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Bendeka bendamustine hydrochloride 25 mg/mL Injection, Solution — NDC 63459-0348-04 package photo

Bendeka bendamustine hydrochloride 25 mg/mL Injection, Solution

by Teva Pharmaceuticals USA, Inc. · 1 VIAL, MULTI-DOSE in 1 CARTON (63459-348-04) / 4 mL in 1 VIAL, MULTI-DOSE
NDC 63459-0348-04
🏷️ FDA NDC (as labeled) 63459-348-04 billing pads the product segment with a zero
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) 63459-348-04
Product NDC 63459-348
11-digit billing NDC 63459034804
NCPDP billing unit ML — per mL (volume)
RxCUI 1726097, 1726102
UNII 981Y8SX18M
UPC 0363459348049
Application # NDA208194
SPL Set ID ace9a43b-f9bd-4896-abfe-0ef4fec67ddf
Established class (EPC) Alkylating Drug
Mechanism of action Alkylating Activity
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2015-12-08
Route INTRAVENOUS
Dosage form INJECTION, SOLUTION
Substance BENDAMUSTINE HYDROCHLORIDE
GPI-14 21100009102005
GPI class Bendeka
GCN Seq No 075249
GCN 40274
HICL code 016785
Ingredient (HICL) Bendamustine Hcl
HIC1 code V
Therapeutic class — broad (HIC1) Neoplasms
HIC2 code V1
Therapeutic class — intermediate (HIC2) Antineoplastic Drugs
HIC3 code V1A
Therapeutic class — specific (HIC3) Antineoplastic - Alkylating Agents
AHFS code 10:00.00.00
AHFS class Antineoplastic Agents
FDB label name BENDEKA 100 MG/4 ML VIAL
FDB brand name Bendeka
Legend status F — Federal legend — prescription drug or device
Why two NDCs? The FDA registers this code as 63459-348-04 — 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 → 63459-0348-04. 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 Alkylating Drug class.

Pharmacologic class Alkylating Drug
Drug family (ATC) Nitrogen mustard analogues
How it works Alkylating Activity
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerTeva Pharmaceuticals USA, Inc.
Application holderEAGLE PHARMACEUTICALS INC
FDA applicationNDA208194 (NDA)
Labeler code63459
First marketedDec 2015
Product typeHuman Prescription Drug
Portfolio504 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name BENDEKA 100 MG/4 ML VIAL Ingredient Bendamustine Hcl
📗 Our plain-language guide HelloPharmacist
  • Bendamustine targets cancer cells in your blood and lymph system. It's approved to treat chronic lymphocytic leukemia (CLL) — a cancer that starts in white blood cells — and a type...
  • What exactly is bendamustine treating in my body?
  • The most common things people notice are nausea, fatigue, and fever. Because bendamustine lowers your blood counts significantly, you're also at a higher risk for infections. Call...
  • What side effects should I actually expect, and which ones mean I need to call someone right away?
📖 Read our full Bendamustine guide →
1
Nutrient depletion considerations

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

🧪 Full Bendamustine Hydrochloride 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 AAO1P0WSXJ
    Monothioglycerol is a clear liquid derived from glycerin with a sulfur-containing group added. It works as an antioxidant and reducing agent in medicines, helping prevent degradation of active ingredients during storage.
  • UNII B697894SGQ
    Polyethylene glycol 400 is a clear, thick liquid made from petroleum-derived polymers. It acts as a solvent and humectant in medicines, helping dissolve active ingredients and retain moisture in the formulation.
  • UNII 6DC9Q167V3
    Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
  • UNII 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.

4 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 $350.67 $1,402.68 / 4 ml
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J9034 $12.532 / J9034 unit —
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)63459-348-04
11-digit billing NDC63459-0348-04
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ9034
DescriptorInjection, bendamustine hcl (bendeka), 1 mg
Billing units / pkg100 units
Crosswalk sourceCMS ASP NDC-HCPCS Crosswalk
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
Bendamustine Hydrochloride 100 mg 10019-0079-01 Baxter 1 vial — AP FDA listed —
Vivimusta 25 mg/mL 24338-0270-01 Azurity 1 vial — — FDA listed —
Belrapzo 100 mg/4mL 42367-0521-25 Eagle 1 vial — AP FDA listed —
Bendamustine Hydrochloride 25 mg/mL 60505-6228-00 Apotex 1 vial — AP FDA listed —
Bendeka 25 mg/mLthis 63459-0348-04 Teva 1 vial — — FDA listed —
Vivimusta 25 mg/mL 71225-0120-01 Slayback 1 vial — — FDA listed —
Bendamustine Hydrochloride 100 mg/4mL 83831-0183-04 Avyxa 1 vial — — FDA listed —
About this product: this is the brand-name version. Some generic versions are approved by the FDA, but we could not confirm current pharmacy availability from our pricing/market data.
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

🏛️
2015
First FDA approval
Dec 2015
📍
2026
Currently FDA-listed
11 years listed
🛡️
2033
Latest patent/protection listed
not a guaranteed launch date
🔒Generic approved by FDA, but pharmacy availability is not confirmed

