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Xatmep Methotrexate 2.5 mg/mL Solution, 120 mL — NDC 52652-2001-01 package photo

Xatmep Methotrexate 2.5 mg/mL Solution, 120 mL

by Azurity Pharmaceuticals, Inc. · 120 mL in 1 BOTTLE (52652-2001-1)
NDC 52652-2001-01
🏷️ FDA NDC (as labeled) 52652-2001-1 billing pads the package segment with a zero
This package
Contains120 mL Medicaid pays$20.58 / unit · 12 mo Per package$2,469.36 / 120 ml · Medicaid Pack sizes2 compare ↓
Also priced by: Part D plans $22.63/unit — full pricing hub ↓
Also comes in: 60 ml 52652-2001-06
Rx only Brand 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) 52652-2001-1
Product NDC 52652-2001
11-digit billing NDC 52652200101
NCPDP billing unit ML — per mL (volume)
RxCUI 1921592, 1921598
UNII YL5FZ2Y5U1
Application # NDA208400
SPL Set ID aec9984e-34c5-481b-b6bf-9bb5caf1daf8
Established class (EPC) Folate Analog Metabolic Inhibitor
Mechanism of action Folic Acid Metabolism Inhibitors
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2017-05-01
Route ORAL
Dosage form SOLUTION
Substance METHOTREXATE
GPI-14 21300050002080
GPI class Xatmep
GCN Seq No 077337
GCN 43319
HICL code 003906
Ingredient (HICL) Methotrexate
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 XATMEP 2.5 MG/ML ORAL SOLUTION
FDB brand name Xatmep
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 52652-2001-1 — a 5-4-1 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 package segment → 52652-2001-01. 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

LabelerAzurity Pharmaceuticals, Inc.
Application holderAZURITY PHARMACEUTICALS INC
FDA applicationNDA208400 (NDA)
Labeler code52652
First marketedMay 2017
Product typeHuman Prescription Drug
Portfolio57 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name XATMEP 2.5 MG/ML ORAL SOLUTION Ingredient Methotrexate
📖 What it is MedlinePlus · NLM

Methotrexate is used to treat severe psoriasis (a skin disease in which red, scaly patches form on some areas of the body). Methotrexate is also used to treat rheumatoid arthritis (RA; a condition in which the body attacks its own joints, causing pain, swelling, and loss of function). Methotrexate is also used in children to treat polyarticular juvenile idiopathic arthritis (PJIA; a type of childhood arthritis that affects five or more joints during the first six months of the condition, causing pain, swelling, and loss of function). Methotrexate is also used in combination with other chemoth...

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 2968PHW8QP
    A weak organic acid derived from citrus fruits or made through fermentation. It works as a buffer to control pH, a preservative to extend shelf life, and a flavoring agent in medications.
  • 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 CR6K9C2NHK
    A synthetic preservative derived from methylparaben. It prevents bacterial and fungal growth in medicines, extending shelf life and maintaining product safety during storage.
  • UNII 625NNB0G9N
    A preservative derived from benzoic acid that prevents bacterial and fungal growth in medicines. It helps keep the product safe and stable throughout its shelf life.
  • UNII 1Q73Q2JULR
    Sodium citrate is a salt derived from citric acid. It works as a buffer to maintain the medicine's pH level and may also help improve taste or act as a preservative in the formulation.
  • 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.
  • UNII 96K6UQ3ZD4
    Sucralose is a synthetic sweetener made from sugar. It's added to medicines to improve taste without adding calories, helping make bitter or unpleasant-tasting drugs easier to take.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

8 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 $20.58 $2,469.36 / 120 ml
Medicare drug plans payPart D · Q2 2026 $22.63 $2,715.31 / 120 ml
Medicare Part B allowsASP · NONE No ASP payment limit on file for NONE this quarter.
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)52652-2001-1
11-digit billing NDC52652-2001-01
Format5-4-1 as registered → padded to 5-4-2 for billing (zero added to the package segment)
HCPCS J-codeNONE
DescriptorMETHOTREXATE (XATMEP), ORAL, 2.5 MG
Billing units / pkg1 units
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.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Xatmep 2.5 mg/mLthis 52652-2001-01 Azurity 120 ml — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
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

