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METHOTREXATE 50 mg/2mL Injection, Solution — NDC 55150-0510-01 package photo

METHOTREXATE 50 mg/2mL Injection, Solution

by Eugia US LLC · 1 VIAL, SINGLE-DOSE in 1 CARTON (55150-510-01) / 2 mL in 1 VIAL, SINGLE-DOSE
NDC 55150-0510-01
🏷️ FDA NDC (as labeled) 55150-510-01 billing pads the product segment with a zero
This package
Contains2 mL in 1 vial, single-dose Pack sizes2 compare ↓
Also priced by: Part D plans $1.41/unit — full pricing hub ↓
Also comes in: 5 vials 55150-0510-05
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) 55150-510-01
Product NDC 55150-510
11-digit billing NDC 55150051001
RxCUI 1655959, 1655960, 1655967, 1655968
UNII 3IG1E710ZN
UPC 0355150510016, 0355150510054, 0355150511013
Application # ANDA201529
SPL Set ID 63bb6fbf-dd59-4edc-af8f-d0c397ca1262
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 2024-09-11
Route INTRAMUSCULAR, INTRATHECAL, INTRAVENOUS, SUBCUTANEOUS
Dosage form INJECTION, SOLUTION
Substance METHOTREXATE SODIUM
TE code (Orange Book) AP · RLD · RS
Why two NDCs? The FDA registers this code as 55150-510-01 — 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 → 55150-0510-01. 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.

🏭 Manufacturer & labeler

LabelerEugia US LLC
Application holderEUGIA PHARMA SPECIALITIES LTD
FDA applicationANDA201529 (ANDA)
Labeler code55150
First marketedSep 2024
Product typeHuman Prescription Drug
Portfolio241 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

📖 What it is MedlinePlus · NLM

Methotrexate injection is used alone or in combination with other medications: to treat certain types of acute lymphocytic leukemia (ALL) in adults and children; to treat or prevent meningeal leukemia (cancer in the covering of the spinal cord and brain) in adults and children; to treat certain types of non-Hodgkin's lymphoma (types of cancer that begin in a type of white blood cells that normally fights infection) in adults and children; to treat osteosarcoma (cancer that forms in bones) after surgery to remove the tumor in adults and children; to treat cutaneous T-cell lymphoma (CTCL,...

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • That's a great question, and it's really important you keep that in mind. For arthritis and psoriasis, methotrexate is always dosed once weekly — not daily. The drug works in a way...
  • Why am I only taking this once a week? That seems unusual.
  • Mild nausea, some fatigue, or the occasional mouth sore are common and manageable — let your doctor know, but they usually don't require an urgent call. However, if you develop a f...
  • What side effects should I just watch and wait on, versus call the doctor about right away?
📖 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.

🧪 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 QTT17582CB
    A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
  • UNII 451W47IQ8X
    Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
  • UNII 55X04QC32I
    A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.

3 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 mLPer 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 · Q2 2026 $1.41 $2.82 / 2 ml
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
Methotrexate 25 mg/mL 16729-0277-03 Accord 1 vial $0.702 AP Availability likely —
Methotrexate 25 mg/mL 00143-9519-10 Hikma 10 vials $1.238 AP Availability likely —
Methotrexate 25 mg/mL 00703-3671-01 Teva 1 vial $1.756 AP Availability likely —
Methotrexate 50 mg/2mLthis 55150-0510-01 Eugia 1 vial — AP 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

🏛️
2024
On the market since
Sep 2024
📍
2026
Currently FDA-listed
2 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.

📊 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.

🔬 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 Methotrexate — the ingredient across all brands.

Top reported reactions

Rheumatoid Arthritis42,798
Arthralgia40,830
Pain39,716
Fatigue33,049
Nausea28,999
Joint Swelling25,026
Drug Intolerance24,402

Reporter sex

489,806 reports
Male · 29%
Female · 71%
Unknown · 0%
Reports over time (by year) — tap or hover for the count & year
2019 2021 2023 2026 46,596 9,029
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 Marketing startStatus
55150-0510-01 You're viewing this 1 VIAL, SINGLE-DOSE in 1 CARTON (55150-510-01) / 2 mL in 1 VIAL, SINGLE-DOSE 2024-09-11 Active
55150-0510-05 5 VIAL, SINGLE-DOSE in 1 CARTON (55150-510-05) / 2 mL in 1 VIAL, SINGLE-DOSE 2024-09-11 Active

Pack size FAQ

What quantity is in NDC 55150-0510-01?
NDC 55150-0510-01 is listed by the FDA — 1 vial, single-dose in 1 carton / 2 ml in 1 vial, single-dose.
What NDC number is used to bill for this package of METHOTREXATE 50 mg/2mL Injection, Solution?
Bill NDC 55150-0510-01 — the 11-digit billing format is 55150051001. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

