) as part of a metronomic combination chemotherapy regimen.

2.3Recommended Dosage for Rheumatoid Arthritis The recommended starting dosage of methotrexate tablets is 7.5 mg orally once weekly with escalation to achieve optimal response. Dosages of more than 20 mg once weekly result in an increased risk of serious adverse reactions, including myelosuppression. When responses are observed, the majority occurred between 3 and 6 weeks from initiation of treatment; however, responses have occurred up to 12 weeks after treatment initiation.

Administer folic acid or folinic acid to reduce the risk of methotrexate adverse reactions [see Warnings and Precautions (5.10)].

2.4Recommended Dosage for Polyarticular Juvenile Idiopathic Arthritis The recommended starting dosage of methotrexate tablets is 10 mg/m2 orally once weekly with escalation to achieve optimal response. Dosages of more than 30 mg/m2 once weekly result in an increased risk of serious adverse reactions, including myelosuppression. When responses are observed, the majority occurred between 3 and 6 weeks from initiation of treatment; however, responses have occurred up to 12 weeks after treatment initiation.

Administer folic acid or folinic acid to reduce the risk of methotrexate adverse reactions [see Warnings and Precautions (5.10)].

2.5Recommended Dosage for Psoriasis The recommended dosage of methotrexate tablets is… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 22 words ▾

DOSAGE FORMS AND STRENGTHS Tablets: Yellow, oval-shaped, film-coated, scored, biconvex tablet. Debossed with b/572 on the scored side. Tablets: 2.5 mg (3)

⛔ Contraindications 63 words ▾

CONTRAINDICATIONS Methotrexate tablets are contraindicated in: •Pre gnant women receiving methotrexate tablets for treatment of non-neoplastic diseases [see Warnings and Precautions (5.1), and Use in Specific Populations (8.1, 8.3)]. • Patients with a history of a severe hypersensitivity reactions, including anaphylaxis, to methotrexate [see Warnings and Precautions (5.2)]. • In pregnancy for non-neoplastic diseases (4) • History of severe hypersensitivity to methotrexate (4)

🤒 Adverse Reactions ~2 min read ▾

ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Hypersensitivity Reactions [see Warnings and Precautions (5.2)] • Myelosuppression [see Warnings and Precautions (5.3)] • Gastrointestinal Toxicity [see Warnings and Precautions (5.4)] • Hepatotoxicity [see Warnings and Precautions (5.5)] • Pulmonary Toxicity [see Warnings and Precautions (5.6)] • Dermatologic Reactions [see Warnings and Precautions (5.7)] • Renal Toxicity [see Warnings and Precautions (5.8)] • Serious Infections [see Warnings and Precautions (5.11)] • Neurotoxicity [see Warnings and Precautions (5.12)] • Secondary Malignancies [see Warnings and Precautions (5.13)] • Tumor Lysis Syndrome [see Warnings and Precautions (5.14)] • Increased Risk of Adverse Reactions Due to Third-Space Accumulation [see Warnings and Precautions (5.17)] Common adverse reactions include ulcerative stomatitis, leukopenia, nausea, abdominal distress.

(6.1) To report SUSPECTED ADVERSE REACTIONS, Contact AvKARE at 1-855-361-3993 or go to www.avkare.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.DRUG INTERACTIONS Refer to the full prescribing information for drug interactions with methotrexate. (7)

6.1Clinical Trials Experience Because clinical trials and other studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Common adverse reactions were: ulcerative stomatitis, leukopenia, nausea, and abdominal distress. Other clinically relevant adverse reactions were infection, malaise, fatigue, chills, fever, and dizziness.

Rheumatoid Arthritis The most common adverse reactions of methotrexate that exceeded the rate of placebo in 12- to 18-week double-blind studies in patients (n=128) with rheumatoid arthritis are listed below. Patients received methotrexate 7.5 to 15 mg orally once weekly. Most patients received concomitant nonsteroidal anti-inflammatory drugs (NSAIDs) and some also received corticosteroids.

Hepatic histology was not examined in these short-term studies. Incidence ≥10%: Elevated liver tests 15%, nausea/vomiting 10% Incidence 3% to <10%: Stomatitis, thrombocytopenia (platelet count < 100,000/mm3) Incidence 1% to <3%: Rash/pruritus/dermatitis, diarrhea, alopecia, leukopenia (white blood cell count < 3000/mm3), pancytopenia, dizziness Two other controlled trials of patients (n=680) with rheumatoid arthritis who received methotrexate 7.5 mg to 15 mg orally once weekly showed the following serious adverse reaction: Incidence 1%: Interstitial pneumonitis Other less common adverse reactions were: anemia, headache, upper respiratory infection, anorexia, arthralgias, chest pain, coughing, dysuria, eye discomfort, epistaxis, fever, infection, sweating, tinnitus, vaginal discharge.