The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Mar 2033. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Dec 7, 2015 RLD RS ⏳ ~6.5 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 9144568 — method of use (U-1542)
US 9572797 — method of use (U-1971)
US 10052385 — method of use (U-1972)
US 9597399 — method of use (U-1972)
US 9597399 — method of use (U-1971)
US 9034908 — method of use (U-1542)
US 8609707 — method of use (U-1542)
US 10052385 — method of use (U-1971)
US 9597397 — method of use (U-1972)
US 9572887 — method of use (U-1972)
US 9572887 — method of use (U-1971)
US 9572796 — method of use (U-1972)
US 9572797 — method of use (U-1972)
US 9579384 — method of use (U-1971)
US 9579384 — method of use (U-1972)
US 9000021 — method of use (U-1542)
US 9572796 — method of use (U-1971)
US 9597397 — method of use (U-1971)
US 12350257 — method of use (U-1542)
US 12350257 — method of use (U-1971)
US 12350257 — method of use (U-1972)
US 9597398 — method of use (U-1971)
US 11103483 — method of use (U-1971)
US 11103483 — method of use (U-1972)
US 11844783 — method of use (U-1542)
US 11844783 — method of use (U-1972)
US 11844783 — method of use (U-1971)
US 8791270 — method of use (U-1790)
US 11872214 — drug product
US 12138248 — drug product
US 10010533 — drug product
US 9265831 — drug product
2015 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 (32)
PatentTypeUse codeExpires
US 9144568 ↗ Method of use U-1542 Mar 15, 2033
US 9572797 ↗ Method of use U-1971 Jan 28, 2031
US 10052385 ↗ Method of use U-1972 Mar 15, 2033
US 9597399 ↗ Method of use U-1972 Mar 15, 2033
US 9597399 ↗ Method of use U-1971 Mar 15, 2033
US 9034908 ↗ Method of use U-1542 Mar 15, 2033
US 8609707 ↗ Method of use U-1542 Aug 11, 2031
US 10052385 ↗ Method of use U-1971 Mar 15, 2033
US 9597397 ↗ Method of use U-1972 Mar 15, 2033
US 9572887 ↗ Method of use U-1972 Mar 15, 2033
US 9572887 ↗ Method of use U-1971 Mar 15, 2033
US 9572796 ↗ Method of use U-1972 Jan 28, 2031
US 9572797 ↗ Method of use U-1972 Jan 28, 2031
US 9579384 ↗ Method of use U-1971 Mar 15, 2033
US 9579384 ↗ Method of use U-1972 Mar 15, 2033
US 9000021 ↗ Method of use U-1542 Mar 15, 2033
US 9572796 ↗ Method of use U-1971 Jan 28, 2031
US 9597397 ↗ Method of use U-1971 Mar 15, 2033
US 12350257 ↗ Method of use U-1542 Jan 28, 2031
US 12350257 ↗ Method of use U-1971 Jan 28, 2031
US 12350257 ↗ Method of use U-1972 Jan 28, 2031
US 9597398 ↗ Method of use U-1971 Mar 15, 2033
US 11103483 ↗ Method of use U-1971 Jan 28, 2031
US 11103483 ↗ Method of use U-1972 Jan 28, 2031
US 11844783 ↗ Method of use U-1542 Jan 28, 2031
US 11844783 ↗ Method of use U-1972 Jan 28, 2031
US 11844783 ↗ Method of use U-1971 Jan 28, 2031
US 8791270 ↗ Method of use U-1790 Jan 12, 2026
US 11872214 ↗ Drug product — Jan 28, 2031
US 12138248 ↗ Drug product — Jan 28, 2031
US 10010533 ↗ Drug product — Jan 28, 2031
US 9265831 ↗ Drug product — Jan 28, 2031
Common questions
Is there a generic version of BENDEKA 100 MG/4 ML VIAL?
Yes — an FDA-approved generic equivalent is listed in the FDA Orange Book for BENDEKA 100 MG/4 ML VIAL. See the alternatives section for substitutable, lower-cost products.
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 63459-0348-04, 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
1.5K
Units reimbursed last 4 qtrs
10.9K
Gross reimbursed last 4 qtrs
$3.83M
Avg / prescription
$2,478.09
Avg / unit
$350.68
Latest quarter Q4 2025
208Rx
Fee-for-service vs managed care ⓘ
25% FFS 75% MCO
Fee-for-service · 384 Rx Managed care · 1,160 Rx
State Medicaid map
Alaska: 166 units · 22.6 per 100k residents AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: 86 units · 7.6 per 100k residents MT North Dakota: no data reported ND Minnesota: 361 units · 6.3 per 100k residents MN Wisconsin: 197 units · 3.3 per 100k residents WI Michigan: 266 units · 2.7 per 100k residents MI New York: 855 units · 4.4 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: 624 units · 14.7 per 100k residents OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: 124 units · 3.9 per 100k residents IA Illinois: 321 units · 2.6 per 100k residents IL Indiana: 584 units · 8.5 per 100k residents IN Ohio: 184 units · 1.6 per 100k residents OH Pennsylvania: 536 units · 4.1 per 100k residents PA New Jersey: 329 units · 3.5 per 100k residents NJ Massachusetts: 575 units · 8.2 per 100k residents MA California: 1,515 units · 3.9 per 100k residents CA Utah: no data reported UT Colorado: 471 units · 8.0 per 100k residents CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: 568 units · 6.5 per 100k residents VA Maryland: 138 units · 2.2 per 100k residents MD Connecticut: 74 units · 2.0 per 100k residents CT Rhode Island: no data reported RI Arizona: 588 units · 7.9 per 100k residents AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: 62 units · 2.0 per 100k residents AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: 436 units · 1.4 per 100k residents TX Florida: 1,050 units · 4.6 per 100k residents FL
Units reimbursed · per 100k residents
1.422.6
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 Alaska 22.6 /100k
2 Oregon 14.7 /100k
3 Indiana 8.5 /100k
4 Massachusetts 8.2 /100k
5 Colorado 8.0 /100k
6 Arizona 7.9 /100k
7 Montana 7.6 /100k
8 Virginia 6.5 /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.

