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bendamustine hydrochloride 100 mg/20mL Injection, Powder, Lyophilized, For Solution — NDC 16729-0251-05 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

bendamustine hydrochloride 100 mg/20mL Injection, Powder, Lyophilized, For Solution — NDC 16729-251-05 (Billing 16729-0251-05)

by Accord Healthcare, Inc. · 1 VIAL, SINGLE-DOSE in 1 CARTON / 20 mL in 1 VIAL, SINGLE-DOSE

This is a package of bendamustine hydrochloride 100 mg/20mL Injection, Powder, Lyophilized, For Solution from Accord Healthcare, Inc., marketed since Dec 2022 and currently FDA-listed. It is this product's only package size.

NDC 16729-0251-05
🏷️ FDA NDC (as labeled) 16729-251-05 billing pads the product segment with a zero
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

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Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 16729-251-05 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
16729 labeler · 251 product · 05 package
Package marketed since
Dec 7, 2022
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Barcode (UPC)
0316729251051
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 16729-251-05
Product NDC 16729-251
11-digit billing NDC 16729025105
NCPDP billing unit EA — each (per item)
RxCUI 1805001, 1805007
UNII 981Y8SX18M
UPC 0316729251051
Application # ANDA205574
SPL Set ID 33867f0f-f317-1fd0-e054-00144ff8d46c
Established class (EPC) Alkylating Drug
Mechanism of action Alkylating Activity
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2022-12-07
Route INTRAVENOUS
Dosage form INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Substance BENDAMUSTINE HYDROCHLORIDE
TE code (Orange Book) AP · RLD · RS

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

GCN Seq No 042496
GCN 12014
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 BENDAMUSTINE 100 MG VIAL
FDB brand name Bendamustine Hcl
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 042496
  • GCN: 12014
  • HICL (First Databank): 016785
  • AHFS class code: 10:00.00.00
  • RxCUI (RxNorm): 1805001
Why two NDCs? The FDA registers this code as 16729-251-05 — 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 → 16729-0251-05. 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.

Clinical

Label name BENDAMUSTINE 100 MG VIAL Ingredient Bendamustine Hcl
📖 What it is MedlinePlus · NLM

Bendamustine injection is used to treat chronic lymphocytic leukemia (CLL; a type of cancer of the white blood cells). Bendamustine injection is also used to treat a type of non-Hodgkins lymphoma (NHL: cancer that begins in a type of white blood cell that normally fights infection) that is slow spreading, but has continued to worsen during or after treatment with another medication. Bendamustine is in a class of medications called alkylating agents. It works by killing existing cancer cells and limiting the growth of new cancer cells.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • It treats chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphoma that has progressed during or within six months of rituximab. It is a chemotherapy drug given...
  • A healthcare professional gives it as an IV infusion on two days in a row of each cycle. How long each infusion takes depends on the product. Your team will schedule everything and...
  • Nausea, vomiting, tiredness and fever are common. Low blood counts are also common, and your team will monitor them. Diarrhea, constipation, rash and headache can happen too.
  • Call right away for fever, chills or other signs of infection. Also call for rash, itching or swelling during or after an infusion, blistering or peeling skin, redness or pain at t...
📖 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.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J9033 $2.960 / J9033 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)16729-251-05
11-digit billing NDC16729-0251-05
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ9033
DescriptorINJECTION, BENDAMUSTINE HCL (TREANDA), 1 MG
Billing units / pkg100 units
How the units are derivedThis package is 1 EA; the HCPCS unit is 1 MG, so one package = 100 billing units.
Medicare Part B spend (2026 (Q1))$211,335 · 507 claims · $416.83 per claim (all NDCs under J9033)
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
16729-0251-05 You're viewing this Main listing 1 VIAL, SINGLE-DOSE in 1 CARTON / 20 mL in 1 VIAL, SINGLE-DOSE 2022-12-07 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
bendamustine hydrochloride 100 mg/20mLthis 16729-0251-05 Accord 1 vial — AP FDA listed —
Bendamustine Hydrochloride 100 mg/20mL 55150-0392-01 Eugia 1 vial — AP FDA listed —
Treanda 100 mg/20mL 63459-0391-20 Cephalon, 1 vial — AP FDA listed —
bendamustine hydrochloride 100 mg/20mL 68001-0572-41 BluePoint 1 vial — AP FDA listed —
Bendamustine 100 mg/20mL 71288-0103-20 Meitheal 1 vial — AP FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2022
On the market since
Dec 2022
📍
2026
Currently FDA-listed
4 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

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

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

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 3OWL53L36A
    A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.