Polyarticular Juvenile Idiopathic Arthritis (pJIA) The most common adverse reactions reported in patients 2 to 18 years of age with pJIA treated with methotrexate 5 mg/m2 to 20 mg/m2 orally once weekly or 0.1 to 0.65 mg/kg orally once weekly were as follows: elevated liver tests 14%; gastrointestinal reactions (e.g., nausea, vomiting, diarrhea) 11%; stomatitis 2%; leukopenia 2%; headache 1.2%; alopecia 0.5%; dizziness 0.2%; rash 0.2%. Most patients received concomitant NSAIDs and some also received corticosteroids. Psoriasis In two published series of adults with psoriasis (n=204, 248) who received methotrexate up to 25 mg per week for up to 4 years, adverse reaction rates were similar to those in patients with rheumatoid arthritis, except for alopecia, photosensitivity, and “burning of skin lesions” (3% to 10% each).

Painful plaque erosions have been reported.

6.2Postmarketing Experience The following adverse reactions have been identified during postapproval use of methotrexate. Because these reactions are reported voluntarily from a population of… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~1 min read ▾

DRUG INTERACTIONS DRUG INTERACTIONS

7.1Effects of Other Drugs on Methotrexate Drugs that Increase Methotrexate Exposure Coadministration of methotrexate with the following products may increase methotrexate plasma concentrations, which may increase the risk of methotrexate severe adverse reactions. In some cases, the coadministration of methotrexate with these products may also subsequently reduce active metabolite formation, which may decrease the clinical effectiveness of methotrexate. Increased organ specific adverse reactions may also occur when methotrexate is coadministered with hepatotoxic or nephrotoxic products.

If coadministration cannot be avoided, monitor closely for methotrexate adverse reactions when coadministered with: • Oral antibiotics (including neomycin) • Oral or intravenous penicillin or sulfonamide antibiotics • Highly protein-bound drugs (e.g., oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas, and tetracyclines) • Probenecid • Antifolate drugs (e.g., dapsone, pemetrexed, pyrimethamine and sulfonamides) • Aspirin and other nonsteroidal anti-inflammatory drugs • Hepatotoxic products • Proton pump inhibitors • Weak acids (e.g., salicylates) • Nephrotoxic products Nitrous Oxide Coadministration of methotrexate with nitrous oxide anesthesia potentiates the effect of methotrexate on folate-dependent metabolic pathways, which may increase the risk of severe methotrexate adverse reactions.

Avoid nitrous oxide anesthesia in patients receiving methotrexate. Consider alternative therapies in patients who have received prior nitrous oxide anesthesia. Folic Acid Coadministration of methotrexate with folic acid or its derivatives decreases the clinical effectiveness of methotrexate in patients with neoplastic diseases.

Methotrexate competes with reduced folates for active transport across cell membranes. Instruct patients to take folic or folinic acid only as directed by their healthcare provider [see Warnings and Precautions (5.10)].

👥 Use in Specific Populations ~3 min read ▾

USE IN SPECIFIC POPULATIONS USE IN SPECIFIC POPULATIONS

8.1Pregnancy Risk Summary Methotrexate tablets are contraindicated in pregnant women with non-neoplastic diseases [see Contraindications (4)]. Based on published reports and its mechanism of action [see Clinical Pharmacology (12.1)], methotrexate can cause embryo-fetal toxicity and fetal death when administered to a pregnant woman. There are no animal data that meet current standards for nonclinical developmental toxicity studies.

Advise pregnant women with neoplastic diseases of the potential risk to a fetus. 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. Data Human Data Published data from case reports, literature reviews, and observational studies report that methotrexate exposure during pregnancy is associated with an increased risk of embryo-fetal toxicity and fetal death.

Methotrexate exposure during the first trimester of pregnancy is associated with an increased incidence of spontaneous abortions and multiple adverse developmental outcomes, including skull anomalies, facial dysmorphism, central nervous system abnormalities, limb abnormalities, and sometimes cardiac anomalies and intellectual impairment. Adverse outcomes associated with exposure during second and third trimesters of pregnancy include intrauterine growth restriction and functional abnormalities. Because methotrexate is widely distributed and persists in the body for a prolonged period, there is a potential risk to the fetus from preconception methotrexate exposure.