🏛️
2017
First FDA approval
Apr 2017
📍
2026
Currently FDA-listed
9 years listed
🛡️
2033
Latest patent/protection listed
not a guaranteed launch date
🔒No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Jan 2033. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Apr 25, 2017 RLD RS ⏳ ~6.3 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 10231927 — method of use (U-1699)
US 10231927 — method of use (U-1349)
US 11116724 — method of use (U-1349)
US 11116724 — method of use (U-1699)
US 11969503 — drug product
US 12396947 — drug product
US 10610485 — drug product
US 9855215 — drug product
US 9259427 — drug product
2017 2019 2021 2023 2025 2027 2029 2031 2033
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (9)
PatentTypeUse codeExpires
US 10231927 ↗ Method of use U-1699 Jan 2, 2033
US 10231927 ↗ Method of use U-1349 Jan 2, 2033
US 11116724 ↗ Method of use U-1349 Jan 2, 2033
US 11116724 ↗ Method of use U-1699 Jan 2, 2033
US 11969503 ↗ Drug product — Jan 2, 2033
US 12396947 ↗ Drug product — Jan 2, 2033
US 10610485 ↗ Drug product — Jan 2, 2033
US 9855215 ↗ Drug product — Jan 2, 2033
US 9259427 ↗ Drug product — Jan 2, 2033
Common questions
Is there a generic version of XATMEP 2.5 MG/ML ORAL SOLUTION?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for XATMEP 2.5 MG/ML ORAL SOLUTION. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Jan 2033 — an estimate, not a guaranteed launch date.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

🗺️ Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for 52652-2001-01, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q4 2025 · 4 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
2.5K
Units reimbursed last 4 qtrs
78.9K
Gross reimbursed last 4 qtrs
$1.62M
Avg / prescription
$640.53
Avg / unit
$20.5781
Latest quarter Q4 2025
679Rx
Fee-for-service vs managed care ⓘ
35% FFS 65% MCO
Fee-for-service · 900 Rx Managed care · 1,636 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: 3,137 units · 53.1 per 100k residents WI Michigan: 928 units · 9.2 per 100k residents MI New York: 11,011 units · 56.3 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: 1,085 units · 8.6 per 100k residents IL Indiana: no data reported IN Ohio: 279 units · 2.4 per 100k residents OH Pennsylvania: 1,066 units · 8.2 per 100k residents PA New Jersey: 4,222 units · 45.4 per 100k residents NJ Massachusetts: no data reported MA California: 17,480 units · 44.9 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: 1,523 units · 24.6 per 100k residents MO Kentucky: 1,907 units · 42.1 per 100k residents KY West Virginia: 320 units · 18.1 per 100k residents WV Virginia: 1,711 units · 19.6 per 100k residents VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: 3,816 units · 51.4 per 100k residents AZ New Mexico: 1,982 units · 93.8 per 100k residents NM Kansas: 1,603 units · 54.5 per 100k residents KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: 8,647 units · 79.8 per 100k residents NC South Carolina: 795 units · 14.8 per 100k residents SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: 1,787 units · 39.1 per 100k residents LA Mississippi: no data reported MS Alabama: 471 units · 9.2 per 100k residents AL Georgia: 198 units · 1.8 per 100k residents GA D.C.: no data reported DC Hawaii: no data reported HI Texas: 6,614 units · 21.7 per 100k residents TX Florida: 8,356 units · 37.0 per 100k residents FL
Units reimbursed · per 100k residents
1.893.8
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 New Mexico 93.8 /100k
2 North Carolina 79.8 /100k
3 New York 56.3 /100k
4 Kansas 54.5 /100k
5 Wisconsin 53.1 /100k
6 Arizona 51.4 /100k
7 New Jersey 45.4 /100k
8 California 44.9 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

💊 Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
12 ml this page52652-2001-01 2,536 Rx · $1,624,384
6 ml52652-2001-06 1,120 Rx · $895,504
Drug total (last 4 qtrs): 3,656 Rx · 121,218 units · $2,519,888 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

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

Medicare Part D (outpatient prescription) spending for Xatmep — the program that covers self-administered drugs. 1 manufacturer.
⚠️ 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 Xatmep. 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
$83.2K
Claims incl. refills
64
Beneficiaries
46
Spend / beneficiary
$1,807.69
Spend / claim
$1,299.28
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.

📦 Packaging — all sizes for this product

Package NDCDescription Per unit Per pack Marketing startStatus
52652-2001-01 You're viewing this 120 mL in 1 BOTTLE (52652-2001-1) — — 2017-05-01 Active
52652-2001-06 60 mL in 1 BOTTLE (52652-2001-6) $21.76 / mL $1,305.81 2018-08-13 Active

You're viewing the largest of 2 pack sizes for this product.

In Medicaid, this is the most-dispensed pack of this product — about 69% of fills over the last four reported quarters. See all packs ↓

Pack size FAQ

What quantity is in NDC 52652-2001-01?
NDC 52652-2001-01 contains 120 mL — 120 ml in 1 bottle.
What is the difference between NDC 52652-2001-01 and NDC 52652-2001-06?
Both are Xatmep Methotrexate 2.5 mg/mL Solution — the drug itself is identical. NDC 52652-2001-01 is the 120 mL package, while NDC 52652-2001-06 is the 60 ml package.
What NDC number is used to bill for this package of Xatmep Methotrexate 2.5 mg/mL Solution?
Bill NDC 52652-2001-01 — the 11-digit billing format is 52652200101. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

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

🧭 About this NDC listing & data coverage

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 ✓ Available
Medicaid utilization (CMS SDUD) ✓ Available
“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 52652-2001-1, 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: 52652-2001-01, written without dashes as 52652200101. 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 52652-2001-01, the first segment (52652) is the labeler code FDA assigned to Azurity Pharmaceuticals, Inc.; the middle segment (2001) 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 Azurity Pharmaceuticals, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 60 ml (52652-2001-06). 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?
Azurity Pharmaceuticals, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
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.