1 inactive ingredient listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerAccord Healthcare, Inc.
Application holderACCORD HEALTHCARE INC
FDA applicationANDA205574 (ANDA)
Labeler code16729
First marketedDec 2022
Product typeHuman Prescription Drug
Portfolio67 products on file

More NDCs from Accord Healthcare, Inc. labeler code 16729

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 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 🍼 Nursing Mothers 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📚 References 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 131 words ▾

1 INDICATIONS AND USAGE Bendamustine hydrochloride for 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) Bendamustine hydrochloride for Injection 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) Bendamustine hydrochloride for Injection 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 Bendamustine hydrochloride is available in two formulations, a solution (Bendamustine Hydrochloride Injection) and a lyophilized powder (Bendamustine Hydrochloride for Injection). ( 2.1 ) For CLL : 100 mg/m 2 infused intravenously over 30 minutes on Days 1 and 2 of a 28-day cycle, up to 6 cycles ( 2.2 ) For NHL : 120 mg/m 2 infused intravenously over 60 minutes on Days 1 and 2 of a 21-day cycle, up to 8 cycles ( 2.3 )

2.1Selection of Bendamustine Hydrochloride Formulation to Administer Bendamustine hydrochloride is available in two formulations, a solution (Bendamustine hydrochloride Injection) and a lyophilized powder (Bendamustine hydrochloride for Injection). Bendamustine hydrochloride Injection and the reconstituted Bendamustine hydrochloride for Injection have different concentrations of bendamustine hydrochloride. The concentration of bendamustine hydrochloride in the solution is 90 mg/mL and the concentration of bendamustine hydrochloride in the reconstituted solution of lyophilized powder is 5 mg/mL.

Do not mix or combine the two formulations. If a closed system transfer device (CSTD) or adapter that contains polycarbonate or acrylonitrile-butadiene-styrene (ABS) is used as supplemental protection prior to dilution 1 , only use Bendamustine hydrochloride for Injection, the lyophilized powder formulation [see How Supplied/Storage and Handling ( 16 )] .

2.2Dosing Instructions for CLL Recommended Dosage: The recommended dose is 100 mg/m 2 administered intravenously over 30 minutes on Days 1 and 2 of a 28-day cycle, up to 6 cycles. Dose Delays, Dose Modifications and Reinitiation of Therapy for CLL: Delay Bendamustine hydrochloride for Injection administration in the event of Grade 4 hematologic toxicity or clinically significant ≥ 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) ≥ 1 x 10 9 /L, platelets ≥ 75 x 10 9 /L], reinitiate Bendamustine hydrochloride for Injection at the discretion of the treating physician.

In addition, consider dose reduction. [see Warnings and Precautions ( 5.1 )] Dose 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. Dose 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 dose re-escalation in subsequent cycles at the discretion of the treating physician.

2.3Dosing Instructions for NHL Recommended Dosage: The recommended dose is 120 mg/m 2 administered intravenously over 60 minutes on Days 1 and 2 of a 21-day cycle, up to 8 cycles. Dose Delays, Dose Modifications and Reinitiation of Therapy for NHL: Delay Bendamustine hydrochloride for Injection 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 ≤ Grade 1 and/or the blood counts have improved [Absolute Neutrophil Count (ANC) ≥ 1 x 10 9 /L, platelets ≥ 75 x 10 9 /L], reinitiate Bendamustine hydrochloride for Injection at the discretion of the treating physician.

In addition, consider dose reduction. [see Warnings and Precautions ( 5.1 )] Dose 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. Dose 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.

2.4Preparation for Intravenous Administration Bendamustine hydroc… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 45 words ▾

3 DOSAGE FORMS AND STRENGTHS Bendamustine hydrochloride for Injection, USP: 25 mg or 100 mg white to off-white lyophilized powder in a single-dose vial for reconstitution. For Injection : 25 mg or 100 mg lyophilized powder in a single-dose vial for reconstitution. ( 3 )

⛔ Contraindications 57 words ▾

4 CONTRAINDICATIONS Bendamustine hydrochloride for Injection is contraindicated in patients with a known hypersensitivity (e.g., anaphylactic and anaphylactoid reactions) to bendamustine. [see Warnings and Precautions ( 5.4 )] Bendamustine hydrochloride for Injection is contraindicated in patients with a history of a hypersensitivity reaction to bendamustine. Reactions 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. ( 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 and 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 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). 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 were observed 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 ( 2.2 ) and ( 2.3 )]

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 [see Adverse Reactions ( 6.1 , 6.2 )] . Patients with myelosuppression following treatment with Bendamustine hydrochloride for Injection are more susceptible to infections. Advise patients with myelosuppression following bendamustine hydrochloride treatment to contact a physician if they have symptoms or signs of infection.