🧭 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 ✓ 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 ✓ Available
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

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 55150-510-01, 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: 55150-0510-01, written without dashes as 55150051001. 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 55150-0510-01, the first segment (55150) is the labeler code FDA assigned to Eugia US LLC; the middle segment (0510) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (01) 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 Eugia US LLC. 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 1 other package presentation of this same product, including 5 vials (55150-0510-05). 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?
Eugia US LLC 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.
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 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.
🚨 Boxed Warning 🎯 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
🚨 Boxed Warning ~2 min read ▾

WARNING: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, BENZYL ALCOHOL TOXICITY, and OTHER SERIOUS ADVERSE REACTIONS Methotrexate Injection can cause embryo-fetal toxicity, including fetal death. For non-neoplastic diseases, Methotrexate Injection is contraindicated in pregnancy. Advise females and males of reproductive potential to use effective contraception [see Contraindications (4) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.1 , 8.3 )] .

Methotrexate Injection is contraindicated in patients with a history of severe hypersensitivity reactions to methotrexate, including anaphylaxis [see Contraindications (4) and Warnings and Precautions (5.2) ] . Formulations with benzyl alcohol can cause severe central nervous toxicity or metabolic acidosis. Use only preservative-free Methotrexate Injection for treatment of neonates or low birth weight infants and for intrathecal use.

Do not use benzyl alcohol-containing formulations for high-dose regimens unless immediate treatment is required and preservative-free formulations are not available [see Dosage and Administration (2.1) and Warnings and Precautions (5.3) ] . Other serious adverse reactions, including death, have been reported with methotrexate. Closely monitor for infections and adverse reactions of the bone marrow, kidneys, liver, nervous system, gastrointestinal tract, lungs, and skin.

Withhold or discontinue Methotrexate Injection as appropriate [see Warnings and Precautions (5.4 , 5.5 , 5.6 , 5.7 , 5.8 , 5.9 , 5.10 , 5.11 )] . WARNING: EMBRYO-FETAL TOXICITY, HYPERSENSITIVITY REACTIONS, BENZYL ALCOHOL TOXICITY, and OTHER SERIOUS ADVERSE REACTIONS See full prescribing information for complete boxed warning. Methotrexate Injection can cause embryo-fetal toxicity, including fetal death.

Use in non-neoplastic diseases is contraindicated during pregnancy. Advise females and males of reproductive potential to use effective contraception during and after treatment with Methotrexate Injection. ( 4 , 5.1 , 8.1 , 8.3 ) Methotrexate Injection is contraindicated in patients with a history of severe hypersensitivity reactions to methotrexate, including anaphylaxis.

( 4 , 5.2 ) Formulations with benzyl alcohol can cause severe central nervous toxicity or metabolic acidosis. Use only preservative-free Methotrexate Injection for treatment of neonates or low birth weight infants, and for intrathecal use. Do not use benzyl alcohol-containing formulations for high-dose regimens unless immediate treatment is required and preservative-free formulations are not available.

( 2.1 , 5.3 ) O ther serious adverse reactions, including death, have been reported with methotrexate. Closely monitor for infections and adverse reactions of the bone marrow, kidneys, liver, nervous system, gastrointestinal tract, lungs, and skin. Withhold or discontinue Methotrexate Injection as appropriate.

( 5.4 , 5.5 , 5.6 , 5.7 , 5.8 , 5.9 , 5.10 , 5.11 )

🎯 Indications and Usage ~2 min read ▾

1 INDICATIONS AND USAGE Methotrexate Injection is a folate analog metabolic inhibitor indicated for: The following neoplastic diseases for the: ◦ Treatment of adult and pediatric patients with acute lymphoblastic leukemia as part of a combination chemotherapy regimen. ( 1.1 ) ◦ Prophylaxis and treatment of adult and pediatric patients with meningeal leukemia. ( 1.2 ) ◦ Treatment of adult and pediatric patients with non-Hodgkin lymphoma.

( 1.3 ) ◦ Treatment of adult and pediatric patients with osteosarcoma as part of a combination chemotherapy regimen. ( 1.4 ) ◦ Treatment of adults with breast cancer as part of a combination chemotherapy regimen. ( 1.5 ) ◦ Treatment of adults with squamous cell carcinoma of the head and neck as a single agent.

( 1.6 ) ◦ Treatment of adults with gestational trophoblastic neoplasia as part of a combination chemotherapy regimen. ( 1.7 ) Treatment of adults with rheumatoid arthritis (RA). ( 1.8 ) Treatment of pediatric patients with polyarticular juvenile idiopathic arthritis (pJIA).

( 1.9 ) Treatment of adults with severe psoriasis. ( 1.10 )

1.1Acute Lymphoblastic Leukemia Methotrexate Injection is indicated for the treatment of adult and pediatric patients with acute lymphoblastic leukemia (ALL) as part of a combination chemotherapy regimen.