📄 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 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🚨 Boxed Warning ~2 min read ▾

WARNING: SEVERE TOXIC REACTIONS, INCLUDING EMBRYO-FETAL TOXICITY, AND RISK OF MEDICATION ERRORS Methotrexate can cause the following severe or fatal adverse reactions. Monitor closely and modify dose or discontinue methotrexate as appropriate. o Bone marrow suppression [see Warnings and Precautions ( 5.1 )] o Serious infections [see Warnings and Precautions ( 5.2 )] o Renal toxicity and increased toxicity with renal impairment [see Warnings and Precautions ( 5.3 )] o Gastrointestinal toxicity [see Warnings and Precautions ( 5.4 )] o Hepatic toxicity [see Warnings and Precautions ( 5.5 )] o Pulmonary toxicity [see Warnings and Precautions ( 5.6 )] o Hypersensitivity and dermatologic reactions [see Warnings and Precautions ( 5.7 )] Methotrexate can cause embryo-fetal toxicity, including fetal death.

Use in pJIA is contraindicated in pregnancy. Consider the benefits and risks of XATMEP and risks to the fetus when prescribing XATMEP to a pregnant patient with a neoplastic disease. Advise females and males of reproductive potential to use effective contraception during and after treatment with XATMEP [see Contraindications ( 4 ), Warnings and Precautions (5.9), Use in Specific Populations ( 8.1 , 8.3 )].

Oral methotrexate when inadvertently administered once daily has resulted in death [see Warnings and Precautions ( 5.15 )]. WARNING: SEVERE TOXIC REACTIONS, INCLUDING EMBRYO-FETAL TOXICITY, AND RISK OF MEDICATION ERRORS See full prescribing information for complete boxed warning. Methotrexate can cause severe or fatal toxicities.

Monitor closely and modify dose or discontinue for the following toxicities: bone marrow suppression ( 5.1 ), infection ( 5.2 ), renal ( 5.3 ), gastrointestinal ( 5.4 ), hepatic ( 5.5 ), pulmonary ( 5.6 ), hypersensitivity and dermatologic ( 5.7 ). Methotrexate can cause embryo-fetal toxicity and fetal death. Use in polyarticular juvenile idiopathic arthritis is contraindicated in pregnancy ( 4 ).

Consider the benefits and risks of XATMEP and risks to the fetus when prescribing XATMEP to a pregnant patient with a neoplastic disease. Advise patients to use effective contraception during and after treatment with XATMEP ( 5.9 , 8.1 , 8.3 ). Oral methotrexate when inadvertently administered once daily has resulted in death [see Warnings and Precautions ( 5.15 )] .

🎯 Indications and Usage 134 words ▾

1 INDICATIONS AND USAGE XATMEP is a folate analog metabolic inhibitor indicated for the: Treatment of pediatric patients with acute lymphoblastic leukemia (ALL) as a component of a combination chemotherapy maintenance regimen ( 1.1 ). Management of pediatric patients with active polyarticular juvenile idiopathic arthritis (pJIA) who are intolerant of or had an inadequate response to first-line therapy ( 1.2 ).

1.1Acute Lymphoblastic Leukemia XATMEP is indicated for the treatment of pediatric patients with acute lymphoblastic leukemia (ALL) as part of a multi-phase, combination chemotherapy maintenance regimen.

1.2Polyarticular Juvenile Idiopathic Arthritis XATMEP is indicated in the management of pediatric patients with active polyarticular juvenile idiopathic arthritis (pJIA) who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose non-steroidal anti-inflammatory agents (NSAIDs).

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION Use another formulation of methotrexate for patients requiring dosing via routes of administration other than oral ( 2.1 ). Measure with an accurate measuring device ( 2.1 ). Recommended Dosage: ALL: 20 mg/m 2 one time weekly ( 2.2 ). pJIA: Starting dose of 10 mg/m 2 one time weekly ( 2.3 ).

2.1Important Administration Information XATMEP is intended for oral use only. Use another formulation of methotrexate for alternative dosing in patients who require dosing via other routes of administration. Instruct patients and caregivers that the recommended dose should be taken weekly, as directed, and that mistaken daily use of the recommended dose has led to fatal toxicity [see Warnings and Precautions ( 5.15 ), Overdosage ( 10 )].

It is important that XATMEP be measured with an accurate measuring device [see Warnings and Precautions ( 5.15 ), Patient Counseling Information ( 17 )] . A household teaspoon is not an accurate measuring device. A pharmacist can provide an appropriate device and can provide instructions for measuring the correct dose.