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

Medicare Part D (outpatient prescription) spending for Bendeka — 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 Bendeka. 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
$184.2K
Claims incl. refills
23
Beneficiaries
15
Spend / beneficiary
$12,282.61
Spend / claim
$8,010.40
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 Bendamustine hydrochloride — the ingredient across all brands.

Top reported reactions

Pyrexia861
Disease Progression572
Rash556
Febrile Neutropenia535
Neutropenia501
Pneumonia466
Platelet Count Decreased438

Age at onset

Child4
Adolescent8
Adult743
Elderly1,133

Reporter sex

11,906 reports
Male · 59%
Female · 40%
Unknown · 1%

Serious outcomes

Hospitalization4,485
Death2,055
Life-threatening607
Disabling176
Reports over time (by year) — tap or hover for the count & year
2021 2022 2024 2026 793 0
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDCDescription Marketing startStatus
63459-0348-04 You're viewing this 1 VIAL, MULTI-DOSE in 1 CARTON (63459-348-04) / 4 mL in 1 VIAL, MULTI-DOSE 2015-12-08 Active

🧭 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 63459-348-04, 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: 63459-0348-04, written without dashes as 63459034804. 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 63459-0348-04, the first segment (63459) is the labeler code FDA assigned to Teva Pharmaceuticals USA, Inc.; the middle segment (0348) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (04) identifies this exact package size and type. Together they name one specific package of one specific product.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Teva Pharmaceuticals USA, Inc.. Listing status can change — the directory data on this page refreshes weekly.
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📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🎯 Indications and Usage 124 words ▾

1 INDICATIONS AND USAGE BENDEKA injection is an alkylating drug indicated for treatment of patients with: Chronic lymphocytic leukemia (CLL). Efficacy relative to first line therapies other than chlorambucil has not been established. ( 1.1 ) Indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. ( 1.2 )

1.1Chronic Lymphocytic Leukemia (CLL) BENDEKA ® is indicated for the treatment of patients with chronic lymphocytic leukemia. Efficacy relative to first line therapies other than chlorambucil has not been established.

1.2Non-Hodgkin Lymphoma (NHL) BENDEKA is indicated for the treatment of patients with indolent B-cell non-Hodgkin lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION For CLL : 100 mg/m 2 infused intravenously over 10 minutes on Days 1 and 2 of a 28-day cycle, up to 6 cycles. ( 2.1 ) For NHL : 120 mg/m 2 infused intravenously over 10 minutes on Days 1 and 2 of a 21-day cycle, up to 8 cycles. ( 2.2 )

2.1Dosing Instructions for CLL Recommended Dosage : The recommended dosage is 100 mg/m 2 administered intravenously over 10 minutes on Days 1 and 2 of a 28-day cycle, up to 6 cycles. Dose Delays, Dosage Modifications and Reinitiation of Therapy for CLL : Delay BENDEKA administration in the event of Grade 4 hematologic toxicity or clinically significant greater than or equal to Grade 2 non-hematologic toxicity. Once non-hematologic toxicity has recovered to less than or equal to Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) greater than or equal to 1 x 10 9 /L, platelets greater than or equal to 75 x 10 9 /L], reinitiate BENDEKA (bendamustine hydrochloride) injection at the discretion of the treating physician.

In addition, consider dose reduction. [see Warnings and Precautions (5.1) ] Dosage modifications for hematologic toxicity: for Grade 3 or greater toxicity, reduce the dose to 50 mg/m 2 on Days 1 and 2 of each cycle; if Grade 3 or greater toxicity recurs, reduce the dose to 25 mg/m 2 on Days 1 and 2 of each cycle. Dosage modifications for non-hematologic toxicity: for clinically significant Grade 3 or greater toxicity, reduce the dose to 50 mg/m 2 on Days 1 and 2 of each cycle. Consider dosage re-escalation in subsequent cycles at the discretion of the treating physician.

2.2Dosing Instructions for NHL Recommended Dosage : The recommended dose is 120 mg/m 2 administered intravenously over 10 minutes on Days 1 and 2 of a 21-day cycle, up to 8 cycles. Dose Delays, Dosage Modifications and Reinitiation of Therapy for NHL : Delay BENDEKA administration in the event of a Grade 4 hematologic toxicity or clinically significant greater than or equal to Grade 2 non-hematologic toxicity. Once non-hematologic toxicity has recovered to less than or equal to Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) greater than or equal to 1 x 10 9 /L, platelets greater than or equal to 75 x 10 9 /L], reinitiate BENDEKA at the discretion of the treating physician.