Patients treated with bendamustine hydrochloride 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 bendamustine hydrochloride treatment and perform appropriate diagnostic evaluations.

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

5.4Anaphylaxis and Infusion Reactions Infusion rea… [Excerpted — this section continues on DailyMed.]

🤒 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 label. 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, 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 , 6.2 ) To report SUSPECTED ADVERSE REACTIONS, contact Accord Healthcare Inc. at 1-866-941-7875 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. Chronic Lymphocytic Leukemia The data described below reflect exposure to bendamustine hydrochloride in 153 patients. Bendamustine hydrochloride was studied in an active-controlled, randomized trial.

The population was 45-77 years of age, 63% male, 100% white, and had treatment naïve CLL. All patients started the study at a dose of 100 mg/m 2 intravenously over 30 minutes on Days 1 and 2 every 28 days. Adverse reactions were reported according to NCI CTC v.2.0.

In the randomized CLL clinical study, non-hematologic adverse reactions (any grade) in the bendamustine hydrochloride group that occurred with a frequency greater than 15% were pyrexia (24%), nausea (20%), and vomiting (16%). Other adverse reactions seen frequently in one or more studies included asthenia, fatigue, malaise, and weakness; dry mouth; somnolence; cough; constipation; headache; mucosal inflammation and stomatitis. Worsening hypertension was reported in 4 patients treated with bendamustine hydrochloride in the randomized CLL clinical study and in none treated with chlorambucil.

Three of these 4 adverse reactions were described as a hypertensive crisis and were managed with oral medications and resolved. The most frequent adverse reactions leading to study withdrawal for patients receiving bendamustine hydrochloride were hypersensitivity (2%) and pyrexia (1%). Table 1 contains the treatment emergent adverse reactions, regardless of attribution, that were reported in ≥ 5% of patients in either treatment group in the randomized CLL clinical study.

Table 1: Non- Hematologic Adverse Reactions Occurring in Randomized CLL Clinical Study in at Least 5% of Patients Number (%) of patients Bendamustine hydrochloride (N=153) Chlorambucil (N=143) Body System/ Adverse Reaction All Grades Grade 3/4 All Grades Grade 3/4 Total number of patients with at least 1 adverse reaction 121 (79) 52 (34) 96 (67) 25 (17) Gastrointestinal disorders Nausea 31 (20) 1 (<1) 21 (15) 1 (<1) Vomiting 24 (16) 1 (<1) 9 (6) 0 Diarrhea 14 (9) 2 (1) 5 (3) 0 General disorders and administration site conditions Pyrexia 36 (24) 6 (4) 8 (6) 2 (1) Fatigue 14 (9) 2 (1) 8 (6) 0 Asthenia 13 (8) 0 6 (4) 0 Chills 9 (6) 0 1 (<1) 0 Immune system disorders Hypersensitivity 7 (5) 2 (1) 3 (2) 0 Infections and infesta… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 120 words ▾

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

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

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

👥 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 x ULN and AST or ALT 2.5-10 x ULN, or total bilirubin >3 x 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/m 2 (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 bendamustine hydrochloride, and for 1 week after the last dose.

8.3Females and Males of Reproductive Potential Bendamustine hydrochloride can cause 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 treatment with bendamustine hydrochloride. Contraception Females Bendamustine hydrochloride can cause embryo-fetal harm when administered to pregnant women [see Use in Specific Populations ( 8.1 )].

Advise female patients of reproductive potential to use effective contraception during treatment with bendamustine hydrochloride 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 bendamustine hydrochloride and for 3 months after the last dose [see Nonclinical Toxicology ( 13.1 )] . Infertility Males Based on findings from clinical studies, bendamustine hydrochloride may impair male fertility.

Impaired… [Excerpted — this section continues on DailyMed.]