2.2Acute Lymphoblastic Leukemia The recommended starting dose of XATMEP, in multi-agent combination chemotherapy maintenance regimens, is 20 mg/m 2 given one time weekly. After initiating XATMEP, continuation of appropriate dosing requires periodic monitoring of absolute neutrophil count (ANC) and platelet count to assure sufficient drug exposure (that is to maintain ANC at a desirable level) and to adjust for excessive hematological toxicity.

2.3Polyarticular Juvenile Idiopathic Arthritis The recommended starting dose of XATMEP is 10 mg/m 2 given one time weekly. Dosages should be tailored to the individual patient and adjusted gradually to achieve an optimal response. Although there is experience with doses up to 30 mg/m 2 /week in pediatric patients, doses greater than 20 mg/m 2 /week may result in a significant increase in the incidence and severity of serious toxic reactions, especially bone marrow suppression.

Doses between 20 and 30 mg/m 2 /week (0.65 to 1 mg/kg/week) may have better absorption and fewer gastrointestinal side effects if methotrexate is administered by an alternative route using another formulation. Therapeutic response usually begins within 3 to 6 weeks and the patient may continue to improve for another 12 weeks or more. Certain side effects such as mouth sores may be reduced by folate supplementation with methotrexate in pJIA.

2.4Evaluations Prior to Starting Methotrexate Assess hematologic, hepatic, and renal function before beginning, as well as periodically during and before reinstituting, therapy with XATMEP [see Warnings and Precautions ( 5.1 , 5.3 , 5.5 , 5.7 , 5.14 )] . Exclude pregnancy in females of reproductive potential before starting XATMEP [see Contraindications ( 4 ), Warnings and Precautions ( 5.9 ), Use in Specific Populations ( 8.1 , 8.3 )] .

2.5Handling Information XATMEP is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1

💊 Dosage Forms and Strengths 29 words ▾

3 DOSAGE FORMS AND STRENGTHS XATMEP is a clear yellow to orange oral solution that contains 2.5 mg of methotrexate per milliliter. Oral solution: 2.5 mg/mL ( 3 ).

⛔ Contraindications 76 words ▾

4 CONTRAINDICATIONS XATMEP is contraindicated in the following: Pregnancy in patients with non-malignant diseases. XATMEP can cause embryo-fetal toxicity and fetal death when administered during pregnancy [see Warnings and Precautions ( 5.9 ), Use in Specific Populations ( 8.1 )] . Patients with severe hypersensitivity to methotrexate [see Warnings and Precautions ( 5.7 ), Adverse Reactions ( 6.1 , 6.2 )] .

Pregnancy (patients with pJIA) ( 4 ). Severe hypersensitivity to methotrexate ( 4 ).

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS Secondary malignancies can occur. In case of immunosuppression-associated lymphoma, discontinue methotrexate before starting treatment for lymphoma ( 5.8 ). Immunizations may be ineffective ( 5.10 ). Effects on reproduction: May cause impairment of fertility, oligospermia and menstrual dysfunction ( 5.11 , 8.3 ).

5.1Bone Marrow Suppression XATMEP suppresses hematopoiesis and can cause severe and life-threatening pancytopenia, anemia, leukopenia, neutropenia, and thrombocytopenia. Obtain blood counts at baseline and periodically during treatment. Monitor patients for possible clinical complications of bone marrow suppression. Provide supportive care and modify dose or discontinue XATMEP as needed.

5.2Serious Infections Patients treated with XATMEP are at increased risk for developing life-threatening or fatal bacterial, fungal, or viral infections including opportunistic infections such as Pneumocystis jiroveci pneumonia, invasive fungal infections, hepatitis B reactivation, tuberculosis primary infection or reactivation, and disseminated Herpes zoster and cytomegalovirus infections. Monitor patients for the signs and symptoms of infection during and after treatment with XATMEP and treat promptly. Consider dose modification or discontinuation of XATMEP in patients who develop serious infections [see Warnings and Precautions ( 5.1 )] .

5.3Renal Toxicity and Increased Toxicity with Renal Impairment XATMEP can cause renal damage including acute renal failure. Monitor renal function to decrease the risk of renal injury and mitigate renal toxicity. Consider administration of glucarpidase in patients with toxic plasma methotrexate concentrations (> 1 micromole per liter) and delayed clearance due to impaired renal function [see glucarpidase Prescribing Information] .

5.4Gastrointestinal Toxicity XATMEP can cause diarrhea, vomiting, stomatitis, hemorrhagic enteritis, and fatal intestinal perforation. Patients with peptic ulcer disease or ulcerative colitis are at a greater risk of developing severe gastrointestinal adverse reactions. Interrupt or discontinue XATMEP and institute appropriate supportive care as needed.

Unexpectedly severe and fatal gastrointestinal toxicity can occur with concomitant administration of XATMEP (primarily at high dosage) and nonsteroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions ( 7.1 )] .