In addition, consider dose reduction. [see Warnings and Precautions (5.1) ] Dosage modifications for hematologic toxicity: for Grade 4 toxicity, reduce the dose to 90 mg/m 2 on Days 1 and 2 of each cycle; if Grade 4 toxicity recurs, reduce the dose to 60 mg/m 2 on Days 1 and 2 of each cycle. Dosage modifications for non-hematologic toxicity: for Grade 3 or greater toxicity, reduce the dose to 90 mg/m 2 on Days 1 and 2 of each cycle; if Grade 3 or greater toxicity recurs, reduce the dose to 60 mg/m 2 on Days 1 and 2 of each cycle.

2.3Preparation for Intravenous Administration BENDEKA is a hazardous drug. Follow applicable special handling and disposal procedures. 1 BENDEKA is in a multiple-dose vial.

At room temperature, BENDEKA is a clear, and colorless to yellow ready-to-dilute solution. Store BENDEKA at recommended refrigerated storage conditions (2°C to 8°C or 36°F to 46°F). When refrigerated, the contents may freeze.

Allow the vial to reach room temperature (15°C to 30°C or 59°F to 86°F) prior to use. Do not use the product if particulate matter is observed after achieving room temperature. Intravenous Infusion Aseptically withdraw the volume needed for the required dose from the 25 mg/mL solution as per Table A below and immediately transfer the solution to a 50 mL infusion bag of one of the following diluents: – 0.9% Sodium Chloride Injection, USP; or – 2.5% Dextrose/0.45% Sodium Chloride Injection, USP; or – 5% Dextrose Injection, USP.

The resulting final concentration of bendamustine hydrochloride in the infusion bag should be within 0.49 mg/mL to 5.6 mg/mL. After transferring, thoroughly mix the contents of the infusion bag. The admixture should be a…

💊 Dosage Forms and Strengths 37 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: 100 mg/4 mL (25 mg/mL) as a clear and colorless to yellow ready-to-dilute solution in a multiple-dose vial. Injection: 100 mg/4 mL (25 mg/mL) in a multiple-dose vial. ( 3 )

⛔ Contraindications 67 words ▾

4 CONTRAINDICATIONS BENDEKA is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine, polyethylene glycol 400, propylene glycol, or monothioglycerol. [see Warnings and Precautions (5.4) ] BENDEKA is contraindicated in patients with a history of a hypersensitivity reaction to bendamustine, polyethylene glycol 400, propylene glycol, or monothioglycerol. Reactions to bendamustine hydrochloride have included anaphylaxis and anaphylactoid reactions ( 4 , 5.4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Myelosuppression: Delay or reduce dose, and restart treatment based on ANC and platelet count recovery. ( 2.1 , 5.1 ) Infections: Monitor for fever and other signs of infection or reactivation of infections and treat promptly. ( 5.2 ) Progressive multifocal leukoencephalopathy (PML): Monitor for new or worsening neurological, cognitive or behavioral signs or symptoms suggestive of PML.

( 5.3 ) Anaphylaxis and Infusion Reactions: Severe anaphylactic reactions have occurred. Monitor clinically and discontinue drug for severe reactions. Pre-medicate in subsequent cycles for milder reactions.

( 5.4 ) Tumor Lysis Syndrome: May lead to acute renal failure and death; anticipate and use supportive measures in patients at high risk. ( 5.5 ) Skin Reactions: Discontinue for severe skin reactions. Cases of SJS, DRESS and TEN, some fatal, have been reported.

( 5.6 ). Hepatotoxicity: Monitor liver chemistry tests prior to and during treatment. ( 5.7 ) Other Malignancies: Pre-malignant and malignant diseases have been reported.

( 5.8 ) Extravasation Injury: Take precautions to avoid extravasation, including monitoring intravenous infusion site during and after administration. ( 5.9 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus and to use an effective method of contraception.

( 5.10 , 8.1 , 8.3 )

5.1Myelosuppression Bendamustine hydrochloride caused severe myelosuppression (Grade 3-4) in 98% of patients in the two NHL studies [see Adverse Reactions (6.1) ] . Three patients (2%) died from myelosuppression-related adverse reactions; one each from neutropenic sepsis, diffuse alveolar hemorrhage with Grade 3 thrombocytopenia, and pneumonia from an opportunistic infection (CMV). BENDEKA causes myelosuppression.

Monitor complete blood counts, including leukocytes, platelets, hemoglobin (Hgb), and neutrophils frequently. In the clinical trials, blood counts were monitored every week initially. Hematologic nadirs occurred predominantly in the third week of therapy.

Myelosuppression may require dose delays and/or subsequent dose reductions if recovery to the recommended values has not occurred by the first day of the next scheduled cycle. Prior to the initiation of the next cycle of therapy, the ANC should be ≥ 1 x 10 9 /L and the platelet count should be ≥ 75 x 10 9 /L. [see Dosage and Administration (2.1) ]

5.2Infections Infection, including pneumonia, sepsis, septic shock, hepatitis and death has occurred in adult and pediatric patients in clinical trials and in postmarketing reports for bendamustine hydrochloride [see Adverse Reactions ( 6.1 , 6.2 )] . Patients with myelosuppression following treatment with bendamustine hydrochloride are more susceptible to infections. Advise patients with myelosuppression following BENDEKA treatment to contact a physician immediately if they have symptoms or signs of infection.