1.2Meningeal Leukemia: Prophylaxis and Treatment Methotrexate Injection is indicated for the prophylaxis and treatment of meningeal leukemia in adult and pediatric patients.

1.3Non-Hodgkin Lymphoma Methotrexate Injection is indicated for the treatment of adults and pediatric patients with non-Hodgkin lymphoma.

1.4Osteosarcoma Methotrexate Injection is indicated for the treatment of adults and pediatric patients with osteosarcoma as part of a combination chemotherapy regimen.

1.5Breast Cancer Methotrexate Injection is indicated for the treatment of adults with breast cancer as part of a combination chemotherapy regimen.

1.6Squamous Cell Carcinoma of the Head and Neck Methotrexate Injection is indicated for the treatment of adults with squamous cell carcinoma of the head and neck as a single agent.

1.7Gestational Trophoblastic Neoplasia Methotrexate Injection is indicated for the treatment of adults with gestational trophoblastic neoplasia (GTN) as part of a combination chemotherapy regimen.

1.8Rheumatoid Arthritis Methotrexate Injection is indicated for the treatment of adults with rheumatoid arthritis (RA).

1.9Polyarticular Juvenile Idiopathic Arthritis Methotrexate Injection is indicated for the treatment of pediatric patients with polyarticular Juvenile Idiopathic Arthritis (pJIA).

1.10Psoriasis Methotrexate Injection is indicated for the treatment of adults with severe psoriasis.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Verify pregnancy status in females of reproductive potential before starting Methotrexate Injection. ( 2.1 , 4 , 5.1 ) Neoplastic diseases: Refer to the prescribing information for disease specific dosing recommendations. Follow guidelines for high-dose regimens.

( 2.2 , 2.3 , 2.4 , 2.5 , 2.6 , 2.7 , 2.8 , 2.9 ) RA: Recommended starting dosage of 7.5 mg once weekly intramuscularly; adjust dose to achieve an optimal response. ( 2.10 ) pJIA: Recommended starting dosage of 10 mg/m 2 once weekly subcutaneously or intramuscularly; adjust dose to achieve an optimal response. ( 2.11 ) Psoriasis: Recommended dosage of 10 mg to 25 mg once weekly intramuscularly or intravenously; adjust dose to achieve optimal response.

Once achieved, reduce to lowest possible dosage. ( 2.12 )

2.1Important Dosage and Safety Information Use only preservative-free Methotrexate Injection for treatment of neonates or low birth weight infants and for intrathecal use. Do not use benzyl alcohol-containing formulations for high-dose regimens unless immediate treatment is required and preservative-free formulations are not available [see Warnings and Precautions (5.3) and Use in Specific Populations (8.4) ]. Verify pregnancy status in females of reproductive potential before starting Methotrexate Injection [see Contraindications (4) and Warnings and Precautions (5.1) ].

For patients switching between a methotrexate product administered orally and Methotrexate Injection, consider potential differences in bioavailability .

2.2Recommended Monitoring and Concomitant Therapies for Intermediate- and High-Dose Regimens To decrease the risk of severe adverse reactions [see Warnings and Precautions (5) ] : Administer leucovorin rescue in patients receiving Methotrexate Injection doses of 500 mg/m 2 or greater (e.g., high-dose) . Consider leucovorin rescue for patients receiving Methotrexate Injection doses between 100 mg/m 2 to less than 500 mg/m 2 (e.g., intermediate-dose). Refer to the leucovorin prescribing information for additional information.

For high-dose Methotrexate Injection regimens, follow the supportive care and monitoring instructions below. Also consider for patients receiving intermediate-dose Methotrexate Injection regimens. - Monitor serum creatinine, electrolytes, at baseline and at least daily during therapy - Administer intravenous fluids starting before the first dose and continuing throughout treatment to maintain adequate hydration and urine output - Alkalinize urine starting before the first dose and continuing throughout treatment to maintain a urinary pH of 7 or higher - Monitor methotrexate concentrations at least daily and adjust hydration and leucovorin dosing as needed Administer glucarpidase in patients who have toxic plasma methotrexate concentrations (>1 micromole per liter) and delayed methotrexate clearance due to impaired renal function (refer to the glucarpidase prescribing information for additional information).

2.3Recommended Dosage for Acute Lymphoblastic Leukemia Methotrexate Injection is used as part of a multi-drug regimen. The recommended dosage varies from 10 to 5,000 mg/m 2 intravenously. For high-dose Methotrexate Injection regimens, use leucovorin rescue in accordance with high-dose methotrexate regimen guidelines [see Dosage and Administration (2.2) ] .