5.5Hepatic Toxicity XATMEP can cause severe and potentially irreversible hepatotoxicity including fibrosis, cirrhosis, and fatal liver failure. Avoid use of XATMEP in patients with chronic liver disease. Assess liver function prior to initiating XATMEP and monitor liver function tests during treatment.

Interrupt or discontinue XATMEP as appropriate. Transient asymptomatic acute liver enzyme elevations are common and are not predictive of subsequent hepatic disease. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis.

Other risk factors for hepatotoxicity include alcoholism, obesity, diabetes, hyperlipidemia, previous significant exposure to liver toxins, history of liver disease, family history of inheritable liver disease, persistent abnormal liver chemistry findings, duration of therapy, and advanced age.

5.6Pulmonary Toxicity Methotrexate-induced pulmonary toxicity including acute or chronic interstitial pneumonitis and irreversible or fatal cases can occur at all dose levels. Monitor patients for signs of pulmonary toxicity and interrupt or discontinue XATMEP as appropriate.

5.7Hypersensitivity and Dermatologic Reactions Severe, including fatal, dermatologic reactions, such as toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, skin necrosis, erythema multiforme, can occur with methotrexate. Discontinue XATMEP if severe dermatologic reactions occur. Anaphylaxis can occur with methotrexate.

If anaphylaxis or any other serious hypersensitivity reaction occurs, immediately discontinue methotrexate and i…

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling. Bone Marrow Suppression [see Warnings and Precautions ( 5.1 )] Serious Infections [see Warnings and Precautions ( 5.2 )] Renal Toxicity and Increased Toxicity with Renal Impairment [see Warnings and Precautions ( 5.3 )] Gastrointestinal Toxicity [see Warnings and Precautions ( 5.4 )] Hepatic Toxicity [see Warnings and Precautions ( 5.5 )] Pulmonary Toxicity [see Warnings and Precautions ( 5.6 )] Hypersensitivity and Dermatologic Reactions [see Warnings and Precautions ( 5.7 )] Secondary Malignancies [see Warnings and Precautions ( 5.8 )] Ineffective Immunization and Risks Associated with Live Vaccines [see Warnings and Precautions ( 5.10 )] Infertility [see Warnings and Precautions ( 5.11 )] Increased Toxicity Due to Third‑Space Accumulation [see Warnings and Precautions ( 5.12 )] Soft Tissue and Bone Toxicity with Radiation Therapy [see Warnings and Precautions ( 5.13 )] Most common adverse reactions are: ulcerative stomatitis, leukopenia, nausea, abdominal distress, and elevated liver function tests.

Other frequently reported adverse reactions are malaise, fatigue, chills and fever, dizziness and decreased resistance to infection ( 6 ). To report SUSPECTED ADVERSE REACTIONS, contact Azurity Pharmaceuticals, Inc., at 1-800-461-7449 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience Because clinical trials 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. The most frequently reported adverse reactions include ulcerative stomatitis, leukopenia, nausea, and abdominal distress. Other frequently reported adverse reactions are malaise, fatigue, chills, fever, dizziness, and decreased resistance to infection.

Folate deficiency states may increase methotrexate toxicity. Polyarticular Juvenile Idiopathic Arthritis The approximate incidences of adverse reactions reported in pediatric patients with JIA treated with oral, weekly doses of methotrexate (5 to 20 mg/m 2 /week or 0.1 to 0.65 mg/kg/week) were as follows (virtually all patients were receiving concomitant nonsteroidal anti-inflammatory drugs, and some also were taking low doses of 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%; and rash, 0.2%.

Although there is experience with dosing up to 30 mg/m 2 /week in JIA, the published data for doses above 20 mg/m 2 /week are too limited to provide reliable estimates of adverse reaction rates.

6.2Postmarketing Experience Additional adverse reactions which have been identified during postmarketing use of methotrexate are listed below by organ system. Blood and Lymphatic System Disorders: Suppressed hematopoiesis causing anemia, aplastic anemia, pancytopenia, leukopenia, neutropenia, thrombocytopenia, lymphadenopathy, lymphoproliferative disorders (including reversible), hypogammaglobulinemia Cardiovascular: Thromboembolic events (including arterial thrombosis, cerebral thrombosis, deep vein thrombosis, retinal vein thrombosis, thrombophlebitis, and pulmonary embolus), pericarditis, pericardial effusion, hypotension Eye Disorders: Optic neuropathy, transient blindness, blurred vision, ocular irritation, conjunctivitis, xerophthalmia Gastrointestinal Disorders: Gingivitis, pharyngitis, stomatitis, anorexia, nausea, vomiting, diarrhea, hematemesis, melena, gastrointestinal ulceration and bleeding, enteritis, pancreatitis Hepatobiliary Disorders: Hepatotoxicity, acute hepatitis, chronic fibrosis and cirrhosis, decreased serum albumin, liver enzyme elevations Immune System Disorders: Vasculitis, lymphomas, and anaphylactoid reactions Infections: Fatal opportun…

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Oral Antibiotics: May increase hematologic and gastrointestinal toxicity. Monitor patients accordingly ( 7.1 ). Nitrous Oxide: May increase the risk of toxicity ( 7.1 ). NSAIDs, Aspirin, and Steroids: May elevate and prolong serum methotrexate levels and increase gastrointestinal toxicity. Monitor patients accordingly ( 7.1 ).