🤰 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/m 2 (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 177 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 in the Phase 2 portion of the trial at a dose of 120 mg/m 2 . However, 2 patients with ALL achieved CR at a dose of 90 mg/m 2 in the Phase 1 portion of the study. 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 87 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 hydrochloride (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 HCl 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 NHL patients, 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 Absorption Following a single IV dose of bendamustine hydrochloride C max typically occurred at the end of infusion. The dose proportionality of bendamustine has not been studied. 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 dihydroxy-bendamustine (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 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 of Bendamustine on CYP Substrates Bendamustine did not inhibit CYP1A2, 2C9/10, 2D6, 2E1, or 3A4/5. Bendamustine did not induce metabolism of CYP1A2, CYP2… [Excerpted — this section continues on DailyMed.]

🧬 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 212 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Safe Handling and Disposal Bendamustine hydrochloride 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 Bendamustine hydrochloride for Injection, USP.

The use of gloves and safety glasses is recommended to avoid exposure in case of breakage of the vial or other accidental spillage. If gloves come in contact with Bendamustine hydrochloride for Injection, USP prior to dilution, remove gloves and follow disposal procedures 1 . If a solution of bendamustine hydrochloride contacts the skin, wash the skin immediately and thoroughly with soap and water.

If bendamustine hydrochloride contacts the mucous membranes, flush thoroughly with water. How Supplied Bendamustine hydrochloride for Injection, USP is supplied in individual cartons as follows: NDC 16729-250-03: 25 mg white to off-white lyophilized powder in a 10 mL amber single-dose vial NDC 16729-251-05: 100 mg white to off-white lyophilized powder in a 20 mL amber single-dose vial Storage Bendamustine hydrochloride for Injection, USP (25 mg/vial or 100 mg/vial lyophilized powder) Bendamustine hydrochloride for Injection, USP may be stored up to 25°C (77°F) with excursions permitted up to 30°C (86°F) (see USP Controlled Room Temperature).

Retain in original package until time of use to protect from light.

📋 Description 145 words ▾

11 DESCRIPTION Bendamustine hydrochloride is an alkylating agent. The chemical name of bendamustine hydrochloride, USP 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: Bendamustine hydrochloride for Injection, USP (25 mg/vial or 100 mg/vial lyophilized powder) Bendamustine hydrochloride for Injection, USP for intravenous use is supplied as a sterile non-pyrogenic white to off-white lyophilized powder in a single-dose vial. Each 25-mg vial contains 25 mg of bendamustine hydrochloride, USP and 42.5 mg of mannitol, USP.

Each 100-mg vial contains 100 mg of bendamustine hydrochloride, USP and 170 mg of mannitol, USP. The pH of the reconstituted solution is 2.5 to 3.5. Structural Formula

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Allergic (Hypersensitivity) Reactions Inform patients of the possibility of mild or serious allergic reactions and to immediately report rash, facial swelling, or difficulty breathing during or soon after infusion [see Warnings and Precautions ( 5.4 )] . Myelosuppression Inform patients of the likelihood that Bendamustine hydrochloride for Injection will cause a decrease in white blood cells, platelets, and red blood cells, and the need for frequent monitoring of blood counts. Advise patients 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 )] . Hepatotoxicity Inform patients of the possibility of developing liver function abnormalities and serious hepatic toxicity. Advise patients to immediately contact their health care provider if signs of liver failure occur, including jaundice, anorexia, bleeding or bruising [see Warnings and Precautions ( 5.7 )] .

Fatigue Advise patients that Bendamustine hydrochloride for 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 Bendamustine hydrochloride for 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 Bendamustine hydrochloride for Injection may cause diarrhea. Patients should report diarrhea to the physician so that symptomatic treatment may be provided [see Adverse Reactions ( 6.1 )] . Rash Advise patients that a rash or itching may occur during treatment with Bendamustine hydrochloride for Injection.

Advise patients to immediately report severe or worsening rash or itching [see Warnings and Precautions ( 5.6 )] . 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 ( 8.1 , 8.3 ), and Nonclinical Toxicology ( 13.1 )] . Advise female patients of reproductive potential to use effective contraception during treatment with Bendamustine hydrochloride for Injection 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 Bendamustine hydrochloride for Injection 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 Bendamustine hydrochloride for Injection and for 1 week after the last dose [see Use in Specific Populations ( 8.2 )] . Infertility Advise males of reproductive potential that Bendamustine hydrochloride for Injection may impair fertility [see Use in Specific Populations ( 8.3 )] . Manufactured For: Accord Healthcare, Inc., 8041 Arco Corporate Drive, Suite 200, Raleigh, NC 27617, USA.