A prospective multicenter study evaluated pregnancy outcomes in women taking methotrexate less than or equal to 30 mg/week after conception. The rate of spontaneous abortion and miscarriage in pregnant women exposed to methotrexate was 42% (95% confidence interval [95% CI] 29, 59), which was higher than in unexposed patients with autoimmune disease (22%; 95% CI: 17, 30) and unexposed patients with nonautoimmune disease (17%; 95% CI: 13, 23). Of the live births, the rate of major birth defects in pregnant women exposed to methotrexate after conception was higher than in unexposed patients with autoimmune disease (adjusted odds ratio (OR) 1.8 [95% CI: 0.6, 6]) and unexposed patients with non-autoimmune disease (adjusted OR 3.1 [95% CI: 1, 10]) (2.9%).

Major birth defects associated with pregnancies exposed to methotrexate after conception were not always consistent with methotrexate-associated adverse developmental outcomes.

8.2Lactation Risk Summary Limited published literature report the presence of methotrexate in human milk in low amounts, with the highest breast milk to plasma concentration ratio reported to be 0.08:1. There are no data on the effects of methotrexate or its metabolites on the breastfed child or their effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, instruct women not to breastfeed during treatment with methotrexate tablets and for 1 week after the final dose.

8.3Females and Males of Reproductive Potential Methotrexate can cause malformations and fetal death at doses less than or equal to the recommended clinical doses [Use in Specific Populations (8.1)]. Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating methotrexate tablets [see Contraindications (4), Use in Specific Populations (8.1)]. Contraception Females Advise females of reproductive potential to use effective contraception during treatment with methotrexate tablets and for 6 months after the final dose.

Males Methotrexate can cause chromosomal damage to sperm cells. Advise males with female partners of reproductive potential to use effective contraception during treatment with methotrexate tablets and for 3 months after the final dose. Infertility Females Based on published reports of female infertility after methotrexate,… [Excerpted — this section continues on DailyMed.]

🆘 Overdosage 187 words ▾

OVERDOSAGE Overdosage, including fatal overdosage, has occurred with methotrexate [see Warnings and Precautions (5. 9)]. Manifestations Manifestations of methotrexate overdosage include adverse reactions reported at pharmacologic doses, particularly hematologic and gastrointestinal reactions (e.g., leukopenia, thrombocytopenia, anemia, pancytopenia, myelosuppression, mucositis, stomatitis, oral ulceration, nausea, vomiting, gastrointestinal ulceration, or gastrointestinal bleeding).

In some cases, no symptoms were reported; however, sepsis or septic shock, renal failure, and aplastic anemia were also reported. Management Leucovorin and levoleucovorin are indicated for diminishing the methotrexate adverse reactions of methotrexate overdosage. Administer leucovorin or levoleucovorin as soon as possible after methotrexate overdosage).

Monitor serum creatinine and methotrexate levels to guide leucovorin or levoleucovorin therapy. Refer to the leucovorin or levoleucovorin prescribing information for additional dosage information. Glucarpidase is indicated for the treatment of toxic plasma methotrexate concentrations (>1 micromole per liter) in patients with delayed methotrexate clearance due to impaired renal function.

Refer to the glucarpidase prescribing information for additional dosage information. Administer concomitant hydration and urinary alkalinization. Neither hemodialysis nor peritoneal dialysis has been shown to improve methotrexate elimination; however, methotrexate has been effectively cleared with acute, intermittent hemodialysis using a high-flux dialyzer.

🧬 Clinical Pharmacology ~2 min read ▾

CLINICAL PHARMACOLOGY Clinical Pharmacology

12.1Mechanism of Action Methotrexate inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by this enzyme before they can be utilized as carriers of one-carbon groups in the synthesis of purine nucleotides and thymidylate. Therefore, methotrexate interferes with DNA synthesis, repair, and cellular replication.

Actively proliferating tissues such as malignant cells, bone marrow, fetal cells, buccal and intestinal mucosa, and cells of the urinary bladder are in general more sensitive to this effect of methotrexate. The mechanism of action in rheumatoid arthritis and in psoriasis is unknown.

12.3Pharmacokinetics Absorption At doses of 30 mg/m2 or less, the mean bioavailability is approximately 60%. Peak plasma concentrations are reached within 0.75 to 6 hours following oral administration. Methotrexate may undergo enterohepatic recirculation; however, this pathway has not been fully characterized.

Effect of Food Food has been shown to delay absorption and reduce peak concentration. Distribution Methotrexate in serum is approximately 50% protein bound. Methotrexate does not penetrate the blood-cerebrospinal fluid barrier at concentrations achieved with the recommended dosages.

