Identification
- Summary
Bendamustine is an antineoplastic agent used for the treatment of chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed following rituximab therapy.
- Brand Names
- Belrapzo, Bendeka, Treanda, Vivimusta
- Generic Name
- Bendamustine
- DrugBank Accession Number
- DB06769
- Background
Bendamustine is a nitrogen mustard drug indicated for use in the treatment of chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. Bendamustine is a bifunctional mechlorethamine derivative capable of forming electrophilic alkyl groups that covalently bond to other molecules. Through this function as an alkylating agent, bendamustine causes intra- and inter-strand crosslinks between DNA bases resulting in cell death. It is active against both active and quiescent cells, although the exact mechanism of action is unknown.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Bendamustine (DB06769)
- Weight
- Average: 358.263
Monoisotopic: 357.101082345 - Chemical Formula
- C16H21Cl2N3O2
- Synonyms
- Bendamustina
- Bendamustine
- Ribomustine
- External IDs
- SDX 105
- SDX-105
- SDX105
Pharmacology
- Indication
Bendamustine is indicated for use in the treatment of chronic lymphocytic leukemia (CLL) and indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.
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- Contraindications & Blackbox Warnings
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No mean changes in QTc interval greater than 20 milliseconds were detected up to one hour post-infusion.
- Mechanism of action
Bendamustine is a bifunctional mechlorethamine derivative capable of forming electrophilic alkyl groups that covalently bond to other molecules. Through this function as an alkylating agent, bendamustine causes intra- and inter-strand crosslinks between DNA bases resulting in cell death. It is active against both active and quiescent cells, although the exact mechanism of action is unknown.
- Absorption
Following a single IV dose of bendamustine hydrochloride Cmax typically occurred at the end of infusion. The dose proportionality of bendamustine has not been studied.
- Volume of distribution
The mean steady-state volume of distribution (Vss) of bendamustine was approximately 20-25 L. Steady-state volume of distribution for total radioactivity was approximately 50 L, indicating that neither bendamustine nor total radioactivity are extensively distributed into the tissues.
- Protein binding
In vitro, the binding of bendamustine to human serum plasma proteins ranged from 94-96% and data suggest that bendamustine is not likely to displace or to be displaced by highly protein-bound drugs.
- Metabolism
In vitro data indicate that bendamustine is primarily metabolized via hydrolysis to monohydroxy (HP1) and dihydroxy-bendamustine (HP2) metabolites with low cytotoxic activity. Two active minor metabolites, M3 and M4, are primarily formed via CYP1A2. However, concentrations of these metabolites in plasma are 1/10th and 1/100th that of the parent compound, respectively, suggesting that the cytotoxic activity is primarily due to bendamustine. Results of a human mass balance study confirm that bendamustine is extensively metabolized via hydrolytic, oxidative, and conjugative pathways.
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- Route of elimination
Mean recovery of total radioactivity in cancer patients following IV infusion of [14C] bendamustine hydrochloride was approximately 76% of the dose. Approximately 50% of the dose was recovered in the urine and approximately 25% of the dose was recovered in the feces. Urinary excretion was confirmed as a relatively minor pathway of elimination of bendamustine, with approximately 3.3% of the dose recovered in the urine as parent. 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.
- Half-life
40 minutes
- Clearance
700 mL/min
- Adverse Effects
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Risk for tumor-lysis syndrome. Discontinue use in the event of severe/progressive skin reactions. Hematologic malignancies of different forms reported. Discontinue use in the case of severe infusion reactions. May cause extravasation. Mild to moderate renal impairment. Mild hepatic impairment. Sepsis (infections) may occur. Avoid use if pregnant. Possibility of anaphylaxis or infusion reactions- severe in rare cases.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Bendamustine can be increased when it is combined with Abametapir. Abatacept The metabolism of Bendamustine can be increased when combined with Abatacept. Abciximab The risk or severity of bleeding can be increased when Abciximab is combined with Bendamustine. Abiraterone The serum concentration of Bendamustine can be increased when it is combined with Abiraterone. Abrocitinib The serum concentration of Bendamustine can be increased when it is combined with Abrocitinib. Acenocoumarol The metabolism of Bendamustine can be decreased when combined with Acenocoumarol. Acetaminophen The metabolism of Bendamustine can be decreased when combined with Acetaminophen. Acetylsalicylic acid The risk or severity of bleeding can be increased when Acetylsalicylic acid is combined with Bendamustine. Acyclovir The metabolism of Bendamustine can be decreased when combined with Acyclovir. Adagrasib The serum concentration of Bendamustine can be increased when it is combined with Adagrasib. 
