Bendamustine

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]]	US FDA: Treanda
Pregnancy category	US: D (Evidence of risk)
Routes of administration	Intravenous infusion
Legal status
Legal status	US: ℞-only
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[[]]

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) and lymphomas. It belongs to the family of drugs called alkylating agents. It is also being studied for the treatment of sarcoma.

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.

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.

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.

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.

External links

• Manufacturer's official website intended for US patients