Bendamustine

Source: Wikipedia, the free encyclopedia.
Bendamustine
Clinical data
Trade namesTreanda, others
Other namesSDX-105
AHFS/Drugs.comMonograph
MedlinePlusa608034
License data
Intravenous infusion
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityNA (intravenous only)
Protein binding94–96%
MetabolismHydrolyzed to inactive metabolites. Two minor metabolites (M3 and M4) formed by CYP1A2
Elimination half-life40 min (bendamustine), 3 h (M3), 30 min (M4)
Excretion~50% urinary, ~25% fecal [2]
Identifiers
  • 4-[5-[Bis(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl]butanoic acid
JSmol)
  • ClCCN(c2ccc1c(nc(n1C)CCCC(=O)O)c2)CCCl
  • 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) checkY
  • Key:YTKUWDBFDASYHO-UHFFFAOYSA-N checkY
  (verify)

Bendamustine, sold under the brand name Treanda among others, is a

injection into a vein.[3]

Common side effects include

allergic reactions and increased risk of infection.[3] Use in pregnancy is known to harm the baby.[3] Bendamustine is in the alkylating agents family of medication.[3] It works by interfering with the function of DNA and RNA.[3]

Bendamustine was approved for medical use in the United States in 2008.[3] It is on the World Health Organization's List of Essential Medicines.[5][6] It was originally made from nitrogen mustard.[3]

Medical uses

Bendamustine has been used both as sole therapy and in combination with other agents including etoposide, fludarabine, mitoxantrone, methotrexate, prednisone, rituximab, vincristine and 90Y-ibritumomab tiuxetan.[citation needed]

Lymphomas

Adult Atypical Sporadic Burkitt Lymphoma successfully treated with Bendamustine and Rituximab

One combination for stage III/IV relapsed or refractory indolent

R-CHOP treatment.[9]

Adverse effects

Common adverse reactions are typical for the class of nitrogen mustards, and include nausea, fatigue, vomiting, diarrhea, fever, constipation, loss of appetite, cough, headache, unintentional weight loss, difficulty breathing, rashes, and stomatitis, as well as immunosuppression, anemia, and low platelet counts. Notably, this drug has a low incidence of hair loss (

alopecia) unlike most other chemotherapy drugs.[10]

Warning

Bendamustine solution is not compatible with Closed System Transfer Devices (CSTD) Situation: *Most CSTD vendors have adapted their system to become compatible.

  • FDA issued a warning on March 11, 2015, not to use bendamustine solution with CSTDs, adapters and syringes which contain either polycarbonate or acrylonitrile-butadiene-styrene (ABS) due to the incompatibility with N,N-dimethylacetamide (DMA).

Background:

  • PhaSealR & SpirosR CSTDs contain either polycarbonate or ABS can dissolve when coming into contact with bendamustine (which contains DMA).

Assessment:

  • This can lead to device failure, possible product contamination, and potential serious adverse health consequences, including skin reactions in health care professionals preparing and administering this product and the risk of small blood vessel blockage in patients.

Recommendations:

  • Immediately, stop using all PhaSealR &/or SpirosR products including adapters when preparing & administering bendamustine.
  • Only use polypropylene syringes with bendamustine. These syringes are translucent in appearance.
  • Continue to use all universal PPE & safety precautions for hazardous drugs when preparing & administering bendamustine.

Pharmacology

Bendamustine is a white, water-soluble microcrystalline powder with amphoteric properties. It acts as an alkylating agent causing intra-strand and inter-strand cross-links between DNA bases.

After intravenous infusion it is extensively metabolised in the

cytochrome p450. More than 95% of the drug is bound to protein – primarily albumin. Only free bendamustine is active. Elimination is biphasic with a half-life of 6–10 minutes and a terminal half-life of approximately 30 minutes. It is eliminated primarily through the kidneys
.

History

Bendamustine was first made in 1963 by Ozegowski and Krebs in

non-Hodgkin's lymphoma, multiple myeloma and lung cancer
.

Bendamustine received its first marketing approval in Germany, where it is marketed under the tradename Ribomustin, by Astellas Pharma GmbH's licensee, Mundipharma International Corporation Limited. It is indicated as a single-agent or in combination with other anti-cancer agents for indolent

non-Hodgkin's lymphoma
, multiple myeloma, and chronic lymphocytic leukemia. SymBio Pharmaceuticals Ltd. holds exclusive rights to develop and market bendamustine HCl in Japan and selected Asia Pacific Rim countries.

In March 2008, Cephalon received approval from the United States Food and Drug Administration to market bendamustine in the US, where it is sold under the tradename Treanda, for treatment of chronic lymphocytic leukemia.[12]

In October 2008, the FDA granted further approval to market Treanda for the treatment of indolent B-cell non-Hodgkin's lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.[13]

Research

It is also being studied for the treatment of sarcoma.[14] It is also being investigated in phase II trials for the non-cancer treatment of AL amyloidosis.[15]

References

  1. ^ "Prescription medicines: registration of new chemical entities in Australia, 2014". Therapeutic Goods Administration (TGA). 21 June 2022. Archived from the original on 10 April 2023. Retrieved 10 April 2023.
  2. PMID 23322528
    .
  3. ^ a b c d e f g h i "Bendamustine Hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
  4. ISBN 9780857111562
    .
  5. hdl:10665/325771
    . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  6. hdl:10665/345533
    . WHO/MHP/HPS/EML/2021.02.
  7. S2CID 2381354
    .
  8. ^ Susman E (December 2012). Zaleznik DF (ed.). "New Combo Replaces CHOP for Lymphoma". MedPageToday. Archived from the original on 2014-09-11.
  9. ^ Mundell EJ (June 3, 2012). "'Rediscovered' Lymphoma Drug Helps Double Survival: Study". U.S. News & World Report. Archived from the original on July 12, 2012.
  10. S2CID 25605764
    .
  11. doi:10.1002/prac.19630200310
    .
  12. ^ "Cephalon Receives FDA Approval for TREANDA, a Novel Chemotherapy for Chronic Lymphocytic Leukemia". Cephalon press release. Archived from the original on 2008-04-21. Retrieved 2008-03-23.
  13. ^ "Cephalon Receives FDA Approval for TREANDA to Treat Patients with Relapsed Indolent Non-Hodgkin's Lymphoma". Cephalon press release. Archived from the original on 2008-12-07. Retrieved 2008-11-03.
  14. PMID 17726779
    .
  15. ^ Lagos GG, Lentzsch S, Comenzo RL, Zonder JA, Osman K, Gould J, et al. (8 December 2017). "Long Term Follow up of Patients with Relapsed/Refractory Systemic Light Chain (AL) Amyloidosis Treated with Bendamustine and Dexamethasone in a Phase 2 Study". Blood. 130 (supplement 1): 1838.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Bendamustine&oldid=1211492126"