Lower doses (e.g., 20 to 30 mg/m 2 per week) may be used intramuscularly. Individualize the dose and schedule of Methotrexate Injection based on disease state, patient risk category, concurrent drugs used, phase of treatment, and response to treatment.

2.4Recommended Dosage for Meningeal Leukemia: Prophylaxis and Treatment Use only preservative-free Methotrexate Injection for intrathecal use. Prior to administration, dilute preservative-free Methotrexate Injection to a concentration of 1 mg/mL in preservative-free 0.9% Sodium Chloride Injection, USP. The recommended intrathecal dose of Methotrexate Injection (preservative-free) is based on…

💊 Dosage Forms and Strengths 62 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: Methotrexate Injection, USP is a clear, yellowish solution and is supplied in single-dose vials (preservative-free) in the following strengths: Preservative-Free (Single-Dose Vial) 50 mg/2 mL, 100 mg/4 mL, 200 mg/8 mL and 250 mg/10 mL (25 mg/mL) Injection: Preservative-free (single-dose vials): 50 mg/2 mL, 100 mg/4 mL, 200 mg/8 mL and 250 mg/10 mL (25 mg/mL)

⛔ Contraindications 59 words ▾

4 CONTRAINDICATIONS Methotrexate Injection is contraindicated in: Patients with history of severe hypersensitivity to methotrexate [see Warnings and Precautions (5.2) ] . Pregnancy in patients with non-neoplastic diseases [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1) ] . History of severe hypersensitivity to methotrexate. ( 4 ) Pregnancy: in patients with non-neoplastic diseases. ( 4 )

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS Secondary malignancies can occur. ( 5.13 ) Tumor lysis syndrome can occur in patients with rapidly growing tumors. ( 5.14 ) Immunizations and Risks associated with Live Vaccines: Immunizations may be ineffective. Live vaccines are not recommended due to risk of disseminated infection. ( 5.15 ) Infertility: Can cause impairment of fertility, oligospermia, and menstrual dysfunction. ( 5.16 , 8.3 )

5.1Embryo-Fetal Toxicity Based on published reports and its mechanism of action, methotrexate can cause embryo-fetal toxicity, including fetal death when administered to a pregnant woman. Methotrexate Injection is contraindicated for use in pregnant women with non-neoplastic diseases. Advise pregnant women with neoplastic diseases of the potential risk to a fetus.

The preservative benzyl alcohol can cross the placenta; when possible, use the preservative-free formulation when Methotrexate Injection is needed during pregnancy to treat a neoplastic disease [see Warnings and Precautions (5.3) ] . Advise females of reproductive potential to use effective contraception during Methotrexate Injection treatment and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during Methotrexate Injection treatment and for 3 months after the last dose [see Contraindications (4) and Use in Specific Populations (8.1 , 8.3 , 8.4 )] .

5.2Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis, can occur with methotrexate [see Adverse Reactions (6.1) ]. If signs or symptoms of anaphylaxis or any other serious hypersensitivity reaction occurs, immediately discontinue Methotrexate Injection and institute appropriate therapy [see Contraindications (4) ] .

5.3Risks of Serious Adverse Reactions due to Benzyl Alcohol-Preservative Formulations with benzyl alcohol can cause severe central nervous toxicity or metabolic acidosis, if used in neonates or low birth weight infants, intrathecally, or in high-dose regimens. Use only preservative-free Methotrexate Injection for treatment of neonates or low birth weight infants and for intrathecal use. Do not use benzyl alcohol-containing formulations for high-dose regimens unless immediate treatment is required, and preservative-free formulations are not available.

The preservative benzyl alcohol can cross the placenta; when possible, use the preservative-free formulation when Methotrexate Injection is needed during pregnancy to treat a neoplastic disease [see Use in Specific Populations (8.1) ] . Serious and Fatal Adverse Reactions Including Gasping Syndrome in Neonates and Low Birth Weight Infants Serious and fatal adverse reactions including “gasping syndrome” can occur in neonates and low birth weight infants treated with drugs containing benzyl alcohol, including Methotrexate Injection with preservative.

The “gasping syndrome” is characterized by central nervous system (CNS) depression, metabolic acidosis, and gasping respirations. When prescribing in infants (non-neonate, non-low birth weight), if a preservative-free formulation of Methotrexate Injection is not available and use of a benzyl alcohol-containing formulation is necessary, consider the combined daily metabolic load of benzyl alcohol from all sources including Methotrexate Injection (Methotrexate Injection contains 9.4 mg of benzyl alcohol per mL) and other drugs containing benzyl alcohol.

The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known [see Use in Specific Populations (8.4) ]. Neurotoxicity Due to Intrathecal Administration Serious neurotoxicity can occur following the intrathecal administration of Methotrexate Injection containing the preservative benzyl alcohol. Metabolic Acidosis with High-Dose Therapy Severe metabolic acidosis can occur with Methotrexate Injection that contains the preservative benzyl alcohol.