7.1Effect of Other Drugs on XATMEP Oral Antibiotics Penicillins may reduce the renal clearance of methotrexate; increased serum concentrations of methotrexate with concomitant hematologic and gastrointestinal toxicity have been observed with methotrexate. Monitor patients accordingly [see Warnings and Precautions ( 5.1 , 5.4 )] . Trimethoprim/sulfamethoxazole has been reported to increase bone marrow suppression in patients receiving methotrexate.

Monitor patients accordingly [see Warnings and Precautions ( 5.1 )] . Hepatotoxins The potential for increased hepatotoxicity when methotrexate is administered with other hepatotoxic agents has not been evaluated; however, hepatotoxicity has been reported in such cases. Monitor patients receiving XATMEP with other potential hepatotoxins (e.g., azathioprine, retinoids, and sulfasalazine) for possible signs of hepatotoxicity.

Probenecid Probenecid may reduce renal elimination of methotrexate. Consider alternative drugs. Nitrous Oxide The use of nitrous oxide anesthesia potentiates the effect of methotrexate on folate-dependent metabolic pathways, resulting in the potential for increase toxicity.

Avoid the simultaneous use of nitrous oxide and methotrexate. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), Aspirin, and Steroids Concomitant administration of some NSAIDs with high dose methotrexate therapy has been reported to elevate and prolong serum methotrexate levels, resulting in deaths from severe hematologic and gastrointestinal toxicity. Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate, including XATMEP.

These drugs have been reported to reduce the tubular secretion of methotrexate in an animal model and may enhance its toxicity. Despite the potential interactions, studies of methotrexate in patients with rheumatoid arthritis, including patients with polyarticular juvenile idiopathic arthritis (pJIA), have usually included concurrent use of constant dosage regimens of NSAIDs, without apparent problems. It should be appreciated, however, that the doses used in pJIA (10 mg/m 2 /week as starting dose) are somewhat lower than those used in acute lymphoblastic leukemia and that larger doses could lead to unexpected toxicity.

Aspirin, NSAIDs, and/or low dose steroids may be continued, although the possibility of increased toxicity with concomitant use of NSAIDs including salicylates has not been fully explored. Steroids may be reduced gradually in patients who respond to methotrexate.

7.2Effect of XATMEP on Other Drugs Theophylline Methotrexate may decrease the clearance of theophylline. Monitor theophylline levels when coadministered with XATMEP.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Advise women not to breastfeed ( 8.2 ).

8.1Pregnancy Risk Summary Based on published reports and methotrexate’s mechanism of action, methotrexate is a teratogen that can cause embryo-fetal toxicity and fetal death when administered to a pregnant woman [see Data and Clinical Pharmacology ( 12.1 )] . In pregnant women with non-malignant disease, XATMEP is contraindicated. Consider the benefits and risks of XATMEP and risks to the fetus when prescribing XATMEP to a pregnant patient with a neoplastic disease.

There are no animal data that meet current standards for nonclinical developmental toxicity studies. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data Human Data Published data from cases, 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 by U.S. and European teratology information services evaluated pregnancy outcomes in women taking methotrexate less than or equal to 30 mg/week after conception.

The rate of spontaneous abortion/miscarriage in pregnant women exposed to methotrexate was 42.5% (95% confidence interval [95% CI] 29.2-58.7), which was higher than in unexposed autoimmune disease comparators (22.5%, 95% CI 16.8-29.7) and unexposed nonautoimmune disease comparators (17.3%, 95% CI 13-22.8). Of the live births, the rate of major birth defects in pregnant women exposed to methotrexate after conception was higher than in autoimmune disease comparators (adjusted odds ratio (OR) 1.8 [95% CI 0.6-5.7]) and nonautoimmune disease comparators (adjusted OR 3.1 [95% CI 1.03-9.5]).

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. The highest breast milk to plasma concentration ratio demonstrated was 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, including myelosuppression, from methotrexate in breastfed infants, advise women not to breastfeed during XATMEP therapy.

8.3Females and Males of Reproductive Potential Pregnancy Testing Test for pregnancy prior to initiating therapy with XATMEP. Contraception Females XATMEP can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 )] . Advise females of reproductive potential to use effective contraception during and for 6 months after the final methotrexate dose.

Males Methotrexate can cause chromosomal damage to sperm cells. Advise males with female partners of reproductive potential to use effective contraception during and for at least 3 months after the final methotrexate dose. Infertility Females Based on published reports of female infertility after therapy with methotrexate, advise fem…

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary Based on published reports and methotrexate’s mechanism of action, methotrexate is a teratogen that can cause embryo-fetal toxicity and fetal death when administered to a pregnant woman [see Data and Clinical Pharmacology ( 12.1 )] . In pregnant women with non-malignant disease, XATMEP is contraindicated. Consider the benefits and risks of XATMEP and risks to the fetus when prescribing XATMEP to a pregnant patient with a neoplastic disease.