Manufactured By: Intas Pharmaceuticals Limited, Plot No. : 457, 458, Village – Matoda, Bavla Road, Ta.- Sanand, Dist.- Ahmedabad – 382 210. India. 10 3737 2 6026184 Issued October 2023

🍼 Nursing Mothers 67 words ▾

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 bendamustine hydrochloride, and for 1 week after the last dose.

🧬 Pharmacokinetics ~2 min read ▾

12.3Pharmacokinetics Absorption Following a single IV dose of bendamustine hydrochloride C max typically occurred at the end of infusion. The dose proportionality of bendamustine has not been studied. 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 dihydroxy-bendamustine (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 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 of Bendamustine on CYP Substrates Bendamustine did not inhibit CYP1A2, 2C9/10, 2D6, 2E1, or 3A4/5. Bendamustine did not induce metabolism of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2E1, or CYP3A4/5.

Effect of Transporters on Bendamustine Hydrochloride Bendamustine is a substrate of P-glycoprotein and breast cancer resistance protein (BCRP).

🧬 Pharmacodynamics 101 words ▾

12.2Pharmacodynamics Based on the pharmacokinetics/pharmacodynamics analyses of data from adult NHL patients, 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.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Chronic Lymphocytic Leukemia (CLL) The safety and efficacy of bendamustine hydrochloride were evaluated in an open-label, randomized, controlled multicenter trial comparing bendamustine hydrochloride to chlorambucil. The trial was conducted in 301 previously-untreated patients with Binet Stage B or C (Rai Stages I - IV) CLL requiring treatment. Need-to-treat criteria included hematopoietic insufficiency, B-symptoms, rapidly progressive disease or risk of complications from bulky lymphadenopathy.

Patients with autoimmune hemolytic anemia or autoimmune thrombocytopenia, Richter’s syndrome, or transformation to prolymphocytic leukemia were excluded from the study. The patient populations in the bendamustine hydrochloride and chlorambucil treatment groups were balanced with regard to the following baseline characteristics: age (median 63 vs. 66 years), gender (63% vs.

61% male), Binet stage (71% vs. 69% Binet B), lymphadenopathy (79% vs. 82%), enlarged spleen (76% vs.

80%), enlarged liver (48% vs. 46%), hypercellular bone marrow (79% vs. 73%), “B” symptoms (51% vs.

53%), lymphocyte count (mean 65.7x10 9 /L vs. 65.1x10 9 /L), and serum lactate dehydrogenase concentration (mean 370.2 vs. 388.4 U/L).

Ninety percent of patients in both treatment groups had immuno-phenotypic confirmation of CLL (CD5, CD23 and either CD19 or CD20 or both). Patients were randomly assigned to receive either bendamustine hydrochloride at 100 mg/m 2 , administered intravenously over a period of 30 minutes on Days 1 and 2 or chlorambucil at 0.8 mg/kg (Broca’s normal weight) administered orally on Days 1 and 15 of each 28-day cycle. Efficacy endpoints of objective response rate and progression-free survival were calculated using a pre-specified algorithm based on NCI working group criteria for CLL.

The results of this open-label randomized study demonstrated a higher rate of overall response and a longer progression-free survival for bendamustine hydrochloride compared to chlorambucil (see Table 5). Survival data are not mature. Table 5: Efficacy Data for CLL Bendamustine hydrochloride (N=153) Chlorambucil (N=148) p-value Response Rate n (%) Overall response rate 90 (59) 38 (26) <0.0001 (95% CI) (51.0, 66.6) (18.6, 32.7) Complete response (CR)* 13 (8) 1 (<1) Nodular partial response (nPR)** 4 (3) 0 Partial response (PR) † 73 (48) 37 (25) Progression-Free Survival †† Median, months (95% CI) 18 (11.7, 23.5) 6 (5.6, 8.6) Hazard ratio (95% CI) 0.27 (0.17, 0.43) <0.0001 CI = confidence interval * CR was defined as peripheral lymphocyte count ≤ 4.0 x 10 9 /L, neutrophils ≥ 1.5 x 10 9 /L, platelets >100 x 10 9 /L, hemoglobin > 110g/L, without transfusions, absence of palpable hepatosplenomegaly, lymph nodes ≤ 1.5 cm, < 30% lymphocytes without nodularity in at least a normocellular bone marrow and absence of “B” symptoms.