5.4 Myelosuppression Methotrexate suppresses hematopoiesis and can cause sev…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are described, or described in greater detail, in other sections: Hypersensitivity Reactions [see Warnings and Precautions (5.2) ] Myelosuppression [see Warnings and Precautions (5.4) ] Serious Infections [see Warnings and Precautions (5.5) ] Renal Toxicity [see Warnings and Precautions (5.6) ] Hepatotoxicity [see Warnings and Precautions (5.7) ] Neurotoxicity [see Warnings and Precautions (5.8) ] Gastrointestinal Toxicity [see Warnings and Precautions (5.9) ] Pulmonary Toxicity [see Warnings and Precautions (5.10) ] Dermatologic Reactions [see Warnings and Precautions (5.11) ] 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, and abdominal distress.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eugia US LLC at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

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. Commonly reported adverse reactions include ulcerative stomatitis, leukopenia, nausea, and abdominal distress. Other frequently reported adverse reactions are infection, malaise, fatigue, chills, fever, and dizziness.

Rheumatoid Arthritis The approximate incidences of methotrexate-attributed (i.e., placebo rate subtracted) adverse reactions in 12- to 18-week double-blind studies in patients (n = 128) with RA treated with low-dose oral (7.5 mg per week to 15 mg per week) pulse methotrexate are listed below. Most patients were on concomitant NSAIDs and some received corticosteroids. Hepatic histology was not examined in these short-term studies.

Incidence ≥10%: Elevated liver function tests 15%, nausea/vomiting 10%. Incidence 3% to <10%: Stomatitis, thrombocytopenia (platelet count less than 100,000/mm 3 ). Incidence 1% to <3%: Rash/pruritus/dermatitis, diarrhea, alopecia, leukopenia (white blood cell count less than 3,000/mm 3 ), pancytopenia, dizziness.

Two other controlled trials of patients (n = 680) with RA on 7.5 mg per week to 15 mg per week oral doses showed the following adverse reactions: Incidence 1%: Interstitial pneumonitis. Other less common adverse reactions: Decreased hematocrit, 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 approximate incidences of adverse reactions reported in patients 2 to 18 years of age with pJIA treated with oral, weekly doses of methotrexate (5 mg/m 2 per week to 20 mg/m 2 per week or 0.1 mg/kg per week to 0.65 mg/kg per week) were as follows (most patients were receiving concomitant NSAIDs, and some received corticosteroids): elevated liver function 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%.

Psoriasis In two published series of adult psoriasis patients (n = 204, 248) treated with methotrexate doses up to 25 mg per week for up to 4 years, adverse reaction rates were similar to those in patients with RA, except for alopecia, photosensitivity, and “burning of skin lesions” (each 3% to 10%). Painful plaque erosions have been reported.

6.2Postmarketing Experience The following adverse reactions have been identified during post-approval use of methotrexate. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their fr…

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS Refer to full prescribing information for drug interactions with Methotrexate Injection.

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. 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: Penicillin or sulfonamide antibiotics Highly protein bound drugs (e.g., oral anticoagulants, phenytoin, salicylates, sulfonamides, sulfonylureas, and tetracyclines) Proton pump inhibitors Probenecid Antifolate drugs (e.g., dapsone, pemetrexed, pyrimethamine and sulfonamides) Aspirin and other nonsteroidal anti-inflammatory drugs Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of methotrexate (primarily at high dose) and nonsteroidal anti-inflammatory drugs (NSAIDs).

Mercaptopurine Hepatotoxic products Weak acids (e.g., salicylates) Nephrotoxic products Hematotoxic agents 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 (5.12) ].

7.2Effects of Methotrexate on Other Drugs Theophylline Coadministration of methotrexate with theophylline increases theophylline plasma concentrations which may increase the risk of theophylline adverse reactions. Monitor theophylline levels and adjust the theophylline dosage in accordance with approved product labeling.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) Pediatric use: Intermediate-dose methotrexate can cause serious neurotoxicity in patients with acute lymphoblastic leukemia. ( 8.4 )

8.1Pregnancy Risk Summary Methotrexate Injection is contraindicated in pregnant women with non-neoplastic diseases. Based on published reports and its mechanism of action, methotrexate can cause embryo-fetal toxicity and fetal death when administered to a pregnant woman [see Data and Clinical Pharmacology (12.1) ]. 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. The preservative benzyl alcohol can cross the placenta; when possible, use the preservative-free formulation when Methotrexate Injection is needed during pregnancy to treat a neoplastic disease [see Warnings and Precautions (5.3) and Use in Specific Populations (8.4) ] . 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, CNS 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 per week after conception.