There are no animal data that meet current standards for nonclinical developmental toxicity studies. The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data Human Data Published data from cases, 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 by U.S. and European teratology information services evaluated pregnancy outcomes in women taking methotrexate less than or equal to 30 mg/week after conception.

The rate of spontaneous abortion/miscarriage in pregnant women exposed to methotrexate was 42.5% (95% confidence interval [95% CI] 29.2-58.7), which was higher than in unexposed autoimmune disease comparators (22.5%, 95% CI 16.8-29.7) and unexposed nonautoimmune disease comparators (17.3%, 95% CI 13-22.8). Of the live births, the rate of major birth defects in pregnant women exposed to methotrexate after conception was higher than in autoimmune disease comparators (adjusted odds ratio (OR) 1.8 [95% CI 0.6-5.7]) and nonautoimmune disease comparators (adjusted OR 3.1 [95% CI 1.03-9.5]).

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

🧒 Pediatric Use 55 words ▾

8.4Pediatric Use Safety and effectiveness of XATMEP in pediatric patients have been established for the treatment of pediatric patients with acute lymphoblastic leukemia (ALL) as part of a multi-phase, combination chemotherapy maintenance regimen and for the management of pediatric patients with active polyarticular juvenile idiopathic arthritis (pJIA) [see Clinical Studies ( 14 )] .

🆘 Overdosage ~1 min read ▾

10 OVERDOSAGE Manifestations Fatal overdosage has occurred with methotrexate. Manifestations of overdosage include adverse reactions reported at pharmacologic doses, particularly hematologic and gastrointestinal reactions (e.g., leukopenia, thrombocytopenia, anemia, pancytopenia, bone marrow suppression, mucositis, stomatitis, oral ulceration, nausea, vomiting, gastrointestinal ulceration, or gastrointestinal bleeding). In some cases, no symptoms were 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.

In cases of massive overdosage, 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 ~3 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 pJIA is unknown; it may affect immune function.

12.2Pharmacodynamics Two reports describe in vitro methotrexate inhibition of DNA precursor uptake by stimulated mono-nuclear cells, and another describes in animal polyarthritis partial correction by methotrexate of spleen cell hyporesponsiveness and suppressed IL 2 production. Other laboratories, however, have been unable to demonstrate similar effects.

12.3Pharmacokinetics Absorption In pediatric patients with ALL, oral absorption of methotrexate appears to be dose dependent; the absorption of doses greater than 40 mg/m 2 is significantly less than that of lower doses. The extent of oral absorption ranges from 23% to 95%, and the time to peak concentration (T max ) ranges from 0.7 hours to 4 hours after an oral dose of 15 mg/m 2 . In pediatric patients with pJIA, mean serum concentrations were 0.59 micromolar (range, 0.03 to 1.40) at 1 hour, 0.44 micromolar (range, 0.01 to 1.00) at 2 hours, and 0.29 micromolar (range 0.06 to 0.58) at 3 hours following oral administration of methotrexate at a dose of 6.4 mg/m 2 /week to 11.2 mg/m 2 /week.

Effect of Food The administration of XATMEP with food did not affect the area under the curve (AUC), but decreased the maximal concentrations (C max ) by 50% and delayed the absorption. Distribution After intravenous administration, the initial volume of distribution is approximately

0.18L/kg (18% of body weight) and steady-state volume of distribution is approximately 0.4 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 does not penetrate the blood-cerebrospinal fluid barrier in therapeutic amounts when given orally. Elimination In adults, the half-life of methotrexate following administration of low dose methotrexate (less than 30 mg/m 2 ) ranges from 3 hours to 10 hours.

In pediatric patients receiving methotrexate for ALL (6.3 mg/m 2 to 30 mg/m 2 ), the terminal half-life has been reported to range from 0.7 hours to 5.8 hours. In pediatric patients receiving methotrexate for JIA (3.75 mg/m 2 to 26.2 mg/m 2 ), the terminal half-life has been reported to range from 0.9 hours to 2.3 hours. Metabolism Methotrexate undergoes hepatic and intracellular metabolism to polyglutamated forms which 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.

A small amount of metabolism to 7‑hydroxymethotrexate may occur at doses commonly prescribed. The aqueous solubility of 7‑hydroxymethotrexate is 3- to 5-fold lower than the parent compound. Methotrexate is partially metabolized by intestinal flora after oral administration.

Excretion Renal excretion is the primary route of elimination and is dependent upon dosage and route of administration. With IV administration, 80% to 90% of the administ…

🧬 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 pJIA is unknown; it may affect immune function.

