Bendamustine

From Self-sufficiency
Jump to: navigation, search
Bendamustine
File:Bendamustine.png
Systematic (IUPAC) name
4-[5-[Bis(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl]butanoic acid
Clinical data
[[Regulation of therapeutic goods |Template:Engvar data]]
Pregnancy
category
  • US: D (Evidence of risk)
Routes of
administration
Intravenous infusion
Legal status
Legal status
Pharmacokinetic data
Bioavailability NA (intravenous only)
Protein binding 94–96%
Metabolism Hydrolyzed to inactive metabolites. Two minor metabolites (M3 and M4) formed by CYP1A2
Biological half-life 40 min (bendamustine), 3 h (M3), 30 min (M4)
Excretion Mostly fecal
Identifiers
CAS Number 16506-27-7
ATC code L01AA09 (WHO)
PubChem CID 65628
Chemical data
Formula C16H21Cl2N3O2
Molar mass 358.262 g/mol[[Script error: No such module "String".]]
Script error: No such module "TemplatePar".Expression error: Unexpected < operator.

Bendamustine (INN, trade names Ribomustin and Treanda; also known as SDX-105) is a nitrogen mustard used in the treatment of chronic lymphocytic leukemias (CLL)[1] and lymphomas. It belongs to the family of drugs called alkylating agents. It is also being studied for the treatment of sarcoma.[2]

History

Bendamustine was first synthesized in 1963 by Ozegowski and Krebs in East Germany (the former German Democratic Republic). It is a white, water soluble microcrystalline powder with amphoteric properties. Until 1990 it was available only in East Germany. East German investigators found that it was useful for treating chronic lymphocytic leukemia, Hodgkin’s disease, non-Hodgkin’s lymphoma, multiple myeloma and lung cancer.

Bendamustine received its first marketing approval in Germany, which is marketed under the tradename Ribomustin, by Astellas Pharma GmbH's licensee, Mundipharma International Corporation Limited, which it is indicated as a single-agent or in combination with other anti-cancer agents for indolent NHL, multiple myeloma, and CLL. 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 CLL.[3]

In October 2008, the FDA granted further approval to market Treanda for the treatment of indolent B-cell non-Hodgkin's lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. [4]

Pharmacology

Betamustine 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 liver by cytochrome p450. >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 by the renal route.

Chemotherapeutic 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.

One combination for stage III/IV relapsed or refractory indolent lymphomas and mantle cell lymphoma (MCL), with or without prior rituximab-containing chemoimmunotherapy treatment, is bendamustine with mitoxantrone and rituximab.[5]

Adverse effects

Common adverse reactions are typical for its class of chemotherapeutic drugs, 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.

References

Cite error: Invalid <references> tag; parameter "group" is allowed only.

Use <references />, or <references group="..." />

External links

  1. Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  2. Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  3. "Cephalon press release - Cephalon Receives FDA Approval for TREANDA, a Novel Chemotherapy for Chronic Lymphocytic Leukemia". Retrieved 2008-03-23. 
  4. "Cephalon press release -Cephalon Receives FDA Approval for TREANDA to Treat Patients with Relapsed Indolent Non-Hodgkin's Lymphoma". Retrieved 2008-11-03. 
  5. Weide R, Hess G, Köppler H, et al. (2007) High anti–lymphoma activity of bendamustine/mitoxantrone/rituximab in rituximab pretreated relapsed or refractory indolent lymphomas and mantle cell lymphomas. A muticenter phase II study of the German Low Grade Lymphoma Study Group (GLSG). Leuk. Lymphoma. 48:1299–1306