Patients treated with BENDEKA are at risk for reactivation of infections including (but not limited to) hepatitis B, cytomegalovirus, Mycobacterium tuberculosis, and herpes zoster. Patients should undergo appropriate measures (including clinical and laboratory monitoring, prophylaxis, and treatment) for infection and infection reactivation prior to administration.

5.3Progressive Multifocal Leukoencephalopathy (PML) Progressive multifocal leukoencephalopathy (PML), including fatal cases, have occurred following treatment with bendamustine, primarily in combination with rituximab or obinutuzumab [see Adverse Reactions (6.2) ] . Consider PML in the differential diagnosis in patients with new or worsening neurological, cognitive or behavioral signs or symptoms. If PML is suspected, withhold BENDEKA treatment and perform appropriate diagnostic evaluations.

Consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML. 5.4…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions have been associated with bendamustine hydrochloride in clinical trials and are discussed in greater detail in other sections of the prescribing information. Myelosuppression [see Warnings and Precautions (5.1) ] Infections [see Warnings and Precautions (5.2) ] Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.3) ] Anaphylaxis and Infusion Reactions [see Warnings and Precautions (5.4) ] Tumor Lysis Syndrome [see Warnings and Precautions (5.5) ] Skin Reactions [see Warnings and Precautions (5.6) ] Hepatotoxicity [see Warnings and Precautions (5.7) ] Other Malignancies [see Warnings and Precautions (5.8) ] Extravasation Injury [see Warnings and Precautions (5.9) ] Adverse reactions (frequency >5%) during infusion and within 24 hours post-infusion are nausea and fatigue.

( 6.1 ) Most common adverse reactions (≥15%) for CLL are anemia, thrombocytopenia, neutropenia, lymphopenia, leukopenia, hyperbilirubinemia, pyrexia, nausea, vomiting. ( 6.1 , 6.2 ) Most common adverse reactions (≥15%) for NHL are lymphopenia, leukopenia, anemia, neutropenia, thrombocytopenia, nausea, fatigue, vomiting, diarrhea, pyrexia, constipation, anorexia, cough, headache, weight decreased, dyspnea, rash, and stomatitis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals at 1-888-483-8279 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 data described below reflect exposure to bendamustine hydrochloride in 329 patients who participated in an actively controlled trial (N=153) for the treatment of CLL and two single arm studies (N=176) for the treatment of indolent B cell NHL.

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 safety of BENDEKA administered IV as a 50 mL admixture over a 10-minute infusion is supported by clinical trials using bendamustine hydrochloride administered IV as a 500 mL admixture over 30-60 minutes infusion time, as well as an open-label, crossover study in 81 ‘end-of-life’ cancer patients treated with BENDEKA.

In total, safety data from clinical studies are available from over 400 cancer patients exposed to bendamustine hydrochloride at doses in the range used in the treatment of CLL and NHL. No clinically significant differences in the adverse reaction profile were noted among bendamustine hydrochloride administered as a 500 mL admixture over standard infusion time (30-60 minutes) and BENDEKA administered as a 50 mL admixture in a ‘short-time’ infusion over 10 minutes. The safety and tolerability of BENDEKA was evaluated in an 8-week clinical study of BENDEKA in 81 ‘end-of-life’ cancer patients, diagnosed with solid tumors and hematologic malignancies (excluding CLL).

The population was 40-82 years of age, 58% females, 84% white, 12.3% Black, 1.2% Asian and 2.5% were classified as ‘other’. BENDEKA was administered IV at a 120 mg/m 2 dose as a 50 mL admixture over 10 minutes. Patients in the study received BENDEKA (50 mL IV, over 10 minutes) or bendamustine hydrochloride (500 mL IV, over 60 minutes) on Days 1 and 2 every 28 days for two consecutive 2-day cycles.

Adverse reactions (any grade) that occurred with a frequency greater than 5% during BENDEKA infusion and within one hour post-infusion were nausea (8.2%) and fatigue (5.5%). Adverse reactions (any grade) that occurred with a frequency greater than 5% within 24 hours of BENDEKA were nausea (10.9%) and fatigue (8.2%). Adverse reactions leading…

🔄 Drug Interactions 110 words ▾

7 DRUG INTERACTIONS Consider alternative therapies that are not CYP1A2 inducers or inhibitors during treatment with BENDEKA. ( 7.1 )

7.1Effect of Other Drugs on BENDEKA CYP1A2 Inhibitors The coadministration of BENDEKA with CYP1A2 inhibitors may increase bendamustine plasma concentrations and may result in increased incidence of adverse reactions with BENDEKA [see Clinical Pharmacology (12.3) ] . Consider alternative therapies that are not CYP1A2 inhibitors during treatment with BENDEKA. CYP1A2 Inducers The coadministration of BENDEKA with CYP1A2 inducers may decrease bendamustine plasma concentrations and may result in decreased efficacy of BENDEKA [see Clinical Pharmacology (12.3) ] .