📦 How Supplied / Storage and Handling 127 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING XATMEP is a clear yellow to orange oral solution that contains 2.5 mg of methotrexate per milliliter (equivalent to 2.74 mg of methotrexate sodium/mL). It is packaged in a high-density polyethylene (HDPE) bottle with a child-resistant cap and tamper-evident seal. XATMEP is available in bottles of 60 mL (NDC 52652-2001-6) and 120 mL (NDC 52652-2001-1).

Store XATMEP refrigerated (2°C to 8°C/36°F to 46°F) tightly closed in the original container prior to dispensing. Once dispensed, patients may store XATMEP either refrigerated (2°C to 8°C/36°F to 46°F) or at room temperature (20°C to 25°C/68°F to 77°F) with excursions permitted to 15°C to 30°C/59°F to 86°F [see USP Controlled Room Temperature]. If stored at room temperature, discard after 60 days.

Avoid freezing and excessive heat.

📋 Description 71 words ▾

11 DESCRIPTION XATMEP contains methotrexate, a folate analog metabolic inhibitor. Chemically methotrexate is N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]-benzoyl]-L-glutamic acid. The structural formula is: XATMEP is a clear yellow to orange oral solution that contains 2.5 mg of methotrexate per milliliter (equivalent to 2.74 mg of methotrexate sodium/mL).

Inactive ingredients include purified water, sodium citrate, citric acid, methylparaben sodium, propylparaben sodium, and sucralose. It may also contain sodium hydroxide or hydrochloric acid for pH adjustment. structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Importance of Proper Dosing and Administration Advise patients that the recommended dose should be taken one time weekly, as directed, and that mistaken daily use of the recommended dose has led to fatal toxicity [see Dosage and Administration ( 2.1 ), Warnings and Precautions ( 5.15 )] . Advise patients and caregivers to measure XATMEP with an accurate milliliter measuring device. A household teaspoon is not an accurate measuring device.

Advise patients and caregivers to ask their pharmacist to recommend an appropriate measuring device and for instructions for measuring the correct dose. Bone Marrow Suppression and Serious Infections Advise patients to contact their healthcare provider for new onset fever, symptoms of infection, easy bruising or persistent bleeding [see Warnings and Precautions ( 5.1 , 5.2 )] . Renal Toxicity Advise patients that methotrexate can cause renal toxicity [see Warnings and Precautions ( 5.3 )] .

Gastrointestinal Toxicity Advise patients to contact their healthcare provider if they develop diarrhea, vomiting, or stomatitis [see Warnings and Precautions ( 5.4 )] . Hepatic Toxicity Advise patients concerning the risk of hepatic toxicity and avoidance of alcohol during methotrexate treatment [see Warnings and Precautions ( 5.5 )] . Pulmonary Toxicity Advise patients to contact their healthcare provider for symptoms of cough, fever, and dyspnea [see Warnings and Precautions ( 5.6 )] .

Hypersensitivity Reactions Advise patients concerning the risk for severe hypersensitivity reactions due to XATMEP treatment. These can be fatal and may include severe dermatologic reactions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, exfoliative dermatitis, and erythema multiforme. Advise patients to contact their healthcare provider for signs of a new or worsening rash [see Warnings and Precautions ( 5.7 )] .

Secondary Malignancies Advise patients that there is a risk of secondary malignancies during or following treatment with XATMEP [see Warnings and Precautions ( 5.8 )] . 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 Boxed Warning, Contraindications ( 4 ), Warnings and Precautions ( 5.9 ), Use in Specific Populations ( 8.1 )] . Advise females of reproductive potential to use effective contraception during XATMEP therapy and for 6 months after the final dose [see Use in Specific Populations ( 8.3 )] .

Advise males of reproductive potential to use effective contraception during XATMEP therapy and for 3 months after the final dose [see Use in Specific Populations ( 8.3 )] . Ineffective Immunization and Risks Associated with Live Vaccines Advise patients to avoid receiving vaccines during treatment with XATMEP because they may not be effective and live virus vaccines may cause infection [see Warnings and Precautions ( 5.10 )] . Infertility Advise patients of reproductive potential that XATMEP may cause impairment of fertility, oligospermia, and menstrual dysfunction [see Warnings and Precautions ( 5.11 ), Use in Specific Populations ( 8.3 )] .

Lactation Advise females not to breastfeed during therapy with XATMEP [see Use in Specific Populations ( 8.2 )] . Proper Storage and Disposal Advise patients to store XATMEP either refrigerated (2°C to 8°C/36°F to 46°F) or at room temperature (20°C to 25°C/68°F to 77°F) with excursions permitted to 15°C to 30°C/59°F to 86°F. If stored at room temperature, discard after 60 days.

Inform patients and caregivers of the need for proper storage and disposal of dispensing bottles and dosing devices [see References ( 15 )] . Manufactured for: Woburn, MA 01801 USA Patent: https://azurity.com/patents_and_trademarks/ This product’s label may have been updated. For current Full Prescribing Information, please visit www.xatmep.com REV05 azurity-logo

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