The clinical and laboratory criteria were required to be maintained for a period of at least 56 days. ** nPR was defined as described for CR with the exception that the bone marrow biopsy shows persistent nodules. † PR was defined as ≥ 50% decrease in peripheral lymphocyte count from the pretreatment baseline value, and either ≥50% reduction in lymphadenopathy, or ≥50% reduction in the size of spleen or liver, as well as one of the following hematologic improvements: neutrophils ≥ 1.5 x 10 9 /L or 50% improvement over baseline, platelets >100 x 10 9 /L or 50% improvement over baseline, hemoglobin >110g/L or 50% improvement over baseline without transfusions, for a period of at least 56 days. †† PFS was defined as time from randomization to progression or death from any cause.

Kaplan-Meier estimates of progression-free survival comparing bendamustine hydrochloride with chlorambucil are shown in Figure 1. Figure 1. Progression-Free Survival

14.2Non-Hodgkin Lymphoma (NHL) The efficacy of bendamustine hydrochloride was evaluated in a single arm study of 100 patients with indolent B-cell NHL that had progressed during or within… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 198 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Bendamustine was carcinogenic in mice. After intraperitoneal injections at 37.5 mg/m 2 /day (the lowest dose tested, approximately 0.3 times the maximum recommended human dose [MRHD])) and 75 mg/m 2 /day (approximately 0.6 times the MRHD) for 4 days, peritoneal sarcomas in female AB/Jena mice were produced. Oral administration at 187.5 mg/m 2 /day (the only dose tested, approximately 1.6 times the MRHD) for 4 days induced mammary carcinomas and pulmonary adenomas.

Bendamustine is a mutagen and clastogen. In a bacterial reverse mutation assay (Ames assay), bendamustine was shown to increase revertant frequency in the absence and presence of metabolic activation. Bendamustine was clastogenic in human lymphocytes in vitro, and in rat bone marrow cells in vivo (increase in micronucleated polychromatic erythrocytes) from 37.5 mg/m 2 (the lowest dose tested, approximately 0.3 times the MRHD).

Bendamustine induced morphologic abnormalities in spermatozoa in mice. Following tail vein injection of bendamustine at 120 mg/m 2 or a saline control on days 1 and 2 for a total of 3 weeks, the number of spermatozoa with morphologic abnormalities was 16% higher in the bendamustine-treated group as compared to the saline control group.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 195 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Bendamustine was carcinogenic in mice. After intraperitoneal injections at 37.5 mg/m 2 /day (the lowest dose tested, approximately 0.3 times the maximum recommended human dose [MRHD])) and 75 mg/m 2 /day (approximately 0.6 times the MRHD) for 4 days, peritoneal sarcomas in female AB/Jena mice were produced. Oral administration at 187.5 mg/m 2 /day (the only dose tested, approximately 1.6 times the MRHD) for 4 days induced mammary carcinomas and pulmonary adenomas.

Bendamustine is a mutagen and clastogen. In a bacterial reverse mutation assay (Ames assay), bendamustine was shown to increase revertant frequency in the absence and presence of metabolic activation. Bendamustine was clastogenic in human lymphocytes in vitro, and in rat bone marrow cells in vivo (increase in micronucleated polychromatic erythrocytes) from 37.5 mg/m 2 (the lowest dose tested, approximately 0.3 times the MRHD).

Bendamustine induced morphologic abnormalities in spermatozoa in mice. Following tail vein injection of bendamustine at 120 mg/m 2 or a saline control on days 1 and 2 for a total of 3 weeks, the number of spermatozoa with morphologic abnormalities was 16% higher in the bendamustine-treated group as compared to the saline control group.

📚 References 8 words ▾

15 REFERENCES OSHA Hazardous Drugs. OSHA . http://www.osha.gov/SLTC/hazardousdrugs/index.html

📄 Package Label / Principal Display Panel 20 words ▾

PRINCIPAL DISPLAY PANEL Bendamustine label

PRINCIPAL DISPLAY PANEL Bendamustine label

PRINCIPAL DISPLAY PANEL Bendamustine label

PRINCIPAL DISPLAY PANEL Bendamustine label

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

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
Rash557
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

Hospitalization4,484
Death2,055
Life-threatening607
Disabling176
Reports over time (by year) — tap or hover for the count & year
2023 2024 2025 2026 1,068 160
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.

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
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“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.
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Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
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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 Accord Healthcare, Inc.. Listing status can change — the directory data on this page refreshes weekly.
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Accord Healthcare, 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.
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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 J9033 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.
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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.