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- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Bendamustine hydrochloride 981Y8SX18M 3543-75-7 ZHSKUOZOLHMKEA-UHFFFAOYSA-N Bendamustine hydrochloride monohydrate X15906D285 1374784-02-7 TWBJYCLUHINEDN-UHFFFAOYSA-N - International/Other Brands
- Levact (NAPP Pharmaceuticals ) / Treakisym (Teva Pharmaceutical Industries Ltd.)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Belrapzo Injection 100 mg/1 Intravenous Eagle Pharmaceuticals, Inc 2019-06-03 Not applicable US 
Bendamustine Hydrochloride Injection, solution 25 mg/1mL Intravenous Apotex Corp 2023-04-26 Not applicable US Bendamustine Hydrochloride Injection 100 mg/1 Intravenous Eagle Pharmaceuticals, Inc 2018-05-15 2020-09-30 US Bendamustine Hydrochloride Injection 100 mg/1 Intravenous Baxter Healthcare Corporation 2022-12-15 Not applicable US Bendamustine Hydrochloride for Injection Powder, for solution 25 mg / vial Intravenous Hikma Canada Limited Not applicable Not applicable Canada 
Bendamustine Hydrochloride for Injection Powder, for solution 25 mg / vial Intravenous Auro Pharma Inc 2021-03-02 Not applicable Canada Bendamustine Hydrochloride for Injection Powder, for solution 100 mg / vial Intravenous Mylan Pharmaceuticals 2021-03-12 Not applicable Canada Bendamustine Hydrochloride for Injection Powder, for solution 25 mg / vial Intravenous Accord Healthcare Inc 2021-03-02 Not applicable Canada Bendamustine Hydrochloride for Injection Powder, for solution 100 mg / vial Intravenous Jamp Pharma Corporation 2021-05-06 Not applicable Canada Bendamustine Hydrochloride for Injection Powder, for solution 25 mg / vial Intravenous Mylan Pharmaceuticals 2021-05-28 Not applicable Canada - Generic Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Bendamustine Hydrochloride Injection, powder, lyophilized, for solution 25 mg/5mL Intravenous Accord Healthcare, Inc. 2022-12-07 Not applicable US Bendamustine Hydrochloride Injection, powder, lyophilized, for solution 100 mg/20mL Intravenous Mylan Institutional LLC 2018-04-26 Not applicable US Bendamustine Hydrochloride Injection, powder, lyophilized, for solution 25 mg/5mL Intravenous BluePoint Laboratories 2023-02-22 Not applicable US Bendamustine Hydrochloride Injection, powder, lyophilized, for solution 25 mg/5mL Intravenous Mylan Institutional LLC 2018-04-26 Not applicable US Bendamustine Hydrochloride Injection, powder, lyophilized, for solution 100 mg/20mL Intravenous Accord Healthcare, Inc. 2022-12-07 Not applicable US Bendamustine Hydrochloride Injection, powder, lyophilized, for solution 100 mg/20mL Intravenous BluePoint Laboratories 2023-02-22 Not applicable US Nat-bendamustine Powder, for solution 100 mg / vial Intravenous Natco Pharma Limited 2021-02-25 Not applicable Canada Nat-bendamustine Powder, for solution 25 mg / vial Intravenous Natco Pharma Limited 2021-02-25 Not applicable Canada
Categories
- ATC Codes
- L01AA09 — Bendamustine
- Drug Categories
- Acids, Acyclic
- Alkylating Activity
- Alkylating Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Alkylating
- Antineoplastic and Immunomodulating Agents
- Benzimidazoles
- Butyrates
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Substrates
- Heterocyclic Compounds, Fused-Ring
- Hydrocarbons, Halogenated
- Immunosuppressive Agents
- Mustard Compounds
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- Nitrogen Mustard Analogues
- Nitrogen Mustard Compounds
- Noxae
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Toxic Actions
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as benzimidazoles. These are organic compounds containing a benzene ring fused to an imidazole ring (five member ring containing a nitrogen atom, 4 carbon atoms, and two double bonds).