Consider alternative therapies that are not CYP1A2 inducers during treatment with BENDEKA.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. ( 8.2 ) Infertility: May impair fertility. ( 8.3 ) Renal Impairment: Do not use in patients with creatinine clearance <30 mL/min. ( 8.6 ) Hepatic Impairment: Do not use in patients with total bilirubin 1.5-3 × ULN and AST or ALT 2.5-10 × ULN, or total bilirubin > 3 × ULN. ( 8.7 )

8.1Pregnancy Risk Summary In animal reproduction studies, intraperitoneal administration of bendamustine to pregnant mice and rats during organogenesis at doses 0.6 to 1.8 times the maximum recommended human dose (MRHD) resulted in embryo-fetal and/or infant mortality, structural abnormalities, and alterations to growth (see Data) . There are no available data on bendamustine hydrochloride use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

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 Animal Data Bendamustine hydrochloride was intraperitoneally administered once to mice from 210 mg/m 2 (approximately 1.8 times the MRHD) during organogenesis and caused an increase in resorptions, skeletal and visceral malformations (exencephaly, cleft palates, accessory rib, and spinal deformities) and decreased fetal body weights. This dose did not appear to be maternally toxic and lower doses were not evaluated.

Repeat intraperitoneal administration of bendamustine hydrochloride to mice on gestation days 7 to 11 resulted in an increase in resorptions from 75 mg/m2 (approximately 0.6 times the MRHD) and an increase in abnormalities from 112.5 mg/m 2 (approximately 0.9 times the MRHD), similar to those seen after a single intraperitoneal administration. Bendamustine hydrochloride was intraperitoneally administered once to rats from 120 mg/m 2 (approximately the MRHD) on gestation days 4, 7, 9, 11, or 13 and caused embryo and fetal lethality as indicated by increased resorptions and a decrease in live fetuses.

A significant increase in external (effect on tail, head, and herniation of external organs [exomphalos]) and internal (hydronephrosis and hydrocephalus) malformations were seen in dosed rats.

8.2Lactation Risk Summary There are no data on the presence of bendamustine hydrochloride or its metabolites in either human or animal milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in the breastfed child, advise patients that breastfeeding is not recommended during treatment with BENDEKA, and for 1 week after the last dose.

8.3Females and Males of Reproductive Potential BENDEKA can cause embryo-fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing Pregnancy testing is recommended for females of reproductive potential prior to initiation of BENDEKA [see Use in Specific Populations (8.1) ] . Contraception Females Advise female patients of reproductive potential to use effective contraception during treatment with BENDEKA and for 6 months after the last dose.

Males Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with BENDEKA and for 3 months after the last dose [see Nonclinical Toxicology (13.1) ] . Infertility Males Based on findings from clinical studies, BENDEKA may impair male fertility. Impaired spermatogenesis, azoospermia, and total germinal aplasia have been reported in male patients treated with alkylating agents, especially in combination with other drugs.

In some instances, spermatogenesis may return…

🤰 Pregnancy ~1 min read ▾

8.1Pregnancy Risk Summary In animal reproduction studies, intraperitoneal administration of bendamustine to pregnant mice and rats during organogenesis at doses 0.6 to 1.8 times the maximum recommended human dose (MRHD) resulted in embryo-fetal and/or infant mortality, structural abnormalities, and alterations to growth (see Data) . There are no available data on bendamustine hydrochloride use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

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 Animal Data Bendamustine hydrochloride was intraperitoneally administered once to mice from 210 mg/m 2 (approximately 1.8 times the MRHD) during organogenesis and caused an increase in resorptions, skeletal and visceral malformations (exencephaly, cleft palates, accessory rib, and spinal deformities) and decreased fetal body weights. This dose did not appear to be maternally toxic and lower doses were not evaluated.

Repeat intraperitoneal administration of bendamustine hydrochloride to mice on gestation days 7 to 11 resulted in an increase in resorptions from 75 mg/m2 (approximately 0.6 times the MRHD) and an increase in abnormalities from 112.5 mg/m 2 (approximately 0.9 times the MRHD), similar to those seen after a single intraperitoneal administration. Bendamustine hydrochloride was intraperitoneally administered once to rats from 120 mg/m 2 (approximately the MRHD) on gestation days 4, 7, 9, 11, or 13 and caused embryo and fetal lethality as indicated by increased resorptions and a decrease in live fetuses.

A significant increase in external (effect on tail, head, and herniation of external organs [exomphalos]) and internal (hydronephrosis and hydrocephalus) malformations were seen in dosed rats.

🧒 Pediatric Use 139 words ▾

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established. Safety, pharmacokinetics and efficacy were assessed in a single open-label trial (NCT01088984) in patients aged 1 to 19 years with relapsed or refractory acute leukemia, including 27 patients with acute lymphocytic leukemia (ALL) and 16 patients with acute myeloid leukemia (AML). Bendamustine hydrochloride was administered as an intravenous infusion over 60 minutes on Days 1 and 2 of each 21-day cycle.

There was no treatment response (CR+ CRp) in any patient. The safety profile in these patients was consistent with that seen in adults, and no new safety signals were identified. The pharmacokinetics of bendamustine in 43 patients, aged 1 to 19 years (median age of 10 years) were within range of values previously observed in adults given the same dose based on body surface area.

🧓 Geriatric Use 86 words ▾

8.5Geriatric Use No overall differences in safety were observed between patients ≥65 years of age and younger patients. Efficacy was lower in patients 65 and over with CLL receiving bendamustine hydrochloride based upon an overall response rate of 47% for patients 65 and over and 70% for younger patients. Progression free survival was also longer in younger patients with CLL receiving bendamustine (19 months vs.

12 months). No overall differences in efficacy in patients with non-Hodgkin Lymphoma were observed between geriatric patients and younger patients.