The rate of spontaneous abortion/miscarriage in pregnant women exposed to methotrexate was 42.5% (95% confidence interval [95% CI] 29.2 to 58.7), which was higher than in unexposed patients with autoimmune disease (22.5%, 95% CI 16.8 to 29.7) and unexposed patients with non-autoimmune disease (17.3%, 95% CI 13 to 22.8). 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 to 5.7]) and unexposed patients with non-autoimmune disease (adjusted OR 3.1 [95% CI 1.03 to 9.5]) (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 reports the presence of methotrexate in human milk in low amounts, with the highest breast milk to plasma concentration ration reported to be 0.08:1. No information is available on the effects of methotrexate on a breastfed infant or on milk production. Because of the potential for serious adverse reactions from methotrexate in breastfed infants, advise women not to breastfeed during treatment with Methotrexate Injection and for 1 week after the last 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 [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating Methotrexate Injection [see Contraindications (4) and Use in Specific Populations (8.1) ]. Contraception Females Advise females of reproductive potential to use effective…

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary Methotrexate Injection is contraindicated in pregnant women with non-neoplastic diseases. Based on published reports and its mechanism of action, methotrexate can cause embryo-fetal toxicity and fetal death when administered to a pregnant woman [see Data and Clinical Pharmacology (12.1) ]. 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. The preservative benzyl alcohol can cross the placenta; when possible, use the preservative-free formulation when Methotrexate Injection is needed during pregnancy to treat a neoplastic disease [see Warnings and Precautions (5.3) and Use in Specific Populations (8.4) ] . 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, CNS 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 per week after conception.

The rate of spontaneous abortion/miscarriage in pregnant women exposed to methotrexate was 42.5% (95% confidence interval [95% CI] 29.2 to 58.7), which was higher than in unexposed patients with autoimmune disease (22.5%, 95% CI 16.8 to 29.7) and unexposed patients with non-autoimmune disease (17.3%, 95% CI 13 to 22.8). 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 to 5.7]) and unexposed patients with non-autoimmune disease (adjusted OR 3.1 [95% CI 1.03 to 9.5]) (2.9%).

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

🧒 Pediatric Use ~2 min read ▾

8.4Pediatric Use The safety and effectiveness of Methotrexate Injection in pediatric patients have been established for ALL, meningeal leukemia prophylaxis and treatment, non-Hodgkin lymphoma, osteosarcoma and in pJIA. Clinical studies evaluating the use of methotrexate in pediatric patients with pJIA demonstrated safety comparable to that observed in adults with RA [see Adverse Reactions (6.1) ]. The safety and effectiveness of Methotrexate Injection have not been established in pediatric patients for the treatment of breast cancer, squamous cell carcinoma of the head and neck, gestational trophoblastic neoplasia, rheumatoid arthritis, and psoriasis.

Additional risk information is described below. Risks of Serious Adverse Reactions due to Benzyl Alcohol-Preservative Due to the risk of serious adverse reactions and fatal gasping syndrome following administration of intravenous solutions containing the preservative benzyl alcohol in neonates, use only preservative-free Methotrexate Injection in neonates and low birth weight infants. The “gasping syndrome” is characterized by CNS depression, metabolic acidosis, and gasping respirations.

Serious adverse reactions including fatal reactions and the “gasping syndrome” occurred in premature neonates and low birth weight infants in the neonatal intensive care unit who received drugs containing benzyl alcohol as a preservative. In these cases, benzyl alcohol dosages of 99 to 234 mg/kg/day produced high levels of benzyl alcohol and its metabolites in the blood and urine (blood levels of benzyl alcohol were 0.61 to 1.378 mmol/L). Additional adverse reactions include gradual neurological deterioration, seizures, intracranial hemorrhage, hematological abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse.

Preterm, low birth weight infants may be more likely to develop these reactions because they may be less able to metabolize benzyl alcohol. When prescribing in infants (non-neonate, non-low birth weight), if a preservative-free formulation of Methotrexate Injection is not available and use of a benzyl alcohol-containing formulation is necessary, consider the combined daily metabolic load of benzyl alcohol from all sources including Methotrexate Injection (Methotrexate Injection contains 9.4 mg of benzyl alcohol per mL) and other drugs containing benzyl alcohol.

The minimum amount of benzyl alcohol at which serious adverse reactions may occur is not known . Do not administer methotrexate formulations containing benzyl alcohol intrathecally due to the risk of severe neurotoxicity [see Warnings and Precautions (5.3) ]. Leukemia/Lymphoma Serious neurotoxicity, frequently manifested as generalized or focal seizures, has been reported with unexpectedly increased frequency among pediatric patients with acute lymphoblastic leukemia who were treated with intermediate-dose intravenous methotrexate (1 g/m 2 ) [see Warnings and Precautions (5.8) ].