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Benzimidazoles
- Sub Class
- Not Available
- Direct Parent
- Benzimidazoles
- Alternative Parents
- Nitrogen mustard compounds / Dialkylarylamines / N-substituted imidazoles / Benzenoids / Heteroaromatic compounds / Amino acids / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds show 5 more
- Substituents
- Alkyl chloride / Alkyl halide / Amine / Amino acid / Amino acid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzenoid / Benzimidazole show 20 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 9266D9P3PQ
- CAS number
- 16506-27-7
- InChI Key
- YTKUWDBFDASYHO-UHFFFAOYSA-N
- InChI
- InChI=1S/C16H21Cl2N3O2/c1-20-14-6-5-12(21(9-7-17)10-8-18)11-13(14)19-15(20)3-2-4-16(22)23/h5-6,11H,2-4,7-10H2,1H3,(H,22,23)
- IUPAC Name
- 4-{5-[bis(2-chloroethyl)amino]-1-methyl-1H-1,3-benzodiazol-2-yl}butanoic acid
- SMILES
- CN1C(CCCC(O)=O)=NC2=CC(=CC=C12)N(CCCl)CCCl
References
- General References
- Hartmann JT, Mayer F, Schleicher J, Horger M, Huober J, Meisinger I, Pintoffl J, Kafer G, Kanz L, Grunwald V: Bendamustine hydrochloride in patients with refractory soft tissue sarcoma: a noncomparative multicenter phase 2 study of the German sarcoma group (AIO-001). Cancer. 2007 Aug 15;110(4):861-6. [Article]
- Bagchi S: Bendamustine for advanced sarcoma. Lancet Oncol. 2007 Aug;8(8):674. [Article]
- Dennie TW, Kolesar JM: Bendamustine for the treatment of chronic lymphocytic leukemia and rituximab-refractory, indolent B-cell non-Hodgkin lymphoma. Clin Ther. 2009;31 Pt 2:2290-311. doi: 10.1016/j.clinthera.2009.11.031. [Article]
- Teichert J, Baumann F, Chao Q, Franklin C, Bailey B, Hennig L, Caca K, Schoppmeyer K, Patzak U, Preiss R: Characterization of two phase I metabolites of bendamustine in human liver microsomes and in cancer patients treated with bendamustine hydrochloride. Cancer Chemother Pharmacol. 2007 May;59(6):759-70. Epub 2006 Sep 7. [Article]
- Darwish M, Bond M, Hellriegel E, Robertson P Jr, Chovan JP: Pharmacokinetic and pharmacodynamic profile of bendamustine and its metabolites. Cancer Chemother Pharmacol. 2015 Jun;75(6):1143-54. doi: 10.1007/s00280-015-2727-6. Epub 2015 Apr 1. [Article]
- External Links
- KEGG Drug
- D07085
- PubChem Compound
- 65628
- PubChem Substance
- 310264882
- ChemSpider
- 59069
- BindingDB
- 173621
- 134547
- ChEBI
- 135515
- ChEMBL
- CHEMBL487253
- ZINC
- ZINC000004214955
- Wikipedia
- Bendamustine
- FDA label
- Download (170 KB)
- MSDS
- Download (174 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Advanced Follicular Lymphoma 1 4 Completed Treatment Chronic Lymphocytic Leukemia 1 3 Active Not Recruiting Treatment Chronic Lymphocytic Leukemia 2 3 Active Not Recruiting Treatment Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma 2 3 Active Not Recruiting Treatment Follicular Lymphoma ( FL) 2 3 Active Not Recruiting Treatment Lymphoma 1 3 Active Not Recruiting Treatment Mantle Cell Lymphoma (MCL) 1 3 Active Not Recruiting Treatment Non-Hodgkin's Lymphoma (NHL) 1 3 Active Not Recruiting Treatment Refractory Angioimmunoblastic T-cell Lymphoma / Relapsed Angioimmunoblastic T-Cell Lymphoma 1 3 Active Not Recruiting Treatment Stage I Chronic Lymphocytic Leukemia / Stage II Chronic Lymphocytic Leukemia / Stage III Chronic Lymphocytic Leukemia / Stage IV Chronic Lymphocytic Leukemia 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Intravenous 100 mg Injection Intravenous 25 mg Injection, powder, lyophilized, for solution Intravenous 100.00 mg Injection, powder, lyophilized, for solution Intravenous 25.00 mg Injection, solution, concentrate Intravenous 100 mg Injection, powder, for solution Parenteral 2.5 mg/ml Injection, powder, for solution Parenteral Injection Intravenous 100 mg/1 Injection, powder, lyophilized, for