Elimination The elimination half-life of methotrexate is approximately 3 to 10 hours. Small amounts of methotrexate polyglutamates may remain in tissues for extended periods. The retention and prolonged drug action of these active metabolites vary among different cells, tissues, and tumors.

Nonlinear elimination due to saturation of renal tubular reabsorption has been observed in studies of patients with psoriasis receiving methotrexate doses between 7.5 mg and 30 mg. Metabolism Methotrexate is partially metabolized by intestinal flora after oral administration. Methotrexate primarily undergoes hepatic and intracellular metabolism to active polyglutamated forms which can be converted back to methotrexate by hydrolase enzymes.

Methotrexate also undergoes minor metabolism to active 7-hydroxymethotrexate. Excretion Methotrexate primarily undergoes renal excretion by glomerular filtration and active tubular secretion that is dependent upon dosage and route of administration. Biliary excretion accounts for ≤10% of the methotrexate dose.

Specific Populations The effect of hepatic impairment on the pharmacokinetics of methotrexate is unknown. Pediatric Patients In pediatric patients with leukemia, oral absorption (23% to 95%) of methotrexate is variable and dose dependent. The difference between highest and lowest peak methotrexate concentrations (Cmax 0.11 to 2.3 micromolar after a 20 mg/m2 dose) was 20-fold.

The time to peak concentration (Tmax 0.67 to 4 hours after a 15 mg/m2 dose) and fraction of dose absorbed is variable. The absorption of doses greater than 40 mg/m2 is significantly less than that of lower doses. In pediatric patients with pJIA, plasma concentrations of methotrexate are variable.

Following oral administration of methotrexate 6.4 mg/m2/week to 11.2 mg/m2/week, mean serum concentrations were 0.59 micromolar (0.03 to 1.40) at 1 hour, 0.44 micromolar (0.01 to 1) at 2 hours, and 0.29 micromolar (0.06 to 0.58) at 3 hours. In pediatric patients receiving methotrexate for acute lymphoblastic leukemia (6.3 mg/m2 to 30 mg/m2) or for JIA (3.75 mg/m2 to 26.2 mg/m2), the terminal half-life has been reported to range from 0.7 to 5.8 hours or from 0.9 to 2.3 hours, respectively. Patients with Renal impairment The elimination half-life of methotrexate is variable and increases with the severity of renal impairment.

📦 How Supplied / Storage and Handling 85 words ▾

HOW SUPPLIED Methotrexate Tablets, USP are supplied as follows: 2.5 mg: Yellow, oval-shaped, film-coated, scored, biconvex tablet. Debossed with b/572 on the scored side. Available in bottles 100 tablets (NDC 42291-594-01).

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

Methotrexate Tablets is a cytotoxic drug. Follow applicable special handling and disposal procedures.1

📋 Description 83 words ▾

DESCRIPTION Methotrexate, USP is dihydrofolate reductase inhibitor with the chemical name of L-glutamic acid, N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]. The molecular formula is C20H22N8O5 and the molecular weight is 454.45 g/mol. The structural formula is: : Methotrexate tablets, USP for oral use are available in bottles of 36 and 100 tablets.

Each tablet contains 2.5 mg methotrexate, USP equivalent to 2.74 mg methotrexate sodium. Inactive Ingredients: Anhydrous lactose, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, pregelatinized corn starch, propylene glycol, sodium carbonate monohydrate, and talc. Structural Formula

🧪 Nonclinical Toxicology 41 words ▾

NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Methotrexate has been evaluated in a number of animal studies for carcinogenic potential with inconclusive results. There is evidence that methotrexate causes chromosomal damage to animal somatic cells and human bone marrow cells.

📚 References 7 words ▾

REFERENCES 1. “OSHA Hazardous Drugs.” OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html.

📄 Package Label / Principal Display Panel 6 words ▾

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL 42291-594-01 1

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

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

Medicare Part D (outpatient prescription) spending for Methotrexate — the program that covers self-administered drugs. 15 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 Methotrexate. 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
$13.05M
Claims incl. refills
612.4K
Beneficiaries
415.6K
Spend / beneficiary
$31.40
Spend / claim
$21.31
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.

About this NDC listing & data coverage

Finished prescription product
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 — Not published for this NDC No photo available yet for this listing.
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 ✓ Available
HCPCS J-code billing crosswalk ✓ Available
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

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 form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
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 AvKARE. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
AvKARE 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.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
Does this product have a billing J-code?
Yes — this NDC cross-references HCPCS code NONE for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.
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.
← 42291-0590-84 · AvKARE 42291-0596-90 · AvKARE →
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.