🧓 Geriatric Use 27 words ▾

8.5Geriatric Use Clinical studies of methotrexate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

🆘 Overdosage ~1 min read ▾

10 OVERDOSAGE Manifestations Overdosage, including fatal overdosage, has occurred with methotrexate [see Warnings and Precautions (5.19) ]. Manifestations of 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.

Manifestations of intrathecal overdosage include CNS symptoms (e.g., headache, nausea and vomiting, seizure or convulsion, and acute toxic encephalopathy). In some cases, no symptoms were reported; however, cerebellar herniation associated with increased intracranial pressure and acute toxic encephalopathy have also been reported. Management Leucovorin and levoleucovorin are indicated to diminish the toxicity and counteract the effect of inadvertently administered overdosages of methotrexate.

Administer leucovorin or levoleucovorin as soon as possible after overdosage (refer to the leucovorin or levoleucovorin prescribing information). Monitor serum methotrexate concentrations closely to guide leucovorin or levoleucovorin therapy. Monitor serum creatinine concentrations closely because high serum methotrexate concentrations may cause renal damage leading to acute renal failure.

Glucarpidase is indicated for the treatment of toxic methotrexate concentrations in patients with delayed methotrexate clearance due to impaired renal function (refer to the glucarpidase prescribing information). If glucarpidase is used, do not administer leucovorin within 2 hours before or after a dose of glucarpidase because leucovorin is a substrate for glucarpidase. Hydration and urinary alkalinization may be necessary to prevent the precipitation of methotrexate and/or its metabolites in the renal tubules.

Neither hemodialysis nor peritoneal dialysis has been shown to improve methotrexate elimination. However, effective clearance of methotrexate has been reported with acute, intermittent hemodialysis using a high-flux dialyzer.

🧬 Clinical Pharmacology ~2 min read ▾

12 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, pJIA, and in psoriasis is unknown.

12.3Pharmacokinetics Distribution After intravenous administration, the initial volume of distribution is approximately

0.18 L/kg (18% of body weight) and steady-state volume of distribution is approximately

0.4 L/to

0.8L/kg (40% to 80% of body weight). Methotrexate competes with reduced folates for active transport across cell membranes by means of a single carrier-mediated active transport process. At serum concentrations greater than 100 micromolar, passive diffusion becomes a major pathway by which effective intracellular concentrations can be achieved.

Methotrexate in serum is approximately 50% protein bound. Methotrexate may be displaced from plasma albumin by various compounds, including sulfonamides, salicylates, tetracyclines, chloramphenicol, and phenytoin. Methotrexate does not penetrate the blood-cerebrospinal fluid barrier in therapeutic amounts when given intravenously, intramuscularly, or subcutaneously.

Elimination The terminal half-life reported for methotrexate is approximately 3 to 10 hours for patients receiving treatment for psoriasis, or rheumatoid arthritis or low-dose antineoplastic therapy (less than 30 mg/m 2 ). Following intravenous administration of high-dose methotrexate, the terminal half-life is 8 hours to 15 hours. Metabolism Methotrexate undergoes hepatic and intracellular metabolism to polyglutamated forms that can be converted back to methotrexate by hydrolase enzymes.

These polyglutamates act as inhibitors of dihydrofolate reductase and thymidylate synthetase. 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.

Methotrexate undergoes minor metabolism to 7-hydroxymethotrexate, and accumulation may become significant following high dosages. The aqueous solubility of 7-hydroxymethotrexate is 3- to 5-fold lower than the solubility of methotrexate. Excretion Renal excretion is the primary route of elimination and is dependent upon dosage and route of administration.

With intravenous administration, 80% to 90% of the administered dose is excreted unchanged in the urine within 24 hours. There is limited biliary excretion amounting to 10% or less of the administered dose. Enterohepatic recirculation of methotrexate has been proposed.

Renal excretion occurs by glomerular filtration and active tubular secretion. Nonlinear elimination due to saturation of renal tubular reabsorption has been observed in psoriatic patients at doses between 7.5 mg and 30 mg. Specific Populations Pediatric Patients In pediatric patients receiving methotrexate for acute lymphoblastic leukemia (6.3 mg/m 2 to 30 mg/m 2 ), or for JIA (3.75 mg/m 2 to 26.2 mg/m 2 ), 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 [see Use in Specific Populations (8.4) ] .

Patients with Renal impairment The elimination half-life of methotrexate increases with the severity of renal impairment, with high inter-individual variability [see Use in Specific Populations (8.6) ].

🧬 Mechanism of Action 90 words ▾

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, pJIA, and in psoriasis is unknown.