🆘 Overdosage 120 words ▾

10 OVERDOSAGE The intravenous LD 50 of bendamustine hydrochloride is 240 mg/m 2 in the mouse and rat. Toxicities included sedation, tremor, ataxia, convulsions and respiratory distress. Across all clinical experience, the reported maximum single dose received was 280 mg/m 2 .

Three of four patients treated at this dose showed ECG changes considered dose-limiting at 7 and 21 days post-dosing. These changes included QT prolongation (one patient), sinus tachycardia (one patient), ST and T wave deviations (two patients) and left anterior fascicular block (one patient). Cardiac enzymes and ejection fractions remained normal in all patients.

No specific antidote for bendamustine hydrochloride overdose is known. Management of overdosage should include general supportive measures, including monitoring of hematologic parameters and ECGs.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Bendamustine is a bifunctional mechlorethamine derivative containing a purine-like benzimidazole ring. Mechlorethamine and its derivatives form electrophilic alkyl groups. These groups form covalent bonds with electron-rich nucleophilic moieties, resulting in interstrand DNA crosslinks.

The bifunctional covalent linkage can lead to cell death via several pathways. Bendamustine is active against both quiescent and dividing cells. The exact mechanism of action of bendamustine remains unknown.

12.2Pharmacodynamics Based on the pharmacokinetics/pharmacodynamics analyses of data from adult patients with NHL, nausea increased with increasing bendamustine C max . Cardiac Electrophysiology The effect of bendamustine on the QTc interval was evaluated in 53 patients with indolent NHL and mantle cell lymphoma on Day 1 of Cycle 1 after administration of rituximab at 375 mg/m 2 intravenous infusion followed by a 30-minute intravenous infusion of bendamustine at 90 mg/m 2 /day. No mean changes greater than 20 milliseconds were detected up to one hour post infusion.

The potential for delayed effects on the QT interval after one hour was not evaluated.

12.3Pharmacokinetics Following a single dose of 120 mg/m 2 of bendamustine hydrochloride over 10-minute infusion, the mean C max achieved was 35 µg/mL (range 6 to 49 µg/mL), occurring typically at the end of infusion. Little or no accumulation in plasma is expected for bendamustine administered on Days 1 and 2 of a 28-day cycle. Distribution The protein binding of bendamustine ranged from 94 to 96% and was concentration independent from 1 to 50 µg/mL.

The blood to plasma concentration ratios in human blood ranged from 0.84 to 0.86 over a concentration range of 10 to 100 µg/mL. The mean steady-state volume of distribution (V SS ) of bendamustine was approximately 20 to 25 L. Elimination After a single intravenous dose of 120 mg/m 2 of bendamustine over 1 hour, the intermediate half-life (t ½ ) of the parent compound is approximately 40 minutes.

The mean terminal elimination t ½ of two active metabolites, γ-hydroxybendamustine (M3) and N desmethylbendamustine (M4) are approximately 3 hours and 30 minutes, respectively. Bendamustine clearance in humans is approximately 700 mL/min. Metabolism Bendamustine is extensively metabolized via hydrolytic, oxidative, and conjugative pathways.

Bendamustine is primarily metabolized via hydrolysis to monohydroxy (HP1) and dihydroxybendamustine (HP2) metabolites with low cytotoxic activity in vitro. Two active minor metabolites, M3 and M4, are primarily formed via CYP1A2 in vitro. M3 and M4 concentrations of these metabolites in plasma are 1/10 th and 1/100 th that of the parent compound, respectively.

Excretion Following IV infusion of radiolabeled bendamustine hydrochloride in cancer patients, approximately 76% of the dose was recovered. Approximately 50% of the dose was recovered in the urine (3.3% unchanged) and approximately 25% of the dose was recovered in the feces. Less than 1% of the dose was recovered in the urine as M3 and M4, and less than 5% of the dose was recovered in the urine as HP2.

Specific Populations No clinically meaningful effects on the pharmacokinetics of bendamustine were observed based on age (31 to 84 years), sex, mild to moderate renal impairment (CLcr ≥ 30 mL/min), or hepatic impairment with total bilirubin 1.5 < ULN and AST or ALT < 2.5 × ULN. The effects of severe renal impairment (CLcr < 30 mL/min), or hepatic impairment with total bilirubin 1.5-3 × ULN and AST or ALT 2.5-10 × ULN or total bilirubin > 3 × ULN on the pharmacokinetics of bendamustine is unknown. Race/Ethnicity Exposures in Japanese subjects (n=6) were 40% higher than that in non-Japanese subjects receiving the same dose.

The clinical importance of this difference on the safety and efficacy of bendamustine hydrochloride in Japanese subjects has not been established. Drug Interaction Studies In Vitro Studies Effect…

🧬 Mechanism of Action 67 words ▾

12.1Mechanism of Action Bendamustine is a bifunctional mechlorethamine derivative containing a purine-like benzimidazole ring. Mechlorethamine and its derivatives form electrophilic alkyl groups. These groups form covalent bonds with electron-rich nucleophilic moieties, resulting in interstrand DNA crosslinks.

The bifunctional covalent linkage can lead to cell death via several pathways. Bendamustine is active against both quiescent and dividing cells. The exact mechanism of action of bendamustine remains unknown.