solution Intravenous 100 mg/20mL Injection, powder, lyophilized, for solution Intravenous 25 mg/5mL Powder 100 mg Powder 25 mg Injection, solution Intravenous 25 mg/1mL Injection Intravenous Solution Intravenous 25 mg / mL Injection, powder, lyophilized, for solution Intravenous Solution Intravenous 45 mg / mL Injection Parenteral 100 mg Injection Parenteral 25 mg Injection, powder, for solution Solution, concentrate Intravenous 45 mg Injection, powder, for solution; powder Powder Powder 100 mg/1vial Injection, powder, for solution Intravenous Powder 25 mg/1vial Injection, solution, concentrate Intravenous; Parenteral 180 MG/4ML Injection, powder, lyophilized, for solution Intravenous 100 mg Injection, powder, lyophilized, for solution Intravenous 25 mg Injection, solution, concentrate Intravenous 180 mg/2mL Injection, solution, concentrate Intravenous 45 mg/0.5mL Powder, for solution Intravenous 100 mg / vial Powder, for solution Intravenous 25 mg / vial Injection Intravenous 25 mg/1mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8791270 Yes 2014-07-29 2026-07-12 US US8344006 Yes 2013-01-01 2030-03-23 US US8445524 Yes 2013-05-21 2029-09-26 US US8669279 Yes 2014-03-11 2029-09-26 US US8883836 Yes 2014-11-11 2029-09-26 US US8436190 Yes 2013-05-07 2031-04-26 US US8895756 Yes 2014-11-25 2026-07-12 US US8609863 Yes 2013-12-17 2026-07-12 US US9034908 No 2015-05-19 2033-03-15 US US9144568 No 2015-09-29 2033-03-15 US US9000021 No 2015-04-07 2033-03-15 US US8609707 No 2013-12-17 2031-08-11 US US9265831 No 2016-02-23 2031-01-28 US US9533955 Yes 2017-01-03 2029-09-26 US US9597397 No 2017-03-21 2033-03-15 US US9597399 No 2017-03-21 2033-03-15 US US9597398 No 2017-03-21 2033-03-15 US US9579384 No 2017-02-28 2033-03-15 US US9572797 No 2017-02-21 2031-01-28 US US9572796 No 2017-02-21 2031-01-28 US US9572887 No 2017-02-21 2033-03-15 US US10010533 No 2018-07-03 2031-01-28 US US10052385 No 2018-08-21 2033-03-15 US US11103483 No 2021-08-31 2031-01-28 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0618 mg/mL ALOGPS logP 3.07 ALOGPS logP 1.8 Chemaxon logS -3.8 ALOGPS pKa (Strongest Acidic) 4.36 Chemaxon pKa (Strongest Basic) 6.41 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 58.36 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 92.92 m3·mol-1 Chemaxon Polarizability 38.19 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9947 Blood Brain Barrier + 0.773 Caco-2 permeable + 0.5348 P-glycoprotein substrate Substrate 0.6887 P-glycoprotein inhibitor I Non-inhibitor 0.8236 P-glycoprotein inhibitor II Non-inhibitor 0.7294 Renal organic cation transporter Non-inhibitor 0.5462 CYP450 2C9 substrate Non-substrate 0.7141 CYP450 2D6 substrate Non-substrate 0.7322 CYP450 3A4 substrate Substrate 0.5545 CYP450 1A2 substrate Non-inhibitor 0.8012 CYP450 2C9 inhibitor Non-inhibitor 0.9027 CYP450 2D6 inhibitor Non-inhibitor 0.878 CYP450 2C19 inhibitor Non-inhibitor 0.8587 CYP450 3A4 inhibitor Non-inhibitor 0.8756 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8882 Ames test Non AMES toxic 0.618 Carcinogenicity Non-carcinogens 0.9235 Biodegradation Not ready biodegradable 0.9798 Rat acute toxicity 3.2636 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.7196 hERG inhibition (predictor II) Non-inhibitor 0.7584
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Teichert J, Baumann F, Chao Q, Franklin C, Bailey B, Hennig L, Caca K, Schoppmeyer K, Patzak U, Preiss R: Characterization of two phase I metabolites of bendamustine in human liver microsomes and in cancer patients treated with bendamustine hydrochloride. Cancer Chemother Pharmacol. 2007 May;59(6):759-70. Epub 2006 Sep 7. [Article]
- Bendamustine FDA label [File]
Drug created at September 14, 2010 16:21 / Updated at June 06, 2023 09:53