📦 How Supplied / Storage and Handling 139 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Methotrexate Injection, USP is a sterile, clear, yellowish solution available with preservative-free (single-dose vials) as follows: Strength/Fill volume NDC number Pack style Preservative-free 50 mg/2 mL 55150-510-01 Single-Dose Vial packaged individually 55150-510-05 Single-Dose Vials in a carton of 5 100 mg/4 mL 55150-511-01 Single-Dose Vial packaged individually 55150-511-10 Single-Dose Vials in a carton of 10 200 mg/8 mL 55150-512-01 Single-Dose Vial packaged individually 55150-512-10 Single-Dose Vials in a carton of 10 250 mg/10 mL 55150-513-01 Single-Dose Vial packaged individually Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Protect from light. Methotrexate Injection, USP is a hazardous drug. Follow applicable special handling and disposal procedures.

1 The vial stopper is not made with natural rubber latex.

📋 Description 134 words ▾

11 DESCRIPTION Methotrexate, USP is a folate analog metabolic inhibitor with the chemical name of N -[4-[[(2,4-diamino-6-pteridinyl) methyl]methylamino]benzoyl]-L-glutamic acid and a molecular weight of 454.44. The molecular formula is C 20 H 22 N 8 O 5, and the structural formula is shown below: Preservative-free Methotrexate Injection, USP is supplied in sterile single-dose vials for intravenous, intramuscular, subcutaneous, or intrathecal use. Each 25 mg/mL, 2 mL, 4 mL, 8 mL and 10 mL vial contains 50 mg, 100 mg, 200 mg, and 250 mg methotrexate, USP equivalent to 54.8 mg, 109.6 mg, 219.3 mg and 274.18 mg of methotrexate sodium respectively, and the following inactive ingredients: Sodium chloride 9.8 mg, 19.6 mg, 39.2 mg and 49 mg respectively.

May contain sodium hydroxide and/or hydrochloric acid to adjust pH between 7.0 to 9.0. checmical structure

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Contraindications (4) , Warnings and Precautions (5.1) , and Use in Specific Populations (8.1) ]. Advise females of reproductive potential to use effective contraception during Methotrexate Injection therapy and for 6 months after the last dose [see Use in Specific Populations (8.3) ].

Advise males of reproductive potential to use effective contraception during Methotrexate Injection therapy and for 3 months after the last dose [see Use in Specific Populations (8.3) ]. Hypersensitivity Reactions Advise patients of the potential risk of hypersensitivity and that Methotrexate Injection is contraindicated in patients with a history of severe hypersensitivity to methotrexate. Advise patients to seek immediate medical attention if signs or symptoms of a hypersensitivity reaction occur [see Warnings and Precautions (5.2) ].

Myelosuppression and Serious Infections Advise patient to contact their healthcare provider immediately for new onset fever, symptoms of infection, easy bruising or persistent bleeding [see Warnings and Precautions (5.4 , 5.5 )]. Renal Toxicity Advise patients that methotrexate can cause renal toxicity. Advise patients to immediately contact their healthcare provider for signs or symptoms of renal toxicity, such as marked increases or decreases in urinary output [see Warnings and Precautions (5.6) ].

Hepatotoxicity Advise patients to report signs or symptoms of hepatic toxicity and avoidance of alcohol during methotrexate treatment [see Warnings and Precautions (5.7) ]. Neurotoxicity Advise patient to contact their healthcare provider immediately if they develop new neurological symptoms [see Warnings and Precautions (5.8) ]. Gastrointestinal Toxicity Advise patients to contact their healthcare provider if they develop diarrhea, vomiting, or stomatitis.

Advise patients to immediately contact their healthcare provider for high fever, rigors, persistent or severe abdominal pain, severe constipation, hematemesis, or melena [see Warnings and Precautions (5.9) ]. Pulmonary Toxicity Advise patients to contact their healthcare provider for symptoms of cough, fever, and dyspnea [see Warnings and Precautions (5.10) ]. Dermatologic Toxicity Advise patients that Methotrexate Injection can cause serious skin rash and to immediately contact their healthcare provider for new or worsening skin rash.

Advise patients to avoid excessive sun exposure and to use sun protection measures [see Warnings and Precautions (5.11) ] . Secondary Malignancies Advise patients on the risk of second primary malignancies during treatment with Methotrexate Injection [see Warnings and Precautions (5.13) ]. Lactation Advise women not to breastfeed during treatment with Methotrexate Injection and for 1 week after the last dose [see Use in Specific Populations (8.2) ].

Infertility Advise females and males of reproductive potential that Methotrexate Injection may cause impairment of fertility [see Use in Specific Populations (8.3) ] . Drug Interactions Advise patients and caregivers to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products [see Drug Interactions (7) ] . Instruct patients being treated for neoplastic indication to not take products containing folic acid or folinic acid unless directed to do so by their healthcare provider [see Warnings and Precautions (5.12) ].

Distributed by: Eugia US LLC 279 Princeton-Hightstown Rd. E. Windsor, NJ 08520 Manufactured by: Eugia Pharma Specialities Limited Hyderabad - 500032 India

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