📦 How Supplied / Storage and Handling 164 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Safe Handling and Disposal BENDEKA (bendamustine hydrochloride) injection is a hazardous drug. Follow applicable special handling and disposal procedures. 1 Care should be exercised in the handling and preparation of solutions prepared from BENDEKA (bendamustine hydrochloride) injection.

The use of gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage. If a solution of BENDEKA (bendamustine hydrochloride) injection contacts the skin, wash the skin immediately and thoroughly with soap and water. If BENDEKA (bendamustine hydrochloride) injection contacts the mucous membranes, flush thoroughly with water.

How Supplied BENDEKA (bendamustine hydrochloride) injection is supplied in individual cartons of 5 mL clear multiple-dose vials containing 100 mg of bendamustine hydrochloride as a clear, and colorless to yellow ready-to-dilute solution. NDC 63459-348-04, 100 mg/4 mL (25 mg/mL) Storage Store BENDEKA (bendamustine hydrochloride) injection in refrigerator, 2°C to 8°C (36°F to 46°F). Retain in original carton until time of use to protect from light.

📋 Description 133 words ▾

11 DESCRIPTION BENDEKA (bendamustine hydrochloride) injection is an alkylating agent. The chemical name of bendamustine hydrochloride is 1H-benzimidazole-2-butanoic acid, 5-[bis(2-chloroethyl)amino]-1 methyl-, monohydrochloride. Its empirical molecular formula is C 16 H 21 Cl 2 N 3 O 2 · HCl, and the molecular weight is 394.7.

Bendamustine hydrochloride contains a mechlorethamine group and a benzimidazole heterocyclic ring with a butyric acid substituent, and has the following structural formula: BENDEKA (bendamustine hydrochloride) injection for intravenous use is supplied as a sterile, clear, and colorless to yellow ready-to-dilute solution in a multiple-dose clear glass vial. Each milliliter contains 25 mg of bendamustine hydrochloride, USP, 0.1 mL of Propylene Glycol, USP, 5 mg of Monothioglycerol, NF, in Polyethylene Glycol 400, NF. Sodium hydroxide may have been used to adjust the acidity of polyethylene glycol 400.

Chemical Structure

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Myelosuppression Inform patients of the likelihood that BENDEKA (bendamustine hydrochloride) injection will cause a decrease in white blood cells, platelets, and red blood cells. They will need frequent monitoring of these parameters. They should be instructed to report shortness of breath, significant fatigue, bleeding, fever, or other signs of infection [see Warnings and Precautions (5.1) ] .

Progressive Multifocal Leukoencephalopathy (PML) Inform patients to immediately contact their healthcare provider if they experience confusion, memory loss, trouble thinking, difficulty talking or walking, vision loss or other neurological or cognitive symptoms [see Warnings and Precautions (5.3) ] . Anaphylaxis and Infusion Reactions Inform patients of the possibility of serious or mild allergic reactions and to immediately report rash, facial swelling, or difficulty breathing during or soon after infusion [see Warnings and Precautions (5.4) ] .

Skin Reactions Advise patients that a mild rash or itching may occur during treatment with BENDEKA (bendamustine hydrochloride) injection. Advise patients to immediately report severe or worsening rash or itching [see Warnings and Precautions (5.6) ] . Hepatotoxicity Inform patients of the possibility of developing liver function abnormalities and serious hepatic toxicity.

Advise patients to immediately contact their healthcare provider if signs of liver failure occur, including jaundice, anorexia, bleeding or bruising [see Warnings and Precautions (5.7) ] . Fatigue Advise patients that BENDEKA (bendamustine hydrochloride) injection may cause tiredness and to avoid driving any vehicle or operating any dangerous tools or machinery if they experience this side effect [see Adverse Reactions (6.1) ] . Nausea and Vomiting Advise patients that BENDEKA (bendamustine hydrochloride) injection may cause nausea and/or vomiting.

Patients should report nausea and vomiting so that symptomatic treatment may be provided [see Adverse Reactions (6.1) ] . Diarrhea Advise patients that BENDEKA (bendamustine hydrochloride) injection may cause diarrhea. Patients should report diarrhea to the physician so that symptomatic treatment may be provided [see Adverse Reactions (6.1) ] .

Non-melanoma Skin Cancer (NMSC) Advise patients to undergo regular skin cancer screenings, and to report any suspicious skin changes to their healthcare provider [see Warnings and Precautions (5.8) ] . Embryo-Fetal Toxicity Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.10) , Use in Specific Populations (8.2, 8.3) and Nonclinical Toxicology (13.1) ] .

Advise female patients of reproductive potential to use effective contraception during treatment with BENDEKA and for 6 months after the last dose [see Use in Specific Populations (8.1 , 8.3) ] . Advise males with female partners of reproductive potential to use effective contraception during treatment with BENDEKA and for 3 months after the last dose [see Use in Specific Populations (8.3) , and Nonclinical Toxicology (13.1) ] . Lactation Advise females not to breastfeed during treatment with BENDEKA and for 1 week after the last dose [see Use in Specific Populations (8.2) ] .

Infertility Advise males of reproductive potential that BENDEKA may impair fertility [see Use in Specific Populations (8.3) ] . BEN-012 Manufactured For: Teva Pharmaceuticals 400 Interpace Parkway #3, Parsippany, NJ 07054 All rights reserved.

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.